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on March 1, 2007

Arteriosclerosis, Thrombosis, and Vascular Biology. 2007
Published online before print March 1, 2007, doi: 10.1161/01.ATV.0000261570.85983.4f
A more recent version of this article appeared on May 1, 2007
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Submitted on August 23, 2006
Accepted on February 12, 2007

Hydrogen Peroxide Derived From Beating Heart Mediates Coronary Microvascular Dilation During Tachycardia

Yasunori Kokusho ; Tatsuya Komaru *; Satoru Takeda ; Katsuaki Takahashi ; Ryoji Koshida ; Kunio Shirato ; and Hiroaki Shimokawa

From the Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan.

* To whom correspondence should be addressed. E-mail: komaru{at}cardio.med.tohoku.ac.jp.

Objective--Coronary flow is closely correlated to the myocardial metabolic demand. We tested the hypothesis that hydrogen peroxide (H2O2) derived from beating hearts mediates metabolic coronary microvascular dilation.

Methods and Results--We used a bioassay method in which an isolated microvessel is placed on a beating heart to detect myocardium-derived vasoactive mediators. A rabbit coronary arterial microvessel (detector vessel [DV], n=25) was pressurized and placed on a canine beating heart. After intrinsic tone of DV had developed, we observed DV at rest (heart rate, 120 bpm) and during tachypacing (heart rate, 240 bpm) using an intravital microscope equipped with a floating objective. The tachypacing produced DV dilation by 8.2% (P<0.01 versus baseline), and the dilation was abolished by cell-impermeable catalase (a H2O2 scavenger, 500 U/mL). We performed myocardial biopsy at rest and tachypacing. The biopsy specimens were loaded with 2',7'-dichlorodihydrofluorescein diacetate (10 µmol/L) to visualize H2O2, and observed with confocal microscopy. Dichlorofluorescein fluorescence was diffusely identified in the myocardium and the tachypacing increased the fluorescence intensity (P<0.01). Exogenous H2O2 caused vasodilation of arterial microvessels in vitro in a concentration-dependent manner that was abolished by catalase.

Conclusions--H2O2 derived from the beating heart mediates tachypacing-induced metabolic coronary vasodilation in vivo.


Key words: coronary circulation • myocardium • reactive oxygen species • tachycardia • vasodilation




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