Browsing by Author "Pennel, Timothy"

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    Open Access
    A 23-year retrospective review of heart transplant donor and recipient referrals to Groote Schuur hospital between 1997 and 2019
    (2025) Kanyongo, Rusununguko; Pennel, Timothy
    Background. Heart transplantation in South Africa faces numerous challenges related to organ scarcity and unequal access to advanced heart therapy. There is an urgent need to analyse the current transplant referral pathway to optimise equitable access to transplantation. Objectives. To provide an audit of heart transplant referrals to Groote Schuur Hospital, Cape Town, over a 23-year period, focusing on patient demographics, indications for referral, waiting-list dynamics, and transplant referral outcomes. Methods. The study utilised a retrospective patient folder review for the period 1 January 1997 - 31 December 2019 and audited the trends in heart transplant referrals and associated outcomes of the referral at a tertiary academic hospital. Results. A total of 625 recipients were referred for heart transplantation, with the majority being male (n=412; 65.9%), while gender was undocumented for 69 cases (11.0%). The mean age was 38.1 (14.6) years, and 153 (24.5%) were listed for transplant, while 215 (34.4%) were deemed ineligible for listing. Contraindications for listing included social (n=106; 49.3%), medical (n=83; 38.6%) and psychological (n=26; 12.0%) factors, while 134 patients (21.4%) were considered too well. Poor social circumstances (n=38; 39.6%), poor insight (n=28; 29.2%) and poor compliance (n=21; 21.9%) were the most common non-medical reasons for not listing recipients, while obesity (n=30; 31.3%) and smoking (n=23; 24.0%) were notable medical contraindications. Forty-nine patients (7.8%) died during work-up, while 130 (85.0%) of the listed patients received a heart transplant. Of the 429 donor referrals, 139 (32.4%) were accepted for organ procurement. Reasons for declining donors included unsuitability for transplantation (30.3%), lack of capacity (1.8%), and recipient-donor mismatch (66.9%). Conclusion. Three-quarters of the referred patients were deemed unsuitable for heart transplantation for medical and/or social reasons. The ratio of referral to listing has decreased over time. However, once listed, the likelihood of receiving a transplant was high.
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    Open Access
    The performance of cross-linked acellular arterial scaffolds as vascular grafts; pre-clinical testing in direct and isolation loop circulatory models
    (2016) Pennel, Timothy; Bezuidenhout, Deon; Zilla, Peter
    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.
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    Stabilised decellularised vascular grafts in an ovine carotid model
    (2018) Mentor, Keno; Bezuidenhout, Deon; Pennel, Timothy
    Background: There is an urgent clinical need for an alternative vascular graft, especially for smaller artery applications such as in below-knee and coronary artery bypass. Currently available synthetic grafts have unacceptably low patency rates, while autologous saphenous vein grafts are not feasible in one third of patients. Decellularised vascular grafts have been investigated as alternative conduits, but this chemical treatment results in degradation of the extracellular matrix. Chemical stabilization of elastin with penta-galloyl glucose (PGG) combined with collagen stabilisation during covalent heparinisation was previously investigated by our group in a small animal model and shown to be effective and safe. The current study describes their evaluation in a large animal (ovine) model. Methods: Porcine mammary arteries were harvested, decellularised according to an established protocol involving rinsing with sodium hydroxide, alcohol (ETOH), treatment with DNAse/RNAse enzymes, immersion in PGG and subsequently surface modified with covalently bound heparin. Samples of the grafts were also tested for radial and suture retention strength. The prepared grafts were implanted as interposition grafts into the carotid arteries of 6 sheep, using industry standard 6mm expanded polytetrafluoroethylene (ePTFE) on the contralateral side of each animal as control. In-situ patency was determined by ultrasound and angiography at two months, following which the grafts were explanted for macro- and microscopic analysis. Results: In-vitro evaluation: Grafts showed significant levels of bound heparin (14.56 mg/g vs 0.69mg/g in untreated tissue) and demonstrated similar mechanical properties to those of human carotid arteries. Survival: Five out of six sheep survived the full 2-month implant period, while the remaining animal developed sepsis shortly after implantation and was euthanized on day 4. Patency: None of the decellularised grafts were patent at explant, as assessed by ultrasound, angiography and macroscopic examination. Two of the five control (ePTFE) grafts were patent. Microscopic analysis: An inflammatory cell infiltrate with vascularised granulation tissue was found encasing the decellularised xenografts with little or no sign of endothelial cell infiltration. Signs of early occlusion, likely due to technical factors, was noted at the sites of anastomosis. Conclusion: Although demonstrating similar mechanical properties to human carotid arteries, and promising results in the small animal model, the stabilised decellularised vascular grafts failed to achieve endothelialisation or patency in this sheep carotid model. Significant calibre mismatch between the test graft and the native artery is thought to be the primary factor in the failure of these grafts, highlighting the potential difficulty in acquiring grafts of an appropriate size from animal sources.
