Hemodynamic effects of intravenous prostacyclin in stable angina pectoris

Prostacyclin (PGI₂) is a naturally occurring vasodilator and inhibitor of platelet aggregation that produces vasodilatation of the systemic, pulmonary and coronary vascular beds in animal models. Because the endogenous production of PGI₂ is reduced in those with coronary arterial disease (CAD), it may have a therapeutic role in patients with ischemic heart disease. To assess its safety and efficacy in this clinical setting, 17 patients with stable angina and CAD received an incremental intravenous infusion of either PGI₂ (n = 10) to a maximum dose of 10 ng/kg/min (average 9.8 ± 0.8 [mean ± standard deviation]), or diluent buffer solution (placebo) (n = 7). All patients who received PGI₂ became flushed, but experienced no other adverse effects. PGI₂ caused an increase in heart rate (66 ± 11 to 80 ± 11 beats/min, p <0.001) and cardiac index (2.88 ± 0.65 to 3.97 ± 1.17 liters/min/m², p <0.001) and a decrease in mean femoral arterial pressure (96 ± 18 to 86 ± 11 mm Hg, p <0.001), but no change in mean pulmonary arterial or capillary wedge pressure. Total systemic and pulmonary vascular resistance decreased significantly (p <0.001). In response to PGI₂, mean coronary sinus blood flow did not change significantly (100 ± 40 to 121 ± 52 ml/min), but coronary vascular resistance decreased (1.07 ± 0.40 to 0.83 ± 0.36 U, p <0.001). No variable was altered by placebo infusion. PGI₂ caused a marked increase in 6-keto PGF_1α (the stable metabolite of PGI₂) concentrations in both arterial (42 ± 29 to 567 ± 216 pg/ml, p <0.001) and venous (46 ± 31 to 604 ± 229 pg/ml, p <0.001) blood but no demonstrable change in plasma renin activity. Thus, intravenous PGI₂ to a dosage of 10 ng/kg/min is a safe and effective systemic, pulmonary and coronary arterial vasodilator in patients with CAD and stable angina pectoris.