Effect of a hypoglycemic agent on ischemic preconditioning in patients with type 2 diabetes and stable angina pectoris.
OBJECTIVE
Ischemic preconditioning is an increased tolerance to myocardial ischemia during the second of two consecutive exercise tests. ATP-sensitive K(+) channel blockers, such as glinides and sulfonylurea drugs, can induce loss of ischemic preconditioning. This study aimed to investigate the effects of repaglinide, a hypoglycemic agent with an affinity for myocardial ATP-sensitive K (+)channels, on the results of consecutive exercise tests in patients with diabetes and multivessel coronary artery disease.


METHODS
Forty-two patients with type 2 diabetes and chronic stable angina pectoris, and two-vessel or three-vessel disease participated in this study. The patients underwent two consecutive treadmill exercise tests (phase 1). On the day after these exercise tests, 2 mg of oral repaglinide was given to the patients. One week later, two exercise tests were repeated consecutively (phase 2).


RESULTS
All patients achieved 1.0-mm ST-segment depression during the four exercise tests (T1, T2, T3, and T4). In phase 2, seven patients improved in time to onset of 1.0-mm ST-segment depression. The worsening of the time to onset of 1.0-mm ST-segment depression in phase 2 demonstrated ischemic preconditioning block in 83.3% of patients (P=0.0001). Even the postexercise electrocardiographic parameters (ST-segment depression morphology and magnitude and arrhythmias) were significantly different between the groups with and without pharmacologic ischemic preconditioning block (P=0.031).


CONCLUSIONS
Repaglinide, an oral hypoglycemic agent with ATP-sensitive K(+) channel-blocker activity, eliminated the myocardial ischemic preconditioning in patients with coronary disease and diabetes.
Hueb
Whady
W
Heart Institute of the University of São Paulo, São Paulo, Brazil.
Uchida
Augusto H
AH
Gersh
Bernard J
BJ
Betti
Roberto T B
RT
Lopes
Neuza
N
Moffa
Paulo J
PJ
Ferreira
Beatriz M A
BM
Ramires
Jose A F
JA
Wajchenberg
Bernardo L
BL
D000787:Angina Pectoris / Q000150:complications*; D002219:Carbamates / Q000494:pharmacology*; D003924:Diabetes Mellitus, Type 2 / Q000150:complications*; D004562:Electrocardiography; D005080:Exercise Test / Q000187:drug effects; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D019157:Ischemic Preconditioning, Myocardial; D008297:Male; D008875:Middle Aged; D010880:Piperidines / Q000494:pharmacology*; D013997:Time Factors
D002219:Carbamates; D007004:Hypoglycemic Agents; D010880:Piperidines; C072379:repaglinide