Browsing by Department "Division of Cardiology"
Now showing 1 - 20 of 81
Results Per Page
Sort Options
- ItemOpen AccessAbnormal myocardial perfusion correlates with impaired systolic strain and diastolic strain rate in systemic lupus erythematosus: a cardiovascular magnetic resonance study(BioMed Central Ltd, 2015) Ntusi, Ntobeko; Sever, Emily; Lockey, Joseph; Francis, Jane; Piechnik, Stefan; Ferreira, Vanessa; Matthews, Paul; Wordsworth, Paul; Neubauer, Stefan; Karamitsos, TheodorosSystemic lupus erythematosus (SLE) is a systemic autoimmune disorder that commonly affects the heart, resulting in a 7 to 9 times greater incidence of cardiovascular disease (CVD) in SLE patients compared to healthy controls. Female patients with SLE between 35 and 44 years old have an incidence of myocardial infarction over 50 times greater than that observed in the Framingham cohort. The clinical utility of cardiovascular magnetic resonance (CMR) first-pass perfusion for assessment of myocardial ischaemia is well-established. We hypothesised that CMR including stress first-pass perfusion would be able to detect coronary microvascular disease and subtle functional abnormalities in SLE and aimed to detect myocardial ischaemia in SLE using adenosine stress perfusion CMR.
- ItemOpen AccessAdenosine and its role in cardioplegia : experimental evaluation in the isolated rat heart and in an-vivo primate model(1997) Boehm, Dieter Hermann; Opie, Lionel H; Reichart, BThis 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.
- ItemOpen AccessAn analysis of defibrillation and cardiac resynchronization therapy strategies in patients with failing systemic right ventricles(2007) Michael, Kevin A; Morgan, John MThe expanding application of cardiac resynchronization (CRT) and implantable cardioverter-defibrillator therapy (lCD) to include patients with congenital heart disease requires careful evaluation of selection criteria and unconventional adaptive strategies to ensure clinical efficacy. A single centre prospective analysis of adults post atrial redirection surgery (Mustard operation) for dextro-transposition of the great arteries (d-TGA) presenting with systemic right ventricular (sRV) dysfunction and at risk of sudden cardiac death (SCD). All patients ( mean age 25 years, range 18-35) with varying functional disability{New York Heart Association (NYHA) II-III} receiving ICDs ± concomitant CRT were evaluated. Total follow-up period was 24 months. A patient individualized approach was used for device implantation. Endocardial, epicardial and transthoracic defibrillation strategies were examined in 5 consecutive cases. A hybridized form of CRT was employed in two patients. Only one patient demonstrated response to therapy while the other deteriorated during biventricular pacing (BVP). This prompted a novel approach to CRT using noncontact mapping (NCM) and acute intra-arterial blood pressure response to guide endocardialsRV lead placement in a single patient. The ejection fraction increased from 23 -33% within 1week post procedure and clinical improvement was sustained after 6-months follow-up. Application of CRT II CD therapy to patients with sRV dysfunction requires individualized and adaptive strategies to overcome anatomical constraints. This study represents a chronological and evolutionary account of these measures.
- ItemOpen AccessArrhythmogenic right ventricular cardiomyopathy type 6 (ARVC6): support for the locus assignment, narrowing of the critical region and mutation screening of three candidate genes(BioMed Central Ltd, 2006) Matolweni, Luzuko; Bardien, Soraya; Rebello, George; Oppon, Ekow; Munclinger, Miroslav; Ramesar, Rajkumar; Watkins, Hugh; Mayosi, BonganiBACKGROUND:Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a heritable disorder characterized by progressive degeneration of right ventricular myocardium, arrhythmias and an increased risk of sudden death at a young age. By linkage analysis, ARVC type 6 was previously mapped to a 10.6 cM region on chromosome 10p12-p14 in a large North American kindred. To date, the genetic defect that causes ARVC6 has not been identified. METHODS: We identified a South African family of 13 members with ARVC segregating as an autosomal dominant disorder. The diagnosis of ARVC was based on international diagnostic criteria. All available family members were genotyped with microsatellite markers at six known ARVC loci, and positional candidate gene screening was performed. RESULTS: Genetic linkage and haplotype analysis provided lod scores that are highly suggestive of linkage to the ARVC6 locus on chromosome 10p12-p14, and the narrowing of the critical region to ~2.9 Mb. Two positional candidate genes (ITG8 and FRMD4A) were screened in which defects could possibly disrupt cell-cell adhesion. A non-positional candidate gene with apoptosis inducing properties, LAMR1P6 (laminin receptor 1 pseudogene 6) was also screened. Direct sequencing of DNA from affected individuals failed to detect disease-causing mutations in the exonic sequences of the three genes investigated. CONCLUSION: The narrowing of the ARVC6 critical region may facilitate progress towards the identification of the gene that is involved in ARVC. Identification of the causative genes for ARVC will contribute to the understanding of the pathogenesis and management of this poorly understood condition.
