Effect of adrenergic agonists on coronary blood flow: a laboratory study in healthy volunteers

Abstract

Myocardial oxygen supply and demand mismatch is fundamental to the pathophysiology of ischemia and infarction. The sympathetic nervous system, through α‐adrenergic receptors and β‐adrenergic receptors, influences both myocardial oxygen supply and demand. In animal models, mechanistic studies have established that adrenergic receptors contribute to coronary vascular tone. The purpose of this laboratory study was to noninvasively quantify coronary responses to adrenergic receptor stimulation in humans. Fourteen healthy volunteers (11 men and 3 women) performed isometric handgrip exercise to fatigue followed by intravenous infusion of isoproterenol. A subset of individuals also received infusions of phenylephrine (n = 6), terbutaline (n = 10), and epinephrine (n = 4); all dosages were based on fat‐free mass and were infused slowly to achieve steady‐state. The left anterior descending coronary artery was visualized using Doppler echocardiography. Beat‐by‐beat heart rate (HR), blood pressure (BP), peak diastolic coronary velocity (CBVpeak), and coronary velocity time integral were calculated. Data are presented as M ± SD. Isometric handgrip elicited significant increases in BP, HR, and CBVpeak (from 23.3 ± 5.3 to 34.5 ± 9.9 cm/sec). Isoproterenol raised HR and CBVpeak (from 22.6 ± 4.8 to 43.9 ± 12.4 cm/sec). Terbutaline and epinephrine evoked coronary hyperemia whereas phenylephrine did not significantly alter CBVpeak. Different indices of coronary hyperemia (changes in CBVpeak and velocity time integral) were significantly correlated (R = 0.803). The current data indicate that coronary hyperemia occurs in healthy humans in response to isometric handgrip exercise and low‐dose, steady‐state infusions of isoproterenol, terbutaline, and epinephrine. The contribution of β1 versus β2 receptors to coronary hyperemia remains to be determined. In this echocardiographic study, we demonstrate that coronary blood flow increases when β‐adrenergic receptors are stimulated (i.e., during exercise and different intravenous infusions). Our infusion paradigms and beat‐by‐beat imaging methodologies can be used in future studies to evaluate age‐, sex‐, and disease‐ differences in adrenergic control of coronary blood flow.

Influence of increased heart rate and aortic pressure on resting indices of functional coronary stenosis severity

“…Imposing controlled metabolic stressors elicited individual responses resulting in additional variability. Consistent with the previous findings in dogs [ 13 , 19 ] and humans [ 24 , 34 , 39 , 40 ], tachycardia increased oxygen consumption, inducing commensurate arteriolar vasodilation and a consequential increase in coronary flow velocity, while raising coronary distending pressure caused an increase of BMR as an autoregulatory response. Yet, one would expect some metabolic vasodilation because of increased cardiac afterload [ 2 ], which, however, was offset by reflex bradycardia, as reflected by the essentially unchanged RPP from control.…”

Esmolol infusion versus propranolol infusion: effects on heart rate and blood pressure in healthy volunteers

“…HR and BP were measured on a beat-by-beat basis. After 15 min of rest, another blood sample was obtained from the left arm; then an 18-min isoproterenol hydrochloride (0.2 mg in 700 ml of saline) infusion was administered in the right arm as previously described (53). Isoproterenol is a nonselective ␤-agonist that has been used previously to challenge ␤-blockade with esmolol and/or propranolol (37,38,42 for the remainder of the study.…”

Vasopressor-Induced Generalized Coronary Vasospasm Presenting as Inferior ST-Segment Elevation in Post-Cardiopulmonary Resuscitation

“…In our patient, the post-ROSC shock state required support with 3 vasopressors to maintain a MAP goal of >65 mm Hg. The overall effects of adrenergic vasopressors on the coronary arteries have usually been found to be vasodilatory and hyperemic in prior studies (7) . However, there have been case reports where the use of vasopressor support with adrenergic agents to correct hypotension occurring with anesthesia has been associated with coronary spasm (8) .…”