ELECTROPHYSIOLOGIC EFFECTS OF ACUTE MYOCARDIAL-ISCHEMIA - A MECHANISTIC INVESTIGATION OF ACTION-POTENTIAL CONDUCTION AND CONDUCTION FAILURE

A multicellular ventricular fiber model was used to determine mechanis ms of slowed conduction and conduction failure during acute ischemia. We simulated the three major pathophysiological component conditions o f acute ischemia: elevated [K+](o), acidosis, and anoxia. Elevated [K](o) was the major determinant of conduction, causing supernormal cond uction, depressed conduction, and conduction block as [K+](o) was grad ually increased from 4.5 to 14.4 mmol/L. Only elevated [K+](o) caused conduction failure when varied within the range reported for acute isc hemia. Before block, depressed upstrokes consisted of two distinct com ponents: the first to the fast Na+ current (I-Na) and the second to th e L-type Ca2+ current (I-Ca(L)) Even in highly depressed conduction, e xcitability was maintained by I-Na, With conduction block occurring at 95% I-Na inactivation. However, because I-Ca(L) supported the later p hase of the depressed upstroke, I-Ca(L) enhanced conduction and delaye d block by increasing the electrotonic source current. At [K+](o)=18 m mol/L, slow action potentials generated by I-Ca(L) were obtained with 10% I-Ca(L) augmentation. However, in the presence of acidosis and ano xia, significantly larger (120%) I-Ca(L), augmentation was required. T he depressant effect was due mostly to anoxic activation of outward AT P-sensitive K+ current, which counteracts inward I-Ca(L) and, by lower ing the action potential amplitude, decreases the electrotonic current available to depolarize downstream cells. The simulations highlight t he interactive nature of electrophysiological ischemic changes during propagation and demonstrate that both membrane changes and load factor s (by downstream fiber) must be considered.