Metabolic aspects of rhythm disturbances

[Profound alterations in metabolism occur within the first few minutes of myocardial ischaemia which may induce or modulate myocardial electrophysiological abnormalities and arrhythmogenesis, Fatty acid oxidation is inhibited with accumulation of long-chain acyl CoA esters and glycolysis is stimulated but later inhibited. This may be worsened by a peripheral sympathetic response. In particular regional variations in glycolytic ATP productions which can modulate "slow channel" ion flux and hence slow conducting "slow response" potential activity, could influence patterns of slow conduction in ischaemic myocardium of importance in generating early re-entrant arrhythmias. This possibility has been examined in open chest anaesthetised dogs following experimental coronary occlusion by detailed computer aided analysis and construction of three dimensional maps of regional metabolism, blood flow and epicardial activation patterns at the time of early ventricular arrhythmias. Activation patterns were obtained using an electronic multiplexing system, flow using tracer microspheres and metabolic changes by analysis of multiple tissue samples for lactate and indices of glycolytic activity after rapid excision and freezing of the heart. Marked spacial inhomogeneities in flow, lactate and glycolytic activity were associated with delayed and fragmented activation in the central ischaemic region. Within the border region of flow, however, glycolytic activity was enhanced and conduction generally little impaired. It is suggested that transient changes in the homogeneity of myocardial metabolism and flow are critical in determining patterns of conduction and hence arrhythmogenesis. This may provide a basis for understanding anti-arrhythmic effects of metabolic interventions.