The well-documented morning increase in myocardial infarction, sudden cardiac death, and other cardiovascular disorders provides a new opportunity to identify the causes of disease onset. In this issue of Circulation, Middlekauff and Sontz 1 report on efforts to determine whether the sympathetic nervous system is responsible for the increase in disease onset in the morning. They have picked a prime candidate for a causal role, because (1) events associated with increased sympathetic discharge, such as heavy exertion, have been shown to trigger infarction onset 2;(2) morning is a time associated with a transition from low to high sympathetic activity 3; and (3) both observational and randomized studies have demonstrated elimination of the morning peak of disease onset in individuals receiving β-adrenergic blocking agents. 4 5

Middlekauff and Sontz directly measured firing rates of sympathetic nerves to skeletal muscle at rest and during stress in the morning and afternoon. The study was conducted in eight healthy subjects who had spent the previous night in the Clinical Research Center. The morning measurements (obtained between 6: 30 and 8: 30 am) were compared with afternoon measurements (obtained between 2 and 4 pm). After basal levels were recorded, lower-body negative pressure was applied (to simulate the stress of assuming the upright posture), and a handgrip exercise was performed. The study convincingly demonstrates that, under these experimental conditions and in these supine subjects, there is no difference in basal or stressed sympathetic firing rate to skeletal muscles in morning versus afternoon testing.