Anti-arrhythmic effects of hypercalcemia in hyperkalemic, Langendorff-perfused mouse hearts

The present study examined the ventricular arrhythmic and electrophysiological properties during hyperkalemia (6.3 mM [K+] vs. 4 mM in normokalemia) and anti‑arrhythmic effects of hypercalcemia (2.2 mM [Ca2+]) in Langendorff‑perfused mouse hearts. Monophasic action potential recordings were obtained from the left ventricle during right ventricular pacing. Hyperkalemia increased the proportion of hearts showing provoked ventricular tachycardia (VT) from 0 to 6 of 7 hearts during programmed electrical stimulation (Fisher's exact test, P<0.05). It shortened the epicardial action potential durations (APDx) at 90, 70, 50 and 30% repolarization and ventricular effective refractory periods (VERPs) (analysis of variance, P<0.05) without altering activation latencies. Endocardial APDx and VERPs were unaltered. Consequently, ∆APDx (endocardial APDx‑epicardial APDx) was increased, VERP/latency ratio was decreased and critical intervals for reexcitation (APD90‑VERP) were unchanged. Hypercalcemia treatment exerted anti‑arrhythmic effects during hyperkalemia, reducing the proportion of hearts showing VT to 1 of 7 hearts. It increased epicardial VERPs without further altering the remaining parameters, returning VERP/latency ratio to normokalemic values and also decreased the critical intervals. In conclusion, hyperkalemia exerted pro‑arrhythmic effects by shortening APDs and VERPs. Hypercalcemia exerted anti‑arrhythmic effects by reversing VERP changes, which scaled the VERP/latency ratio and critical intervals.