This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Vatner, D. E. Search for Related Content PubMed PubMed Citation Articles by Vatner, D. E. Related Collections Congestive Gene therapy Receptor pharmacology

(Circulation Research. 2001;88:645.)
© 2001 American Heart Association, Inc.

Editorial

Stimulating G Protein–Coupled Receptors

Cure or Cause for Heart Failure?

Dorothy E. Vatner

From the Cardiovascular Research Institute, University of Medicine and Dentistry of New Jersey, New Jersey Medical School, Newark, NJ, and Hackensack University Medical Center, Hackensack, NJ.

Correspondence to Dorothy E. Vatner, MD, Cardiovascular Research Institute, The Jurist Research Building, Hackensack University Medical Center, 30 Prospect Ave, Hackensack, NJ 07601. E-mail dvatner@humed.com

Key Words: heart failure • ß-adrenergic receptors • vasopressin 2 receptors

	Introduction

 
Historically there has been intense interest in restoring to the failing heart the ability to improve contractility to normal levels. This concept, which has been pursued with almost religious zeal for the last half century, is based on the intuitive assumption that the defect in heart failure resides at the end point, which is defective myocyte contraction.

This concept was given additional impetus by the observation by Chidsey et al¹ that failing human hearts exhibit norepinephrine depletion. Over the last half century, the pharmaceutical industry has responded to this concept with a variety of ß-adrenergic agonists designed to improve the contractility of the failing heart. For several years, isoproterenol was administered, which provided some short-term relief but was found to exert deleterious effects in most patients. Most likely, the isoproterenol-induced increases in cardiac rate, contractility, and oxygen consumption are maladaptive in patients with limited coronary reserve. This was followed by a series of ß₁-predominant or ß₁-selective agonists that induce enhanced contractility with little or no effect on heart rate or arterial pressure. Some of these agents were used for many years in clinical setting as well as under experimental conditions. It was not until carefully controlled long-term studies were carried out that it was found that mortality was increased in patients with heart failure on these drugs.^{2 3 4} The results of these studies suggest that agents that increase oxygen consumption over an extended period of time may not be salutary in patients with limited coronary reserve.

During the last . . . [Full Text of this Article]