Fukushima J. Med. Sci.,
Vol. 51, No. 2, 2005

[Review Article]

NONINVASIVE MYOCARDIAL ENDOTHELIAL INTERVENTION
IN THE PERSISTENCE OF CORONARY STENOSIS :
A CONCEPT OF MYOCARDIAL ENDOTHELIAL NITRIC OXIDE
ACTIVATOR THROUGH HEART FAILURE RESEARCH
ON CLINICAL DEMAND

HIROYUKI YAOITA, KENICHI WATANABE, KAZUEI OGAWA
and YUKIO MARUYAMA

Department of Internal Medicine I, Fukushima Medical University School of Medicine,
Fukushima, 960-1295, Japan

(Received May 19 2005, accepted July 11, 2005)

Abstract: Protection of ischemic myocardium has been attempted by a variety of pharmaceutical and non-pharmaceutical methods. When the coronary intervention is not indicated by some reasons in patients with ischemic heart failure, medical treatments are expected to offer cardioprotection against the persistence of stenotic/occlusive lesions of the epicardial coronary artery. The pharmaceuticals such as the angiotensin-converting enzyme inhibitor, angiotensin receptor blocker, beta blocker, Ca antagonist, ATP-sensitive K channel opener and statin, or non-pharmaceutical approaches such as physical exercise, cardiac resynchronization, ventricular assist devices, and preconditioning upon ischemic insults appear to improve myocardial endothelial nitric oxide (NO) synthase (eNOS) function. Such eNOS activation contributes to amelioration of the cardiac dysfunction and remodeling induced by myocardial ischemia. Therefore, based on clinical evidence and basic research on clinical demand, we postulate a concept of ?emyocardial endothelial NO activator' from the standpoint of mechanistic insights beyond the class-effects of each pharmaceutical category and each non-pharmaceutical intervention. In addition to such continuous eNOS activation for treating chronic ischemic heart failure, rapid eNOS activation in the setting of acute ischemic events upon chronic myocardial ischemia by new strategies such as postconditioning seems to be also essential for developing further effective anti-heart-failure therapies.

Key words: nitric oxide, heart failure, endothelium, ischemia



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Correspondence to: Yukio Maruyama, Department of Internal Medicine I, Fukushima Medical University, School of Medicine, Fukushima City 960-1295, Japan.
E-mail: maruyama@fmu.ac.jp
Dr. Hiroyuki Yaoita received the 2004 Fukushima Society of Medical Science Award.