The effects of glibenclamide, a K(ATP) 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 (DMG) 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.mmHg.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.min-1.mmHg.10(2), P=0.019), but it did not change in patients in DMG group (130.7+/-14.5 vs 132.1+/-4.7 beats/min, P=ns, and 251.7+/-47.2 vs 250.3+/-42.8 beats.min-1.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).


CONCLUSIONS
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.
Ferreira
Beatriz M A
BM
Heart Institute of the University of Sao Paulo, Brazil. psbia@incor.usp.br
Moffa
Paulo J
PJ
Falcão
Andrea
A
Uchida
Augusto
A
Camargo
Paulo
P
Pereyra
Pascual
P
Soares
Paulo R
PR
Hueb
Whady
W
Ramires
Jose A F
JA
D000704:Analysis of Variance; D000787:Angina Pectoris / Q000503:physiopathology; D016009:Chi-Square Distribution; D002908:Chronic Disease; D017023:Coronary Angiography; D003324:Coronary Artery Disease / Q000503:physiopathology; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D004562:Electrocardiography / Q000187:drug effects; D005080:Exercise Test; D005260:Female; D005905:Glyburide / Q000627:therapeutic use*; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D019157:Ischemic Preconditioning, Myocardial / Q000379:methods*; D008297:Male
D007004:Hypoglycemic Agents; D005905:Glyburide