Coronary responses to cold air inhalation following afferent and efferent blockade

Abstract

Cardiac ischemia and angina pectoris are commonly experienced during exertion in a cold environment. In the current study we tested the hypotheses that oropharyngeal afferent blockade (i.e., local anesthesia of the upper airway with lidocaine) as well as systemic β-adrenergic receptor blockade (i.e., intravenous propranolol) would improve the balance between myocardial oxygen supply and demand in response to the combined stimulus of cold air inhalation (-15 to -30°C) and isometric handgrip exercise (Cold + Grip). Young healthy subjects underwent Cold + Grip following lidocaine, propranolol, and control (no drug). Heart rate, blood pressure, and coronary blood flow velocity (CBV, from Doppler echocardiography) were continuously measured. Rate-pressure product (RPP) was calculated, and changes from baseline were compared between treatments. The change in RPP at the end of Cold + Grip was not different between lidocaine (2,441 ± 376) and control conditions (3,159 ± 626); CBV responses were also not different between treatments. With propranolol, heart rate (8 ± 1 vs. 14 ± 3 beats/min) and RPP responses to Cold + Grip were significantly attenuated. However, at peak exercise propranolol also resulted in a smaller ΔCBV (1.4 ± 0.8 vs. 5.3 ± 1.4 cm/s, P = 0.035), such that the relationship between coronary flow and cardiac metabolism was impaired under propranolol (0.43 ± 0.37 vs. 2.1 ± 0.63 arbitrary units). These data suggest that cold air breathing and isometric exercise significantly influence efferent control of coronary blood flow. Additionally, β-adrenergic vasodilation may play a significant role in coronary regulation during exercise.

Keywords: blood pressure; heart rate; lidocaine; oropharynx; propranolol; vascular resistance.

Fig. 1.

Experimental timeline. For both experiments, control trials (without drug) were performed on separate days. For experiment 1, the absence of the gag reflex following tactile stimulation of the oropharynx confirmed that afferent blockade was effective. For experiment 2, the absence of tachycardia in response to intravenous isoproterenol confirmed that efferent blockade was effective. Please see main text for details.

Fig. 2.

Hemodynamic and coronary response to experiment 1 (n = 9). Lidocaine trials (dashed line with white diamonds) and control trials (solid line with black squares) were performed on separate days. In response to the Cold + Grip protocol, lidocaine had no effect on mean arterial pressure (MAP), heart rate [HR, in bpm (beats/min)], rate-pressure product (RPP), or coronary blood flow velocity (CBV). Data are means ± SE.

Fig. 3.

Hemodynamic and coronary response to experiment 2 (n = 8). Propranolol trials (dashed line with white diamonds) and control trials (solid line with black squares) were performed on separate days. In response to the Cold + Grip protocol, propranolol had no effect on MAP but lowered the HR and RPP response compared with control. Propranolol also impaired the coronary vasodilator response at peak exercise (i.e., the change in CBV was significantly less with propranolol than control). Data are means ± SE. *Difference between treatments at the specific time point.

Fig. 4.

A: individual coronary O₂ demand (RPP, x-axis) and coronary O₂ supply (CBV, y-axis) are displayed for experiment 2. The arrows point from baseline to the peak of handgrip exercise; bold lines represent group averages. Note that the slopes of the control trials are significantly more steep (more coronary hyperemia) than the slopes of the propranolol trials (2.1 ± 0.63 vs. 0.43 ± 0.37 arbitrary units, P = 0.041). B: mean changes in RPP and CBV in response to Cold + Grip protocol. *Difference between treatments.