Dissertations / Theses on the topic 'Cardiothoracic surgery'

Bibliography: leaves 54-60.<br>From recent statistics (79,59) it has been concluded that COPD is the most common lung disease in the United States affecting almost 16 million people. The mortality is rising, COPD is the fourth most common cause of death in USA after myocardial infarctions, cancer and stroke (91). COPD is clearly under diagnosed in the early stages (101). Early smoking cessation would have an enormous impact on the progression of the disease (7,24,25,58,106).

This thesis investigated the potential of synthetic polyethylene glycol (PEG) hydrogels for restoration of biomechanical integrity and for controlled cardiac release of drugs. ... The aim of this study was to directly compare the effect of injecting an enzymatically degradable polyethylene glycol (PEG) hydrogel into the myocardium immediately or seven days after permanent ligation of the left anterior descending artery in rats on pathological remodeling.

This study was designed to investigate the role of adenosine, an endogenous cardioprotectant agent, without high potassium and as cardioplegic additive to high potassium solutions. Adenosine cardioplegia and potassium cardioplegia supplemented by adenosine (K + ADO) were investigated in terms of hemodynamic, metabolic and ultrastructural recovery in the isolated rat heart and in the in-vivo baboon model during periods of global myocardial ischemia, simulating the clinical situation during open heart surgery. The results obtained in both models show that adenosine improved postischemic hemodynamic function when used without high potassium cardioplegia. The combination of adenosine and high potassium was less effective in both models in terms of hemodynamic recovery; however, improved rhythm stability and coronary vasodilatation were still present. In addition adenosine alone was able to induce fast electromechanical arrest in the isolated rat heart. However, failure of even high concentrations of adenosine to limit ventricular fibrillation in the baboon exclude its use as cardioplegic agent on its own without additional interventions. It appears likely that adenosine without high potassium is cardioprotective via activation of A₁ receptors and opening of ATP-sensitive potassium channels, a mechanism which is probably non-functional in a high potassium environment. In view of the limited cardioprotection achieved with the combination of adenosine and high potassium further studies should aim for additional interventions to induce cardioplegia with adenosine and normokalemic solutions.

Objectives: Rheumatic heart disease remains a significant cause of morbidity and mortality and it is the leading cause of acquired paediatric cardiac disease in the developing world. The aim of this study was to understand the burden of rheumatic heart disease and to review the surgical management of rheumatic mitral valve disease at our institution. Methods: We retrospectively reviewed 76 consecutive patients who underwent mitral valve surgery for rheumatic heart disease between 1998 and 2010. The results and follow-up were reviewed, where death and reoperation were the primary endpoints. The follow up included a review of the latest information from the patients' medical records and telephonic interviews or home visits. Results: A 91% follow up was achieved over a median follow up period of 7.4 years (range 0.1-15.2 years). The mean age at surgery was 10.7 years (SD +- 2.7 years). The females constituted 66% and males 34%. Mitral valve repairs were performed in 64% of patients and of the 64% repairs, 0.06% only had commissurotomies. Replacements were performed in 36% of patients. All mitral valve replacements were mechanical prostheses. The actuarial freedom from reoperation for repairs was 83% (+-2.2) and 66% (+-3.4) at 5 and 10 years and for replacements was 87% (+-4.8) and 87%(+-4.8) respectively (p=0.27). Actuarial freedom from embolic cerebrovascular accidents in the repair group at both 5 and 10 years was 100%, compared to 90.2% (+-6.6) and 79% (+-12.0) for the replacement group at 5 and 10 years respectively (p=0.02). Actuarial freedom from death at 5 and 10 years for children over 12.8 years was 77.7% (+-9.9) and 69.1% (+-12.0) respectively, compared to 93.6% (+-3.6) and 93.6% (+-3.6) for children under 12.8 years (p=0.03). No statistical significant difference was noted in freedom from valve related failure and death between repairs and replacements. Conclusions: There was no significant difference in survival between mitral valve repairs and replacements. There was surprisingly worse survival among children who were above 12.8 years at time of the surgery.

Includes abstract.<br>Includes bibliographical references.<br>Rheumatic heart disease is still the most common cause of valvular heart lesions requiring replacement or repair procedures worldwide. In South Africa, where there is an interesting mix of first and third world dynamics, factors sustaining the epidemic of rheumatic disease are still commonplace. The choice of appropriate valve procedure and prosthesis in our setting will depend on an adequate knowledge of short and long term outcomes of valve replacement and repair. The aim of this thesis was to evaluate the demographics and presentation of our rheumatic and non-rheumatic patients and to determine if our current implantation choices could be validated.

Includes abstract.<br>Includes bibliographic references (leaves 53-62).<br>Off-pump coronary artery bypass grafting (OPCAB) was developed to avoid the deleterious effects of CPB. Current literature reveals some peri-operative advantages of OPCAB, with few studies detailing these in Africa. We review our institutional experience with both approaches in higher risk patients to determine pre-operative characteristics, short and mid-term outcomes in a developing country.

Includes bibliographical references.<br>A retrospective study was done at Red Cross Children's Hospital, Rondebosch, Cape Town in which two separate case-matched groups of children undergoing different surgical closure techniques for their isolated perimembranous ventricular septal defects were compared. Group I consisted of 77 children who had their VSDs closed between 1987 to 1990, mainly with a double velour dacron patch using interrupted alternating 5.0 silicone coated braided polyester suture ( Ticron®) and 5.0 polypropylene (Prolene®) pledgetted sutures (n=71). Five patients in Group I had bovine pericardium used and 1 patient's VSD was closed by a direct suture technique. Group II consisted of 93 children operated on between 1995 to 1998, and had their VSDs closed with a 0.6% glutaraldehyde-treated autologous pericardial patch using 5.0 polypropylene suture material in a continuous horizontal mattress suture without pledgets. Surgical time, discharge echocardiograms and follow up records were reviewed to assess the incidence of complications, reoperation or residual VSD needing further follow up.

Includes bibliographical references (leaves 45-48).<br>Retrospective institutional review of the pathology, aetiology classification and surgical management of left ventricular submitral aneurysms (LVSMA). These aneurysms are a well recognized but relatively rare disease found commonly in patients from African ancestry. The series comprises 20 consecutive patients treated surgically at three institutions from 1985 to 2002. Natural history, clinical presentation, histo-pathological findings, suspected aetiology, operative techniques, along with a discussion of the condition is presented. There were 10 female and 10 male patients and the mean age was 17+-6 (range 8-34) years. Patients were grouped as to the degree of posterior mitral annulus involvement by the aneurysm. In Group I, (n=12) a single aneurysm neck was found. In Group II, (n=3) multiple necks and in Group III, (n=5) involvement of the entire posterior annulus by teh aneurysm was found. Mean age in Group III (29 +/-5 years) was older than that of Groups I and II (15.5 +/- 4 years) suggesting a progressive nature of these aneurysms to enlarge. Clinically patients were in New YOrk Heart Association (NYHA) class I-IV. An intra-cardiac surgical approach was used in 11, extra-cardiac approach in two and a combined approach in seven patients. Mitral valve repair was attempted in 14 patients, with two intra-operative mitral valve repair failures. Failure to control the aneurysm neck (n=2) and failure of mitral valve repair (n=2) resulted in subsequent re-operation. There was no operative mortality. Histology of the aneurysm tissue suggested co-existing rheumatic heart disease in two, tuberculosis in four and infective endocarditis in two. Unknown or congenital disease was postulated in nine patients. Although LVSMA are thought to be congenital, 8 out of 20 patients (40%) had evidence of co-existent inflammatory pathology. The etiology of LVSMA remains uncertain. Many are thought to be congenital, but the findings in this study strongly support the view that rheumatic disease, chronic infections and malnutrition also play a role. A new classification is proposed based on the pathological findings. Involvement of the entire annulus in the older patients suggests a possible progressive nature of the disease. Surgery should be the difinitive therapy in all patients. Surgical approach must be individualized but the intra cardiac approach is suitable for the surgical repair in most cases. Success in mangement is dependent on the appropriate understanding of the relationship between aneurysm and valve.

