The insulin sensitizer pioglitazone improves the deterioration of ischemic preconditioning in type 2 diabetes mellitus rats.
We investigated the effects of ischemic preconditioning (IP) on reperfusion arrhythmias in type 2 diabetic rats as well as the effects of the insulin sensitizer pioglitazone. Thirty-week-old OLETF rats with or without pioglitazone (10 mg/kgBW, orally) were used as a model for type 2 diabetes. LETO rats served as controls. The incidences and durations of reperfusion ventricular tachyarrhythmias (RVT) were evaluated using a working heart method. After 5 minutes of initial perfusion, the rats were divided into the following groups: 1) control rats without IP (CIP(-)), 2) control rats with IP (CIP(+)), 3) diabetic rats without IP (DIP(-)), 4) diabetic rats with IP (DIP(+)), 5) pioglitazone-treated diabetic rats without IP (TDIP(-)), and 6) pioglitazone-treated diabetic rats with IP (TDIP(+)). Three 2-minute cycles of global diastolic ischemia and 5 minutes of reperfusion before long ischemia were performed as IP. The incidence and duration of RVT in CIP(+) were significantly lower than in CIP(-). There was no significant difference in the duration of RVT between DIP(+) and DIP(-). However, the duration of RVT in TDIP(+) was significantly shorter than TDIP(-). These results suggested that the effects of IP on reperfusion arrhythmias are deteriorated in type 2 diabetic rats. The insulin sensitizer pioglitazone can improve the deterioration of IP against reperfusion arrhythmias in type 2 diabetic rats.
Sasaki
Hideki
H
Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan.
Ogawa
Kazuhiko
K
Shimizu
Mitsuyuki
M
Mori
Chikara
C
Takatsuka
Hisashi
H
Okazaki
Fumiko
F
Kawai
Makoto
M
Taniguchi
Ikuo
I
Mochizuki
Seibu
S
D000818:Animals; D001145:Arrhythmias, Cardiac / Q000097:blood / Q000209:etiology* / Q000517:prevention & control*; D003326:Coronary Circulation / Q000502:physiology; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000150:complications* / Q000503:physiopathology; D004195:Disease Models, Animal; D006442:Glycated Hemoglobin / Q000378:metabolism; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D019157:Ischemic Preconditioning, Myocardial / Q000009:adverse effects*; D015428:Myocardial Reperfusion Injury / Q000150:complications; D000077205:Pioglitazone; D051381:Rats; D020334:Rats, Inbred OLETF; D045162:Thiazolidinediones / Q000627:therapeutic use*
D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D000077205:Pioglitazone; D045162:Thiazolidinediones; C517652:hemoglobin A1c protein, human