ROLE OF HIGH GLYCOGEN IN UNDERPERFUSED DIABETIC RAT HEARTS WITH ADDEDNOREPINEPHRINE

The relationship between cardiac dysfunction and glycogen level and/or duration of diabetes was examined during underperfusion (2 ml/min/g h eart weight) with 10(-6)M norepinephrine (NE) in isolated 1- and 6-wee k streptozotocin-diabetic rat (diabetes mellitus, DM) hearts and non-D M hearts. Glycogen levels in non-DM and 1- and 6-week DM hearts were 8 5, 120, and 206 mu mol/g dry weight, respectively, in the subendocardi um. About 13 min after the start of underperfusion with NE, the diasto lic tension in 1-week DM hearts began to increase when the glycogen le vel had decreased to half; in 6-week DM hearts, glycogen decreased mor e markedly without greater lactate accumulation, but these glycogen le vels were still higher (104 mu mol/g dry weight) than those in 1-week DM hearts and the diastolic tension did not increase. About 17 min aft er the onset of underperfusion, the glycogen decreased to the 13-min l evel of 1-week DM hearts (64 mu mol/g dry weight) and the diastolic te nsion began to increase. Until 20 min after the onset of underperfusio n, the injury was less in 6-week than in 1-week DM hearts. However, af ter 60-min underperfusion with NE, when the glycogen level was markedl y low in both groups (<20 mu mol/g dry weight), diastolic tension was increased twice as much in 6-week DM as in 1-week DM hearts and was re lated to the decreased subendocardial ATP level. The results indicate that the markedly high glycogen content in diabetic hearts probably he lps delay the start of the increase in left ventricular (LV) stiffness during underperfusion with NE. Ultimately, however, the degree of the injury depends on the duration, i.e., the severity, of the diabetes.