Leukotrienes are potent vasoconstrictors that contribute to myocardial infarction and reperfusion injury. This study was performed to determine the site of action of leukotrienes in the canine coronary circulation.
We examined the effects on coronary blood flow (CBF) of intracoronary leukotriene infusion before and after balloon catheter-induced endothelial damage of the proximal left anterior descending artery (LAD). Quantitative angiography of large coronary artery dimensions and 133Xe measurements of CBF were obtained in closed-chest dogs following leukotriene C4 or leukotriene D4 infusion (n=8), subsequent endothelial damage, and repeat leukotriene infusion.
CBF declined 49% (P < 0.02) following intracoronary infusion of leukotriene C4 or leukotriene D4 (4 μg/min), accompanied by a 43% increase in coronary vascular resistance. However, there was no significant change in proximal LAD diameter associated with this peripheral vasoconstriction. After endothelial damage, intracoronary infusion of leukotrienes resulted in a 66% decline in CBF, a value significantly greater than that produced by leukotriene infusion with intact endothelium (P < 0.05). There were no changes in proximal coronary dimensions after endothelial damage and subsequent intracoronary leukotriene infusion.
Leukotriene-mediated coronary vasoconstriction occurs only at the microvascular level. Endothelial damage followed by leukotriene infusion results in a further reduction of CBF, without change in proximal coronary dimensions. Leukotrienes may contribute to distal coronary vasoconstriction in the setting of proximal coronary arterial injury.
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