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    The role of computerised tomographic angiograms (CTA) and lateral neck radiographs in penetrating neck oesophageal injuries
    (2019) Oompie, Ferdinand Musawenkosi; Pennel, Timothy; Nicol, Andrew
    Background South Africa has a high rate of injuries related to violence which includes penetrating neck injuries (PNI’s). Of the 163 patients that are annually referred for contrast swallow studies to exclude associated pharyngo-oesophageal injuries (PPOI’s), only 0-14% contrast studies confirm injury. The contrast swallow is still viewed as the ‘gold standard’ for oesophageal pathology even in the modern era of digital general radiography and Multidetector Computerized Tomographic Angiogram (MDCTA). This procedure is however time consuming and requires good cooperation, sometimes from acutely ill patients which is not always possible. This contributes to delay in final management of the patient which is the most significant contributor to associated complications. The study reviewed whether the less time-consuming MDCTA’s and lateral soft tissue radiographs usually performed before the contrast swallow studies can also be used to diagnose POI’s. This will reduce dependence and possibly exclude the contrast swallow study, thus reducing the time delay in POI pre-operative investigations. Methods A retrospective review was undertaken of the radiological findings of all patients who presented at Groote Schuur Hospital over a 28-month period with suspected penetrating neck injuries and were investigated with a contrast swallow, MDCTA and lateral soft tissue radiograph. The time interval between request of the contrast swallow study and the final report was calculated as the difference in the time indicated on the Groote Schuur Hospital Philips Extended Internet Radiology Information System (XIRIS) by the requesting clinician and the time indicated on the radiology report after completion of the study on the Philips Picture Archiving and Communicating System (PACS). Results Of the 389 patients referred, 153 patients met the study criteria. Fourteen patients (9%) had PPOI’s on contrast swallow. The majority of the patients with PPOI’s had prevertebral air (12; sensitivity of 85.7%), however a majority of patients with prevertebral air had no POI’s (90; specificity of 35.3%). In 28 MDCTA’s where there was suspicion of PPOI’s, six contrast swallows confirmed oesophageal leaks (42.9% sensitivity). Although there was no suspicion of PPOI’S in 125 patients undergoing MDCTA’s, eight were found to be positive for leaks on contrast swallow (84.2% specificity). The mean time interval between request of the contrast swallow study and final report was 586 minutes. Conclusion Contrast swallow remains the gold ‘standard’ for diagnosing PPOI’s in patients with PNI’s. The lateral soft tissue radiograph was unreliable in predicting POI’s with a low specificity of 35%. MDCTA’s was also not contributory in assisting diagnoses of PPOI’s with a low sensitivity of 43%. The two modalities can thus not be considered as augmentation or alternative diagnostic modalities. The time delay between the request and reporting of the contrast swallow is longer than that in literature and needs improvement.
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    Ultrasonography Evaluation of Patency of Implanted Infra-Renal Vascular Grafts in the Rat Model.
    (2020) Da Silva, Natercia; Pennel, Timothy; Bezuidenhout, Deon; Hadebe, Nkanyiso; Zilla, Peter
    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.