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

Although Ca2+ channel blockers are commonly used to control both blood pressure and angina in patients with corollary artery disease, clinical trials have associated the use of L-type Ca channel blockers with increased cardiovascular mortality. Recent evidence has implicated Ca2+ entry through the L-type Ca2+ channel during transient ischemia as a proximal stimulus for ischemic preconditioning (TPC) in experimental animals. Mie therefore hypothesized that clinical L-type Ca2+ channel blockade prevents IPC in human myocardium. Human atrial trabeculae were suspended in organ baths, field simulated at 1 Hz, and force development was recorded. Following 90 min equilibration, trabeculae from control patients and patients taking L-type Ca2+ channel blockers were subjected to simulated ischemia/reperfusion (I/R: 45/120 min) 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). Whereas IPC failed to increase post-ischemic developed force in myocardium from 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 patients taking L-type Ca2+ channel blockers cannot be preconditioned by transient ischemia; and (3) the increased cardiovascular mortality historically associated with the use of Ca2+ channel blockers in patients with coronary artery disease may be, in part, due to the pharmacological inhibition of ischemic preconditioning, (C) 1999 Academic Press.