Cyclosporine does not reduce myocardial infarct size in a porcine ischemia-reperfusion model.
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.
Karlsson
Lars O
LO
Department of Cardiology, Sahlgrenska University Hospital, Gothenburg, Sweden. lars.o.karlsson@vgregion.se
Zhou
Alex-Xianghua
AX
Larsson
Erik
E
Aström-Olsson
Karin
K
Månsson
Chrichan
C
Akyürek
Levent M
LM
Grip
Lars
L
D000777:Anesthetics / Q000009:adverse effects / Q000494:pharmacology; D000818:Animals; D051033:Apoptosis Inducing Factor / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D016572:Cyclosporine / Q000494:pharmacology*; D004195:Disease Models, Animal; D004347:Drug Interactions; D005260:Female; D006439:Hemodynamics; D007530:Isoflurane / Q000009:adverse effects / Q000494:pharmacology; D008565:Membrane Proteins / Q000378:metabolism; D033681:Mitochondrial Membrane Transport Proteins / Q000037:antagonists & inhibitors*; D000083162:Mitochondrial Permeability Transition Pore; D024101:Mitochondrial Proteins; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000473:pathology; D015428:Myocardial Reperfusion Injury / Q000473:pathology / Q000517:prevention & control*; D009206:Myocardium / Q000473:pathology; D010424:Pentobarbital / Q000009:adverse effects / Q000494:pharmacology; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D011897:Random Allocation; D013552:Swine
D000777:Anesthetics; D051033:Apoptosis Inducing Factor; C505650:BNIP3 protein, rat; D008565:Membrane Proteins; D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D024101:Mitochondrial Proteins; D011518:Proto-Oncogene Proteins; D016572:Cyclosporine; D007530:Isoflurane; D053148:Caspase 3; D010424:Pentobarbital