Makie Higuchi

Role of High Glycogen in Underperfused Diabetic Rat Hearts with Added Norepinephrine

The relationship between cardiac dysfunction and glycogen level and/or duration of diabetes was examined during underperfusion (2 ml/min/g heart weight) with 10(-6)M norepinephrine (NE) in isolated 1- and 6-week streptozotocin-diabetic rat (diabetes mellitus, DM) hearts and non-DM hearts. Glycogen levels in non-DM and 1- and 6-week DM hearts were 85, 120, and 206 mumol/g dry weight, respectively, in the subendocardium. About 13 min after the start of underperfusion with NE, the diastolic tension in 1-week DM hearts began to increase when the glycogen level had decreased to half; in 6-week DM hearts, glycogen decreased more markedly without greater lactate accumulation, but these glycogen levels were still higher (104 mumol/g dry weight) than those in 1-week DM hearts and the diastolic tension did not increase. About 17 min after the onset of underperfusion, the glycogen decreased to the 13-min level of 1-week DM hearts (64 mumol/g dry weight) and the diastolic tension began to increase. Until 20 min after the onset of underperfusion, the injury was less in 6-week than in 1-week DM hearts. However, after 60-min underperfusion with NE, when the glycogen level was markedly low in both groups ( < 20 mumol/g dry weight), diastolic tension was increased twice as much in 6-week DM as in 1-week DM hearts and was related to the decreased subendocardial ATP level. The results indicate that the markedly high glycogen content in diabetic hearts probably helps 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.

Effects of nitroglycerin on regional myocardial function in the underperfused canine heart

Summary: Effects of nitroglycerin (3 μg/kg/min i.v.) on regional myocardial contractility during acute coronary stenosis were studied in open-chest dogs using a strain-gauge arch. Stenosis-induced stepwise decreases in coronary perfusion pressure (CPP) at <40 mm Hg correspondingly reduced contractility in the underperfused area and increased the left ventricular end-diastolic pressure (LVEDP). Nitroglycerin caused significant increases in contractility, along with decreases in arterial and left ventricular pressures; at stenosis-induced CPP <30 mm Hg, contractility in the underperfused area fell precipitously below the control, while LVEDP increased. When nitroglycerin infusion under coronary stenosis (CPP of 40 mm Hg) decreased CPP to <30 mm Hg, contractility fell. When CPP >30 mm Hg was maintained, contractility increased and LVEDP decreased. In conclusion, at least in the absence of well-developed collateral circulation, the critical level of CPP was 40 mm Hg for contractility and LVEDP without nitroglycerin, which shifted to 30 mm Hg with the addition of nitroglycerin. Nitroglycerin resulted in a significant increase in plasma catecholamines, and the increase in contractility diminished with propranolol, indicating participation of β-adrenoceptor in the positive inotropic effect of nitroglycerin. However, catecholamines at high concentrations probably further aggravated the impaired cardiac function at CPP <30 mm Hg.

Participation of the vasodilating property of nipradilol in improving ischemic derangement of myocardial energy metabolism

The effects of equipotent doses in negative inotropic and chronotropic properties of nipradilol [10 μg/kg/min intravenously (i.v.)] and propranolol (20 μg/kg/min i.v.) on hemodynamics and transmural energy metabolites in ischemic hearts were examined in anesthetized dogs. After 5-min infusion of these agents, coronary perfusion pressure of 30 mm Hg was induced by acute coronary stenosis for 10 min. Coronary blood inflow and myocardial contractile force (MCF) in the control ischemic area decreased to about one-third and two-thirds of the respective starting levels. In the nipradilol group, similar changes were observed, but in the propranolol group the MCF tended to decrease further. Cardiac effort index decreased to about two-thirds in both groups. The left ventricular end-diastolic pressure (LVEDP) increased by 4.3 mm Hg with saline, by 8.8 mm Hg with propranolol, and by 1.3 mm Hg with nipradilol. ATP depletion in the ischemic myocardium (by 29 and 22% in inner and outer layers, respectively) was restored to normal level by either agent. A decrease in creatine phosphate and an accumulation of lactate were significantly alleviated by nipradilol (by 74 and 59 → by 39 and 21%, and by 4.9 and 2.3 → by 0.7 and 0.2 times, respectively), but not by propranolol. The results indicate that in addition to a decrease in myocardial oxygen consumption caused by the β-adrenoceptor blocking effects of nipradilol, reductions in preload and afterload caused by the vasodilating property significantly contribute to nipradilol-induced improvement in the ischemic derangement of transmural energy metabolism.