Papers by Arthur Preovolos
Clinical transplantation, Dec 11, 2011
The Annals of Thoracic Surgery, Oct 1, 2004
Background. Severe pulmonary graft failure (PGF) is the most common cause of death within the fir... more Background. Severe pulmonary graft failure (PGF) is the most common cause of death within the first 30 days after lung transplantation. Extracorporeal membrane oxygenation (ECMO) may provide lifesaving temporary support; however, its longer-term efficacy is controversial. Methods. We reviewed the use of ECMO for severe PGF after lung transplantation, and compared the outcomes between our early (1990 to 1999) and recent (2000 to 2003) experience utilizing improved initiation timing, oxygenator technology, and surgical technique. Results. Ten transplant recipients from a total of 481 (2.1%) were managed for PGF on ECMO by a multidisciplinary team at The Alfred Hospital. Four single-lung, 3 bilateral single-lung, and 3 heart-lung recipients were supported for a mean of 96 hours (range 14 to 212 hours). In the early group (operation from 1990 to 1999, n ؍ 4) ECMO was initiated 21 days (range 7 to 40 days) after lung transplantation and in the recent group (operation from 2000 to 2003, n ؍ 6) after 0 to 2 days (p ؍ 0.01). Radial-arterial blood gas analysis 12 hours after initiation of ECMO showed significantly better oxygenation in the recent group (341 ؎ 90 mm Hg) than in the early group (90 ؎ 23 mm Hg, p ؍ 0.03). Four deaths occurred as a result of bleeding (two in each group). In the early group only 1 patient was weaned from ECMO but died. In the recent group 3 were successfully weaned and were discharged from the intensive care unit; of these patients, 2 were discharged from hospital. Conclusions. Extracorporeal membrane oxygenation results have improved with advances in oxygenator technology and surgical techniques. The procedure can allow resolution of early PGF after lung transplantation.
European Journal of Heart Failure, Mar 1, 2011
AimsDown‐regulation of sarcoplasmic reticulum calcium ATPase (SERCA2a) is a key molecular abnorma... more AimsDown‐regulation of sarcoplasmic reticulum calcium ATPase (SERCA2a) is a key molecular abnormality in heart failure (HF), which is not currently addressed by specific pharmacotherapy. We sought to evaluate, in detail, the impact of augmented SERCA2a expression on left ventricular (LV) mechanics in a large animal model of HF.Methods and resultsHeart failure was induced in adult sheep by rapid pacing (180 b.p.m.) for 1 month, followed by delivery of adeno‐associated virus (AAV) 2/1–SERCA, using a percutaneous, recirculating system for gene delivery over a 10 min period. Left ventricular mechanics was investigated by echocardiography and conductance catheter measurements in sheep receiving AAV2/1–SERCA2a after a further 4 weeks of pacing in comparison with untreated HF controls. Left ventricular function was significantly improved in the AAV2/1–SERCA2a‐treated group, despite continued pacing, as measured by fractional shortening (delta absolute FS, control −4.2 ± 1.5% vs. treatment 4.4 ± 1.5%; P < 0.01) and conductance catheterization (delta Ees, control −1.22 ± 0.60 vs. treatment 0.65 ± 0.51; P < 0.05). Western blots showed an increase in SERCA protein in AAV2/1–SERCA2a‐treated animals, and an analysis of gene delivery showed no evidence of regional myocardial heterogeneity in the distribution of AAV2/1–SERCA.ConclusionIn a large animal model, AAV2/1‐mediated SERCA2a gene delivery using percutaneous, recirculating cardiac delivery leads to improved LV function.
The Annals of Thoracic Surgery, Nov 1, 2010
Background. The aim of this review was to analyze our results with extracorporeal membrane oxygen... more Background. The aim of this review was to analyze our results with extracorporeal membrane oxygenation (ECMO) support for primary graft failure (PGF) in heart transplant recipients. Methods. A retrospective review of 239 consecutive patients who underwent heart transplantation between January 2000 and August 2009 was performed. Orthotopic, heterotopic, and heart lung transplants were included in this analysis. Over that time period, 54 patients developed PGF, of whom 39 patients required ECMO support. These 39 patients form the basis of this review. Results. Thirty-four patients (87%) were successfully weaned from ECMO and 29 (74.3%) survived to hospital discharge. There were no significant differences in wean rates or complications between central and peripheral ECMO. Comparison of survival in the 39 ECMO patients to the non-PGF patients (n ؍ 185) showed a significantly worse survival in the ECMO group (p ؍ 0.007). When those patients who died in the first 30 days were excluded, there was no difference in overall survival between groups (p ؍ 0.73). Conclusions. Extracorporeal membrane oxygenation provides excellent circulatory support for patients with PGF after heart transplantation with good wean and survival to discharge rates.
