Abstract
We evaluated the coronary vasoconstrictory action of intracoronary (i.c.) leukotriene D4 (LTD4) in anesthetized mongrel dogs (n=20) . Coronary blood flow (CBF), coronary arterial pressure (CAP), left ventricular enddiastolic pressure (LVEDP), aortic flow (AoF), coronary vascular resistance (CVR), and ST deviation on epicardial ECG were measured. Coronary sinus blood samplings were obtained in order to determine the influence of LTD4 on prostanoids metabolism. In addition, to calarify whether the vasoconstrictory action of LTD4 is primary or mediated by thromboxane A2 (TXA2), LTD4 were administered after intravenous infusion of OKY-046 (a selective TXA2 synthetase inhibitor) . Furthermore, to confirm the LTD4-induced coronary spasm, coronary angiography (CAG) was performed. In results, LTD4 0.33μg i.c. administration caused a significant reduction of CBF (from 0.85±0.05 to 0.66±0.06ml/kg/min. mean±SEM, P<0.01) and a significant elevation of CVR (from 4.7±0.4 to 7.3±0.9×103 dynes⋅sec⋅cm-5, P<0.05) concomitant with a marked elevation of ST segment on epicardial ECG (peak voltage 1.8±0.2mv, duration time 46±6sec) . LVEDP elevated significantly (from 8.7±0.6 to 9.7±0.7 mmHg, P<0.01), meanwhile, AoF and coronary sinus thromboxane B2 (TXB2) level were not changed. OKY-046 did not influence these changes induced by LTD4. Furthermore, LTD4-induced coronary spasm was directly documented by CAG. It was concluded that the coronary vasoconstrictory action of LTD4 is independent of TXA2 and may play an important role in the pathogenesis of coronary spasm and ischemic heart disease.
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