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(Circulation. 2006;114:365-367.)
© 2006 American Heart Association, Inc.

Editorial

Cyclic Adenosine Monophosphate in Acute Myocardial Infarction With Heart Failure

Slayer or Savior?

Kirsten Leineweber, PhD; Michael Böhm, MD; Gerd Heusch, MD, FRCP

From the Institut für Pathophysiologie des Universitätsklinikums, Essen (K.L., G.H.), and Medizinische Universitätsklinik, Homburg/Saar (M.B.), Germany.

Correspondence to Professor Gerd Heusch, Institut für Pathophysiologie, Universitätsklinikum Essen, Hufelandstrasse 55, 45122 Essen, Germany. E-mail Gerd.heusch@uni-essen.de

Key Words: Editorials • apoptosis • arrhythmia • catecholamines • pharmacology • heart failure • myocardial infarction

An extract of the first 250 words of the full text is provided, because this article has no abstract.

Cyclic adenosine monophosphate (cAMP) is a tightly regulated second messenger that is critically involved in many intracellular processes. In cardiomyocytes, the activation of a number of membrane receptors, notably ß-receptors and muscarinic receptors, acts through stimulatory or inhibitory G-proteins (Gs/Gi) on adenylyl cyclase (AC), which synthesizes cAMP from ATP. cAMP is degraded by phosphodiesterases (PDE). Thereafter, cAMP activates protein kinase A (PKA), which, in turn, through phosphorylation of L-type calcium channels, ryanodine receptors, phospholamban, and troponin I, improves excitation-contraction coupling and increases heart rate, as well as contraction amplitude and relaxation. PKA also phosphorylates nuclear cAMP-response element binding proteins to activate transcription.¹ There are at least 9 isoforms of AC; the mammalian myocardium expresses mainly AC V and VI. AC V is the predominant isoform in adult cardiac tissue, whereas AC VI expression decreases with age. Both isoforms are phosphorylated by PKA and thereby inhibited, thus providing a feedback regulation and potential desensitization pathway.^2,3 Transgenic mice with cardiac-directed overexpression of AC VI have normal cAMP and cardiac function at rest but increased responses in both cAMP and function to ß-adrenergic stimulation,⁴ as confirmed in the present study by Takahasi et al.⁵

Article p 388

The prevailing notion is that increased myocardial cAMP in settings of acute myocardial ischemia is detrimental. In fact, ß-adrenergic agonists that increase cAMP formation disrupt perfusion-contraction matching and promote infarction in controlled animal models of myocardial ischemia, both by increasing myocardial energetic requirements and by an unfavorable flow redistribution away from the ischemic subendocardium.⁶ . . . [Full Text of this Article]

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