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Extracellular magnesium depletion and ischemic tolerance in the isolated rat heart
34 B2 EXTRACELLULAR MAGNESIUM DEPLETION AND ISCHEMIC TOLERANCE IN T H E ISOLATED RAT HEART. P.C. Borchgrevink, P. Jynge. Department of Pharmacology a n d Toxicology, University of Trondheim, Norway. M a g n e s i u m deficiency states m a y lead to a reduction of extracellular m a g n e s i u m and of myocardial intracellular magnesium. T h e present study was u n d e r t a k e n in order to assess the potential effects of a total, purely extracellular depletion of m a g n e s i u m during global subtotal ischemia (coronary flow rate 2.5 ml/min, duration 20 rain) and/ or during postischemic reperfusion (duration 20 rain) in the normothermic Langendorffperfused rat heart. Tissue injury was assessed b y physiological (L.V. balloon technique), enzymatic (CK-release) and metabolic (myocardial A T P ) indices. M a g n e s i u m depletion during ischemia influenced postischemic recovery of L V P , L V dp/dt and C F R only to a minor degree whereas m a g n e s i u m depletion during the reperfusion period led to a more p r o n o u n c e d reduction of L V P , L V dp/dt and C F R . C K release during ischemia and reperfusion was not influenced b y variations in perfusate magnesium. Myocardial A T P at the end of the experiment was lower in the groups of hearts deprived of m a g n e s i u m during ischemia and/or reperfusion. It is concluded that in a minor to moderate ischemic injury as in the present study, the acute removal of extracellular m a g n e s i u m m a y lead to an impairment of postischemic cardiac function a n d metabolism.
B3 EFFLUX OF 2 8 - M A G N E S I U M F R O M THE ISOLATED RAT HEART: EFFECTS OF ISCHAEMIA, REPERFUSION, TEMPERATURE AND EXTRACELLULAR MAGNESIUM CONCENTRATION. M.E. Maguire*, R. Crome, D.J. Hearse, A.S. Manning. The Rsyne Institute, St. Thomas' Hospital, London SE1, UK. *Pharmacology Dept., Case Western Reserve University, Cleveland, Ohio, U.S.A. During infarction serum m a g n e s i u m rises acutely, presumably due to myocardial tissue damage. Magnesium efflux from ischaemic myocardium has never been measured. R a d i o a c t i v e m a g n e s i u m was a d m i n i s t e r e d i.v. to male rats (300g) 2 h prior to sacrifice. Excised hearts were perfused in the L a n g e n d o r f f m o d e with b i c a r b o n a t e buffer plus glucose (11mM) gassed with 95% 02 plus 5% CO 2. After 30 min control perfusion at 37~ hearts were made ischaemic {coronary flow 1.0 ml/min) for 40 min, flow was then returned to control for 15 min. In other studies, perfusate magnesium was changed from 1.2 to 0.5ram or 5mM. Sequential I min samples of coronary effluent were taken for radioactivity measurements. Hypotharmia reduced efflux from t•2 <40 min at 37~ to >12h at 21~ This suggests efflux is energy-dependent, Ischaemia caused a sharp but transient (5 min) decline in efflux which then returned to control for the 40 min period. Reperfusion caused a large bolus release before establishment of a slightly increased efflux rate. Efflux was modified by extracellular magnesium c o n c e n t r a t i o n such that increases from 1.2 to 5.0mM gave e transient (10 min) increase in efflux which then returned to control. Reducing magnesium to 0.5mM resulted in s rapid drop in efflux which was m a i n t a i n e d for the entire 40 min period.
B4 TRANSMURAL DIFFERENCES IN PERFORMANCE OF DOG MYOCARDIUM REPERFUSED AFTER ONE HOUR OF ISCHEMIA. G.J. van der Vusse, F.H. van der Veen and R.S. Reneman. Department of Physiology, University of Limburg, M~astricht, The Netherlands. Subendocardial layers are most severely affected during isehemia, but transmural differences in recovery, if any, are less well documented. After one hr of reperfusion following one hr of regional ischemia (occlusion of the LAD; 13 open-chest dogs), epicardial shortening during the ejection phase as assessed by an inductive technique, recovered by 21% in the subepicardial fiber direction, but changed into lengthening in the subendoeardial fiber direction. After an initial period of reactive hyperaemia (4.4 x control flow, endo/epi ratio = 0.49 at 3-5 min) myocardial blood flow (MBF) remained elevated (1.8 x control flow, endo/epi ratio = 2.4 at one hr). Restoration of flow resulted in a substantial release of lactate and purine bases (adenosine, inosine, hypoxanthine and xanthine) from the affected area. After one hr of reperfusion the ATP, creatine phosphate (CP) and glycogen (G) levels in the subepi and subendocardial layers, were 85 and 27, 107 and i00, 79 and 28% of the control values, respectively. Morphological examination showed i0 and 80% damaged cells in these layers, respectively. Conclusions: (I) one hr of regional ischemia followed by one hr of reperfusion results in only partial recovery of subepicardial shortening, despite adequate restoration of MBF, content of ATP, CP and G, and morphology (2) dilation of subendoeardial layers is associated with decreased ATP and G levels and elevated perfusion.
