Effects Of Acute Myocardial Infarction And Simulated Ischemia On The Ionic Channel Currents In Rabbit Ventricular Myocytes

Severe ventricular arrhythmias related to myocardial ischemia is one of the most common complications in acute coronary syndrome, and is the most important reason for sudden cardiac death. Previous studies have described the important regional differences in the electrophysiology and electropharmacolgy of ventricular myocardium in mammalian hearts, which are termed as electrophysiological heterogeneity. It exists within the ischemic or infarcted zone between the ischemic or infarcted myocardium and those with normal blood flow and can induce reentrant activity and afterdepolarization, therefore, the electrophysiological heterogeneity plays an important role in arrhythmogenesis. There were no systemic studies on the changes of ionic channel currents in cardiac myocytes after acute myocardial infarction, especially during the first 24 hours after coronery artery occlusion. The midmyocardial myocytes and transmural electrophysiological heterogeneity are the most popular subjects in recent years, but the cellular mechanism is still uncertain. The effects of simulated ischemia on the transmural heterogeneity of ionic channel currents are unknown.To explore the cellular basis of the ventricular arrhythmias, both the current and kinetics of Na+ channel current(INa),L-type Ca2+ current(ICa-L),and transient outward K+ current(Ito) in the surviving epicardial myocytes in and around the infarcted zone of rabbit hearts were studied at the time of 1-hour and 1-week after coronary artery ligation. In the meantime, the INa and Ito in epicardial, endocardial and midmyocardial cells were recorded using patch clamp techniques in the whole-cell configuration from the three cellular subtypes of the left ventricular free wall. Then the simulatedischemia (hypoxia, absence of glucose, low pH) was given to the myocytes and the electrophysiological response of these cell types to the simulated ischemia (10, 20 and 30 minutes' ischemia) was compared before and after the ischemia. The experimental animals were healthy Newsland pure white rabbits weighing 1.5 to 2.0 kg with either sex, which were bought from HuaBei pharmaceutical group and were qualified for experiments.The study included five parts.Part I: Alteration of Sodium Channel Currents of Ventricular Myocytes in the Ischemic or Acute Infarcted ZoneMaterials and methods: Twenty-two rabbits were used in the study. The rabbits were divided into four groups: ①Acute coronary artery occlusion for 1-hour group (AMI-1h). ②Acute coronary artery occlusion for 1 week group (AMI-1w). Twelve rabbits were myocardium-infarcted by ligation of the left anterior descending coronary artery, 1 hour as well as 1 week later, single ventricular myocytes were enzymatically dissociated and isolated, then INa was recorded by means of patch clamp whole-cell recording techniques under voltage clamp. ③Sham operated group (Sham). Five rabbits underwent the same operation except that the coronary artery was isolated but not ligated. ④In addition, five rabbits that had not undergone any previous surgery were defined as control group (Con). The currents in cells from epicardial border zone around the infarcted areas in AMI-1h and AMI-1w groups were compared with cells from the same anatomic region of noninfarcted hearts in control group. The infarcted region of the heart was identified on gross examination as a pale area on the epicardial surface adjacent to the ligated artery. The experiments were performed at room temperature (20~25℃). The data were expressed as means±SD, statistical analysis was performed using one-way analysis of variance (ANOVA) with SPSS 10.0 software package to test for the significance of the effects of coronary occlusion on the three ion channel activity and kinetics. A value of P<0.05 was considered significantstatistically. Results: ①The INa current density-voltage relationship (I-V) curves and activation curves were voltage-dependent and showed as "V" type current properties. Peak INa current density (at -20mV) was significantly reduced i...