Effect of diabetic ketosis on enzyme release from isolated perfused rat hearts with experimental myocardial infarction

Coronary ligated rat hearts from ketotic or nonketotic alloxan diabetic rats were perfused via the left atrium using one of the following substrates: 11 mm glucose, 10 mm dl-β-hydroxybutyrate (β-OHB), or 0.9 mm palmitate bound to 0.25 mm albumin (FFA). A series of normal non-diabetic hearts was similarly perfused. Release of lactate dehydrogenase (LDH) was taken as an index of ischaemic damage. In perfusions with 11 mm glucose, release of LDH from hearts from non-ketotic diabetic rats was 60±6 mu/g/min and 147±27 mu/g/min in hearts from ketotic rats (P < 0.005 vs non-ketotic). In perfusions with β-OHB, release of LDH from hearts from normal rats was 279±28 mu/g/min compared with 127±8 mu/g/min in perfusions with glucose (P ≪ 0.001). LDH release rose further in hearts from ketotic rats perfused with β-OHB (526±38). In perfusions with FFA, LDH release from hearts from normal rats was 295±26 mu/g/min per 60 min and 344±26 mu/g/min per 90 min; these values rose to 683±67 mu/g/min and 782±59 mu/g/min (P < 10-6) respectively in hearts from ketotic rats. In hearts perfused with β-OHB, the addition of insulin (2 mu/ml) diminished enzyme release after coronary ligation. A blood ketone lowering agent, tizoprolic acid (n-propyl-2-thiazole carboxylic-5 acid, RU 15350, Roussel) decreased enzyme release nearly as much as did insulin. Effects of substrates on the mechanical performance of the heart, as assessed by the cardiac output and heart rate, could not explain the effects of the ketotic states nor of the addition of insulin to the perfusate nor the effects of pretreatment with tizoprolic acid. We conclude that the rate of release of lactate dehydrogenase from the ischaemic myocardium is exaggerated by acute diabetic ketosis, and that the factors concerned include increased circulating concentrations of β-OHB and FFA, as well as insulin deficiency. © 1978.