title: Intravenous phentolamine abolishes coronary vasoconstriction in response to mild central hypovolemia.
abstract: Animal studies indicate alpha-adrenergic coronary vasoconstriction helps maintain left ventricular function during physiological stress. Whether this process occurs in humans is unknown. In the current study, we used transthoracic Doppler echocardiography to test the effect of lower body negative pressure (LBNP) on coronary blood flow velocity (CBV, left anterior descending coronary artery) and myocardial function in eight young healthy subjects before and after systemic infusion of phentolamine, a nonselective alpha blocker. Heart rate (HR) and blood pressure (BP) were monitored on a beat-by-beat basis. Peak diastolic CBV and myocardial systolic and diastolic tissue velocities (Sm and Em), were quantified at baseline, and at -5 mmHg, -10 mmHg, and -15 mmHg LBNP. Coronary vascular resistance index (CVRI) was calculated as the quotient of diastolic BP and CBV. Phentolamine reduced baseline diastolic BP and increased HR but did not affect the reflex adjustments to LBNP. The reduction in CBV due to LBNP was blunted by phentolamine at -10 mmHg and -15 mmHg. Importantly, the increase in CVRI (i.e., coronary vasoconstriction) was abolished by phentolamine at -5 mmHg (0.21 ± 0.06 vs. 0.83 ± 0.13), -10 mmHg (0.24 ± 0.03 vs. 1.68 ± 0.31), and -15 mmHg (0.27 ± 0.10 vs. 2.34 ± 0.43). These data indicate that alpha-adrenergic coronary vasoconstriction is present during low levels of LBNP. With alpha blockade, more coronary flow is needed to maintain cardiac function. Our data suggest that alpha-adrenergic tone enhances coronary flow efficiency, presumably by redistributing flow from the epicardium to the endocardium.
authors: Penn State Hershey Heart and Vascular Institute, The Pennsylvania State University College of Medicine, The Milton S. Hershey Medical Center, Hershey, Pennsylvania.
authors: Zhaohui
authors: Z
authors: Gao
authors: Matthew D
authors: MD
authors: Muller
authors: Lawrence I
authors: LI
authors: Sinoway
authors: Urs A
authors: UA
authors: Leuenberger
mesh_terms: D000317:Adrenergic alpha-Antagonists / Q000008:administration & dosage*; D000328:Adult; D001783:Blood Flow Velocity / Q000187:drug effects / Q000502:physiology; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D003331:Coronary Vessels / Q000187:drug effects* / Q000502:physiology; D018592:Cross-Over Studies; D005260:Female; D006321:Heart / Q000187:drug effects* / Q000503:physiopathology; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D006801:Humans; D020896:Hypovolemia / Q000188:drug therapy* / Q000503:physiopathology; D008150:Lower Body Negative Pressure / Q000379:methods; D008297:Male; D010646:Phentolamine / Q000008:administration & dosage*; D012018:Reflex / Q000187:drug effects / Q000502:physiology; D012039:Regional Blood Flow / Q000187:drug effects / Q000502:physiology; D014655:Vascular Resistance / Q000187:drug effects / Q000502:physiology; D014661:Vasoconstriction / Q000187:drug effects* / Q000502:physiology
chemical_list: D000317:Adrenergic alpha-Antagonists; D010646:Phentolamine
keywords: Doppler echocardiography; left ventricular function; sympathetic nervous system