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Differential effects of fatty acids on reperfusion recovery of ischemic hearts from control and diabetic rats
J Mol
Cell
Cardiol
22 (Supplement
I) (1990)
P124EFFECTS OF PHOSPHATIDYLCHOLINE ON MECHANISMS OF REPERFUSION ARRHYTHMIAS IN ISOLATED GUINEA PIG VENTRICULAR TISSUES. Jianmin Duan and Margaret P. Moffat, Dept. of Pharmacology and Toxicology, -. University of Western Ontario, London, Canada, N6A 5Cl. The effects ofphosphatidylcholine (PC-50 @l) were testedusing the superfused right ventricular free wall of ttie guinea pig. Exposure of the preparation to simulated "ischemia" resulted in marked depolarization in both endocardium (Endo) and epicardium and conduction delay followed by conduction block. Following 40 min of (Epi), “ischemia,” transmural conduction block persisted until 45 min of reperfusion. Both coupled beats and abnormal automaticity were observed in the Endo. Superfusion with PC during both "ischemia" and reperfusion, or during reperfusion only, significantly altered the response of the preparations. Following 40 min "ischemia", preparations treated with PC recovered from transmural conduction block more rapidly and exhibited improved earlier recovery of MDP in the Epi. Neither PC treatment altered the incidence of coupled beats but abnormal automaticity was abolished in both groups. Following 20 min of "ischemia", recovery from transmural conduction block occurred sooner and coupled beats and abnormal automaticity were detected in both Epi and Endo layers. PC reduced the duration of coupled beats, the incidence of abnormal automaticity and abolished VT, in both treated groups. This study demonstrates that PC can antagonize important cellular mechanisms which may underlie reperfusion arrhythmias. Supported by the Heart and Stroke Foundation of Ontario.
.Pl2.5.-- DIFFERENTIAL ISCHEMIC
EFFECTS OF FATTY HEARTS FROM CONTROL
ACIDS ON REPERFUSION AND DIABETIC RATS.
RECOVERY
OF
Gary D. Louaschuk. Ray A. Muzyka, Li M. Huang. Heritage Cardiovascular Research Group, University of Aiberta, &lmonton, danada T6ij 2S2. Recently we have demonstrated that a reduction in glucose utilization caused by fatty acids during reperfusion of ischemic hearts depresses recovery of mechanical function in non-diabetic rat hearts. Since the diabetic rat hearts are more reliant on fatty acids as energy substrate, we determined the optimal substrate for recoverv of heart function durinrr and followine ischemia in isolated working hearts from 6-week streptozot&n diabetic and control Gts. Hearts w&e perfused with 1 ImM gluc%e at a 11.5 mm Hg preload and 80 mm He afterload and then subiected to 25 minutes of global ischemia followed by 30 minutes of aerobic reperfision. Three groups ofcontrol and diabetic ratswere studied; 1) 1.2mM p&nitate present prior to, during and following ischemia; 2) 1.2mM palmitate present prior to and during ischemia followed
by in the absence of palmitate during reperfusion; and 3) no palmitate prior to and during ischemia followed by 1.2mM palmitatc: drlrinp repetfusion. In control hearts, palmitate depressed reperfusion recovery of function reeardless of whether IT;ilmitate was Dresent or absent during ischemia. Optimal recovery of function was seen in these hear;> rlrrfused wiih palmitate during ischemia and glucose during reperfusion In contrast, palmitate did not deprc\> reperfusion recovery of mechanical function in the diabetic heart. However, tGe presence of palm&e dui;ng ischemia was detrimental to mechanical recovery during reperfusion. We conclude therefore that high concentrations of fatty acids connibute to ischemic injury in non-diabetic rat hearts during reperfusion. but contribute to injury during ischemia in the diabetic rat heart.