- ItemOpen AccessBalloon mitral valvuloplasty at Groote Schuur Hospital : results, complications and short-term follow-up(1995) Lawrenson, John Bernard; Commerford, PatrickBalloon dilatation of the stenosed mitral valve, in an attempt to relieve symptoms, was developed to replace the surgical procedure of closed mitral valvotomy. This procedure, whereby a balloon tipped catheter is introduced from the femoral vein and directed across the mitral valve after an atrial septal puncture, was developed in 1982. The procedure was first performed at Groote Schuur Hospital in 1988. Two types of dilating balloon (Inoue and Bifoil types) have been used. The aim of this retrospective study was to analyze the results of balloon mitral valvuloplasty procedures performed from 1988 until November 1992. In addition a detailed analysis was made of all complications of the procedure. 118 patients (mean age 30.7 years) underwent 124 attempted procedures. 93 % of attempts were successfully completed and an optimal result was achieved in 76% of patients. Mitral valve area increased from 0.9cm² to 2.0cm². Equivalent results have been achieved with both balloon types. Death occurred in 1.6 % of patients. 2.4 % of patients had severe mitral regurgitation as a complication. 4% of procedures resulted in cardiac chamber perforation. The experience at Groote Schuur has been similar to other centres treating young patients with rheumatic mitral stenosis.
- ItemOpen AccessBioprosthetic heart valves : ultrastructure and calcification(1998) Zhang, Yinxing; Zilla, PeterBackground: Due to the geographic distance between abattoirs and commercial valve plants delays between harvest and fixation usually range from 48 to 72 hours. In order to assess the pre-fixation tissue damage arising from the hypoxic period and the resulting calcific degeneration after implantation, we used an ultrastructural damage score and transmission electron microscopy. Materials and Methods: In a step by step manner, three major issues were clarified: 1) The degree of pre-fixation tissue damage was determined in the four most widely used commercially produced tissue heart valves. Since stentless bioprostheses represent the latest promising trend in the development of biological heart valves, stentless models of the following makes were compared: Baxter, Medtronic, St. Jude and Biocor. Due to the fact that the aortic wall component of these valves proved most resistant to all anticalcification treatments, aortic wall tissue stood in the centre of our analyses. 2) Subsequently, three main determinants of the fixation process namely: delay, temperature and fixative-concentration were varied with the goal of significantly improving the ultrastructural preservation of the bioprosthetic tissue. 3) Eventually, the influence of improved ultrastructural preservation on calcific degeneration was evaluated under in vivo conditions in the non-human primate and the rat model. Results: The comparison of the four most commonly used stentless bioprosthetic heart valves revealed a disturbing degree of tissue damage in all valves. Using a damage score from 1 to 21 (21 being the worst), aortic wall tissue of commercial valves ranged from 10 to 18 and that of leaflet tissue from 12 to 20. When fixation conditions were permutated, tissue damage could almost be abolished by immediate fixation (within 30 minutes of slaughter), low-temperature fixation(4°C) and high glutaraldehyde concentrations (> 1 %). Our in vivo experiments confirmed that commercially used fixation (delayed fixation, room-temperature and I ow concentrations of glutaraldehyde) with its concomitant high degree of tissue damage results in high levels of calcification. Apart from a distinctly improved calcification potential in ultrastructurally well preserved tissue, there was also an inverse correlation between tissue calcification and the concentration of glutaraldehyde used for fixation. Conclusion: We could demonstrate that commercially produced bioprosthetic heart valves uniformly show badly damaged tissue and that tissue damage contributes to the calcific degeneration of these valves. We were also able to determine ideal fixation conditions which in turn significantly reduced tissue calcification.