There is a significant need for small diameter vascular grafts to be used in peripheral vascular surgery; however autologous grafts are not always available, synthetic grafts perform poorly and allografts and xenografts degenerate, dilate and calcify after implantation. We hypothesized that chemical stabilization of acellular xenogenic arteries would generate off-the-shelf grafts resistant to thrombosis, dilatation and calcification. To test this hypothesis, we decellularized porcine renal arteries, stabilized elastin with pentagalloyl glucose and collagen with carbodiimide/activated heparin and implanted them as trans- position grafts in the abdominal aorta of rats as direct implants and separately as indirect, isolation-loop implants. All implants resulted in high patency and animal survival rates, ubiquitous encapsulation within a vascularized collagenous capsule, and exhibited lack of lumen thrombogenicity and no graft wall calcification. Peri-anastomotic neo-intimal tissue overgrowth was a normal occurrence in direct implants; however this reaction was circumvented in indirect implants. Notably, implantation of non- treated control scaffolds exhibited marked graft dilatation and elastin degeneration; however PGG significantly reduced elastin degradation and prevented aneurismal dilatation of vascular grafts. Overall these results point to the outstanding potential of crosslinked arterial scaffolds as small diameter vascular grafts.

Infective endocarditis was initially described in the early 16th century and only methodically reviewed after the 19th century when Osler gave the drive to the Royal College of Physicians in 1885 through his contribution. The last 25 years has not shown much change in the mortality from infective endocarditis (IE) despite diagnostic and therapeutic advances. The current in-hospital mortality rate for patients with IE is 15% to 20%, with 1-year mortality approaching 40%. The morbidity associated with infective endocarditis includes valvular incompetence, embolization, cerebrovascular accidents and congestive heart failure and this has influenced the surgical options to a great extent. The EuroSCORE II is the current model available for predicting the early mortality after cardiac surgery. HYPOTHESIS: Infective endocarditis has a high risk for mortality due to certain risk factors and the currently available EuroSCORE II model may not predict early mortality accurately and may not be suitable for our patient population. OBJECTIVES: To evaluate the major risk factors for adverse short and long term outcomes in patients with active native valve infective endocarditis needing cardiac surgery, and to validate the EuroSCORE II in our cohort of patients. PATIENTS AND METHODS: A retrospective review will be undertaken on patients with infective endocarditis requiring cardiac surgery from 2000-2012 at the Christian Barnard Division of Cardiothoracic surgery (Groote Schuur Hospital, UCT Private Academic Hospital) and follow-up with respect to mortality, re-operation and major adverse cardiac events, as well as an evaluation of the validity of the EuroSCORE II. DATA COLLECTION AND ANALYSIS: The standardized data extraction form in the appendix will be used for extracting data from various databases and telephonic interviews. Data will be analyzed using STATA to determine the most significant predictors of adverse outcome and conducting Kaplan Meier actuarial analysis for early and late survival and freedom from adverse events. The EuroSCORE II will be evaluated and validated to our cohort of patients.

Introduction: Intensive research over the last six decades has resulted in minimal improvement in vascular graft development. Small animal models are the first line of species exposed to vascular graft implantation and invasive monitoring of experimental graft patency may contribute to pain, suffering, higher cost and earlier sacrifice. Non-invasive ultrasonographic evaluation of vascular implants during the conduction of animal studies allows for chronic follow-up with multiple assessments. This study aims to apply and endorse the utilization of ultrasound as a less invasive diagnostic method in determining patency of vascular grafts in units where imaging modalities like Computerized Tomography (CT) and Magnetic Resonance Imaging (MRI) are not readily available. Methods: Pre-operative control ultrasound evaluation of the ejection fraction, aortic diameter and aortic velocity were conducted on Wistar rats (250-350g). Infra-renal aortic vascular graft implantation was then performed, with 8 rats receiving straight (1.8mm ID, 18mm length) expanded polytetrafluoroethylene (ePTFE) grafts, while 12 rats received a long (1.8mm ID, 100mm length) looped ePTFE conduit with a sealed mid-graft (10mm length) section. Ultrasonography was conducted on days 1, 3, 7 and weeks 4, 8 and 12 post operatively. Grafts were explanted if there was any ultrasonographic evidence of occlusion or at twelveweek termination of the study. Explant was preceded by angiography and followed by histological assessment of the grafts for patency. Results: Three of the looped and all 8 of the straight grafts were patent at the 12 week explant time point, as correctly assessed by ultrasound and confirmed by angiography and histology. Three of the nine occluded looped grafts were explanted at eight weeks due to early ultrasonographic detection of occlusion; the remaining 6 were explanted at twelve weeks. There were two false positive results, which were incorrectly assessed as patent at twelve weeks of implantation on ultrasonographic evaluation, but confirmed to be occluded on angiography at explant. The results of ultrasonography evaluation of implanted infra-renal vascular grafts had a high specificity of 100% with a sensitivity of 78%. The outcome of the results between ultrasound and angiography corresponded in 18 out of 20 vascular grafts, with a calculated positive predictive value (PPV) of 100% and a negative predictive value (NPV) of 85%. 4 Conclusion: Ultrasound is easily available and a non-invasive diagnostic modality allowing for safe and reliable results, which may be repeated at different time frames following vascular implants in small animal models. Ultrasonographic limitations exist, emphasizing the need for an experienced operator with adequate knowledge and training. Its use may be complicated by tortuous geometries of vessels, which is technically more challenging to evaluate with ultrasound than with imaging techniques like CT and MRI. It does, however, add information without additional loss of life or increased use of animal numbers. Ultrasound is an essential additive diagnostic tool for chronic follow-up and evaluation of vascular graft implants.

The use ofCPB is associated with significant lung dysfunction. Apart from factors such as, hypothermia, systemic heparinisation, and the artificial circuit itself, lung injury can result from pulmonary IR. The lungs have a unique trimodal oxygen supply for lung tissue oxygenation; bronchial arteries, pulmonary arteries, and oxygen from alveolar ventilation. During CPB, only a compromised low pressure bronchial artery perfusion to the lupgs is maintained, therefore a certain degree of lung ischemia is inevitable. Pulmonary ischemia and subsequent reperfusion injury causes a k>cal and systemic inflammatory response, and lung cellular necrosis and apoptosis, resulting in lung dysfunction. The significance of stopping ventilation during clinical CPB in the development of lung IR and inflammation is unknown. Furthermore, apoptosis ofthe lung tissue following IR involves a complex network of interacting enzyme pathways, which over the past decade, are becoming clearer. However, the early and upstream intracellular molecules which promote the expression of these apoptotic enzymes remain to be elucidated. Microarray is a powerful tool which has been used in lung tissue to detect gene expression changes following various insults, including ventilator induced lung injury and ischemia reperfusion. The previous studies of lung IR have focus on microarray gene expression changes following lung transplant in a rodent model, and also pulmonary artery occlusion for 4 to 72 hours in a murine model. Although they are in themselves invaluable to the understanding ofgene expression changes following lung IR, nevertheless those studies do not reflect conditions oflung IR. encountered during the more common procedures ofcoronary artery bypass grafting or valve replacement when lung ischemia times are much shorter. The murine model maintains nonnal ventilation and bronchial artery blood flow to ischemic lung, which is different from lung ischemia encountered during clinical CPB when ventilation is stopped and bronchial blood flow and pressure is reduced. In the first part ofthe study, the effects ofshort durations of lung ischaemia and reperfusion (without ventilation, and with low/no bronchial artery flow), which closely reflect conditions encountered during routine clinical coronary artery bypass graft and valve surgery, on early gene expression changes in the lungs involved in pulmonary apoptosis and inflammation is investigated using an experimental rodent model oflung IR. injury. It is hoped that important insight is gained into the early mechanisms oflung IR following CPB in clinical cardiac surgery. The second part is a clinical randomized prospective study, investigating the effects ofrestoring a source ofoxygenation by maintaining ventilation to the lung during clinical CPB, and how it may affect the degree ofischemia and subsequent reperfusion injury, associated pulmonary and systemic inflammatory and cytokine responses, and cardiovascular-pulmonary function following open heart surgery. The study will improve. our understanding ofthe mechanisms behind, and the relative contribution ofstopping ventilation during CPB towards postoperative pulmonary dysfunction.