pi26
VASOCONSTRICTOR EFFECTS OF END~THELIN ARE ENHANCED FOLLOWING ISCHEMIA Christopher J Gordon, John A Watts. Department of Biology, University of North Carolina at Charlotte, Charlotte, NC 28223. The present atudiea examine the vascular responses to endothelin, a vaaoconstrictor peptide, in control and ischemic/reperfused hearts. Isolated rat hearts were perfused by the Langendorff technique with a drain placed through the left ventricular wall to avoid retention of fluid in the ventricle. Perfusion was maintained at 37oC, under constant flow conditions (14 ml/min, Tranaonic Endothelin was infused for 3 q in and flowmeter), in a non-recirculating system. Endothelin vasoconatriction was indicated by a rise in perfusion pressure. infusion caused a concentration-dependent increase in perfusion presaure in control hearts. When endothelin was infused following 30 ain of zero flow, global the increase in perfusion pressure was ischemia and 15 min of reperfusion, significantly greater than control hearts (64 vs 19, 128 vs 38, 172 va 58, 217 vs 76 percent increase in perfusion pressure) for each concentration of endothelin Thus, the response to endothelin ia tested (2.5, 5.0, 7.5, 10 X 10-l%). This increased response increased by ischemia/reperfusion in isolated rat hearts. may contribute to the no reflow phenomenon observed following transient ischemia. (Supported by the Foundation of UNCC and the State of North Carolina). S.42
Cell
Cardiol
22 (Supplement
I) (1990)
P124EFFECTS OF PHOSPHATIDYLCHOLINE ON MECHANISMS OF REPERFUSION ARRHYTHMIAS IN ISOLATED GUINEA PIG VENTRICULAR TISSUES. Jianmin Duan and Margaret P. Moffat, Dept. of Pharmacology and Toxicology, -. University of Western Ontario, London, Canada, N6A 5Cl. The effects ofphosphatidylcholine (PC-50 @l) were testedusing the superfused right ventricular free wall of ttie guinea pig. Exposure of the preparation to simulated "ischemia" resulted in marked depolarization in both endocardium (Endo) and epicardium and conduction delay followed by conduction block. Following 40 min of (Epi), “ischemia,” transmural conduction block persisted until 45 min of reperfusion. Both coupled beats and abnormal automaticity were observed in the Endo. Superfusion with PC during both "ischemia" and reperfusion, or during reperfusion only, significantly altered the response of the preparations. Following 40 min "ischemia", preparations treated with PC recovered from transmural conduction block more rapidly and exhibited improved earlier recovery of MDP in the Epi. Neither PC treatment altered the incidence of coupled beats but abnormal automaticity was abolished in both groups. Following 20 min of "ischemia", recovery from transmural conduction block occurred sooner and coupled beats and abnormal automaticity were detected in both Epi and Endo layers. PC reduced the duration of coupled beats, the incidence of abnormal automaticity and abolished VT, in both treated groups. This study demonstrates that PC can antagonize important cellular mechanisms which may underlie reperfusion arrhythmias. Supported by the Heart and Stroke Foundation of Ontario.
.Pl2.5.-- DIFFERENTIAL ISCHEMIC
EFFECTS OF FATTY HEARTS FROM CONTROL
ACIDS ON REPERFUSION AND DIABETIC RATS.
RECOVERY
OF
Gary D. Louaschuk. Ray A. Muzyka, Li M. Huang. Heritage Cardiovascular Research Group, University of Aiberta, &lmonton, danada T6ij 2S2. Recently we have demonstrated that a reduction in glucose utilization caused by fatty acids during reperfusion of ischemic hearts depresses recovery of mechanical function in non-diabetic rat hearts. Since the diabetic rat hearts are more reliant on fatty acids as energy substrate, we determined the optimal substrate for recoverv of heart function durinrr and followine ischemia in isolated working hearts from 6-week streptozot&n diabetic and control Gts. Hearts w&e perfused with 1 ImM gluc%e at a 11.5 mm Hg preload and 80 mm He afterload and then subiected to 25 minutes of global ischemia followed by 30 minutes of aerobic reperfision. Three groups ofcontrol and diabetic ratswere studied; 1) 1.2mM p&nitate present prior to, during and following ischemia; 2) 1.2mM palmitate present prior to and during ischemia followed
by in the absence of palmitate during reperfusion; and 3) no palmitate prior to and during ischemia followed by 1.2mM palmitatc: drlrinp repetfusion. In control hearts, palmitate depressed reperfusion recovery of function reeardless of whether IT;ilmitate was Dresent or absent during ischemia. Optimal recovery of function was seen in these hear;> rlrrfused wiih palmitate during ischemia and glucose during reperfusion In contrast, palmitate did not deprc\> reperfusion recovery of mechanical function in the diabetic heart. However, tGe presence of palm&e dui;ng ischemia was detrimental to mechanical recovery during reperfusion. We conclude therefore that high concentrations of fatty acids connibute to ischemic injury in non-diabetic rat hearts during reperfusion. but contribute to injury during ischemia in the diabetic rat heart.
pi26
VASOCONSTRICTOR EFFECTS OF END~THELIN ARE ENHANCED FOLLOWING ISCHEMIA Christopher J Gordon, John A Watts. Department of Biology, University of North Carolina at Charlotte, Charlotte, NC 28223. The present atudiea examine the vascular responses to endothelin, a vaaoconstrictor peptide, in control and ischemic/reperfused hearts. Isolated rat hearts were perfused by the Langendorff technique with a drain placed through the left ventricular wall to avoid retention of fluid in the ventricle. Perfusion was maintained at 37oC, under constant flow conditions (14 ml/min, Tranaonic Endothelin was infused for 3 q in and flowmeter), in a non-recirculating system. Endothelin vasoconatriction was indicated by a rise in perfusion pressure. infusion caused a concentration-dependent increase in perfusion presaure in control hearts. When endothelin was infused following 30 ain of zero flow, global the increase in perfusion pressure was ischemia and 15 min of reperfusion, significantly greater than control hearts (64 vs 19, 128 vs 38, 172 va 58, 217 vs 76 percent increase in perfusion pressure) for each concentration of endothelin Thus, the response to endothelin ia tested (2.5, 5.0, 7.5, 10 X 10-l%). This increased response increased by ischemia/reperfusion in isolated rat hearts. may contribute to the no reflow phenomenon observed following transient ischemia. (Supported by the Foundation of UNCC and the State of North Carolina). S.42