Long-term treatment with glibenclamide increases susceptibility of streptozotocin-induced diabetic rat heart to reperfusion-induced ventricular tachycardia.
This study investigated the effects of long-term treatment with glibenclamide (GLIB) on the susceptibility of streptozotocin (STZ)-induced diabetic heart to ischemia/reperfusion insults. Starting 4 weeks after the injection of STZ, rats were treated with GLIB (0.1 mg/kg, ip, three times a week, STZ-GLIB group) or vehicle (STZ-VEH group) for 8 weeks. The recovery of cardiac performance, released creatine kinase (CK), and incidence of ventricular arrhythmias were studied during the reperfusion period in isolated hearts from rats in STZ-GLIB (n = 14) and in STZ-VEH groups (n = 13) and from age-matched control rats (CNT group, n = 14). Each heart was subjected to 5 min of global low-flow ischemia followed by 25 min of no-flow ischemia, with a subsequent 30 min of reperfusion. Plasma glucose level was not significantly different between the STZ-GLIB and STZ-VEH groups. The recovery of cardiac performance and the released CK during reperfusion period were significantly lower in both STZ-VEH and STZ-GLIB groups than in the CNT group (P < 0.01 and P < 0.05, respectively). Reperfusion resulted in an incidence of ventricular fibrillation in 23% and 21% in STZ-VEH and STZ-GLIB groups, respectively (P = ns). These values were significantly lower than that of the CNT group (100%, P < 0.001 for both). More importantly, the incidence of ventricular tachycardia in the STZ-GLIB group was significantly higher than that in the STZ-VEH group (93% vs 54%, P < 0.05) and was not significantly different from that in the CNT group (93% vs 100%, P = ns). The results suggest that STZ-induced protection against reperfusion-induced ventricular arrhythmias in diabetic heart may be partially abrogated by long-term treatment with GLIB.
Takahashi
Naohiko
N
Department of Internal Medicine I, School of Medicine, Oita Medical University, Oita 879-5593, Japan. takanao@oita-med.ac.jp
Ooie
Tatsuhiko
T
Saikawa
Tetsunori
T
Iwao
Tetsu
T
Yoshimatsu
Hironobu
H
Sakata
Toshiie
T
D000818:Animals; D001145:Arrhythmias, Cardiac / Q000503:physiopathology; D001786:Blood Glucose / Q000032:analysis; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight; D003402:Creatine Kinase / Q000187:drug effects / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000150:complications* / Q000188:drug therapy; D004198:Disease Susceptibility; D005905:Glyburide / Q000009:adverse effects* / Q000627:therapeutic use*; D006321:Heart / Q000187:drug effects* / Q000503:physiopathology; D008297:Male; D017202:Myocardial Ischemia / Q000503:physiopathology; D015428:Myocardial Reperfusion Injury / Q000209:etiology* / Q000503:physiopathology; D009929:Organ Size; D051381:Rats; D017208:Rats, Wistar; D017180:Tachycardia, Ventricular / Q000139:chemically induced* / Q000209:etiology / Q000503:physiopathology*; D016277:Ventricular Function, Left / Q000187:drug effects
D001786:Blood Glucose; D003402:Creatine Kinase; D005905:Glyburide