- ItemOpen AccessCardioprotective role of signal transducer activator of transcription 3 (STAT-3) against ischaemai reperfusion injuries(2011) King, Jonathan Chan; Lecour, Sandrine; Opie, Lionel HIntroduction: Sphingosine 1 phosphate (S1P) is a major constituent of high density lipoprotein (HDL) cholesterol. Both S1P preconditioning and ischaemic postconditioning reduce myocardial damage following an ischaemia-reperfusion insult but the mechanisms involved remain unclear. Janus kinase/Signal transducer and activator of transcription 3 (JAK/STAT-3) form part of a recently discovered powerful prosurvival path termed as the Survivor Activating Factor Enhancement (SAFE) pathway. The SAFE pathway plays a critical role in ischaemic preconditioning to promote cell survival but whether activation of STAT-3 is required for S1P preconditioning and ischaemic postconditioning induced cardioprotection is unknown. Hypothesis: Activation of the STAT-3 is required for S1P preconditioning and ischaemic postconditioning.
- ItemOpen AccessCharacterisation of the global transcriptional response to heat shock and the impact of individual genetic variation(BioMed Central, 2016-08-24) Humburg, Peter; Maugeri, Narelle; Lee, Wanseon; Mohr, Bert; Knight, Julian CBackground: The heat shock transcriptional response is essential to effective cellular function under stress. This is a highly heritable trait but the nature and extent of inter-individual variation in heat shock response remains unresolved. Methods: We determined global transcription profiles of the heat shock response for a panel of lymphoblastoid cell lines established from 60 founder individuals in the Yoruba HapMap population. We explore the observed differentially expressed gene sets following heat shock, establishing functional annotations, underlying networks and nodal genes involving heat shock factor 1 recruitment. We define a multivariate phenotype for the global transcriptional response to heat shock using partial least squares regression and map this quantitative trait to associated genetic variation in search of the major genomic modulators. Results: A comprehensive dataset of differentially expressed genes following heat shock in humans is presented. We identify nodal genes downstream of heat shock factor 1 in this gene set, notably involving ubiquitin C and small ubiquitin-like modifiers together with transcription factors. We dissect a multivariate phenotype for the global heat shock response which reveals distinct clustering of individuals in terms of variance of the heat shock response and involves differential expression of genes involved in DNA replication and cell division in some individuals. We find evidence of genetic associations for this multivariate response phenotype that involves trans effects modulating expression of genes following heat shock, including HSF1 and UBQLN1. Conclusion: This study defines gene expression following heat shock for a cohort of individuals, establishing insights into the biology of the heat shock response and hypotheses for how variation in this may be modulated by underlying genetic diversity.
- ItemOpen AccessClinical characteristics and initial management of patients with tuberculous pericarditis in the HIV era: the Investigation of the Management of Pericarditis in Africa (IMPI Africa) registry(BioMed Central Ltd, 2006) Mayosi, Bongani; Wiysonge, Charles; Ntsekhe, Mpiko; Volmink, Jimmy; Gumedze, Freedom; Maartens, Gary; Aje, Akinyemi; Thomas, Baby; Thomas, Kandathil; Awotedu, Abolade; Thembela, Bongani; Mntla, Phindile; Maritz, Frans; Blackett, Kathleen; Nkouonlack,BACKGROUND:The incidence of tuberculous pericarditis has increased in Africa as a result of the human immunodeficiency virus (HIV) epidemic. However, the effect of HIV co-infection on clinical features and prognosis in tuberculous pericarditis is not well characterised. We have used baseline data of the Investigation of the Management of Pericarditis in Africa (IMPI Africa) registry to assess the impact of HIV co-infection on clinical presentation, diagnostic evaluation, and treatment of patients with suspected tuberculous pericarditis in sub-Saharan Africa. METHODS: Consecutive adult patients in 15 hospitals in three countries in sub-Saharan Africa were recruited on commencement of treatment for tuberculous pericarditis, following informed consent. We recorded demographic, clinical, diagnostic and therapeutic information at baseline, and have used the chi-square test and analysis of variance to assess probabilities of significant differences (in these variables) between groups defined by HIV status. RESULTS: A total of 185 patients were enrolled from 01 March 2004 to 31 October 2004, 147 (79.5%) of whom had effusive, 28 (15.1%) effusive-constrictive, and 10 (5.4%) constrictive or acute dry pericarditis. Seventy-four (40%) had clinical features of HIV infection. Patients with clinical HIV disease were more likely to present with dyspnoea (odds ratio [OR] 3.2, 95% confidence interval [CI] 1.4 to 7.4, P = 0.005) and electrocardiographic features of myopericarditis (OR 2.8, 95% CI 1.1 to 6.9, P = 0.03). In addition to electrocardiographic features of myopericarditis, a positive HIV serological status was associated with greater cardiomegaly (OR 3.89, 95% CI 1.34 to 11.32, P = 0.01) and haemodynamic instability (OR 9.68, 95% CI 2.09 to 44.80, P = 0.0008). However, stage of pericardial disease at diagnosis and use of diagnostic tests were not related to clinical HIV status. Similar results were obtained for serological HIV status. Most patients were treated on clinical grounds, with microbiological evidence of tuberculosis obtained in only 13 (7.0%) patients. Adjunctive corticosteroids were used in 109 (58.9%) patients, with patients having clinical HIV disease less likely to be put on them (OR 0.37, 95% CI 0.20 to 0.68). Seven patients were on antiretroviral drugs. CONCLUSION: Patients with suspected tuberculous pericarditis and HIV infection in Africa have greater evidence of myopericarditis, dyspnoea, and haemodynamic instability. These findings, if confirmed in other studies, may suggest more intensive management of the cardiac disease is warranted in patients with HIV-associated pericardial disease.