Penetrating injuries of the intrathoracic great vessels are well recognized although uncommon. In the First World War no survivors with thoracic vascular injury were recorded among soldiers treated with penetrating injuries to the chest as recorded by Makins. The first record of successful repair of a penetrating thoracic aortic injury was in 1922 by Dshanelidze in Russia. Similar to Makins' experience, De Bakey and Simeone in the Second World War recorded no surviving patients with involvem_ent of the thoracic aorta and its branches among American soldiers. Furthermore, no injuries to the thoracic aorta and its branches were recorded in Korean war soldiers undergoing vascular surgery by both Jahnke and Hughes. Rich reported 3 survivors of aortic injuries in the Vietnam war among 1000 patients with vascular injuries. By 1969 only 43 successfully treated cases had been reported but increasing numbers of patients sustaining injuries to the great arteries at the level of the thoracic inlet have been reported subsequently in civilian practice. Experience has grown over the years but patient numbers remain small and individual surgeons may only manage 2 or 3 of these patients in his life time. The largest single reported series consists of 93 patients in Memphis over a 13 year period. All victims were rapidly transported to hospital and were resuscitated en route. As a consequence, a large number critically ill patients reached hospital who may have died in earlier years. However some of these patients inevitably died in hospital contributing to the high mortality of 16, 7% reported. Our experience is different in that most of our victims who reach hospital will survive as poor community triage facilities prevent more than 95% of penetrating thoracic vascular trauma victims reaching hospital alive, hence we have a selection of less severely injured patients who eventually reach our hospital alive producing our mortality rate of 5%. Another important difference is that most of our patients suffered stab wounds as compared to gunshot wounds noted in the Memphis. Buchan and Robbs in Durban reported on 52 patients who had penetrating cervicomediastinal vascular injury with a remarkably similar experience to our own in Cape Town with the exception of a larger number of aortic injuries (21 out of 52 patients) recorded and a higher mortality rate of 17% as a result of these aortic injuries.

Congenital Heart Disease (CHD) is one of the main causes of infant mortality in the UK and United States. In 2011, 47% of infants born with CHD in the UK did not survive to their first birthday. Often forms of CHD require the implantation of conduits (tubes) to redirect the blood flow around the reconstructed anatomy in the early days of life. In all cases, these children will require review surgery, often several times to replace the implanted conduit as the child grows. Critically every review procedure carries with it an increased mortality risk. This project represents the first stage in the development of a conduit/ anastomosis technology, which will grow in response to the growing child, matching haemodynamic demand and eliminating the need for revision surgery. Two prototypes were designed and developed. Each using an active drive mechanism to expand a stainless steel expansion strip with the slow and controlled movement required for such an application. Each of the designs were silicone coated using custom designed injection moulding techniques ensuring biocompatibility. Power and control systems were designed for each iteration taking into account their expansion methods to achieve the desired expansion rate of 12mm to 20mm in diameter of the implantation period. Three consecutive implantation studies were carried out throughout the device's development. In the first study, the device was implanted into the right ventricle of a cadaveric pig to determine any potential impediments that would need to be addressed for implantation into live animal models. The second implantation was carried out on 6 piglets, successfully establishing CPB procedures The third implantation was successfully carried out on 3 piglets, 2 of which survived the duration of the testing, confirming a successful encapsulation method to ensure biocompatibility, however it appeared the device failed to expand due to power line breakdown.

INTRODUCTION Complete atrioventricular septal defect (CAVSD) repair is most commonly performed using the double patch (DP) or modified single-patch (MSP) technique. Whilst the DP technique has well-established excellent results, the long-term outcomes of the MSP technique have not been fully elucidated. The aim of this research was to investigate the long-term outcomes after CAVSD repair and to elucidate current risk factors for reoperation and mortality. METHODS This multi-centre study included all CAVSD patients who underwent biventricular surgical repair between January 1990 to December 2015 in Australia. Demographic details, operative data and post-operative outcomes including reoperation and long-term survival were analysed using a competing risks and a propensity-score matched analysis to compare outcomes of DP and MSP repairs with respect to freedom from reintervention and overall survival. Risk factors were analysed using Cox regression. RESULTS A total of 859 patients underwent repair of CAVSD during the study period of which 829 underwent biventricular surgical repair. Competing risks analysis demonstrated no association between repair technique (MSP or DP) and reoperation (p=1.0) or mortality (p=0.9). The propensity-score matched analysis of 223 pairs of patients, demonstrated no significant difference in overall survival (p=0.59) or event-free survival (p=0.90) between the two repair techniques with an estimated event-free survival at 5, 10 and 15 years of 83%, 83% and 74% for DP and 83%, 80% and 77% for the MSP group. Predictors for reoperation include non-Down syndrome and moderate or greater left atrioventricular valve regurgitation, and prior pulmonary artery banding was a risk factor for mortality. CONCLUSIONS Our study reveals that the long-term outcomes of the MSP technique are similar to the DP technique and that excellent overall survival after CAVSD repair can be achieved in the current surgical era irrespective of the operative technique used.

BACKGROUND: epicardial patch transplantation is a promising approach to restore some of the cardiac function lost after myocardial infarction (MI). Advances in 3D bioprinting, 3D cell culture and transplantation methods at surgery have provided hope that this approach could soon benefit heart failure patients. The optimal content of 3D bioprinted patches (the “bioink” extruded by a 3D bioprinter) is not known. Patches containing a suspension of 3D vascularised cardiac spheroids (VCS; 3D aggregates of cells / microtissues) in hydrogel may confer an advantage compared to freely suspended cells or hydrogel without cells. The mechanisms underlying the benefit of epicardial patch transplantation approaches have not been fully elucidated and this is needed for widespread clinical translation. To be fully compatible with cardiothoracic surgical approaches in future, patches should be transplantable by minimally invasive robotic approaches. METHOD: Alginate-gelatin (AlgGel) patches were optimised ex vivo for cardiac applications, followed by in vivo transplantation of patches in mice modelling MI. For the ex vivo optimisation phase, three different bioprinters were used to bioprint patches with different bioink contents which were incubated up to 28 days and analysed. For the in vivo phase, new patches were 3D bioprinted using the optimal methods determined in the previous (ex vivo) experiments and surgically transplanted to the epicardium in infarcted mice. For these in vivo experiments, we cultured mixed cardiac cells: induced pluripotent stem cell derived cardiomyocytes (iCMs), human coronary artery endothelial cells (HCAECs) and cardiac fibroblasts (CFs). Cells were cultured using hanging drops to generate VCS which were suspended in AlgGel to create bioink for 3D bioprinting of patches. Study control groups (in vivo) were: the same cells freely suspended in AlgGel, AlgGel without cells, MI without treatment and sham surgery (no MI and no treatment). The primary outcome was cardiac function (left ventricular ejection fraction, LVEF%) measured up to day 28 post surgery. Additional analyses included: electrical mapping, histology, cell quantification by flow cytometry and mRNA (gene expression) profiling. Alongside these experiments, we developed novel surgical robotic minimally invasive instruments designed to transplant similar patches at human scale. We prototyped a heart patch transplanter device and demonstrated its potential utility in a world-first operation on a pig cadaver. RESULTS: Ex vivo patches incubated for 28 days allowed for self-organisation of endothelial cells into networks and contractile activity within patches. In vivo transplantation of patches in mice modelling MI resulted in a “return to baseline” improvement in median LVEF%. Our results measured median baseline (pre-surgery) LVEF% for all mice at 66%. Post-surgery, LVEF% was 58% for Sham (non-infarcted) and 41% for MI (no treatment) mice. Patch transplantation increased LVEF%: 55% (acellular; p=0.012), 59% (cells; p=0.106), 64% (spheroids; p=0.010). The VCS group was associated with improved electrical mapping profiles, lower infarct sizes, changes in host immune cell numbers and a gene expression (mRNA) profile which was closest to sham mice (with no MI). As proof-of-concept, similar scaled-up AlgGel patches were successfully transplanted in a porcine cadaver using a prototyped robotic minimally invasive surgical instrument. CONCLUSION: Epicardial transplantation of patches improves cardiac function in mice modelling MI. The use of VCS in alginate-gelatin bioink seems to offer advantages compared to freely suspended cells or hydrogel alone. The fact that hydrogel alone without cells confers some restoration of myocardial function suggests that the mechanism is not fully accounted for by the cellular portion of the bioink. Further studies are needed with a focus on whether host immune cell modulation is a key mechanism underlying the benefit of this approach. Since our most successful treatment group (VCS) had a similar transcriptome compared to non-infarcted (sham) mice, further studies should also include transcriptomic analyses to confirm reproducibility of this finding. If it is confirmed that immuno-genetic mechanisms underly patch-based approaches to myocardial protection after MI, this may change the focus of treatment strategies and avoid wasted resources and potentially patient harm (from treatments which are not aligned with the underlying mechanism). Our robotic minimally invasive patch transplantation operation represents a first step on a potential pathway towards transplantation at human surgery (without the need for traditional open surgery). For translatability, patch development should work towards being compatible with robotic and/or minimally invasive transplantation.

