Heart attacks secondary to acute myocardial infarctions (AMI) commonly lead to life-threatening cardiac rhythm disturbances (ventricular arrhythmias). Our ability to prevent or treat these arrhythmias is limited by our current knowledge of the primary mechanisms responsible. A major obstacle in acquiring this knowledge has been the lack of a suitable experimental model that permits simultaneous recording of the electrical activity of ventricular endocardial, midmyocardial (M) and epicardial cells under conditions comparable to those that exist during occlusion of a coronary vessel within the heart. These cellular alterations form the basis for the ECG changes (primarily ST-segment changes) that precede life-threatening ventricular arrhythmias during or after a heart attack.

Using our recently developed isolated arterially-perfused ventricular wedge preparation, I developed a model that permits correlation of the cellular and ECG changes that occur during coronary occlusion. The data collected thus far suggest that two distinctly different mechanisms are involved in the ST-segment changes that occur in the ECG during this life-threatening clinical condition. One is a marked abbreviation of the ventricular epicardial action potentials secondary to all-or-non repolarization. The other involves a marked delay in transmural conduction (slow propagation of the electrical activity from the endocardium to the epicardium). These phenomena set the stage for the development of malignant arrhythmias (similar to those observed clinically) by greatly increasing the intrinsic heterogeneity in the duration of the action potentials of endocardial, midmyocardial (M) and epicardial cells. This experimental model will hopefully prove to be reliable for screening new mechanism-specific strategies to prevent life-threatening rhythm disturbances attending an AMI as well as for the assessment of new approaches directed at minimizing myocardial damage and consequent ventricular dysfunction (heart failure).

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