PhD Scientific Days 2017

Oral Presentations: Cardiovascular

Reduction of ischemia/reperfusion injury with pharmacological preconditioning of the donor heart

Előadó neve

Dr. Benke, Kálmán

Előadó munkahelye

Semmelweis University, Heart and Vascular Center

Előadó telefonszáma

+36206663858

Előadó e-mail címe

benke.kalman@med.semmelweis-univ.hu

Az előadás címe

Reduction of ischemia/reperfusion injury with pharmacological preconditioning of the donor heart

Szerző(k) neve és munkahelye

Benke Kálmán 1, Mátyás Csaba 1, Sayour Alex Ali 1, Oláh Attila 1, Németh Balázs Tamás 1, Ruppert Mihály 1, Szabó Gábor 2, Hartyánszky István 1, Szabolcs Zoltán 1, Merkely Béla 1, Radovits Tamás 1
1 Heart and Vascular Center, Semmelweis University, Budapest
2 Department of Cardiac Surgery, University of Heidelberg, Germany

Szekció

Oral Presentations: Cardiovascular

Data of the presenter

Doctoral School: Basic Medicine
Program: Cardiovascular Disorders
Supervisors: Zoltán Szabolcs, Tamás Radovits
Email: benke.kalman@med.semmelweis-univ.hu

Text of the abstract

Introduction: The incidence of terminal heart failure is continuously growing, thereby increasing the clinical importance of its definitive treatment, heart transplantation (HTX). Pharmacological activation of soluble guanylate cyclase (sGC) and increased cGMP-signalling have been reported to have cardioprotective effects, however, potent sGC activator compounds are still under development. Gemfibrozil, a widely used lipid-lowering fibrate has recently been shown to exert sGC activator properties in vitro. The aim of the present study was to investigate whether pharmacological preconditioning of donor hearts with gemfibrozil could protect against ischemia/reperfusion injury and preserve myocardial function in a heterotopic rat HTX model.
Aims: The purpose of the present study was to investigate whether pharmacological preconditioning of donor hearts with gemfibrozil could protect against ischemia/reperfusion injury and preserve myocardial function in a heterotopic rat heart transplantation model.
Method: Donor Lewis rats received p.o. gemfibrozil (150mg/kg BW) or vehicle for 2 days. The hearts were explanted, stored for 1h in cold preservation solution, and heterotopically transplanted. 1h after starting reperfusion, left ventricular (LV) pressure-volume relations and coronary blood flow were assessed to evaluate early post-transplant graft function. Additional histological and molecular biological measurements were performed.
Results: After 1h reperfusion, LV contractility (at 140µl LV volume: LV systolic pressure: 125±14 vs. 77±8mmHg, p<0.05; dP/dtmax: 3260±398 vs. 2116±240mmHg, p<0.05; active relaxation (dP/dtmin: -2233±263 vs. -1184±151mmHg, p<0.05) and coronary blood flow (2.7±0.2 vs. 2.1±0.2ml/min/g, p=0.03) were significantly improved in the gemfibrozil pretreated hearts when compared to controls. Additionally, gemfibrozil treatment effectively reduced nitro-oxidative stress and apoptosis and improved the cGMP-signalling (increased plasma/cardiac cGMP levels) in HTX.
Conclusion: Pharmacological preconditioning with gemfibrozil reduces ischemia/reperfusion injury and preserves graft function in a rat HTX model, which could be the consequence of enhanced myocardial cGMP-signalling. Gemfibrozil might represent a useful tool for cardioprotection in the clinical setting of HTX surgery in the future.

Kind

Szabad

Előadás fájl jóváhagyás

nem rendelkezett róla

Előadó

1015

Authors (legacy)

Benke Kálmán 1, Mátyás Csaba 1, Sayour Alex Ali 1, Oláh Attila 1, Németh Balázs Tamás 1, Ruppert Mihály 1, Szabó Gábor 2, Hartyánszky István 1, Szabolcs Zoltán 1, Merkely Béla 1, Radovits Tamás 1
1 Heart and Vascular Center, Semmelweis University, Budapest
2 Department of Cardiac Surgery, University of Heidelberg, Germany