On a daily basis critically ill paediatric patients are admitted in the Paediatric Critical Care Unit (PCCU). Some of these paediatric patients require cardiothoracic surgery and is mechanically ventilated post-operatively. Chapter one of this study gives an orientation to this research and explains that in order to prevent ventilator associated complications and high hospitalisation costs, the mechanically ventilated paediatric patient following cardiothoracic surgery should be extubated as soon as he/she is ready. Chapter two is dedicated to the available literature on this topic and indicates that literature on extubation criteria for the mechanically ventilated paediatric patient is minimal. The methodology of this study is discussed in detail in Chapter three. Chapter four gives a detailed explanation of the research findings and the researcher included the developed clinical pathway for the extubation of the paediatric patient following cardiothoracic surgery in a private hospital in Gauteng. The relevant clinical pathway functions as a guideline and evidence-based tool in the PCCU. Lastly Chapter five gives a summary of this study and a few recommendations are made. The researcher has included a personal reflection in this Chapter.<br>Dissertation (MCur)--University of Pretoria, 2014.<br>tm2015<br>Nursing Science<br>MCur<br>Unrestricted

INTRODUÇÃO: A circulação extracorpórea (CEC) é um fator etiológico importante para a lesão pulmonar, observada após cirurgia cardíaca. No entanto, o impacto da CEC na função mucociliar respiratória é desconhecido. O objetivo do estudo foi avaliar os efeitos imediatos da CEC sobre o sistema de transporte mucociliar. MÉTODOS: 22 porcos mestiços das raças Large White e Landrace com peso entre 33 a 47 kg alocados nos grupos controle (n = 10) e CEC (n = 12) completaram o estudo. As técnicas de anestesia e ventilação mecânica foram padronizadas. Após a indução da anestesia, foi realizada traqueostomia e uma amostra do tecido traqueal foi excisado (T0) em ambos os grupos. Todos os animais foram submetidos a toracotomia e CEC aorto-bicaval foi instalada no grupo CEC e mantida durante 90 minutos. Após o desmame da CEC (T90), uma segunda amostra do tecido traqueal foi obtida 180 minutos após a traqueostomia (T180). Amostras de muco foram coletadas na traquéia por meio de broncoscopia em T0, T90 e T180. Frequência de batimento ciliar (FBC) e transporte mucociliar in situ (TMC) foram estudados em epitélio traqueal ex vivo. As características do muco respiratório in vitro foram estudadas por transportabilidade ciliar no palato de rã (VTM), Transporte do muco respiratório in vitro pela tosse (TMT), Ângulo de contato (AC) e da viscosidade do muco por viscosímetro Cone-Plate (VM). RESULTADOS: A FBC diminuiu no grupo CEC (13,09 ± 1,91 Hz vs 11,06 ± 2,1 Hz, p <0,05), mas não no grupo controle (13,42 ± 0,96 Hz vs 12, 98 ± 2,84 Hz). No momento T90, a viscosidade aparente avaliado em 100 RPM estava aumentada no grupo CEC em relação ao controle. Não foram observadas diferenças significativas no TMC, VTM, TMT e AC. No grupo de CEC, foi percebida a perda do epitélio ciliado, edema submucoso e infiltração de células inflamatórias na avaliação histológica da traqueia. CONCLUSÃO: A CEC compromete agudamente o sistema de transporte mucociliar traqueal. Novos estudos são necessários para avaliar se esse comportamento tem implicações clínicas<br>BACKGROUND: Cardiopulmonary bypass (CPB) is an important etiologic factor for lung injury observed after cardiac surgery. However, the impact of CPB on respiratory mucociliary function is unknown. The objective of this study was to assess the immediate effects of CPB on mucociliary transport system. METHODS: Twenty-two mixed breed of Large White and Landrace pigs with weight between 33 to 47kg assigned to control (n=10) and CPB groups (n=12) completed the study. The techniques of anesthesia and mechanical ventilation were standardized. After anesthesia induction, tracheotomy was performed and a tracheal tissue sample was excised (T0) in both groups. All animals underwent thoracotomy and aorto-bicaval CPB was installed in CPB group and maintained during 90 minutes. After weaning from CPB (T90), a second tracheal tissue sample was obtained 180 minutes after tracheotomy (T180). Mucus samples were collected from the trachea using a bronchoscope at T0, T90 and T180. Ciliary beat frequency (CBF) and in situ mucociliary transport (MCT) were studied in ex vivo tracheal epithelium. In vitro respiratory mucus characteristics were studied by mucociliary transportability in frog palate (MT), Cough clearance (CC), Contact angle (CA) and the mucus viscosity by Cone-Plate viscometer (MV). RESULTS: CBF decreased in CPB group (13.09 ± 1.91 Hz vs. 11.06 ± 2.1 Hz, p < 0.05) but not in control group (13.42 ± 0.96 Hz vs. 12.98 ± 2.84 Hz). At T90 Apparent viscosity evaluated at 100 RPM increased in CPB group compared to control. No significant differences were observed in MCT, MT, CA and CC. In CPB group, it was observed loss of ciliated epithelia, submucosal edema and inflammatory cells infiltration in tracheal histology. CONCLUSION: CPB acutely compromise the tracheal mucociliary transport system. New studies are necessary to investigate if this behavior has any clinical implication

Ischaemic heart disease (IHD) is the leading cause of death worldwide. Currently, even optimal medical therapies do not attenuate deterioration of the left ventricular (LV) function completely. Stem cell therapies, and recently cardiac stem cell therapies, have emerged as potential novel treatments for IHD. However, clinical evidence from randomised controlled studies has shown mixed results. Thus understanding what patient-related factors may affect the therapeutic performance of the cells may help improving treatment outcomes. The studies described in this thesis aim to understand how cardiac progenitor cells (CPCs) can re-vascularise ischaemic myocardium and promote functional repair of the heart. Resident CPCs were isolated and expanded from the right atrial appendage of 68 patients following the ‘cardiosphere’ method (cardiosphere-derived cells or CDCs). They resemble mesenchymal progenitors as they lack the expression of endothelial and haematopoietic cell surface markers but express mesenchymal progenitor cell markers (e.g. CD105, CD90). Cell function was evaluated by support of angiogenesis, mesenchymal lineage differentiation potential in vitro, and improvement in heart function in vivo. Notably in vitro, CDC from different patients differed in their angiogenic supportive and differentiation potentials. In a rodent model of myocardial infarction (MI), transplantation of CDC reduced infarct size significantly (p<0.05). However, only those CDCs with a robust pro-angiogenic ability in vitro improved vessel density and heart systolic function (p<0.05) in vivo. A multiple regression model, which accounted for 51% of the variability observed, identified New York Heart Association (NYHA) class, smoking, hypertension, type of ischaemic disease and diseased vessel as independent predictors of angiogenesis. In addition, gene expression analyses revealed that differential gene expression of several extracellular matrix components (e.g. CUX1, COL1A2, BMP1 genes and microRNA-29b) could explain the differences observed in CDC’s vascular supportive function. In summary, this is the first description of variability in the pro-angiogenic and differentiation potential of CDCs and its correlation with their therapeutic potential. This study indicates that patient stratification may need to be included in the design of future trials to improve the efficacy of cell-based therapies.

