Clinical L-type Ca2+ channel blockade prevents ischemic preconditioning ofhuman myocardium

Although Ca2+ channel blockers are commonly used to control both blood pres sure and angina in patients with corollary artery disease, clinical trials have associated the use of L-type Ca channel blockers with increased cardio vascular mortality. Recent evidence has implicated Ca2+ entry through the L -type Ca2+ channel during transient ischemia as a proximal stimulus for isc hemic preconditioning (TPC) in experimental animals. Mie therefore hypothes ized that clinical L-type Ca2+ channel blockade prevents IPC in human myoca rdium. Human atrial trabeculae were suspended in organ baths, field simulat ed at 1 Hz, and force development was recorded. Following 90 min equilibrat ion, trabeculae from control patients and patients taking L-type Ca2+ chann el blockers were subjected to simulated ischemia/reperfusion (I/R: 45/120 m in) with or without 5 min of simulated ischemia (IPC stimulus) prior to I/R . LPC increased post-ischemic developed force in control patients from 14.6 +/-2.6 to 43.1+/-3.5% baseline developed force (%BDF: P<0.05 I/R vs LPC). W hereas IPC failed to increase post-ischemic developed force in myocardium f rom patients taking L-type Ca2+ channel blockers (15.1+/-1.9 vs 16.0+/-1.7 %BDF, P>0.05 L-type I/R v L-type IPC). We conclude that: (1) atrial muscle can be preconditioned by transient ischemia: (2) atrial muscle from patient s taking L-type Ca2+ channel blockers cannot be preconditioned by transient ischemia; and (3) the increased cardiovascular mortality historically asso ciated with the use of Ca2+ channel blockers in patients with coronary arte ry disease may be, in part, due to the pharmacological inhibition of ischem ic preconditioning, (C) 1999 Academic Press.