- ItemOpen AccessClinical orthotopic and heterotopic heart transplantation: aspects of the University of Cape Town experience(1985) Cooper, David Kempton CartwrightVOLUME 2 - APPENDICES
- ItemOpen AccessThe clinical, electrocardiographic and echocardiographic features and long-term outcome of patients with Tachycardia-induced cardiomyopathy(2010) Chin, Ashley; Okreglicki, A MTachycardia-induced cardiomyopathy (TIC) is a reversible cause of LV systolic dysfunction that can complicate any supraventricular or ventricular tachyarrhythmia. This study is the first to compare features of pure and impure TIC. We found that impure TIC may develop more quickly than pure TIC, as impure TIC patients have a shorter duration and more severe symptoms at presentation, which suggests that underlying structural heart disease is a risk factor in the pathogenesis of TIC.
- ItemOpen AccessClosed mitral valvotomy in pregnancy(1989) Vosloo, S M; Reichart, BHeart disease remains the most important non-obstetric cause of maternal mortality and morbidity during pregnancy, despite its low incidence of less than 1%. This is due to the decline in the number of deaths from haemorrhage, infection and toxemia. In addition, a striking change in the pattern of proportional distribution of organic heart disease in pregnant women is being noted, with a decrease in chronic rheumatic lesions and an increase in congenital cardiac disease. In the Third World rheumatic mitral valve disease remains a most important condition during pregnancy. It is currently rarely seen in Europe and the United States. Mitral stenosis is the most commonly encountered rheumatic heart lesion that complicates pregnancy. The normal circulatory changes during pregnancy aggravate this lesion as the reduced, fixed valve area obstructs blood flow from the left atrium to the left ventricle, causing pulmonary congestion and oedema. Careful and regular follow up of these patients is essential, and surgery is indicated if optimal medical management fails. Cardiac surgery duting pregnancy represents a risk to both the foetus and the mother. For most procedures extracorporeal circulation and heparinization are necessary and adds to the · adverse effects of the operation. Closed mitral valvotomy, however, is an excellent low risk operative procedure in patients with tight mitral stenosis without causing undue harm to the foetus. Cuttler described the first attempted surgery of the mitral valve in 1923 and since then the procedure has been improved to benefit many patients with tight mitral stenosis. The first reports of closed mitral valvotomy during pregnancy were in 1952. Al though a more precise valvotomy can be obtained with an open procedure, the closed operation avoids the risks of extracorporeal circulation, particularly detrimental to the foetus. This report is a review of the Groote Schuur Hospital experience of patients with mitral stenosis requiring closed mitral valvotomy during pregnancy since 1965. The aims of the study are to analyse the outcome of the pregnancy, the effects of valvotomy during pregnancy on both the mother and the foetus, and the outcome regarding restenosis of the mitral valve.
- ItemOpen AccessThe compounding effects of obesity on the development of Intimal Hyperplasia following vascular intervention : a histopathological analysis(2009) Black, Melanie Kim; Human, PaulThis study examines the histopathological response to injury following both balloon angioplasty and endovascular stenting in the Zucker rat, a model that allows interpretation of the role of obesity as well as progressive glucose intolerance and hyperinsulimaemia. Lean and obese Zucker fatty rats and Zucker diabetic fatty rat (ZDF) were subjected to balloon injury with or without stenting. The development of IH, along with the histological response to injury was analyzed.
