Exogenous calcium preconditions myocardium from patients taking oral sulfonylurea agents

We have previously reported that atrial trabeculae from patients taking ora l sulfonylurea hypoglycemic agents cannot be preconditioned by transient is chemia, which may, in part, explain the increased car diovascular mortality historically associated with the use of these agents (J. C. Cleveland et a t, 1997, Circulation 96, 29-32). Recently, we reported that clinically acce ssible and acceptable exogenous Ca2+ pretreatment protects human atrial tra beculae from subsequent ischemia (B. S. Cain et al., 1998, Ann. Thoracic Su rg. 65, 1065-1070). It remains unknown whether this preconditioning strateg y could confer protection to trabeculae from patients taking oral sulfonylu rea drugs. We therefore hypothesized that exogenous Ca2+ confers ischemic p rotection to trabeculae from patients taking oral sulfonylureas. Human atri al trabeculae were suspended in organ baths and field stimulated at 1 Hz, a nd force development was recorded. Following 90 min equilibration, trabecul ae from patients taking oral sulfonylurea agents (n = 6 patients) were subj ected to ischemia/reperfusion (I/R; 45/120 min) with or without Ca2+ (1 mM increase x 5 min) 10 min prior to I/R. I/R decreased postischemic human myo cardial contractility in trabeculae from patients on oral hypoglycemics to 15.3 +/- 2.0% baseline developed force (%BDF). Ca2+ pretreatment increased postischemic human myocardial developed force to 35.3 +/- 2.9 %BDF in these patients (P < 0.05 vs I/R, ANOVA and Bonferroni/Dunn). We conclude that at rial muscle from patients taking oral hypoglycemic agents can be preconditi oned with exogenous Ca2+. This therapy may offer a clinically relevant mean s to precondition the myocardium of diabetics taking oral hypoglycemic agen ts prior to clinical interventions such as coronary angioplasty or cardiac bypass. (C) 1999 Academic Press.