Adrenergic blockade reduces skeletal muscle glycolysis and Na+, K+-ATPase activity during hemorrhage

Background. Recent evidence suggests that hyperlactatemia in shock may refl ect accelerated aerobic glycolysis linked to activity of the Na+, K+-ATPase rather than hypoxia. Epinephrine stimulates glycolysis in resting muscle l argely by stimulating Na+, K+-ATPase activity. This study evaluates the eff ects of hemorrhagic shock, with and without combined alpha- and beta -adren ergic receptor blockade, on lactate production, glycogenolysis, Na+-K+ pump activity, and high-energy phosphates in rat skeletal muscle. Methods. Male Sprague-Dawley rats in four treatment groups were studied: un hemorrhaged control not receiving blockers (CN), controls receiving blocker s (CB), shocked animals not receiving blockers (SN), and shocked rats recei ving blockers (SB). Shocked rats (SN and SB) were bled to a MAP of 40 mm Hg , maintained for 60 min. Blocker groups (CE and SB) received propranolol an d phenoxybenzamine. Arterial blood was drawn for plasma lactate, epinephrin e, norepinephrine, and gas analysis. Lactate, glycogen, glucose 6-phosphate , ATP, phosphocreatine, and intracellular Na+ and K+ were determined in ext ensor digitorum longus and soleus muscles. For comparison, muscles were exp osed to epinephrine and/or ouabain in vitro. Results. With the exception of PaCO2, HCO3, and base excess in the SN group , no significant differences in arterial blood gas parameters were noted. A drenergic blockade significantly reduced plasma lactate concentration. In s hocked rats, adrenergic blockade significantly reduced muscle lactate and g lucose 6-phosphate accumulation. Intracellular Na+:K+ ratio was decreased i n SN rats, implying increased Na+-K+ pump activity. Adrenergic blockade rai sed the intracellular Na+:K+ ratio in shocked animals, implying decreased p ump activity. Epinephrine exposure in vitro stimulated muscle lactate produ ction, raised glucose 6-phosphate content, and significantly reduced soleus phosphocreatine stores. Conclusions. Neither hypoxia nor defective oxidative metabolism appeared re sponsible for increased glycolysis during hemorrhagic shock. Adrenergic blo ckade concurrently reduced plasma lactate, muscle levels of lactate and glu cose 6-phosphate, and muscle Na+-K+ pump activity during shock. Rapid skele tal muscle aerobic glycolysis in response to increased plasma epinephrine l evels may be an important contributor to increased glycolysis in muscle and increased plasma lactate during hemorrhagic shock. (C) 2001 Academic Press .