Changes Of Connexin43 And Its Electrophysiologic Effects During Acute Myocardial Ischemia In Canine Hearts

Background & objective: The cardiac gap junction (GJ) is a channel connecting the neighbor myocytes, characterized by the hydrophilia, lower selectivity and lower resistance. The principal function of gap junction is to mediate the intercellular communication. Connexin 43(Cx43) is the predominant gap junction protein in the ventricular myocardium, the normality of expression and distribution of Cx43 is essential to the normal propagation of action potentials and the coordination of contraction in the heart. The previous studies have showed the decrease of expression and the alternation of distribution pattern of Cx43 correlated with the arrhythmia in the chronic ischemic heart. All the previous studies were carried out on chronic ischemic or hypoxic models, and no study has focused on the acute effects of ischemic on gap junction channel changes. The purpose of this study was to investigate changes of Cx43 and its electrophysiologic effects following short time period (1 to 6 hours) of ischemia. Methods: Studies were carried out in 20 mongrel dog canine which were randomly divided into control group(nM), 1 hour ischemia group (n%), 3 hours ischemia group (n~5) and 6 hours group (n~5). The acute myocardial ischemia was induced by ligation of the left anterior descending coronary artery. Ischemic myocardium was divided into 16 small regions. The conduction velocity of each small region was detected with a electrode array including 56 pairs of electrodes 3 before and after ischemia, and ventricular fibrillation threshold (VET) was detected at last. After detecting of VET the ischemic myocardium was harvested, the ischemic myocardium was divides into 16 lX 1cm2 segments, and each segment was divided into the endo條ayer, middle layer and epi條ayer. The expression and distribution of Cx43 of each segment was studied by laser confocal microscopy with a double條abel immunohistochemistry technique. The correlation among dispersion of Cx43 pixel density, dispersion of conduction velocity and VFT was analysed through the linear regression. Result: (l)The Cx43 degraded rapidly during acute myocardiacl ischemia. There was a 22.2% decrease following 1 hour of ischemia, a 40% decrease following 3 hours of ischemia, and a 54% decrease following 6 hours of ischemia. (2)The Cx43 pixel density at end梩o梕nd junction areas was 1. 37 folds of that at side梩o梥ide junction areas in the control group, on the contrary, the Cx43 pixel density at side梩o梥ide junction areas was 1. 6 folds of that at end梩o梕nd junction areas following 6 hours of ischemia. (3)In control group, there was not significant difference among the Cx43 pixel density of each segment, and the difference became significant following ischemia. (4) There was not significant difference among the Cx43 pixel density of each myocardial layer in control group, the decrease of Cx43 was more significant in the middle layer of myocardium in all the ischemia group. (5) The disn~rcion of conduction velocity before 4 ischemia was small, and increasing following ischernia. There was a significant correlation between the dispersion of Cx43 pixel density and the dispersion of conduction velocity, r~0.9132, P<0. 01. (6)The...