title: Effect of a hypoglycemic agent on ischemic preconditioning in patients with type 2 diabetes and stable angina pectoris.
abstract: 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.
authors.affiliation: Heart Institute of the University of São Paulo, São Paulo, Brazil.
authors.forename: Whady
authors.initials: W
authors.lastname: Hueb
authors.forename: Augusto H
authors.initials: AH
authors.lastname: Uchida
authors.forename: Bernard J
authors.initials: BJ
authors.lastname: Gersh
authors.forename: Roberto T B
authors.initials: RT
authors.lastname: Betti
authors.forename: Neuza
authors.initials: N
authors.lastname: Lopes
authors.forename: Paulo J
authors.initials: PJ
authors.lastname: Moffa
authors.forename: Beatriz M A
authors.initials: BM
authors.lastname: Ferreira
authors.forename: Jose A F
authors.initials: JA
authors.lastname: Ramires
authors.forename: Bernardo L
authors.initials: BL
authors.lastname: Wajchenberg
mesh_terms: 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
chemical_list: D002219:Carbamates; D007004:Hypoglycemic Agents; D010880:Piperidines; C072379:repaglinide