The wisdom of the body revisited: The adrenomedullary response to mild core hypothermia in humans

Objective. In the 1920s, Walter B. Cannon first described the adrenomedullary response to cold, using an ingenious in vivo bioassay based on a denervated heart preparation. Studies in humans about antecubital venous plasma concentrations of norepinephrine, the sympathetic neurotransmitter, and of epinephrine, the main adrenomedullary hormone, have suggested sympathetic nervous system activation without adrenomedullary activation. The present study used arterial levels of these catecholamines, to determine whether adrenomedullary stimulation occurs in response to decreased body temperature. Methods. Eleven healthy volunteers underwent central intravenous infusion of warm (37°C) physiological saline, followed by infusion of the same volume of cold (4°C) saline. Brachial arterial and antecubital venous plasma concentrations of norepinephrine and epinephrine were measured by liquid chromatoraphy with electrochemical detection. Results. Antecubital venous concentrations of norepinephrine increased markedly during cold saline infusion, with smaller and statistically borderline increases in concentrations of epinephrine. In contrast, concurrently obtained arterial concentrations of both norepinephrine and epinephrine increased significantly. Conclusions. The results confirm Cannon's original inference that cold evokes adrenomedullary activation. Prior studies about antecubital venous levels of catecholamines did not take into account the local hemodynamic effects of cold, which would increase extraction of circulating catecholamines and underestimate the arterial epinephrine response.