Effects of Pinacidil on ST-T Wave Alternans During Acute Myocardial Ischemia in the In-situ Pig Heart

ST-T alternans during ischemia is associated with ventricular arrhythmias and reflects primary changes in repolarization, and changes secondary to 2:1 conduction block. We studied the effect of pinacidil, an ATP-sensitive K+ channel activator, on the incidence of ST-T alternans during ischemia. K+- and pH-sensitive electrodes and unipolar and bipolar electrodes were inserted into the midmyocardium in 9 open-chested pigs. Transmembrane action potentials were recorded from the epicardial surface. The carotid artery was shunted to the left anterior descending artery via a roller pump, and 25 μM pinacidil was infused. Prior to pinacidil administration, ST-T alternans occurred in all 9 pigs during control ischemia, at a mean onset time of 4 minutes 23 seconds ± 22 seconds. After pinacidil infusion, no ST-T alternans occurred during the 8-minute ischemic period. Furthermore, after pinacidil infusion, the final rise in extracellular K+ (K+e) and the fall in extracellular pH (pHe) were similar to the those at the onset of ST-T alternans under control conditions (K+e : 7.6 ± 0.9 vs. 6.9 ± 0.9 mM; pHe: 7.08 ± 0.78 vs. 7.05 ± 0.18). Activation delay was also similar with pinacidil administration compared with that at the onset of ST-T alternans, under the control condition (27 ± 18 ms vs. 34 ± 24 ms). With pinacidil, the action potential duration after 8 minutes of ischemia was decreased by 50% (from 250 ± 36 ms to 127 ± 15 ms). The complete suppression of ST-T alternans by pinacidil may reflect an increase in the diastolic interval.