B3 EFFLUX OF 2 8 - M A G N E S I U M F R O M THE ISOLATED RAT HEART: EFFECTS OF ISCHAEMIA, REPERFUSION, TEMPERATURE AND EXTRACELLULAR MAGNESIUM CONCENTRATION. M.E. Maguire*, R. Crome, D.J. Hearse, A.S. Manning. The Rsyne Institute, St. Thomas' Hospital, London SE1, UK. *Pharmacology Dept., Case Western Reserve University, Cleveland, Ohio, U.S.A. During infarction serum m a g n e s i u m rises acutely, presumably due to myocardial tissue damage. Magnesium efflux from ischaemic myocardium has never been measured. R a d i o a c t i v e m a g n e s i u m was a d m i n i s t e r e d i.v. to male rats (300g) 2 h prior to sacrifice. Excised hearts were perfused in the L a n g e n d o r f f m o d e with b i c a r b o n a t e buffer plus glucose (11mM) gassed with 95% 02 plus 5% CO 2. After 30 min control perfusion at 37~ hearts were made ischaemic {coronary flow 1.0 ml/min) for 40 min, flow was then returned to control for 15 min. In other studies, perfusate magnesium was changed from 1.2 to 0.5ram or 5mM. Sequential I min samples of coronary effluent were taken for radioactivity measurements. Hypotharmia reduced efflux from t•2 <40 min at 37~ to >12h at 21~ This suggests efflux is energy-dependent, Ischaemia caused a sharp but transient (5 min) decline in efflux which then returned to control for the 40 min period. Reperfusion caused a large bolus release before establishment of a slightly increased efflux rate. Efflux was modified by extracellular magnesium c o n c e n t r a t i o n such that increases from 1.2 to 5.0mM gave e transient (10 min) increase in efflux which then returned to control. Reducing magnesium to 0.5mM resulted in s rapid drop in efflux which was m a i n t a i n e d for the entire 40 min period.
B4 TRANSMURAL DIFFERENCES IN PERFORMANCE OF DOG MYOCARDIUM REPERFUSED AFTER ONE HOUR OF ISCHEMIA. G.J. van der Vusse, F.H. van der Veen and R.S. Reneman. Department of Physiology, University of Limburg, M~astricht, The Netherlands. Subendocardial layers are most severely affected during isehemia, but transmural differences in recovery, if any, are less well documented. After one hr of reperfusion following one hr of regional ischemia (occlusion of the LAD; 13 open-chest dogs), epicardial shortening during the ejection phase as assessed by an inductive technique, recovered by 21% in the subepicardial fiber direction, but changed into lengthening in the subendoeardial fiber direction. After an initial period of reactive hyperaemia (4.4 x control flow, endo/epi ratio = 0.49 at 3-5 min) myocardial blood flow (MBF) remained elevated (1.8 x control flow, endo/epi ratio = 2.4 at one hr). Restoration of flow resulted in a substantial release of lactate and purine bases (adenosine, inosine, hypoxanthine and xanthine) from the affected area. After one hr of reperfusion the ATP, creatine phosphate (CP) and glycogen (G) levels in the subepi and subendocardial layers, were 85 and 27, 107 and i00, 79 and 28% of the control values, respectively. Morphological examination showed i0 and 80% damaged cells in these layers, respectively. Conclusions: (I) one hr of regional ischemia followed by one hr of reperfusion results in only partial recovery of subepicardial shortening, despite adequate restoration of MBF, content of ATP, CP and G, and morphology (2) dilation of subendoeardial layers is associated with decreased ATP and G levels and elevated perfusion.