Exacerbation of acidosis during ischemia and reperfusion arrhythmia in hearts from type 2 Diabetic Otsuka Long-Evans Tokushima Fatty rats.
BACKGROUND
Sensitivity to ischemia and its underlying mechanisms in type 2 diabetic hearts are still largely unknown. Especially, correlation between reperfusion induced ventricular arrhythmia and changes in intracellular pH has not been elucidated.


RESULTS
Male Otsuka Long-Evans Tokushima Fatty (OLETF) rats at 16 and 32 weeks of age were used along with age-matched nondiabetic Long-Evans Tokushima Otsuka (LETO) rats. Hearts from rats in these 4 groups were perfused in the working heart mode, thus inducing whole heart ischemia. At 16 weeks of age, no differences in blood glucose levels or incidence and duration of reperfusion arrhythmia were found between the strains. At 32 weeks of age, both impaired glucose tolerance and obesity were observed in the OLETF rats. Further, the duration of reperfusion-induced ventricular fibrillation (VF) was significantly longer in the OLETF rats, while the pH level was significantly lower and proton contents were significantly higher in coronary effluent during ischemia in those rats. Following treatment with troglitazone, improvements in pH and proton level in coronary effluent during ischemia were observed, as was the duration of reperfusion-induced VF in OLETF rats at 32 weeks of age.


CONCLUSIONS
The hearts of spontaneously diabetic OLETF rats were found to be more susceptible to ischemic insult. Troglitazone treatment improved ischemic tolerance by improving glucose metabolism in the myocardium of those rats.
Anzawa
Ryuko
R
Division of Cardiology, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan. anzawar@jikei.ac.jp
Seki
Shingo
S
Horikoshi
Kazuaki
K
Taniguchi
Masayuki
M
Mochizuki
Seibu
S
D000818:Animals; D001145:Arrhythmias, Cardiac / Q000209:etiology / Q000378:metabolism*; D001786:Blood Glucose / Q000378:metabolism; D002839:Chromans / Q000627:therapeutic use; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy / Q000378:metabolism*; D016883:Diabetic Ketoacidosis / Q000378:metabolism*; D004195:Disease Models, Animal; D004734:Energy Metabolism / Q000502:physiology; D006706:Homeostasis / Q000502:physiology; D006863:Hydrogen-Ion Concentration; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D008297:Male; D009206:Myocardium / Q000378:metabolism; D009765:Obesity / Q000378:metabolism; D051381:Rats; D020334:Rats, Inbred OLETF / Q000378:metabolism*; D015427:Reperfusion Injury / Q000150:complications / Q000378:metabolism*; D045162:Thiazolidinediones / Q000627:therapeutic use; D000077288:Troglitazone; D014693:Ventricular Fibrillation / Q000209:etiology / Q000378:metabolism
D001786:Blood Glucose; D002839:Chromans; D007004:Hypoglycemic Agents; D045162:Thiazolidinediones; D000077288:Troglitazone