A model for the generation of spontaneous yet predictable ventricular arrhythmias

Development of an experimental preparation aided to investigate arrhythmogenic and antiarrhythmogenic factors influencing incidence of spontaneous and yet predictable ventricular arrhythmias is described. Using the isolated perfused guinea-pig heart and a system for quantitating rhythm disturbances based on computer-aided statistical analysis of beat-to-beat intervals, a number of factors influencing the incidence of rhythm disturbances were investigated. Manipulation of perfusate composition revealed that, after 'moderate' ischaemia, reperfusion arrhythmias were increased in the presence of noradrenaline and non-glucose fuels. Free fatty acids, unless in the presence of catecholamines, were not particularly arrhythmogenic. In contrast, the presence of pyruvate or lactate, endproduct inhibitors of glycolysis, significantly increased incidence of reflow rhythm disturbances. The dose-dependent arrhythmogenic effects of pyruvate and anti-arrhythmogenic effects of glucose support the thesis that inadequate glycolytic flux could be important in the development of arrhythmias.