Vascular disease is the leading cause of death and disability worldwide. Incidence, risk factors, and outcome of coronary artery disease have been extensively studied, but there are fewer data on other forms of arterial disease, including carotid, aortic, visceral, and peripheral arterial disease. Although the burden of these diseases may be increasing due to the ageing population, we lack the most basic epidemiological data on which to base clinical decisions on individual patients (short and long-term prognosis); local service provision (current incidence and projected future burden); public health / screening initiatives (age and sex-specific incidence, risk factors, and outcome); and with which to assess current levels of primary prevention (pre-morbid risk factor control). Indeed, it is this lack of data, rather than a lack of treatments that is the greatest barrier to effective prevention. I have contributed to, cleaned, and analysed data from the Oxford Vascular Study, a prospective, population-based study (n=92,728) of all acute vascular events (2002-2012), and the Oxford Plaque Study, a carotid atherosclerosis biobank of over 1000 carotid plaques, in order to study these conditions. For acute aortic disease, I aimed to assess the risk factors associated with acute abdominal aortic aneurysms (AAA) and the population impact of the current UK AAA screening programme; and the incidence, risk factors, outcome, and projected future burden of acute aortic dissection. For acute peripheral arterial disease, I assessed the risk factors associated with premature onset and poor outcome, together with current levels of primary prevention. For symptomatic carotid artery disease, I studied the timing and benefits of surgical intervention in the current era; and went on to assess whether underlying carotid plaque morphology can be used to improve stroke risk stratification and help explain why ocular and cerebral stroke types have vast differences in future ipsilateral stroke risk. I found that compared with the current UK AAA screening strategy (one-off scan for men aged 65), screening of male smokers at 65 and all men at 75 would prevent nearly four-times as many deaths and three-times as many life-years lost with 21% fewer annual scans. I have also shown that incidence of acute aortic dissection is higher than previous estimates, a third of cases are out-of-hospital deaths, and uncontrolled hypertension is the most significant treatable risk factor for this condition. For acute peripheral arterial disease, the presence of multiple atherosclerotic risk factors are associated with premature onset, and severity of ischaemia, pre-morbid renal dysfunction, cardiac failure, and diabetes mellitus are predictive of future limb loss and survival. A significant proportion of acute peripheral events are AF-related in high risk patients who were not pre-morbidly anticoagulated despite having no contraindications and being at low risk of bleeding. Symptomatic carotid artery disease currently accounts for <10% of incident cerebrovascular events, and only 40% of these patients undergo surgical intervention. Due to improvements in medical therapy and on-going delays to intervention, little benefit is currently obtained from intervening in patients with <70% stenosis. Ipsilateral stroke risk is correlated with several carotid plaque features in a time-dependent manner, confirming the potential utility of plaque morphology in risk stratification. In addition, plaques from patients with cerebral events were significantly more unstable and inflammatory than from those with ocular events, helping explain differences in stroke risk between these groups. My findings advance the understanding of these conditions that form the backbone of modern vascular surgical practice, and I hope will improve prevention, clinical management, and outcome for patients with vascular disease.

Background: Beta blockers are recommended by the American College of Cardiology/American Heart Association Guidelines for high and intermediate-risk cardiac patients undergoing non-cardiac surgery. Beta blockers are a class of drugs that moderate the effects of increased catecholamine levels on the heart by selectively blocking beta receptors in the heart and blood vessels, resulting in a lower heart rate and blood pressure. Beta blocker use perioperatively has been shown to reduce the risk of ischemia and infarction. Purpose: The purpose of this project is to address beta blocker use in a group of anesthesia providers who routinely attend to high-risk and intermediate-risk cardiac patients undergoing non-cardiac surgery in a medium-sized private hospital in suburban South Florida. There are barriers to the implementation of the published guidelines for beta blocker administration, including lack of awareness of the best current practice and a lack of a formal beta blocker protocol at the institutional level. Methods: A simple and inexpensive beta blocker protocol was implemented and evaluated by various means. Beta blocker administration practices were examined and documented prior to and after protocol implementation. Beta blocker usage was examined prior to and after protocol implementation Findings/Implications: It was hypothesized that increased anesthesia provider awareness would lead to increased administration of perioperative beta blockers to high-risk and intermediate-risk cardiac patients undergoing non-cardiac procedures. Although there was a knowledge increase related to the new beta blocker protocol, no change in practice was observed.

Introduction: Identifying potentially modifiable factors leading to patient mortality in cardiothoracic surgery may provide the basis for interventions to improve patient safety. Australia is unique in that all cardiothoracic surgeons participate in a mandatory national surgical audit. All patients who die under the care of a surgeon are referred to the Australian and New Zealand Audit of Surgical Mortality (ANZASM). Surgeons are asked to provide a narrative to patient death and the case is reviewed by independent assessors with case note review if necessary. The aim of this project was to examine the ANZASM database for cardiothoracic mortality and identify possible factors leading to patient mortality. Methods: The ANZASM database was analysed for a seven-year period from February 2009 through December 2015. The surgeons’ narrative and assessors report of all patients who died under the care of a cardiothoracic surgeon were examined. A qualitative analysis using a thematic analysis technique was performed on the data set. Researchers read the surgical narrative and assessor report and common clinical management issues (CMIs) were coded from these extracts and subsequently grouped into a set of common themes. Within these themes, the reports were re-analysed to look in further detail about common factors and subthemes. Specific attention was paid to potentially avoidable themes. This process was repeated for the overall dataset, followed by the most common theme identified (operative technical factors) and again focusing on communication issues, which were identified as prevalent throughout all operative phases. Results: A total of 1440 CMIs were identified in 908 patients in our analysis. The CMIs were grouped into preoperative, intraoperative and postoperative phases. The most common individual CMI was intraoperative technical factors (31.7% of cases) and most CMIs occurred in the postoperative phase. Themes that were identified in the preoperative phase included: decision to operate (18.3%), inadequate assessment (13.1%) and delay to surgery (10.4%). Intraoperative themes comprised technical factors (31.4%), wrong surgical approach (6.6%) and junior surgeon (2.4%). Postoperative themes included inappropriate management (15.9%), delay to recognising complication (3.6%), postoperative bleeding (13.2%), infection (11.6%) and inadequate monitoring (2.6%). Technical factors affecting surgery were made up of unintentional injury to anatomical structures (42% of operative-phase CMIs), perfusion issues related to coronary grafts (15.4%), unaddressed surgical pathology (13%), inadequate myocardial protection (11.2%), air and anastomotic leaks (6.3%), bleeding (13.2%), technical issues with cardiopulmonary bypass (4.2%) and excessive surgery (3.8%). Communication issues identified were broken down into failure of shared decision making (41.8% of communication-related CMIs), failure to notify a patient deterioration (24.1%), misreporting of patient condition (11%) and issues regarding informed consent (10%). Conclusions: This thesis identified many factors leading to cardiothoracic surgical mortality throughout all operative phases. Technical and postoperative factors are the most common issues, however, most mortality results from multifactorial failures spanning the operative phases. National surgical audit is useful in identifying factors and maintaining safety standards for patient care perioperatively. Attention to correcting issues most commonly identified may improve the quality of patient care in cardiothoracic surgery.<br>Thesis (MPhil) -- University of Adelaide, Adelaide Medical School, 2019

