Effects of sustained leukotriene D₄ administration of myocardial contractility and coronary flow

Intracoronary bolus administration of cysteinyl leukotrienes cause profound decrease in myocardial contractility and coronary flow along with ventricular arrhythmias and electrocardiographic signs of ischemia. Such findings suggest that these leukotrienes might participate, in pathophysiologic processes affecting the likely to be more prolonged than bolus administration. To explore the consequences of sustained leukotriene exposure, we infused leukotriene D₄ (LTD₄) into the left anterior descending (LAD) coronary arteries of anethetized, open-chest domestic pigs. LAD coronary flow (CF) was measured with a circumferential electromagnetic flow probe. Contractile function was evaluated in myocardium perfused via the LAD using implanted ultrasound dimension gauges that measured regional shortening fractiopn (SF). Mean results (±SE) were: {A table is presented}{A table is presented}. In summary, LDT₄ infusions induced dose-dependent reductions in both cyocardial contracilityand CF that "escaped" within 2-4 min despite continuing LTD₄ administration. Escape was nearly complete for CF. Incomplete escape of contractility (SF) may reflect residual effects of transiently severe flow deprivation, contractile response to persistent but minor perfusion deficits, or a component of the depressant action of LTD₄ that is not related to flow and dose not escape. Escape of CF and SF was absent in a small fraction of pigs ( 4 40) receiving intracoronary LTD₄. Marked hypotension developed rapidly in these 4 pigs. Severe, persistent fall in CF and SF and the development of ventricular arrhythmias led to death in ventricular fibrillation 4-6 min after initiating LTD₄ infusion. Thus, intracoronary LTD₄ can have lethal cardiac effects in a small group of susceptibles even though its sustained actions are very modest in the great majority of individuals, who manage to escape from LTD₄ influence.