Cyclosporine Does Not Reduce Myocardial Infarct Size in a Porcine Ischemia-Reperfusion Model
- 30 April 2010
- journal article
- other
- Published by SAGE Publications in Journal of Cardiovascular Pharmacology and Therapeutics
- Vol. 15 (2), 182-189
- https://doi.org/10.1177/1074248410362074
Abstract
Cyclosporine A (CsA) has been shown to protect against myocardial ischemia and reperfusion (I/R) injury in small animal models. The aim of the current study was to evaluate the effects of CsA on myocardial I/R injury in a porcine model. Pigs were randomized between CsA (10mg/kg; n = 12) or placebo (n = 15) and anesthetized with either isoflurane (phase I) or pentobarbital (phase II). By catheterization, the left descending coronary artery was occluded for 45 minutes, followed by reperfusion for 2 hours. Hearts were stained to quantify area at risk (AAR) and infarct size (IS). Myocardial biopsies were obtained for terminal dUTP nick end labeling and immunoblot analysis of proapoptotic proteins (apoptosis-inducing factor [AIF], BCL2/adenovirus E1B 19-kd interacting protein 3 [BNIP-3], and active caspase-3). Cyclosporine A did not reduce IS/AAR compared with placebo (49% vs 41%, respectively; P = .21). Pigs anesthetized with isoflurane had lower IS/AAR than pigs anesthetized with pentobarbital (39% vs 51%, respectively; P = .03). This reduction in IS/AAR seemed to be attenuated by CsA. Apoptosis-inducing factor protein expression was higher after CsA administration than after placebo (P = .02). Thus, CsA did not protect against I/R injury in this porcine model. The data suggest a possible deleterious interaction of CsA and isoflurane.Keywords
This publication has 37 references indexed in Scilit:
- Role of apoptosis in cardiovascular diseaseApoptosis, 2009
- Complete loss of ischaemic preconditioning-induced cardioprotection in mice with partial deficiency of HIF-1Cardiovascular Research, 2007
- Myocardial Reperfusion InjuryThe New England Journal of Medicine, 2007
- Bnip3 mediates mitochondrial dysfunction and cell death through Bax and BakBiochemical Journal, 2007
- Postconditioning Does Not Reduce Myocardial Infarct Size in an In Vivo Regional Ischemia Rodent ModelJournal of Cardiovascular Pharmacology and Therapeutics, 2007
- Filamin B deficiency in mice results in skeletal malformations and impaired microvascular developmentProceedings of the National Academy of Sciences of the United States of America, 2007
- Hypoxia-Inducible Factor 1-Alpha Reduces Infarction and Attenuates Progression of Cardiac Dysfunction After Myocardial Infarction in the MouseJournal of the American College of Cardiology, 2005
- Role of apoptosis-inducing factor in myocardial cell death by ischemia–reperfusionBiochemical and Biophysical Research Communications, 2003
- Cyclosporin A Prevents the Hypoxic Adaptation by Activating Hypoxia-inducible Factor-1α Pro-564 HydroxylationPublished by Elsevier BV ,2003
- Differential Protective Effects of Halothane and Isoflurane Against Hypoxic and Reoxygenation Injury in the Isolated Guinea Pig HeartAnesthesiology, 1990