- ItemOpen AccessComputational biomechanics in the remodelling rat heart post myocardial infarction(2016) Masithulela, Fulufhelo James; Franz , Thomas; Davies, Neil; Dubuis, LauraCardiovascular diseases account for one third of all deaths worldwide, more than 33% of which are related to ischemic heart disease, including myocardial infarction (MI). This thesis seeks to provide insight and understanding of mechanisms during different stages of MI by utilizing finite element (FE) modelling. Three-dimensional biventricular rat heart geometries were developed from cardiac magnetic resonance images of a healthy heart and a heart with left ventricular (LV) infarction two weeks and four weeks after infarct induction. From these geometries, FE models were established. To represent the myocardium, a structure-based constitutive model and a rule-based myofibre distribution were developed to simulate both passive mechanics and active contraction.
- ItemOpen AccessComputational biomechanics of acute myocardial infarction and its treatment(2015) Sirry, Mazin Salaheldin; Franz, Thomas; Davies, NeilThe intramyocardial injection of biomaterials is an emerging therapy for myocardial infarction. Computational methods can help to study the mechanical effect s of biomaterial injectates on the infarcted heart s and can contribute to advance and optimise the concept of this therapy. The distribution of polyethylene glycol hydrogel injectate delivered immediately after the infarct induction was studied using rat infarct model. A micro-structural three-dimensional geometrical model of the entire injectate was reconstructed from histological micro graphs. The model provides a realistic representation of biomaterial injectates in computational models at macroscopic and microscopic level. Biaxial and compression mechanical testing was conducted for healing rat myocardial infarcted tissue at immediate (0 day), 7, 14 and 28 days after infarction onset. Infarcts were found to be mechanically anisotropic with the tissue being stiffer in circumferential direction than in longitudinal direction. The 0, 7, 14 and 28 days infarcts showed 443, 670, 857 and 1218 kPa circumferential tensile moduli. The 28 day infarct group showed a significantly higher compressive modulus compared to the other infarct groups (p= 0.0055, 0.028, and 0.018 for 0, 7 and 14 days groups). The biaxial mechanical data were utilized to establish material constitutive models of rat healing infarcts. Finite element model s and genetic algorithms were employed to identify the parameters of Fung orthotropic hyperelastic strain energy function for the healing infarcts. The provided infarct mechanical data and the identified constitutive parameters offer a platform for investigations of mechanical aspects of myocardial infarction and therapies in the rat, an experimental model extensively used in the development of infarct therapies. Micro-structurally detailed finite element model of a hydrogel injectate in an infarct was developed to provide an insight into the micromechanics of a hydrogel injectate and infarct during the diastolic filling. The injectate caused the end-diastolic fibre stresses in the infarct zone to decrease from 22.1 to 7.7 kPa in the 7 day infarct and from 35.7 to 9.7 kPa in the 28 day infarct. This stress reduction effect declined as the stiffness of the biomaterial increased. It is suggested that the gel works as a force attenuating system through micromechanical mechanisms reducing the force acting on tissue layers during the passive diastolic dilation of the left ventricle and thus reducing the stress induced in these tissue layers.
- ItemOpen AccessCongenital long QT syndrome(BioMed Central Ltd, 2008) Crotti, Lia; Celano, Giuseppe; Dagradi, Federica; Schwartz, PeterCongenital long QT syndrome (LQTS) is a hereditary cardiac disease characterized by a prolongation of the QT interval at basal ECG and by a high risk of life-threatening arrhythmias. Disease prevalence is estimated at close to 1 in 2,500 live births.The two cardinal manifestations of LQTS are syncopal episodes, that may lead to cardiac arrest and sudden cardiac death, and electrocardiographic abnormalities, including prolongation of the QT interval and T wave abnormalities. The genetic basis of the disease was identified in the mid-nineties and all the LQTS genes identified so far encode cardiac ion channel subunits or proteins involved in modulating ionic currents. Mutations in these genes (KCNQ1, KCNH2, KCNE1, KCNE2, CACNA1c, CAV3, SCN5A, SCN4B) cause the disease by prolonging the duration of the action potential. The most prevalent LQTS variant (LQT1) is caused by mutations in the KCNQ1 gene, with approximately half of the genotyped patients carrying KCNQ1 mutations.Given the characteristic features of LQTS, the typical cases present no diagnostic difficulties for physicians aware of the disease. However, borderline cases are more complex and require the evaluation of various electrocardiographic, clinical, and familial findings, as proposed in specific diagnostic criteria. Additionally, molecular screening is now part of the diagnostic process.Treatment should always begin with beta-blockers, unless there are valid contraindications. If the patient has one more syncope despite a full dose beta-blockade, left cardiac sympathetic denervation (LCSD) should be performed without hesitation and implantable cardioverter defibrillator (ICD) therapy should be considered with the final decision being based on the individual patient characteristics (age, sex, clinical history, genetic subgroup including mutation-specific features in some cases, presence of ECG signs - including 24-hour Holter recordings - indicating high electrical instability).The prognosis of the disease is usually good in patients that are correctly diagnosed and treated. However, there are a few exceptions: patients with Timothy syndrome, patients with Jervell Lange-Nielsen syndrome carrying KCNQ1 mutations and LQT3 patients with 2:1 atrio-ventricular block and very early occurrence of cardiac arrhythmias.
