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The influence of disease on myocardial susceptability to ischemic damage
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THE INFLUENCE OF DISEASE ON MYOCARDIAL SUSCEPTABILITY TO ISCHEMIC DAMAGE D.J. Hearse, D.A. Stewart and D.G. Green. T h e Myocardial Metabolism Laboratories, St. Thomas' Hospital, London, UK. Experimental studies of ischemic damage are often criticised as they are carried out using hearts from young, healthy animals and as such they may be o f little relevance to the diseased heart. A number o f models o f human disease states exist in the rat. Using an isolated perfused working rat heart we have assessed the extent to which diabetes, obesity, hypertrophy and hypertension can influence the susceptibility o f the myocardium to ischemic damage and to metabolic protection. Hearts from diseased rats were subjected to 70 min global ischemia; upon reperfusion the recovery of aortic flow, and pressure, dP/dt and heart rate were measured and compared with pre-ischemic control values and also with the recovery o f hearts from non-diseased control rats. In diseases, such as experimental diabetes or obesity, which influence the efficiency or adaptability of myocardial energy metabolism, a marked reduction in recovery occurred. In diseases which influence the efficiency o f contractility advantageous and disadvantageous effects were seen. Thus, in surgically induced left ventricular hypertrophy hearts were less able to resume normal function whereas hearts from moderately hypertensive (spontaneous) rats exhibited better postischemic recoveries than hearts from normotensive controls. These results, together with known species differences in susceptibility to ischemic damage stress the difficulties o f extrapolating results obtained in a healthy rat heart to a diseased human heart.
METABOLIC, ELECTROPHYSIOLOGICAL A N D FLOW GRADIENTS WITHIN THE 'BORDER ZONE' DURING REGIONAL ISCHEM~A. D.J. Hearse, L.H. Opie and I. Katzeff*, The Myocardial Metabolism R e s e a r ~ Laboratories, The Rayne Institute, St. Thomas' Hospital, London, UK and *The Department of Medicine, University o f Cape Town, R.S.A. A multiple biopsy drill was used to retrieve simultaneously, and freeze within seconds, twenty-nine individual transmural samples from dog heart left ventricular wall (n = 9) 21-26 min after multiple coronary artery ligation. ATP, CP, glycogen, lactate, potassium, sodium and water were measured i n each sample and were individually related to the blood flow distribution (microspheres) at each sampling site and to the ST segment changes (recorded at up to i00 sites immediately prior to tissue sampling) at each sampling site. Two dimensional metabolic, electrical and flow maps were prepared for each heart and the existence, position and sharpness of the gradients for each parameter were defined in spatial relationship to the edge of the area of visible cyanosis. ATP, CP and lactate were constant until 2-3 mm from the edge of cyanosis. ATP and CP then fell sharply across a zone 8-15 mm wide spanning the visible edge. Across this zone lactate and ST rose sharply and flow fell to 20% of control. ATP, CP and lactate content closely correlated with changes in flow and ST. These studies confirm the existence o f a clearly defined border zone and would suggest that the movement o f gradients associated with this zone could markedly influence the extent of the ultimate infarct.
THE INFLUENCE OF DISEASE ON MYOCARDIAL SUSCEPTABILITY TO ISCHEMIC DAMAGE D.J. Hearse, D.A. Stewart and D.G. Green. T h e Myocardial Metabolism Laboratories, St. Thomas' Hospital, London, UK. Experimental studies of ischemic damage are often criticised as they are carried out using hearts from young, healthy animals and as such they may be o f little relevance to the diseased heart. A number o f models o f human disease states exist in the rat. Using an isolated perfused working rat heart we have assessed the extent to which diabetes, obesity, hypertrophy and hypertension can influence the susceptibility o f the myocardium to ischemic damage and to metabolic protection. Hearts from diseased rats were subjected to 70 min global ischemia; upon reperfusion the recovery of aortic flow, and pressure, dP/dt and heart rate were measured and compared with pre-ischemic control values and also with the recovery o f hearts from non-diseased control rats. In diseases, such as experimental diabetes or obesity, which influence the efficiency or adaptability of myocardial energy metabolism, a marked reduction in recovery occurred. In diseases which influence the efficiency o f contractility advantageous and disadvantageous effects were seen. Thus, in surgically induced left ventricular hypertrophy hearts were less able to resume normal function whereas hearts from moderately hypertensive (spontaneous) rats exhibited better postischemic recoveries than hearts from normotensive controls. These results, together with known species differences in susceptibility to ischemic damage stress the difficulties o f extrapolating results obtained in a healthy rat heart to a diseased human heart.
METABOLIC, ELECTROPHYSIOLOGICAL A N D FLOW GRADIENTS WITHIN THE 'BORDER ZONE' DURING REGIONAL ISCHEM~A. D.J. Hearse, L.H. Opie and I. Katzeff*, The Myocardial Metabolism R e s e a r ~ Laboratories, The Rayne Institute, St. Thomas' Hospital, London, UK and *The Department of Medicine, University o f Cape Town, R.S.A. A multiple biopsy drill was used to retrieve simultaneously, and freeze within seconds, twenty-nine individual transmural samples from dog heart left ventricular wall (n = 9) 21-26 min after multiple coronary artery ligation. ATP, CP, glycogen, lactate, potassium, sodium and water were measured i n each sample and were individually related to the blood flow distribution (microspheres) at each sampling site and to the ST segment changes (recorded at up to i00 sites immediately prior to tissue sampling) at each sampling site. Two dimensional metabolic, electrical and flow maps were prepared for each heart and the existence, position and sharpness of the gradients for each parameter were defined in spatial relationship to the edge of the area of visible cyanosis. ATP, CP and lactate were constant until 2-3 mm from the edge of cyanosis. ATP and CP then fell sharply across a zone 8-15 mm wide spanning the visible edge. Across this zone lactate and ST rose sharply and flow fell to 20% of control. ATP, CP and lactate content closely correlated with changes in flow and ST. These studies confirm the existence o f a clearly defined border zone and would suggest that the movement o f gradients associated with this zone could markedly influence the extent of the ultimate infarct.