Circulatory effects of tolazoline and prostacyclin (PGI2) in chronically instrumented lambs

We used chronically instrumented, unanesthetized lambs to study the circulatory response to tolazoline and prostacyclin. During normoxia, tolazoline given in ten incremental doses from .01 to 6 mg/kg increased heart rate beginning at 1.1 mg/kg, cardiac output, and PVR/SVR. Systemic vascular resistance (SVR) fell, and pulmonary vascular resistance (PVR) did not change. Tolazoline given during hypoxemia, when basal PVR and heart rate were increased, caused SVR to fall at both 3.3 and 6.6 mg/kg doses, while PVR fell only at 6.6 mg/kg. During hypoxemia, even .01 mg/kg of tolazoline caused tachycardia, but cardiac output rose insignificantly, due to high variability. Prostacyclin given during normoxia caused SVR to fall without change in PVR. A significantly greater fall in SVR occurred when 6.6 micrograms/kg of PGI2 was the first dose given than when the same dose was given later in an incremental titration. Thus, neither drug is a selective pulmonary vasodilator in unanesthetized lambs. Dosing protocol may be important in determining the overall circulatory response to a given drug dose.