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Effects of adrenergic (ADR) and glycolytic (GLY) stimulation during myocardial ischemia
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EFFECTS OF ADRENERGIC (ADR) AND GLYCOLYTIC (GLY) STIMULATION and C. DURING MYOCARDIAL ISCHEMIA. W. M. Vogel, G. Pollinger, Boston Univ. School of Medicine, Boston, MA 02118 S. Apstein. Experiments were designed to determine effects of adrenergic and glycolytic stimulation on ischemic myocardial metaIsolated rabbit hearts were bolism and contractile function. Flow was lowered to 6 ml/min for 120' perfused at 30 ml/min. of global ischemia, with 30' recovery at 30 ml/min. Groups were: control ischemia (CON), 120 nM isoproterenol (ADR), 500 mg% glucose + 100 mu/ml insulin (GLY), and both combined (A+G). Treatments were added from 30'-120' of ischemia. Coronary venous-arterial lactate difference (LAC), left ventricular developed pressure (LVP) and dP/dt at 30' and 120' of ischemia, and percent recovery of LVP at 30' of reflow are summarized below. RX LAC mM LVP mmHg dP/dt mmHg/sec n=8 120 30’ __ ___30’ -120' ___30’ ~120' .29+.07 .08+.04a 19+1 2212 410+40 430+40 CON GLY .36z.O8 .26Z.O7b 22x2 21+1 480580 39oT50 .28+.Og .33+.06b 44oL70 600T70ab ADR 2153 25+3a 21+1 21+1 A+G .36+.07 .57+.13ab 370+50 450560 IRecovery = (coN,~o+~) (GL~,65+4) (ADR,45+6b! (A+G,62+5) "a" indicates p<.O5vs 30'; "bTi indicates-p<.05 vs CON. CONCLUSIONS: 1)GLY enhanced lactate production in ischemia with no effect on contractile function; 2)ADR increased contractility and lactate production in ischemia but reduced recovery of contractile function; 3)A+G had additive effects on lactate the ADR inotropic response in ischemia, production, inhibited and prevented impaired recovery OZEcontraction seen with ADR alone.
MYOCARDIAL PROTECTION AND FREE RADICAL SCAVENGIQG l>!ITH GIK. 1l.F. Warner, M.L. Hess, J. Poland and L.J. Greenfield. Medical College of Virginia, Richmond, VA 23298 Glucose-Insulin-Potassium (GIK) has been utilized to protect ischemic myocardium. 1Je hypothesized that GIK might preserve the subcellular components of excitation-contraction coupling system during 60 min of hypothermic ischemia and reperfusion. GIK (300 g glucose + 50 U insulin + 80 meq/l KCl) was administered to dogs (30 ml + 1.5 ml/kg/hr) X 2 hr. Five groups were studied: C, n=6; 60' ischemia both without (I, n=6) and with GIK; 60' ischemia followed by reperfusion without (R, n=6) and with GIK (n=6). Glycogen content was unaffected by GIK. Sarcoplasmic Reticulum (SR) calcium uptake from the I Pr R oroups was significantly protected by GIK. SR CaATPase activity was unaffected by ischemia or GIK. GIK had no effect on maximal myofibrillar ATPase activity in the I group but improved function in the R group. Free radicals generated by xanthine/ xanthine oxidase at pH 7.0 depressed SR Ca-uptake and ATPase activity. This reaction was inhibited by glucose. At pH 6.4, SR Ca-uptake was uncoupled from ATP hydrolysis by free radicals and this reaction could be inhibited by plucose. GIK pretreatment affords protection to the excitation-contraction coupling system in the hypothermic, ischemic and reperfused myocardium. This protection does not appear to be due to myocardial glycogen augmentation but may result from the ability of olucose to serve as a free radical scavenger.
EFFECTS OF ADRENERGIC (ADR) AND GLYCOLYTIC (GLY) STIMULATION and C. DURING MYOCARDIAL ISCHEMIA. W. M. Vogel, G. Pollinger, Boston Univ. School of Medicine, Boston, MA 02118 S. Apstein. Experiments were designed to determine effects of adrenergic and glycolytic stimulation on ischemic myocardial metaIsolated rabbit hearts were bolism and contractile function. Flow was lowered to 6 ml/min for 120' perfused at 30 ml/min. of global ischemia, with 30' recovery at 30 ml/min. Groups were: control ischemia (CON), 120 nM isoproterenol (ADR), 500 mg% glucose + 100 mu/ml insulin (GLY), and both combined (A+G). Treatments were added from 30'-120' of ischemia. Coronary venous-arterial lactate difference (LAC), left ventricular developed pressure (LVP) and dP/dt at 30' and 120' of ischemia, and percent recovery of LVP at 30' of reflow are summarized below. RX LAC mM LVP mmHg dP/dt mmHg/sec n=8 120 30’ __ ___30’ -120' ___30’ ~120' .29+.07 .08+.04a 19+1 2212 410+40 430+40 CON GLY .36z.O8 .26Z.O7b 22x2 21+1 480580 39oT50 .28+.Og .33+.06b 44oL70 600T70ab ADR 2153 25+3a 21+1 21+1 A+G .36+.07 .57+.13ab 370+50 450560 IRecovery = (coN,~o+~) (GL~,65+4) (ADR,45+6b! (A+G,62+5) "a" indicates p<.O5vs 30'; "bTi indicates-p<.05 vs CON. CONCLUSIONS: 1)GLY enhanced lactate production in ischemia with no effect on contractile function; 2)ADR increased contractility and lactate production in ischemia but reduced recovery of contractile function; 3)A+G had additive effects on lactate the ADR inotropic response in ischemia, production, inhibited and prevented impaired recovery OZEcontraction seen with ADR alone.
MYOCARDIAL PROTECTION AND FREE RADICAL SCAVENGIQG l>!ITH GIK. 1l.F. Warner, M.L. Hess, J. Poland and L.J. Greenfield. Medical College of Virginia, Richmond, VA 23298 Glucose-Insulin-Potassium (GIK) has been utilized to protect ischemic myocardium. 1Je hypothesized that GIK might preserve the subcellular components of excitation-contraction coupling system during 60 min of hypothermic ischemia and reperfusion. GIK (300 g glucose + 50 U insulin + 80 meq/l KCl) was administered to dogs (30 ml + 1.5 ml/kg/hr) X 2 hr. Five groups were studied: C, n=6; 60' ischemia both without (I, n=6) and with GIK; 60' ischemia followed by reperfusion without (R, n=6) and with GIK (n=6). Glycogen content was unaffected by GIK. Sarcoplasmic Reticulum (SR) calcium uptake from the I Pr R oroups was significantly protected by GIK. SR CaATPase activity was unaffected by ischemia or GIK. GIK had no effect on maximal myofibrillar ATPase activity in the I group but improved function in the R group. Free radicals generated by xanthine/ xanthine oxidase at pH 7.0 depressed SR Ca-uptake and ATPase activity. This reaction was inhibited by glucose. At pH 6.4, SR Ca-uptake was uncoupled from ATP hydrolysis by free radicals and this reaction could be inhibited by plucose. GIK pretreatment affords protection to the excitation-contraction coupling system in the hypothermic, ischemic and reperfused myocardium. This protection does not appear to be due to myocardial glycogen augmentation but may result from the ability of olucose to serve as a free radical scavenger.