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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2007;27:1057.)
© 2007 American Heart Association, Inc.

Vascular Biology

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

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

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

Correspondence to Tatsuya Komaru, MD, PhD, Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine, Seiryo-machi, Aoba-ku, Sendai, 980-8574, Japan. 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 H₂O_2, 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.

To determine the mediator of metabolic coronary flow increase, we observed isolated coronary microvessels placed on the beating heart. We conclude that H₂O₂ derived from the beating heart mediates tachypacing-induced metabolic coronary vasodilation. The present studies may provide a new insight for the understanding of the coronary flow regulation.

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

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