Journal of the American College of Cardiology, Jul 1, 2007
The purpose of this study was to develop a clinically applicable high-efficiency percutaneous mea... more The purpose of this study was to develop a clinically applicable high-efficiency percutaneous means of therapeutic gene delivery to the failing heart. Background Substantial advances in the understanding of the cellular and molecular basis of heart failure (HF) have recently fostered interest in the potential utility of gene and cell therapy as novel therapeutic approaches. However, successful clinical translation is currently limited by the lack of safe, efficient, and selective delivery systems. Methods We developed a novel percutaneous closed-loop recirculatory system that provides homogeneous myocardial delivery for gene transfer in the failing large animal heart. After 4 weeks' rapid pacing in adult sheep to induce HF, the animals were randomly allocated to receive either adenovirus expressing a pseudophosphorylated mutant (AdS16E) of phospholamban (PLN) or Ad--galactosidase (AdLacZ). Results Two weeks after gene delivery, in the presence of continued pacing, left ventricular (LV) ejection fraction had significantly improved in the AdS16E-treated animals (27 Ϯ 3% to 50 Ϯ 4%; p Ͻ 0.001), whereas a further decline occurred in the AdLacZ group (34 Ϯ 4% to 27 Ϯ 3%; p Ͻ 0.05). In conjunction, AdS16E delivery resulted in significant reductions in LV filling pressures and end-diastolic diameter (both p Ͻ 0.05). In conjunction, AdS16Etreated animals showed significant improvement in the expression of PLN and Ca 2ϩ-adenosine triphosphatase activity. In separate animals, recirculating AdLacZ delivery was shown to achieve superior myocardial gene expression in contrast to intracoronary delivery and was associated with lower systemic expression. Conclusions We report the development of a novel closed-loop system for cardiac gene therapy. Using this approach delivery of AdS16E reversed HF progression in a large animal HF model.
PubMed, Mar 1, 2006
BACKGROUND Current techniques for delivery of gene therapy, deliver the vector to the target orga... more BACKGROUND Current techniques for delivery of gene therapy, deliver the vector to the target organ and also to the systemic circulation. Targeted gene therapy aims at delivering the vector to specific and restricted cell populations, thus sparing all other cells of the 51 PROCEEDINGS INAUGURAL PERFUSION DOWNUNDER
Gene Therapy, Jul 24, 2008
Abnormal excitation-contraction coupling is a key pathophysiologic component of heart failure (HF... more Abnormal excitation-contraction coupling is a key pathophysiologic component of heart failure (HF), and at a molecular level reduced expression of the sarcoplasmic reticulum (SR) Ca 2+ ATPase (SERCA2a) is a major contributor. Previous studies in small animals have suggested that restoration of SERCA function is beneficial in HF. Despite this promise, the means by which this information might be translated into potential clinical application remains uncertain. Using a recently established cardiac-directed recirculating method of gene delivery, we administered adeno-associated virus 2 (AAV2)/1SERCA2a to sheep with pacing-induced HF. We explored the effects of differing doses of AAV2/1SERCA2a (low 1 Â 10 10 d.r.p.; medium 1 Â 10 12 d.r.p. and high 1 Â 10 13 d.r.p.) in conjunction with an intra-coronary delivery group (2.5 Â 10 13 d.r.p.). At the end of the study, haemodynamic, echocardiographic, histopathologic and molecular biologic assessments were performed. Cardiac recirculation delivery of AAV2/1SERCA2a elicited a dose-dependent improvement in cardiac performance determined by left ventricular pressure analysis, (+d P/d t max ; low dose À220 ± 70, P40.05; medium dose 125 ± 53, Po0.05; high dose 287 ± 104, Po0.05) and echocardiographically (fractional shortening: low dose À3 ± 2, P40.05; medium dose 1 ± 2, P40.05; high dose 6.5 ± 3.9, Po0.05). In addition to favourable haemodynamic effects, brain natriuretic peptide expression was reduced consistent with reversal of the HF molecular phenotype. In contrast, direct intra-coronary infusion did not elicit any effect on ventricular function. As such, AAV2/1SERCA2a elicits favourable functional and molecular actions when delivered in a mechanically targeted manner in an experimental model of HF. These observations lay a platform for potential clinical translation.
s n r Background. Severe pulmonary graft failure (PGF) is he most common cause of death within th... more s n r Background. Severe pulmonary graft failure (PGF) is he most common cause of death within the first 30 days fter lung transplantation. Extracorporeal membrane oxyenation (ECMO) may provide lifesaving temporary suport; however, its longer-term efficacy is controversial. Methods. We reviewed the use of ECMO for severe GF after lung transplantation, and compared the outomes between our early (1990 to 1999) and recent (2000 o 2003) experience utilizing improved initiation timing, xygenator technology, and surgical technique. Results. Ten transplant recipients from a total of 481 2.1%) were managed for PGF on ECMO by a multidisiplinary team at The Alfred Hospital. Four single-lung, bilateral single-lung, and 3 heart-lung recipients were upported for a mean of 96 hours (range 14 to 212 hours). n the early group (operation from 1990 to 1999, n 4) CMO was initiated 21 days (range 7 to 40 days) after
Anaesthesia and Intensive Care, 2005
A 45-year-old woman presented to the emergency department of a tertiary referral hospital after t... more A 45-year-old woman presented to the emergency department of a tertiary referral hospital after taking an overdose of verapamil, doxepin, quetiapine, diazepam, temazepam, and clonazepam. She rapidly developed shock refractory to pharmacological support and was placed on percutaneous venoarterial extracorporeal membrane oxygenation (ECMO). She had a severe metabolic acidosis from a combination of shock and drug intoxication that improved with continuous venovenous haemodialysis. Forty-eight hours after presentation, while still on ECMO, the patient had complete cardiac standstill for three and a half hours, attributable to slow-release verapamil, that resolved after the commencement of plasmapheresis. The role of plasmapheresis in verapamil overdose requires further study.
