The effects of glibenclamide, a KATP channel blocker, on the warm-up phenomenon

Background: The warm-up phenomenon observed after the second of two sequential exercise tests is characterized by an increased time to ischemia and ischemic threshold, and the latter is related to ischemic preconditioning. Previous studies have demonstrated that a single dose of glibenclamide, a cardiac ATP-sensitive K (K-ATP) channel blocker, prevents ischemic preconditioning. This study aimed to investigate the effects of chronic treatment with glibenclamide during two sequential exercise tests. Methods: Forty patients with angina pectoris were divided into three groups: 20 nondiabetics (NDM), 10 patients with diabetes in treatment with glibenclamide (CMG) and 10 diabetic patients with other treatments (DMO). All patients underwent two consecutive exercise tests. Results: Heart rate and rate-pressure product at 1.0 mm ST-segment depression significantly increased during the second exercise test in NDM group (121.3 +/- 16.5 vs 127.3 +/- 15.3 beats/min, P < 0.001, and 216.7 + 43.1 vs 232.1 +/- 43.0 beats-min(-1)center dot mmHg center dot 10(2), P < 0.001), and in DMO group (114.1 +/- 19.6 vs 119.6 +/- 18.1 beats/min, P = 0.001, and 199.8 +/- 36.6 vs 222.2 +/- 29.2 beats center dot min(-1)center dot mmHg center dot 10(2), P = 0.019), but it did not change in patients in DMG group (130.7 +/- 14.5 vs 132.1 +/- 14.7 beats/min, P = ns, and 251.7 +/- 47.2 vs 250.3 +/- 42.8 beats/min(-1)center dot mmHg. 10(2), P = ns). In the three groups, NDM, DMO, and DMG, the time to 1.0 mm ST-segment depression during the second exercise test was greater than during the first (225.0 +/- 112.5 vs 267.0 +/- 122.3 seconds, P = 0.006; 187.5 +/- 54.0 vs 226.5 +/- 74.6 seconds, P = 0.029 and 150.0 +/- 78.7 vs 186.0 +/- 81.9 seconds, P < 0.001). Conclusion: The chronic use of glibenclamide may have mediated the loss of preconditioning benefits in the warm-up phenomenon, probably through its KATP channel-blocker activity, but without acting upon the tolerance to exercise.