Intracellular Ca2+ concentration and pH of diabetic rat myocytes during metabolic inhibition

J Mel

Cell

Cardiol

22 (Supplement

II) (1990)

2+ CONCENl'FlATION AND pH OF DIABETIC RAT MYOCYTES DURaNG METAFXlL$C 34INTRACELLLJLAR Ca H. Hayashi, H. Miyata, S. Suzuki, M. Hirano , T. Kawai , INHIBITION. N. Noda. Department of Internal Medicine, Hamamatsu A. Kobayashi, N. Yamazaki. Third University School of Mediciqp, Hamamatsu, Japan., # Hamamatsu Photonics K.K. (D.M.) during TO study the role of Ca2+ metabolism and pH in diabetes mellitus metabolic inhibition, [Ca 11 and pHi of isolated myocytes were measured simultaneously using dual-loading of furaa@ BCECF. We used D.M. rats at 8 weeks i.v.l. [Ca Ii of D.M. was lower than that of after streptozotocin (45 mg/kg, controls (5323 and 7525 nM, mean?S.E., p
35CORRELATION OF CONTRACTILE DYSFUNCTION AND MYOCARDIAL ENERGY METABOLITES CONTENT DURING PARTIAL CORONARY FLOW DISRUPTION WITH NOREPINEPHRINE IN NORMAL AND DIABETIC RAT HEARTS. M. Higuchi, S. Ikema*, M. Sakanashl. Departments of Pharmacology and *Pediatrics, School of Medicine. University of the Ryukyus, Okinawa, Japan. Paced hearts isolated from rats with 11-12 days of streptozotocin-diabetes (DM) were compared with hearts from normal rats (Normal) to determine whether there are differences in the relationships between contractile dysfunction and abnormal tissue high energy phosphate and lactate content under various low-flow rates (0.4-6 ml/g heart wt/min) with lo@ M norepinephrine (NE) for 1 hr. Left ventricular pressure (LVP) was monitored from a balloon in the LV and contractile force (CF) from the apex. Resting CF in DM elevated flow-dependently at flow below 6 ml and to the maximal level at 3 ml or less, while in Normal it elevated at flow below 1 ml, along with elevations in resting LVP. Flow-dependent decreases in developed CF were larger in DM, while those in developed LVP were similar in both groups. These elevations and decreases were closely correlated to the flow-dependent decreases in high energy phosphates cdP) I" the LV inner wall of both groups, but at the same 1owwP level these elevations and the decreases in developed CF were larger in DM. Flow-dependent decreases in creatine P/ inorganic P ratio were similar in both groups, though lactate accumulation was smaller in DM. The contractile dysfunction in DM improved by --ex viva insulin, as is only small recovery of NP. The results indicate that DM was more susceptible to low-flow with NE, which cannot be explained bycP content decrease and lactate accumulation alone.

36

IMPAIRMENT OF MITOCHONDRIAL RESPIRATIORY ACTIVITIES IN MYOCARDIAL INJURY ASSOCIATED WITH EXPERIMENTAL DIABETES MELLITUS M. Tomita, E. Geshi, S. Mukae, S. Itoh, Y. Suwa, K. Umetsu, T. Yanagishita, M. Yaida, T. Katagiri. Third Department of Internal Medicine, Showa University School of Medicine, Tokyo, Japan. We studied metabolic impairment of diabetic myocardium in term of mitochondrial respiratory function. Experimental diabetes mellitus was produced in male Wistar rats by single intravenous injection of streptosotocin at 65 mg/kg for 4 to 16 weeks (D group). Age matched normal control rats were used (C group). Insulin was injected for 3 weeks (I group) in a part of D group. Cardiac mitochondria (Mt) was prepared by method of Sordahl. Respiratory activities and electron transport system activities of Mt were measured. In D group, state 3, RCR, complex I activities decreased of those of C group. In I group these alterations were improved. By electron microscopic observation, Mt of D group were swollen and fused. But in I group, these were slightly changed. These results suggest that in diabetic myocardium, depressed respiratory activities are due to injury of electron transport system. And changes of metabolism in myocardium might be one of causes of relaxation disturbance and congestive heart failure in DM heart noted as diabetic cardiomyopathy. s.39