Anaesthesia and Intensive Care, 2004
Two cases of critically ill patients who received extracorporeal membrane oxygenation (ECMO) usin... more Two cases of critically ill patients who received extracorporeal membrane oxygenation (ECMO) using different forms of circuitry and for different indications are presented. Both patients had life-threatening infections with septic shock and were not able to be supported by conventional means. The first patient had staphylococcal septicaemia and received venoarterial ECMO for circulatory failure. The second patient had psittacosis and received venovenous ECMO for respiratory failure. We discuss the expanding indications for this technology and the role it has to play in adult intensive care.
Heart, Lung and Circulation, 2011
Heart, Lung and Circulation, Volume 20, Issue 12, Pages 781, December 2011, Authors:K. Chaudhuri;... more Heart, Lung and Circulation, Volume 20, Issue 12, Pages 781, December 2011, Authors:K. Chaudhuri; G. Lee; E. Storey; A. Preovolos; S. Marasco.
Circulation, Oct 31, 2007
Critical care and resuscitation : journal of the Australasian Academy of Critical Care Medicine, 2008
To gauge use of extracorporeal membrane oxygenation (ECMO) in Australian and New Zealand intensiv... more To gauge use of extracorporeal membrane oxygenation (ECMO) in Australian and New Zealand intensive care units, to investigate attitudes to and experience with ECMO, and to assess interest in contributing to a national database of ECMO use. The survey was conducted by email in July 2004. A targeted cohort of ICUs across the two countries was chosen, comprising JFICM (Joint Faculty of Intensive Care Medicine) Approved Training Centres, and large regional and private institutions. Directors of the ICUs were invited to participate in the survey of department demographics, ECMO practice rates and experience, and attitudes to ECMO. The survey was registered (http://clinicaltrials.gov registration number NCT00157144), and local ethics approval was obtained. Response rate was 56% (39/70), with 49% of responses (19/39) from JFICM Approved Training Centres. ECMO practice in responding centres was low, with 69% (27/39) having managed no ECMO patients in the past year, and 62% (24/39) having ma...
Perfusion, 2007
This report details the outcomes of four patients supported by extracorporeal membrane oxygenatio... more This report details the outcomes of four patients supported by extracorporeal membrane oxygenation (ECMO) who required thoracotomy. All four patients sustained massive bleeding as a result of the operative intervention, which was not controllable in three of the patients who subsequently died. This experience has led us to review the literature of anticoagulation management of patients on ECMO so we can alter our own protocols and allow safer operative intervention in the future.
The Journal of extra-corporeal technology, 2006
The Asia Pacific Heart Journal, 1997
European Journal of Heart Failure, 2011
European Journal of Cardio-Thoracic Surgery, 1997
To develop a clinically applicable method of minimally invasive mitral valve replacement (MVR) wi... more To develop a clinically applicable method of minimally invasive mitral valve replacement (MVR) with cardioplegia, and examine the ability of carbon dioxide (CO 2) to improve de-airing. Methods: MVR was performed via a 5× 3-cm right lateral minithoracotomy in eight greyhounds. Peripheral cardiopulmonary bypass and an ascending aortic balloon catheter (endoaortic clamp) were used for cardioplegia and aortic root venting. The endoaortic clamp was inflated in the ascending aorta under fluoroscopy and cardioplegic solution was infused. In four dogs, CO 2 at 2 l/min was used to displace air in the chest. A left atriotomy was made, the valve exposed and a mechanical valve implanted. After left atrial closure, retained intracardiac gas was aspirated from the aortic root and collected in a bubble-trap. The endoclamp was deflated and the animal weaned from bypass. Results: A satisfactory MVR was performed in all cases. The clamp time was 64913 min and all dogs were stable post-bypass. In the CO 2 group, intrathoracic CO 2 was maintained above 86% and 0.190.1 ml of gas was collected, compared to 1.39 0.8 ml in the non-CO 2 group (PB0.05). Conclusions: Femoro-femoral bypass and use of the endoaortic clamp allow a safe and efficacious MVR via a right minithoracotomy in the dog. A high intrathoracic CO 2 concentration reduces the amount of retained intracardiac gas.
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Papers by Arthur Preovolos