Mechanisms And Treatment Of T-wave Alternans Inacute Myocardial Ischemia Model

Objective： T-wave alternans (TWA) as a prediction of arrhythmia on myocardial ischemiahas many on the mechanism, but did not reach a unified understanding. We intend to furtherinvestigate the mechanism of TWA under the condition of acute myocardial ischemia byperfusing ranolazine, ryanodine and verapamil，and provide evidence for the prevention andtreatment of arrhythmia under the condition of acute myocardial ischemia.Methods： Arterially perfused rabbit left ventricular preparations were randomly assignedto control, ischemia, ranolazine, ryanodine and verapamil groups. The transmural ECG,myocardial contraction force, transmembrane action potential from endocardium andepicardium were simultaneously recorded. The effects of ranolazine, ryanodine andverapamil on TWAwere tested.In normal group rabbit ventricular wedge preparations were perfused by Tyrode’ssolution, in ischemia group the Tyrode’s solution were stopped perfusing for an hour, andinduced TWA; in ranolazine, ryanodine and verapamil groups, the wedge preparations werepretreated with ranolazine (10μM), ryanodine (3μM) or verapamil (1μM) plused Tyrode’s solution respectively after an hour for perfusing Tyrode’s solution, then stopped perfusing,and induced TWA. The rabbit ventricular wedge preparations were paced at a cycle length of200ms under basic state. TWAwas induced within a cycle length of200ms at the point of20min after stopping perfusing, and observed the occurrence of arrhythmia.Results: Comparing with control group, the incidence of TWA in ischemia group wassignificantly increased. In control group, TWA and arrhythmia were not induced, and inischemia group, TWA was induced in10of10preparations, arrhythmia was induced in5of10preparations. Interestingly, TWA in ischemia group were accompanied by alternations inrepolarization of the action potential in epicardium. Ranolazine (10μM) and ryanodine (3μM) cannot abolish TWA and arrhythmia; however, verapamil (1μM) can abolish TWA andarrhythmia completely. TWA and arrhythmia were induced by ranolazine in10of10preparations and were induced by ryanodine in8of10and4of10respectively. In verapamilgroup, TWAand arrhythmia did not occur.Conclusion: Verapamil can inhibit T-wave alternans; this suggests the calcium disordersmaybe relate to the occurrence of TWAunder the condition of acute myocardial ischemia.