Hemorrhagic shock is associated with lactic acidosis and increased plasma catecholamines. Skeletal muscle increases lactate production under aerobic conditions in response to epinephrine, and this effect is blocked by ouabain, a specific inhibitor of the cell membrane Na+/K+
pump. In this study, we tested whether adrenergic antagonists can block lactate production during shock.
Male Sprague-Dawley rats (250-300 g) were pretreated with phenoxybenzamine (2 mg/kg, IV) and/or propranolol (0.5 mg/kg, IP) before hemorrhaging to a mean arterial pressure of 40 mm Hg for 1 hour. Skeletal muscle perfusion, plasma lactate, and catecholamines were measured at baseline, 55 minutes after shock, and 1 hour after resuscitation. In a separate study, extensor digitorum longus and soleus muscles were incubated in Krebs buffer (95:5, O2
) with 10 mmol/L glucose. One of each muscle pair was incubated in the absence or presence of epinephrine and of one or both adrenergic blockers. Medium lactate concentration was then measured.
The combination of alpha-and beta-blockers significantly reduced plasma lactate levels during hemorrhage. In contrast, beta-blockade alone was associated with a significant increase in plasma lactate and epinephrine. None of the blockers altered tissue perfusion. Epinephrine stimulation of muscle lactate production in vitro was completely blocked by propranolol.
Epinephrine release in response to hypotension is a primary stimulus for muscle lactate production in this model of hemorrhagic shock. Hypoxia alone does not explain the increased lactate levels because tissue perfusion was not altered by the adrenergic antagonists. These observations challenge the rationale behind lactate clearance as an end point for resuscitation after hemorrhagic shock.