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(Circulation. 1995;92:1678-1679.)
© 1995 American Heart Association, Inc.

Articles

`A Riddle Wrapped in a Mystery Inside an Enigma'

Winston S. Churchill, October 1, 1939

Gary L. Stiles, MD

From Duke University Medical Center, Durham, NC.

Correspondence to Gary L. Stiles, MD, Division of Cardiology, Duke University Medical Center, Box 3444, Durham, NC 27710.

Key Words: Editorials • heart failure • receptors • adrenergic • alpha

	Introduction

 
For the most part, the basic pathophysiological mechanisms involved in the perpetuation and exacerbation of congestive heart failure, as Churchill's quote aptly suggests, remain unknown. Why certain groups of patients do "relatively" well and others progress quickly is only beginning to be understood. The article by Parker et al¹ in this issue of Circulation brings to the fore an important component of the autonomic nervous system, the presynaptic nerve terminal, which may well impact on the function of the heart in patients with congestive heart failure and thereby influence morbidity and mortality. The intriguing finding is that nonselective blockade of -adrenergic receptors (ARs) in the heart (selective injection of phentolamine into the left main coronary artery) leads to an increased level of norepinephrine (NE) in the coronary sinus associated with an increase in left ventricular contractility. These changes occur only in patients with congestive heart failure, not in patients with normal left ventricular function. The proposed mechanism for this is that presynaptic ₂-ARs are being blocked, leading to enhanced NE release, and that "basal" release of NE is abnormally high in patients with congestive heart failure.

The role of ARs in modulating cardiac function has long been recognized. Classically, ß-ARs have been documented to increase contractility, heart rate, electrical conduction, and cardiac relaxation.² These effects come about directly as a result of catecholamines acting on the ß-ARs, which reside on the functionally relevant cells (myocardial and conduction tissue) in the heart.³ Much less is known about the contributions of ₁-ARs, . . . [Full Text of this Article]