Clinical L-Type Ca2+Channel Blockade Prevents Ischemic Preconditioning of Human Myocardium

B. S. Cain, D. R. Meldrum, J. C. Cleveland, Jr, X. Meng, A. Banerjee and A. H. Harken. Clinical L-Type Ca2+Channel Blockade Prevents Ischemic Preconditioning of Human Myocardium. Journal of Molecular and Cellular Cardiology (1999) 31, 2191–2197. Although Ca2+channel blockers are commonly used to control both blood pressure and angina in patients with coronary artery disease, clinical trials have associated the use of -type Ca2+channel blockers with increased cardiovascular mortality. Recent evidence has implicated Ca2+entry through the -type Ca2+channel during transient ischemia as a proximal stimulus for ischemic preconditioning (IPC) in experimental animals. We therefore hypothesized that clinical -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 -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. IPC increased post-ischemic developed force in control patients from 14.6±2.6 to 43.1±3.5% baseline developed force (%BDFP <0.05 I/R vs IPC). Whereas IPC failed to increase post-ischemic developed force in myocardium from patients taking -type Ca2+channel blockers (15.1±1.9 vs 16.6±1.7 %BDF,P >0.05 -type I/R v -type IPC). We conclude that: (1) atrial muscle can be preconditioned by transient ischemia; (2) atrial muscle from patients taking -type Ca2+channel blockers cannot be preconditioned by transient ischemia; and (3) the increased cardiovascular mortality historically associated with the use of Ca2channel blockers in patients with coronary artery disease may be, in part, due to the pharmacological inhibition of ischemic preconditioning.