Drug responses in isolated diabetic rat hearts

79 DRUG RESPONSES IN ISOLATED DIABETIC RAT HEARTS. J.H.McNeill, R.V.S.V.Vadlamudi, C.V.Jackson and J.G.Latifpour. Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, Canada, V6T lW5. Previous work from our laboratory has shown that rats made diabetic with streptozotocin (STZ) show a decreased cardiac function about 6 weeks after STZ administration. In the present study we report on the responsiveness of diabetic rat hearts to various Diabetic rat hearts responded to drugs using the isolated working heart preparation. isoproterenol essentially the same as controls when either (+) or (-) dP/dt was measured in hearts from animals which had been diabetic for up to 360 days. Isoproterenol increases in cardiac CAMP were tested in 120 day diabetic animals and were found to be The negative inotropic response to carbachol was found to decrethe same as control. ase in 90 day diabetic animals but enhanced at later time periods up to one year. Using isolated right and left atria an increased responsiveness to phenylephrine in hancement the presence of timolol was noted in 90 day diabetic animals indicating. an The above pharmacological responses coula not be correof q-adrenergic responses. Experiments carried out on 6 month lated with receptor number or affinity changes. diabetic rat hearts showed a decrease in number of Q, B and muscarinic receptors but no change in such receptors in the lung. The results indicate that diabetes has a Supported by CHF, selective effect on cardiac adrenergic and cholinergic responses. CDA and B.C. Branch CDA and MRC (Canada).

80GLYCOGXN i,ZTABOLISII CHANGES 10 UIFil‘ERXNT PARTS til? THE COiTDUCTION SYSTEM OF THE HEART INDUCED BY ISCILZWA. 12etkova. Department of Pathophysiology Medical Academy, Sofia, l3ulgaria. The activity of the total and "a" ghosphorylase (iXOS) as well as the activity of the total and "I" glycogen synthetase (SYNTH) were assayed in AV-node (AV), penetratin& bundle (PB), right bundle branch (IIBB),right atrium (A) and ventricular septum (S) of bovine ileart in the course of 10 to 60-min global ischemia.The SYKTII and PIIOS specific activities decibeased in ischemia in all ;Jarts of the myocartiium and t$ conduction system examined.The 60-min ischemia influenced PROS activity in AV and PB slightly and considerably in R33,A and S.After a 10-m. h ischemia SYNTH activity decreased in S. The data obtained sur)pol+z the tiJpothesis accordiq to l.;hich the conductive tissue is more resistant to ischemia than is the myocardium. 81 CYCLIC GMP IMPROVES ENERGY-STATE IN HYWXIC RAT ATRIA - THE METABOLIC EFFECT OF ANTI-ANGINAL NITRO-COMPOUNDS? K. Laustiola. Department of Biomedical Sciences, University of Tampere, Finland. The effects of 8-bromo-CGMP on creatine phosphate (CL-P), ATP, ADP, AMP and tissue lactate levels were studied in high oxygen saturation (95-100 %) and hypoxia (50 % saturation) in spontaneously beating rat atria. The energy charge (EC) and CrP/ATP ratio were also calculated. After 3 min of hypoxia there was a significant decrease in CrP and a significant increase in ADP and AMP. The CrP/ATP ratio was also decreased significantly. A simultaneous increase in the lactate level was also seen. 8-bromo-cGMP abolished these hypoxia-induced changes and the levels of both CrP, ATP and ADP increased significantly. The lactate level decreased significantly after administration of 8-bromo-cGMP in hypoxia. 8-bromo-cGMP enhanced the level of high-energy phosphates and decreased the lactate level even in high oxygen saturation, though not as remarkably as during hypoxia. 8-bromo-cGMP caused no changes in EC or CrP/ATP during high oxygen saturation, but during hypoxia there was a significant increase in EC after 8-bromo-cGMP was added. It has been shown that sodium nitrite and nitroglycerin increase the level of cGMP in various tissues. Thus, it is proposed that the anti-angina1 nitro-compounds might exert a direct metabolic effect on hypoxic myocardium mediated by cyclic GMP.