Responses of plasma eicosanoids and hemodynamics to myocardial ischemia and the salutary effect of calcium entry blocker.
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The responses of eicosanoids to acute myocardial ischemia induced by either exercise stress testing (EX)or percutaneous transluminal coronary angioplasty (PTCA) were investigated in 23 patients with effort angina pectoris (EAP). EX was useful procedure to determine the therapeutic plan in each cases, and PTCA is the novel therapeutic operation for EAP. The relations between these metabolites and either hemodynamics or coronary circulation were then evaluated. The effect of the calcium entry blocker nisoldipine (oral administration of 5 mg) was also studied in 10 patients with EAP. The plasma levels of thromboxane B<SUB>2</SUB> (TXB<SUB>2</SUB>), 6-keto-prostaglandin F<SUB>1α</SUB>. (6KPGF<SUB>1α</SUB>) and leukotriene C<SUB>4</SUB> (LTC<SUB>4</SUB>) were determined by radioimmunoassay in arterial and coronary sinus blood samples before and immediately after acute myocardial ischemia. The changes in hemodynamics and coronary circulation during exercise stress testing were assessed by measuring direct brachial artery pressure, cardiac output by the dye dilution method and coronary sinus flow by the thermodilution method.<BR>The TXB<SUB>2</SUB>/6KPGF<SUB>1α</SUB> ratio in coronary sinus blood significantly increased after ischemia in both EX and PTCA, but there was no significant change in LTC<SUB>4</SUB> levels of coronary sinus blood immediately after acute ischemia. The 6KPGF<SUB>1α</SUB> levels in both arterial and coronary venous blood were significantly correlated to coronary perfusion pressure and mean brachial artery pressure. Arterial LTC<SUB>4</SUB> levels tended to correlate to mean brachial artery pressure and coronary sinus flow. Nisoldipine improved the ischemic electrocardiography response to EX. Nisoldipine also significantly increased arterial 6KPGF<SUB>1α</SUB> at peak exercise. It significantly decreased brachial artery pressure, pressure rate product (PRP), mean coronary sinus pressure and coronary vascular resistance both at rest and peak exercise. The response of PRP significantly correlated with the response of arterial 6KPGF<SUB>1α</SUB>.<BR>These results suggest: (1) The imbalance of the TXB<SUB>2</SUB>/6KPGF<SUB>1α</SUB> ratio may be induced more rapidly than LTC<SUB>4</SUB> (2) PGI<SUB>2</SUB> and LTC<SUB>4</SUB> may have some role in the regulation of hemodynamics and coronary circulation during acute myocardial ischemia. (3) Nisoldipine may ameliorate myocardial ischemia through improvement of systemic hemodynamics and prostaglandin metabolism apart from through direct action on the heart.
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