Preserved postischemic heart function in sucrose-fed type 2 diabetic OLETF rats.
Cardiovascular disease is one of the most important causes of morbidity and mortality in diabetes mellitus, but there has been controversy over functional impairment of diabetic hearts and their tolerance to ischemia. We studied ischemic heart function in type 2 diabetic rats with different degrees of hyperglycemia and its relationship with cardiac norepinephrine release. Otsuka Long-Evans Tokushima Fatty rats (OLETF) and age-matched Long-Evans Tokushima Otsuka normal rats (LETO) were used. One group of OLETF rats was given 30% sucrose in drinking water (OLETF-S). Hearts were isolated and perfused in a working heart preparation and subjected to 30 min ischemia followed by 40 min reperfusion at age of 12 months. Hemodynamics and coronary norepinephrine overflow were examined. Fasting plasma glucose in OLETF increased markedly at 12 months and sucrose administration exacerbated hyperglycemia in diabetic rats (LETO 6.6 +/- 0.5, OLETF 8.3 +/- 0.7, OLETF-S 15.0 +/- 1.7 mmol/L, P < 0.01). Basic cardiac output in OLETF was decreased as compared with LETO and OLETF-S (LETO 29.4 +/- 2.5, OLETF 24.0 +/- 2.4, OLETF-S 27.0 +/- 0.9 ml/min/g, P < 0.05) and remained very low after ischemia, while in OLETF-S it was well preserved (OLETF 4.2 +/- 2.1, OLETF-S 13.7 +/- 2.6 ml/min/g, P < 0.01). Correspondently, cardiac norepinephrine released during ischemia and reperfusion was lower in OLETF-S (OLETF 2.3 +/- 1.0, OLETF-S 0.7 +/- 0.1 pmol/ml, P < 0.01). Thus, OLETF hearts were more vulnerable to ischemia but sucrose feeding rendered their hearts resistant to ischemia. Less norepinephrine release may play a role in preventing postischemic functional deterioration in sucrose-fed diabetic hearts.
Chen
Hong
H
Department of Pharmacology, Second Military Medical University, 800 Xiang Yin Road, Shanghai 200433, China. hchen100@hotmail.com
Higashino
Hideaki
H
Kamenov
Zdravko A
ZA
Azuma
Makiko
M
Lee
Wen-Hsiung
WH
Yang
Xiang-Qun
XQ
Zhou
Da-Jin
DJ
Yuan
Wen-Jun
WJ
D000375:Aging / Q000502:physiology; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000503:physiopathology; D001786:Blood Glucose / Q000378:metabolism; D003326:Coronary Circulation / Q000502:physiology; D003924:Diabetes Mellitus, Type 2 / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D017202:Myocardial Ischemia / Q000473:pathology / Q000503:physiopathology*; D015425:Myocardial Reperfusion; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D009638:Norepinephrine / Q000378:metabolism / Q000652:urine; D051381:Rats; D020334:Rats, Inbred OLETF; D013395:Sucrose / Q000494:pharmacology*; D013564:Sympathetic Nervous System / Q000502:physiology
D001786:Blood Glucose; D013395:Sucrose; D009638:Norepinephrine