Trabalho Final de Mestrado Integrado, Ciências Farmacêuticas, Universidade de Lisboa, Faculdade de Farmácia, 2017<br>Background: Oral anticoagulation is essential following post-operative atrial fibrillation. Although warfarin is commonly used, its efficacy is dependent on the achievement of a time in therapeutic range above 65%. Non-vitamin K oral anticoagulants are an alternative option, however the optimal time to initiate post-operatively is unknown, due to 'recent surgery' often being cited as an exclusion criteria within phase III clinical trials. Purpose: To compare the management of oral anticoagulation for stroke prevention in postoperative atrial fibrillation after cardiothoracic surgery. Methods: An ambispective study was conducted at large tertiary centre analysing patients that developed postoperative atrial fibrillation after cardiothoracic surgery from January 2016 to January 2017 reviewing both patient and surgical data. Results: Sixty-four patients developed postoperative atrial fibrillation, of which 39 (60.9%) and 25 (39.1%) were prescribed warfarin and non-vitamin K oral anticoagulants (NOACs), respectively. 14 (51.9%) patients had a confirmed time in therapeutic range below 65%, reflecting poor anticoagulant control with warfarin. NOACs were initiated on an average of 8.36 ± 3.74 days post-operatively. 22 (62.9%) patients in the warfarin group and 13 (65.9%) patients in the NOAC group were confirmed to be in sinus rhythm six weeks after discharge. Among these patients, 14 (40.0%) stopped the anticoagulation after restoration of sinus rhythm, of which were more likely to continue if were receiving a NOAC. Conclusion: Whilst warfarin is commonly initiated for post-operative atrial fibrillation, a time in therapeutic range below 65% for warfarin shows that acute optimal anticoagulation management is difficult to achieve, especially for the short term patients that revert back in to sinus rhythm. NOACs may possibly be a more effective alternative, initiating eight days post operatively. However further studies need to be conducted to ensure optimal dose of these agents as well as the ideal timeframe to initiate anticoagulation in the acute post-operative phase.<br>Introdução: A fibrilhação auricular (FA) é a arritmia sustentada mais comum na prática clínica e está associada ao aumento da mortalidade e morbilidade, assim como a hospitalizações frequentes e à redução da qualidade de vida. A fibrilhação auricular pós-operatória (FAPO) é uma variante da FA clássica que se caracteriza pelo diagnóstico de um novo caso de FA, habitualmente auto-limitada, após realização de cirurgia-major (tipicamente cardíaca) em doentes que se encontravam em ritmo sinusal previamente ao procedimento cirurgico e sem historial clínico prévio desta arritmia. Estima-se que a FAPO ocorra em cerca de 30% das cirurgias-major. Neste sentido, a terapêutica anticoagulante é essencial como profilaxia para o acidente vascular cerebral, sendo que tanto os anticoagulantes orais não antagonistas da vitamina K (NACOs) (apixabano; dabigatrano; edoxabano; rivaroxabano) como os antagonistas da vitamina K (AVK) (varfarina; acenocumarol) se revelam eficazes na prevenção do acidente vascular cerebral na fibrilhação auricular. Embora a varfarina seja amplamente usada na prática clínica, a sua eficácia está dependente da manutenção da percentagem de tempo no intervalo terapêutico a um nível superior a 65%. Por sua vez, os NACOs revelam-se como uma alternativa à varfarina, sendo referidos como opção preferencial nos normativos das mais reconhecidas sociedades de cardiologia. No entanto, o tempo ideal para iniciar a terapêutica com estes agentes no perído pós-operatório carece de investigação, devido à exclusão desta população dos ensaios clínicos randomisados de fase III. Desta forma, no âmbito do programa Erasmus, este projeto foi desenvolvido durante os três meses em que tive a oportunidade de integrar o Departamento de Farmácia do Hospital St. Bartholomew sediado em Londres, Reino Unido. Tendo sido proposto pelo responsável deste departamento, este estudo teve como objetivo aprofundar o conhecimento relativamente ao tratamento ótimo e efetivo com anticoagulantes orais e, em última análise, permitir a otimização, eficácia e segurança destes agentes. Além disso, refletindo o importante papel do farmacêutico enquanto membro integrado numa equipa multidisciplinar de profissionais de saúde, este projeto permitiu de igual forma, a promoção da discussão com cirurgiões, médicos e enfermeiros acerca do potencial de possíveis mudanças a adotar futuramente na prática clínica de modo a garantir uma melhor gestão da FAPO, e consequentemente proporcionar os melhores cuidados em saúde a estes utentes. Objetivos: Este estudo teve como propósito comparar a gestão da terapêutica anticoagulante oral na fibrilhação auricular pós-cirurgia cardiotorácica. Deste modo, foram formuladas quatro questões de investigação: 1. Qual percentagem de pacientes prescritos com varfarina que demonstrou um tempo no intervalo terapêutico superior a 65%, seis semanas após a alta hospitalar? 2. Qual é a dosagem adequada de NACOs no período pós-operatório? 3. Qual é o momento ideal para iniciar terapêutica com NACOs no período pós-operatório? 4. Os anticoagulantes orais foram descontinuados nos doentes que revelaram reversão para ritmo sinusal seis semanas após a alta hospitalar? Assim, tendo como ponto de partida as questões supracitadas, foram definidos os seguintes objetivos específicos para este estudo: i) Avaliar a eficácia da varfarina no período pós-operatório; ii) Investigar as tendências e padrões na prática clínica em relação à NACOs (i.e., escolha do NACO prescrito, dosagem, período pós-operatório de iniciação terapêutica); iii) Esclarecer as características envolvidas na hipótese de considerar a redução da dose de NACOs, bem como o prazo ideal para iniciar a terapêutica com estes fármacos no período pós-operatório; iv) Identificar o número de doentes que revertem para ritmo sinusal (RS) seis semanas após a cirurgia cardiotorácica; v) Analisar as taxas de descontinuação de anticoagulantes orais, quando é verificada a reversão para RS. Métodos: Foi conduzido um estudo ambiespectivo em doentes que desenvolveram fibrilhação auricular pós operatória entre janeiro de 2016 e janeiro de 2017. O estudo compreendeu duas fases distintas; Uma retrospetiva e uma prospectiva (desenho ambiespectivo). As informações presentes nos registos médicos dos utentes submetidos a cirurgia entre os dias 1 de janeiro de 2016 e 31 de janeiro de 2017 foram avaliadas retrospectivamente para determinar a amostra de interesse para estudo com base nos critérios de eligibilidade definidos. Foram igualmente consultados retrospectivamente os registos de distribuição da farmácia e os relatórios de controlo de stocks para identificar todos os doentes com prescrições de varfarina ou novos anticoagulantes orais nas alas cardiotorácicas durante o período de coleção de dados. Foram assim constituídos dois coortes de exposição, de acordo com o subgrupo farmacoterapêutico adotado (AVK vs NACO). Foram analisados os registos de prescrição de fármacos e notas médicas eletrónicas, a fim de selecionar de entre os pacientes prescritos com estes anticoagulantes orais, os que foram dispensados do hospital com um diagnóstico confirmado de fibrilhação auricular pós-operatória. Dados demográficos, historial médico e estudos laboratoriais foram analisados. Foram definidas como variáveis de interesse, os valores de tempo no intervalo terapêutico especificamente para o grupo-varfarina; o NACO prescrito, respetiva dose e dia de inicio da terapêutica no período pós-operatório para o grupo-NACO; CHA2DS2‐VASc score, tendo sido realizada a estratificação de risco para tromboembolismo e acidente vascular cerebral para ambas as coortes através da análise dos fatores de risco individuais. A fase prospetiva decorreu desde 31 de Janeiro até 28 de abril de 2017 e serviu para recolher os dados das consultas de follow-up, realizadas em média cerca de seis semanas após cirurgia no Hospital St. Bartolomew. Através da consulta deste dados obteve-se assim informação sobre a reversão para ritmo sinusal (ou não), a consequente descontinuição dos anticoagulantes orais. Os valores de International Normalized Ratio (INR) que estão na origem do cálculo do tempo no intervalo terapêutico foram obtidos através de contactos estabelecidos com as clínicas de anticoagulação onde estes utentes realizavam as mediações do INR. Estes valores foram obtidos prospetivamente para os doentes que continuaram a terapia com varfarina e consequente monitorização de INR coincidente com a fase prospetiva do estudo. Os dados recolhidos foram analisados recorrendo a estatística descritiva univariada e bivariada. Os dados discretos são apresentados como frequências absolutas e relativas, enquanto que os dados contínuos são apresentados através da tendência central e medidas de dispersão, incluindo média, mediana e desvio padrão. A análise bivariada serviu para comparar as características dos utentes das duas coortes de doentes expostas aos dois diferentes tratamentos e verificar se as características dos doentes, nomeadamente o seu perfil de risco de AVC ou risco hemorrágico, poderiam justificar a sua inclusão num ou noutro grupo farmacoterapêutico. Dado o tamanho amostral e a distribuição não-normal dos dados, foram selecionados testes não-paramétricos; o chi-quadrado e a sua extensão peloo teste Exacto de Fisher foram utilizados para analisar dados categóricos e o teste Wilcoxon Mann-Whitney para analisar dados contínuos. O intervalo de confiança considerado foi de 95%. Todos os dados foram analisados usando o IBM Statistical Software Package for Social Sciences (SPSS, versão 24). O protocolo deste estudo foi aprovado pela Comissão de Ética do Hospital St. Bartolomew, sob o número 8021. Resultados: Sessenta e quatro utentes desenvolveram fibrilhação pós-operatória, dos quais 39 (60.9%) e 25 (39.1%) foram medicados com varfarina e NACOs, respetivamente. Foram obtidos 27 dados de valores de tempo no intervalo terapêutico (69% dos medicados com varfarina), sendo que 14 doentes (52%) demonstraram valores de tempo no intervalo terapêutico inferiores a 65%, refletindo fraco controlo e pouca eficácia da terapêutica anticoagulante com varfarina. No que concerne à iniciação de NACOs no período pós-operatório, foi revelado que a terapêutica com estes anticoagulantes teve inicio, em média, 8.36 ± 3.74 dias após realização do procedimento cirurgico. Relativamente à reversão para RS, 22 doentes (62.9%) do grupo da varfarina e 13 doentes (65.0%) do grupo dos NACOs tinham revertido para RS seis semanas após a alta hospitalar. De entre estes doentes, um total de 14 (40.0)% discontinuou os anticoagulantes orais após confirmação de ritmo sinusal. Conclusões: Alcançar um tempo no intervalo terapêutico superior a 65% revela-se desafiante e díficil de alcançar no que diz respeito à terapêutica com varfarina, sendo tal facto demonstrado pela proporção de pacientes que demonstraram valores que expressam a baixa eficácia deste agente, ainda que eventualmente resultante da sua utilização em contexto real onde questões associadas ao estilo de vida, inclusivamente alimentares e de adesão à terapêutica, poderão influenciar profundamente a capacidade de autogestão do doente. Deste modo, os anticoagulantes orais não antagonistas da vitamina K, iniciados oito dias após cirurgia cardiotorácica, podem constituir uma alternativa mais efetiva na tromboprofilaxia associada à fibrilhação auricular. No entanto, será prudente confirmar estes dados em amostras de maior dimensão dadas as limitações deste exercício académico. Estudos adicionais devem igualmente ser realizados de modo a estabelecer a dose ideal, bem como o período apropriado para iniciar a terapêutica anticoagulante com estes agentes na fase aguda do pós-operatório.

