Key result
Activation of pyruvate dehydrogenase by dichloroacetate reduced epicardial ST-segment elevations (-42%) and myocardial release of potassium (-36%), phosphate (-58%), and lactate (-39%).
Why the study?
Do metabolic interventions that stimulate oxidative myocardial carbohydrate metabolism reduce ischemic stress during repeated coronary occlusions in a canine model?
Do metabolic interventions that stimulate oxidative myocardial carbohydrate metabolism reduce ischemic stress during repeated coronary occlusions in a canine model?
In a canine model of myocardial ischemia, dichloroacetate reduced ischemic stress, suggesting that metabolic interventions are beneficial only when systemic hyperosmolality and hypervolemia are avoided.
Answers are grounded in this paper and cite their sources.
No benefit from GIK on ischemic damage in canine models; leaves open metabolic modulation for human ischemia.
We studied the effects of different metabolic interventions, which stimulate oxidative myocardial carbohydrate metabolism, on ischemic stress during repeated coronary occlusions of three minutes in open-chest dog hearts. Increase of glucose concentration in plasma and decrease of peripheral lipolysis by glucose-insulin-potassium (n = 6) had no substantial beneficial effects on myocardial damage indicated by hemodynamic, electrocardiographic, and metabolic parameters. Infusion of lactate and pyruvate (10 mM, n = 6) was detrimental. Only activation of pyruvate dehydrogenase by dichloroacetate (n = 6) without influence on plasma osmolality reduced epicardial ST-segment elevations (-42%) and myocardial release of potassium (-36%), phosphate (-58%), and lactate (-39%). Elevations of plasma osmolalities by 10 and 20 mOsm with the metabolically inert mannitol increased ECG changes, functional loss and release of potassium, phosphate, and lactate during ischemia in our model. It is suggested, that the oxygen-saving potency of metabolic interventions can exert univocal beneficial effects in experimental and in clinical conditions only when systemic hyperosmolality and hypervolemia are avoided.
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Kahles et al. (1984) studied Myocardial ischemia. Metabolic interventions (dichloroacetate, glucose-insulin-potassium, lactate/pyruvate) was evaluated on Myocardial damage indicated by hemodynamic, electrocardiographic, and metabolic parameters. Activation of pyruvate dehydrogenase by dichloroacetate reduced epicardial ST-segment elevations (-42%) and myocardial release of potassium (-36%), phosphate (-58%), and lactate (-39%).
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