- ItemOpen AccessCyclic stretch-mediated release of vascular endothelial growth factor by vascular smooth muscle cells : a role in improved vascular graft patency(1999) Smith, James Douglas; Zilla, PeterIn the light of studies which show the upregulation of VEGF in contractile cells subjected to cyclic stretch and the profound effects which cyclic stretch has been shown to have on the release of other cytokines by SMC, this study investigates the role which cyclic stretch might play in VEGF expression by SMC in a compliant environment. Furthermore, following observations of receptor phosphorylation in response to cyclic stretch in vascular cells, the effect of cyclic strain on the KDR-mediated endothelial response to locally-released VEGF was also investigated. Low passage number bovine aortic SMC and EC were plated on collagen-coated elastomer plates and subjected to 10% repetitive strain at 1 Hz. The mRNA expression of VEGF in SMC and the phosphorylation of KDR on EC were determined by northern blotting and western blotting respectively. The biological activity on EC and levels of VEGF secreted into the medium by SMC under cyclic stretch were investigated using a migration assay and ELISA respectively. Cyclic stretch was found to cause a 3.3 (±1.5 p < 0.005) fold increase in VEGF mRNA levels over unstretched controls at 4 hours. This biomechanically-induced expression was found to drop slightly by 24 hours and to be approximately equivalent to expression induced by the cytokine bFGF over the same time course. These results correlated with an increase in VEGF levels in media from stretched SMC capable of inducing migration of EC by 1.6 fold although additional EC chemotactic factors appear to be released by stretch. Furthermore, although the levels of KDR remained constant under cyclic stretch, average KDR phosphorylation was found to increase weakly over time due to cyclic stretch. These results show that cyclic stretch affects the VEGF communication between SMC and EC at both the level of VEGF expression by SMC and at the level of VEGF recognition by the KDR receptor on EC. It is possible that through the nitric oxide (NO) pathway, VEGF release may alleviate abnormally high levels of cyclic strain. It is hoped that a better understanding of the role of VEGF communication between stretched SMC and EC will enable the design of a graft in which the level of compliance encourages SMC to maintain a functional endothelium. Following this it is hoped that the low levels of SMC and pericytes invading the graft, pacified by endothelial cell mediation, will not result in intimal hyperplasia but rather play a role in microvessel maintenance and more complete healing.
- ItemOpen AccessThe development of a system of 24 hours preservation of the heart for transplantation(1983) Wicomb, Winston Neville; Barnard, Christiaan NeethlingThis thesis describes a series of investigations into the problems that hamper the progress of myocardial preservation for transplantation in man. Six positive aspects of cardiac preservation have emerged from this study: - (1) A clear fluid hyperosmolar solution was formulated that adequately preserved viability of pig and baboon hearts. (2) A pneumatically powered portable preservation unit was designed which successfully preserved pig and baboon hearts when assessed by either functional testing or orthotopic transplantation. (3) A method of in vitro testing of hearts was developed that correlated with results from orthotopic transplantation. (4) A technique of cardiac autotransplantation in baboons was perfected. (5) The high release of lysosomal acid phosphatase during the period of hypothermic preservation was shown to be non-pathological and was reversible after a period of warm blood perfusion. (6) Successful preservation of human hearts for periods longer than 4 hours, not previously achieved, was obtained. The preservation solution and the portable preservation unit that emerged from this experimental study were thoroughly investigated before clinical application. During the development of this perfusate the author had numerous consultations and discussions with colleagues and senior members of neighbouring departments.