Calcium preconditioning, but not ischemic preconditioning, bypasses the adenosine triphosphate-dependent potassium (K-ATP) channel

Background. Recent evidence has implicated the K-ATP channel as an importan t mediator of ischemic preconditioning (IPC). Indeed, patients taking oral sulfonylurea hypoglycemic agents (i.e., K-ATP channel inhibitors) for treat ment of diabetes mellitus are resistant to the otherwise profoundly protect ive effects of IPC. Unfortunately, many cardiopulmonary bypass patients, wh o may benefit from IPC, are chronically exposed to these agents. Calcium pr econditioning (CPC) is a potent form of similar myocardial protection which may or may not utilize the K-ATP channel in its mechanism of protection. T he purpose of this study was to determine whether CPC may bypass the K-ATP channel in its mechanism of action. If so, CPC may offer an alternative to IPC in patients chronically exposed to these agents. Methods. Isolated rat hearts (n = 6-8/group) were perfused (Langendorff) an d received K-ATP channel inhibition (glibenclamide) or saline vehicle 10 mi n prior to either a CPC or IPC preconditioning stimulus or neither (ischemi a and reperfusion, I/R). Hearts were subjected to global warm I/R (20 min/4 0 min). Postischemic myocardial functional recovery was determined by measu ring developed pressure (DP), coronary flow (CF), and compliance (end diast olic pressure, EDP) with a MacLab pressure digitizer. Results. Both CPC and IPC stimuli protected myocardium against postischemic dysfunction (P < 0.05 vs I/R; ANOVA with Bonferroni/Dunn): DP increased fr om 52 +/- 4 (I/R) to 79 +/- 2 and 83 +/- 4 mmHg; CF increased from 11 +/- 0 .7 to 17 +/- 2 and 16 +/- 1 ml/min; and EDP decreased (compliance improved) from 50 +/- 7 to 27 +/- 5 and 31 +/- 7 mmHg. However, K-ATP channel inhibi tion abolished protection in hearts preconditioned with IPC (P < 0.05 vs IP C alone), but not in those preconditioned with CPC (P > 0.05 vs CPC alone). Conclusions. (1) Both IPC and CPC provide similar myocardial protection; (2 ) IPC and CPC operate via different mechanisms; i.e., IPC utilizes the K-AT P channel whereas CPC does not; and (3) CPC may offer a means of bypassing the deleterious effects of K-ATP channel inhibition in diabetic patients ch ronically exposed to oral sulfonylurea hypoglycemic agents. (C) 1999 Academ ic Press.