A research report submitted in fulfilment of the requirements for the degree of Master of Science in Physiotherapy to the Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, 2020<br>Introduction: Cardiovascular diseases contribute significantly to the burden of diseases in South Africa and internationally. A standard intervention is open-heart surgery to repair and improve the functioning of the heart and a median sternotomy is the most commonly used incision during cardiothoracic surgery as it allows for optimal access to the heart and surrounding vessels. To date, few studies have described the effect of cardiothoracic surgery on ventilation kinematics as assessed by clinical bedside physiotherapy outcome measures. Aim: The aim of this research was to determine the impact of a median sternotomy on the ventilation kinematics and to describe the changes from admission to discharge from hospital. Methods: A longitudinal observational study was conducted at a private hospital in Gauteng. Male and female patients undergoing elective cardiothoracic surgery between the ages of 18 to 70 years were consecutively sampled. Participants were assessed pre-operatively and again at hospital discharge. The demographic and clinical profile of study participants were determined. Ventilation kinematics were assessed by measuring upper and lower thoracic expansion and respiratory muscle strength (Maximum Inspiratory Pressure [MIP] and Peak Inspiratory Flow [PIF]). Lastly, it was determined whether a relationship exists between the ventilation kinematics and specific demographic and clinical variables. Analysis included descriptive statistics and the Shapiro-Wilks and Wilcoxon Signed-Rank Tests, Spearman’s Rank-order and Pearson’s Product-Moment correlations. Statistical significance was set at p≤0.05. Results: The study population consisted of 61 participants and most (n=35, 57%) underwent coronary artery bypass graft surgery with the mean amount of time spent in theatre being 5.85 (SD1.30) hours, median mechanical ventilation hours 17.33 (IQR 11.21) and median days in intensive care five (IQR 2.75). Forty-seven (77%) participants were male and seventeen (27%) females with a median age of 59 (IQR 22) years. The median length of stay in hospital was nine (IQR 7) days. All participants were independently mobile at hospital admission but 5 (8.2%) required a mobility aid for independent mobility at hospital discharge. There was a significant difference between upper thoracic and lower thoracic expansion between admission and discharge (Upper: 104.51cm vs 102.51cm; p<0.001, Lower: 100.03cm vs. 98.70cm, p=0.0001). There was a significant difference between MIP and PIF between admission and discharge (MIP: 55cmH20 vs 30.66cmH20, p<0.001; PIF: 2.70l/s vs. 1.66l/s, p<0.001). There was also a significant difference between the predicted MIP achieved between admission and discharge (%Pred MIP: 58.66cmH20 vs. 33.26cmH20, p<0.001). There was a significant difference between admission and discharge for VAS pain scores and chest X-ray total scores (p<0.001). Oxygen saturation (p<0.001), temperature (p<0.001) and diastolic blood pressure (p=0.004) were significantly different from admission to discharge from hospital. There was a fair v negative correlation between predicted MIP and age (r=-0.319, p=0.012). There was a fair positive correlation between lower thoracic expansion and age (r=0.286, p=0.031). There was a fair negative correlation between upper thoracic expansion and length of time intubated (r=-0.261, p=0.05). There was a fair negative correlation between MIP and PIF between chest X-ray scores at admission (PIF: r=-0.278, p=0.03; MIP: r=-0.356, p=0.004). Conclusion There is significant alteration that happens to the respiratory pump that affects ventilation kinematics following a median sternotomy incision during cardiothoracic surgery when changes are evaluated from admission to discharge. Physiotherapy practice should continue with postoperative care after hospital discharge considering the presence of respiratory muscles weakness and presence of mobility dysfunction.<br>TL (2020)

An analysis of the outcome following cardiac valve surgery and coronary artery bypass grafting performed in the Royal Adelaide Hospital Cardiothoracic Surgical Unit over a 25 year period.<br>Thesis (M.S.) -- University of Adelaide, Dept. of Surgery, 1993.

