Skyschally Andreas, Amanakis Georgios, Neuhäuser Markus, Kleinbongard Petra, Heusch Gerd
Institute for Pathophysiology, West German Heart and Vascular Center, University of Essen Medical School, Essen, Germany; and.
Department of Mathematics and Technology, Koblenz University of Applied Sciences, Rhein-Ahr-Campus, Remagen, Germany.
Am J Physiol Heart Circ Physiol. 2017 Nov 1;313(5):H871-H878. doi: 10.1152/ajpheart.00293.2017. Epub 2017 Aug 4.
Ventricular fibrillation (VF) occurs frequently during myocardial ischemia-reperfusion (I/R) and must then be terminated by electrical defibrillation. We have investigated the impact of VF/defibrillation on infarct size (IS) or area of no reflow (NR) without and with ischemic conditioning interventions. Anesthetized pigs were subjected to 60/180 min of coronary occlusion/reperfusion. VF, as identified from the ECG, was terminated by intrathoracic defibrillation. The area at risk (AAR), IS, and NR were determined by staining techniques (patent blue, triphenyltetrazolium chloride, and thioflavin-S). Four experimental protocols were analyzed: I/R ( = 49), I/R with ischemic preconditioning (IPC; = 22), I/R with ischemic postconditioning (POCO; = 22), or I/R with remote IPC (RIPC; = 34). The incidence of VF was not different between I/R (44%), IPC (45%), POCO (50%), and RIPC (33%). IS was reduced by IPC (23 ± 12% of AAR), POCO (31 ± 16%), and RIPC (22 ± 13%, all < 0.05 vs. I/R: 41 ± 12%). NR was not different between protocols (I/R: 17 ± 15% of AAR, IPC: 15 ± 18%, POCO: 25 ± 16%, and RIPC: 18 ± 17%). In pigs with defibrillation, IS was 50% larger than in pigs without defibrillation but independent of the number of defibrillations. Analysis of covariance confirmed the established determinants of IS, i.e., AAR, residual blood flow during ischemia (RMBFi), and a conditioning protocol, and revealed VF/defibrillation as a novel covariate. VF/defibrillation in turn was associated with larger AAR and lower RMBFi. Lack of dose-response relation between IS and the number of defibrillations excluded direct electrical injury as the cause of increased IS. Obviously, AAR size and RMBFi account for both IS and the incidence of VF. IS and NR are mechanistically distinct phenomena. Ventricular fibrillation/defibrillation is associated with increased infarct size. Electrical injury is unlikely the cause of such association, since there is no dose-response relation between infarct size and number of defibrillations. Ventricular fibrillation, in turn, is associated with a larger area at risk and lower residual blood flow.
心室颤动(VF)在心肌缺血再灌注(I/R)期间频繁发生,随后必须通过电除颤来终止。我们研究了有无缺血预处理干预时,VF/除颤对梗死面积(IS)或无复流区(NR)的影响。对麻醉的猪进行60/180分钟的冠状动脉闭塞/再灌注。通过心电图识别出VF后,经胸除颤终止VF。通过染色技术(专利蓝、氯化三苯基四氮唑和硫黄素-S)测定危险面积(AAR)、IS和NR。分析了四个实验方案:I/R(n = 49)、I/R加缺血预处理(IPC;n = 22)、I/R加缺血后处理(POCO;n = 22)或I/R加远隔缺血预处理(RIPC;n = 34)。I/R组(44%)、IPC组(45%)、POCO组(50%)和RIPC组(33%)的VF发生率无差异。IPC(AAR的23±12%)、POCO(31±16%)和RIPC(22±13%,与I/R组:41±12%相比,均P<<0.05)可使IS减小。各方案间NR无差异(I/R组:AAR的17±15%,IPC组:15±18%,POCO组:25±16%,RIPC组:18±17%)。在接受除颤的猪中,IS比未接受除颤的猪大50%,但与除颤次数无关。协方差分析证实了IS的既定决定因素,即AAR、缺血期间的残余血流量(RMBFi)和预处理方案,并揭示VF/除颤是一个新的协变量。反过来,VF/除颤与更大的AAR和更低的RMBFi相关。IS与除颤次数之间缺乏剂量反应关系,排除了直接电损伤是IS增加的原因。显然,AAR大小和RMBFi既决定了IS,也决定了VF的发生率。IS和NR在机制上是不同的现象。心室颤动/除颤与梗死面积增加有关。电损伤不太可能是这种关联的原因,因为梗死面积与除颤次数之间没有剂量反应关系。反过来,心室颤动与更大的危险面积和更低的残余血流量有关。