Effects of myocardial alpha 1-adrenergic receptor stimulation and blockade on contractility in humans.
BACKGROUND
Although alpha-adrenergic receptors are present in both normal and failing human left ventricular myocardium and mediate a positive inotropic effect in several other species, it is not known whether stimulation of myocardial alpha-adrenergic receptors exerts a positive inotropic effect or contributes to basal contractile state in vivo in humans.


RESULTS
We studied 15 patients with angiographically normal coronary arteries (seven with normal left ventricular function and eight with left ventricular failure). To avoid the confounding effects of changes in ventricular loading conditions and systemic reflex mechanisms, the alpha-adrenergic receptor-selective antagonist phentolamine and agonist phenylephrine were infused directly into the left main coronary artery, and the change in contractile state was assessed by measuring left ventricular peak (+)dP/dt. Phentolamine alone had no effect on left ventricular contractility. Phenylephrine exerted a concentration-related positive inotropic effect in patients with normal as well as those with failing ventricles. The alpha-adrenergic effect of phenylephrine, defined as the component blocked by phentolamine, was significantly less in patients with ventricular failure (108 +/- 28 mm Hg/sec) than in normal subjects (248 +/- 54 mm Hg/sec; p less than 0.03).


CONCLUSIONS
Myocardial alpha-adrenergic receptors do not contribute to the maintenance of basal left ventricular contractile state in humans. However, stimulation of myocardial alpha-adrenergic receptors exerts a positive inotropic effect, the magnitude of which may be attenuated in patients with heart failure.
Landzberg
J S
JS
Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115.
Parker
J D
JD
Gauthier
D F
DF
Colucci
W S
WS
D000328:Adult; D005260:Female; D006333:Heart Failure / Q000503:physiopathology*; D006801:Humans; D007261:Infusions, Intra-Arterial; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects* / Q000502:physiology; D010646:Phentolamine / Q000494:pharmacology*; D010656:Phenylephrine / Q000494:pharmacology*; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects / Q000502:physiology*; D013268:Stimulation, Chemical; D016277:Ventricular Function, Left / Q000502:physiology
D011942:Receptors, Adrenergic, alpha; D010656:Phenylephrine; D010646:Phentolamine