The metabolic processes which may be involved in damage to ischaemic tissue have been studied in a recirculating Langendorff perfused rat heart model. Hearts perfused at a low-flow rate of 4 ml/min showed increased carbohydrate utilisation compared with high-flow controls. This was evidence of mild ischaemia. In such low-flow hearts adrenaline challenge stimulated oxygen extraction and lipid and carbohydrate oxidation. The incidence of arrhythmias increased and resting tension rose. Tissue ATP was lower and long chain acyl CoA and lactate higher than in adequately oxygenated hearts. Hearts from rats fed a saturated fat enriched diet oxidised more lipid and less carbohydrate. After adrenaline at the low-flow they were more arrhythmic and developed more contracture than the normally-fed hearts; tissue long chain acyl CoA was higher and lactate and ATP lower. Thus long chain acyl CoA appeared to be more closely related to the process of deterioration than lactate in this model. Tissue lactate may have been a reflection of the degree of carbohydrate oxidation. Antilipolytic agents dichloroacetate and 2-bromopalmitate increased carbohydrate oxidation and anaerobic glycolysis after adrenaline in both types of heart. These effects were accompanied by amelioration in the incidence of arrhythmias and in resting tension rise. Perfusion of hearts at low flow with pyruvate as sole substrate caused a large increase in arrhythmic activity and a rise in resting tension. This is proposed to be due to the inability of these hearts to generate glycolytic ATP, since oxidative metabolism was unimpaired. The large increase in arrhythmias supports the proposed role for glycolytic ATP in maintenance of membrane function. Thus glycolytic ATP in addition to increased carbohydrate oxidation produced marked ameliorations in this model.
|Date of Award||1980|