Zou Wei.<br>Thesis submitted in: December 2001.<br>Thesis (M.Phil.)--Chinese University of Hong Kong, 2002.<br>Includes bibliographical references (leaves 98-119).<br>Abstracts in English and Chinese.<br>Declaration --- p.i<br>Acknowledgements --- p.ii<br>Publication lists --- p.iii<br>Abstract --- p.ix<br>Abbreviations --- p.xiii<br>List of tables and figures --- p.xiv<br>Chapter Chapter 1: --- General Introduction --- p.1<br>Chapter 1.1. --- Endothelium-dependent relaxation in coronary and pulmonary circulation --- p.1<br>Chapter 1.1.1. --- Endothelium-derived relaxing factors --- p.2<br>Chapter 1.1.1.1. --- Nitric Oxide --- p.3<br>Chapter 1.1.1.2. --- PGI2 --- p.5<br>Chapter 1.1.1.3. --- EDHF --- p.6<br>Chapter 1.1.2. --- EDHF in coronary and pulmonary circulation --- p.8<br>Chapter 1.1.2.1. --- EDHF in coronary circulation --- p.8<br>Chapter 1.1.2.2. --- EDHF in pulmonary circulation --- p.9<br>Chapter 1.2. --- Effect of hyperkalemia on EDHF-mediated relaxation --- p.10<br>Chapter 1.3. --- Organ Preservation Solutions --- p.13<br>Chapter 1.3.1. --- Euro-Collins solution --- p.14<br>Chapter 1.3.2. --- University of Wisconsin solution --- p.15<br>Chapter Chapter 2: --- Objectives and research approaches --- p.16<br>Chapter 2.1. --- Objectives --- p.16<br>Chapter 2.1.1. --- "Endothelium-dependent relaxation resistant to INDO, L-NNA, and HbO in porcine and pulmonary coronary micro-arteries" --- p.16<br>Chapter 2.1.2. --- "EET11,12 and EDHF-mediated function in porcine coronary micro-arteries" --- p.17<br>Chapter 2.1.3. --- "Comparison of EC or UW solution on endothelium-dependent relaxation resistant to INDO, l-NNA, and HbO in porcine pulmonary arteries" --- p.17<br>Chapter 2.2. --- Research approaches --- p.18<br>Chapter 2.2.1. --- "Endothelium-dependence of the relaxation by BK or EET11,12" --- p.18<br>Chapter 2.2.2. --- Effect of hypothermic storage with EC and UW solution on EDHF-related relaxation --- p.18<br>Chapter 2.2.3. --- Time-dependent alteration of endothelium-dependent relaxation in pulmonary micro-arteries by EC and UW solution --- p.19<br>Chapter 2.2.4. --- Effect of HbO in endothelium-dependent relaxation --- p.19<br>Chapter Chapter 3: --- Material and Methods --- p.21<br>Chapter 3.1. --- General Methods --- p.21<br>Chapter 3.1.1. --- Porcine heart and lung collection and transportion<br>Chapter 3.1.2. --- Myograph --- p.21<br>Chapter 3.1.3. --- Myosight --- p.24<br>Chapter 3.1.4. --- Anatomizing blood vessel --- p.24<br>Chapter 3.1.5. --- Mounting --- p.24<br>Chapter 3.1.6 --- Normalization --- p.26<br>Chapter 3.1.6.1. --- Normalization of coronary micro-artery --- p.27<br>Chapter 3.1.6.2. --- Normalization of pulmonary micro-artery --- p.28<br>Chapter 3.1.7. --- Precontraction --- p.30<br>Chapter 3.1.8. --- Endothelium-dependent relaxation --- p.31<br>Chapter 3.2. --- Coronary artery studies --- p.32<br>Chapter 3.2.1. --- Porcine heart harvest and anatomy --- p.32<br>Chapter 3.2.2. --- Characteristic of histology of porcine coronary micro-artery --- p.32<br>Chapter 3.3. --- Pulmonary artery studies --- p.35<br>Chapter 3.3.1. --- Porcine lung harvest and anatomy --- p.35<br>Chapter 3.3.2. --- Characteristic of histology of porcine pulmonary micro- artery --- p.36<br>Chapter 3.4. --- Drugs --- p.41<br>Chapter 3.4.1. --- Drugs --- p.41<br>Chapter 3.4.2. --- Preparation of oxyhemoglobin solution --- p.41<br>Chapter 3.5. --- Statistical Analysis --- p.42<br>Chapter 3.5.1. --- Calculation of EC50 --- p.42<br>Chapter 3.5.2. --- Statistical analysis --- p.42<br>Chapter Chapter 4: --- "Epoxyeicosatrienoic Acids (EET11,12) May Partially Restore EDHF-Mediated Function in Coronary Micro-Arteries" --- p.43<br>Chapter 4.1. --- Abstract --- p.43<br>Chapter 4.2. --- Introduction --- p.44<br>Chapter 4.3. --- Experimental Protocol --- p.45<br>Chapter 4.3.1. --- Precontraction --- p.45<br>Chapter 4.3.2. --- "EDHF-mediated (INDO, L-NNA, and HbO-resistant) relaxation" --- p.45<br>Chapter 4.3.3. --- "EET11,12-mediated relaxation after exposure to hyperkalemia" --- p.46<br>Chapter 4.3.4. --- "The effect of incubation with EET11,12 on the BK-induced, EDHF-mediated relaxation" --- p.46<br>Chapter 4.4. --- Results --- p.47<br>Chapter 4.4.1. --- Resting force --- p.47<br>Chapter 4.4.2. --- HbO and U46619-induced contraction force --- p.48<br>Chapter 4.4.3. --- "EET11,12-induced relaxation in coronary micro-arteries after exposure to hyperkalemia" --- p.49<br>Chapter 4.4.4. --- "The EDHF-mediated relaxation to BK resistant to INDO, l- NNA,and HbO" --- p.51<br>Chapter 4.4.4.1. --- Incubated in either hyperkalemic solution (K+ 20mmol/L) or Krebs' solution (control) --- p.51<br>Chapter 4.4.4.2. --- "Incubated in either hyperkalemic solution (K+ 20mmol/L) plus EET11,12 or Krebs' solution (control)" --- p.53<br>Chapter 4.5. --- Discussion --- p.57<br>Chapter 4.5.1. --- EDHF plays an important role in the coronary micro-arteries --- p.57<br>Chapter 4.5.2. --- "EDHF-mediated (INDO, l-NNA, and HbO-resistant) relaxation in the coronary micro-arteries" --- p.58<br>Chapter 4.5.3. --- "EET11,12 may partially mimic the EDHF-mediated relaxation in the porcine coronary micro-artery" --- p.59<br>Chapter 4.5.4. --- "Effect of EET11,12 added in hyperkalemia may partially restore the EDHF-mediated relaxation in the porcine coronary micro-arteries" --- p.59<br>Chapter Chapter 5: --- Impaired EDHF-Mediated Relaxationin Porcine Pulmonary Micro-arteries by Cold Store with Euro-Collin's and University of Wisconsin Solution --- p.61<br>Chapter 5.1. --- Abstract --- p.61<br>Chapter 5.2. --- Introduction --- p.62<br>Chapter 5.3. --- Experimental Protocol --- p.64<br>Chapter 5.3.1. --- Precontraction --- p.64<br>Chapter 5.3.2. --- "Role of EDHF-mediated (INDO, L-NNA and HbO-resistant) relaxation in porcine pulmonary micro-arteries by BK orA23187" --- p.64<br>Chapter 5.3.3. --- Effect of hyperkalemia or preservation solutions (EC or UW) on the EDHF-mediated relaxation by BK or A23187 --- p.65<br>Chapter 5.3.3.1. --- The effect of hyperkalemia --- p.65<br>Chapter 5.3.3.2. --- Effect of EC solution on the EDHF-mediated relaxation --- p.65<br>Chapter 5.3.3.3. --- Effect of UW solution on the EDHF-mediated relaxation --- p.66<br>Chapter 5.3.3.4. --- The effect of UW and EC solutions on the contractility of the pulmonary micro-artery --- p.66<br>Chapter 5.4. --- Results --- p.66<br>Chapter 5.4.1. --- Resting force --- p.66<br>Chapter 5.4.2. --- U46619-induced contraction force --- p.67<br>Chapter 5.4.3. --- Role of EDHF-mediated relaxation induced by BK or A23187 --- p.67<br>Chapter 5.4.4. --- The effect of hyperkalemia --- p.71<br>Chapter 5.4.5. --- Effect of EC solution on the EDHF-mediated relaxation --- p.72<br>Chapter 5.4.6. --- Effect of UW solution on the EDHF-mediated relaxation --- p.73<br>Chapter 5.4.7. --- The effect of UW and EC solution on the contractility of the pulmonary micro-artery --- p.73<br>Chapter 5.5. --- Discussion --- p.77<br>Chapter 5.5.1. --- EDHF-mediated endothelial function exists in the pulmonary micro-circulation --- p.77<br>Chapter 5.5.2. --- Hyperkalemia exposure reduces EDHF-related relaxation and possible mechanism --- p.78<br>Chapter 5.5.3. --- The effect of EC and UW solutions on the EDHF-media relaxation in the pulmonary micro-arteries --- p.79<br>Chapter Chapter 6: --- General Discussion --- p.82<br>Chapter 6.1. --- Endothelium-dependent vasodilators: BK and A23187 --- p.82<br>Chapter 6.2. --- EDHF in porcine coronary and pulmonary micro-arteries --- p.84<br>Chapter 6.2.1. --- EDHF in porcine coronary micro-arteries --- p.84<br>Chapter 6.2.2. --- EDHF in porcine pulmonary micro-arteries --- p.87<br>Chapter 6.2.3. --- Vascular stretch and release of endothelium-derived vasodilators --- p.87<br>Chapter 6.2.4. --- "EET11,12" --- p.88<br>Chapter 6.3. --- "Endothelium-dependent relaxation resistant to INDO, L- NNA, and HbO in porcine coronary and pulmonary microcirculation" --- p.89<br>Chapter 6.4. --- "Alteration of endothelium-dependent relaxation resistant to INDO, l-NNA, and HbO after exposure to hyperkalemia" --- p.90<br>Chapter 6.5. --- "Alteration of endothelium-dependent contraction resistant to INDO, L-NNA, and HbO after exposure to EC or UW solutions" --- p.91<br>Chapter 6.6. --- Clinical implications --- p.92<br>Chapter 6.7. --- Limitations --- p.93<br>Chapter 6.7.1. --- Common limitations --- p.93<br>Chapter 6.7.2. --- Limitation of in vitro study --- p.93<br>Chapter 6.8. --- Future work --- p.94<br>Chapter Chapter 7: --- Conclusion --- p.96<br>References --- p.98<br>Appendies<br>"Wei Zou, Qin Yang, Anthony PC Yim, & Guo-Wei He Epoxyeicosatrienoic acids (EET11,12) may partially restore endothelium- derived hyperpolarizing factor-mediated function in coronary micro- arteries. Annals of Thoracic Surgery. 2001; 72(12): 1970~1976."

Background: Chylothorax occurs in ~4% of children undergoing cardiac surgery. Treatment requires transition to a medium chain triglyceride (MCT) based formula. Breast milk (EBM) is discontinued due to the presence of long chain triglycerides. Objective: To determine the effectiveness of a modified fat breast milk for the treatment of chylothorax. Methods: Infants with chylothorax were eligible. Treatment infants (n=8) received EBM that had been modified by removing the fat layer (centrifugation) from EBM and adding MCT and nutrients to provide 67 kcal/ml and 11 g/100 ml protein. Control infants (n=8) received MCT formula. Results: Volume of chest tube drainage was not different (p<0.40). Treatment infants experienced declines in mean weight (p<0.006), length (p<0.013) and head circumference (p<0.008) z-scores. Conclusion: Modified fat breast milk allowed for successful resolution of chylothorax. Strategies to address poor growth, however, need to be tested before clinical adoption of this novel treatment.