Beta - adrenergic blockade enhances coronary 2 vasoconstrictor response to forehead cooling 3 4 Matthew

25 Forehead cooling activates the sympathetic nervous system and can trigger 26 angina pectoris in susceptible individuals. However, the effect of forehead cooling on 27 coronary blood flow velocity (CBV) is not well understood. In this human experiment, we 28 tested the hypotheses 1) that forehead cooling reduces CBV (i.e., coronary 29 vasoconstriction); and 2) this vasoconstrictor effect would be enhanced under systemic 30 beta-adrenergic blockade. A total of 30 healthy subjects (age range 23-79 years) 31 underwent Doppler echocardiography evaluation of CBV in response to 60 seconds of 32 forehead cooling (1°C ice bag on forehead). A subset of subjects (n = 10) also underwent 33 the procedures following an intravenous infusion of propranolol. Rate pressure product 34 (RPP) was used as an index of myocardial oxygen demand. Consistent with our first 35 hypothesis, forehead cooling reduced CBV from 19.5 ± 0.7 to 17.5 ± 0.8 cm/sec (P < 36 0.001) while MAP increased by 11 ± 2 mmHg (P < 0.001). Consistent with our second 37 hypothesis, forehead cooling reduced CBV under propranolol despite a significant rise in 38 RPP. The current studies indicate that forehead cooling elicits a sympathetically-mediated 39 pressor response and a reduction in CBV and this effect is augmented under beta40 blockade. The results are consistent with sympathetic activation of beta-receptor coronary 41 vasodilation in humans, as has been demonstrated in animals. 42