The effect of adrenergic agonists on the systemic response to hemorrhage

Purpose: Systemic blood loss elicits a variety of reflex cardiovascular responses, which preserve cardiac out-put as possible and preserve arterial blood pressure when cardiac output decreases. When compensatory venoconstriction is exhausted, hemorrhage reduces oxygen delivery (Qo₂), and systemic vasoconstriction competes with local metabolic vasodilation to preserve tissue oxygen uptake (Vo₂). Through their effects on vascular tone and blood flow distribution, adrenergic agents might interfere with the physiological responses to reduced 0₂ delivery. This study was designed to determine the effects of dobutamine and norepinephrine on oxygen extraction and systemic vascular resistance during progressive hemorrhage. Methods: We infused dobutamine or norepinephrine into anesthetized, ventilated dogs and measured the systemic vascular resistance, oxygen consumption, and oxygen extraction ratio as oxygen delivery (blood flow) was reduced by blood withdrawal. Four groups were compared: control (saline), dobutamine (10 μg/ kg/min), high-dose norepinephrine (1.0 gg/kg/min), and low-dose norepinephrine (0.1 μg/kg/min). Results: High-dose norepinephrine increased oxygen demand but did not alter extraction significantly at the critical point. Neither low-dose norepinephrine nor dobutamine affected oxygen extraction during hemorrhage. Dobutamine and norepinephrine both ablated the increase in systemic vascular resistance that accompanies hemorrhage. Low-dose norepinephrine was not different from control. Conclusions: Norepinephrine and dobutamine appear to block reflex vasoconstriction, and mechanistic explanations for this finding remain speculative. Despite inhibition of reflex vasoconstriction, neither dobutamine nor norepinephrine significantly impaired oxygen extraction during hemorrhage.