The Differential Hemodynamic Effects of Norepinephrine and Methoxamine in Systemic Hypotension Complicating Pulmonary Hypertension

Abstract

The authors investigated the acute cardiopulmonary effects of noradrenaline and methoxamine in a canine model in which systemic hypotension complicated an acute increase in pulmonary vascular resistance. In 13 anesthetized ventilated dogs, glass beads were injected to increase right ventricular afterload and to decrease mean blood pressure to approximately 65 mmHg. In the first 7 dogs, corresponding to the decrease in blood pressure, there was a marked fall in cardiac output, from 4.8 to 1 L/minute (P < 0.01). Subsequently, dogs were treated in sequence with norepinephrine and then with methoxamine. Both drugs caused a similar increase in mean blood pressure, from approximately 66 to 121 mmHg (both P < 0.001) and in right ventricular coronary perfusion pressure. However, only norepinephrine increased cardiac output. To determine whether the differential effects of these drugs on cardiac output was explained by differences in coronary artery flow, in a second group of 6 dogs, right coronary artery flow was measured before and after pulmonary embolization and during infusion of both drugs. Coronary artery flow decreased when blood pressure decreased with embolization. As above, while both drugs caused a similar increase in blood pressure and right ventricular coronary perfusion pressure, only norepinephrine increased cardiac output. Also, values for coronary artery blood flow were similar during infusion of both drugs. Most likely, the improvement in cardiac output with norepinephrine is explained by a direct inotropic effect of this agent.