Dynamic Study Of Ionic Mechanism In Ischemia Related Arrhythmia

Ischemia is one of the most common pathological manifestations that have been seen in clinical practice, and also is one of the most important reasons for arrhythmia. Both acute and chronic ischemia can lead to several kinds of atrial arrhythmia. According to studies reported before, during ischemia, cells' hypoxia lead to acidosis. Acidosis can affect ionic current directly and thus the arrhythmia initiate. Furthermore, the abnormal of humoral factors caused by ischemia are also arrhythmogenic. Recent years' researches showed that angiotensin II (AngII) which rise rapidly during acute ischemia could elicit some kinds of atrial or/and ventricular arrhythmias. Especially, the high level of Angll is associated with occurrence of atrial fibrillation (AF). It was reported that arrhythmogenic mechanism of Angll is due to its effects on ion channel. Among all the atrial arrhythmias, AF is one of the most common persistent tachycardia with highest incidence. Ionic remodeling, the change of ionic current density and channel dynamics, play an important role during occurrence and maintenance of AF.Some scientists have observed the changes of action potential (AP) and ion current densities under simulated ischemia that could interpret the mechanisms of ischemia related arrhythmia. But most of their study objects were ventricular myocytes and single time point effects of ischemia were reported. The different ischemic effects in various stages and the effects on atrial myocytes are unknown. At the moment, some data were reported about the effects of Angll on ventricular myocytes. But effects of Angll on ischemic cells, especially on atrial myocytes are not seen. In recent years, the electrophysiologies of AF have been investigated in animal models and in humans. From these studies, electrical remodeling of AF was reported. But most of them are based on rapid pacing animal models. Little information is available about the ionic mechanisms underlying AF in humans. The comparison of ionic remodeling in various stages is rarely mentioned. The present study therefore was to continuously observe the effects of ischemia on electrophysiology of isolated atrial myocytes, compare the effects of Angll on cardiac myocytes in normal condition and in ischemic condition. We also investigated the pathological characters of human atrial and ionic remodeling of human atrial myocytes of different time point during AF occurrence and development. The purpose of our research was to study the dynamic ionic mechanism in ischemia related atrial arrhythmia.In the first part of our research, we continuously observed the effects of simulatedischemia on rabbit cardiac myocytes using patch clamp technique of whole cell mode. We studied the changes of AP and several ion currents such as INa, Ica,L, Ito, Ik, Iki and Ikatp in time points of 0min, 5min, 10min, 20min and 30min during simulated ischemic solution perfusion. Our data showed that under simulated ischemia, the APD was transient prolonged at first, then continuously shortened. When perfuse 5min with simulated ischemic solution, APD50 and APD90 were significant prolonged compared with Omin, while at the moment of 1 Omin perfusion, APD50 and APD90 were shortened significantly. At 20min, APD50 and APD90 were shorter than at the moment of 10min. In the time point of 30min, APD was not shortened significantly than that of 20min. APA and RMP were not significant changed until 1 Omin perfusion, and reduced continuously till 20min. During the perfusion of simulated ischemia solution, Vmax was not significant changed from beginning to end. Ina current densities were not changed in 5min but reduced significantly in 10min, and from 10min to 30min, it decreased continuously. Ica,L current densities were decreased in 5min significantly and continuous decrease till 30min. Ik current densities were reduced continuously from 5min to 20min, and did not changed significantly in 30min compared with 20min. From the beginning to the end of perfusion, IKI current densities were not changed significantly. In Omin, I...