Hydrogen peroxide derived from beating heart mediates coronary microvascular dilation during tachycardia.
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.


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 micromol/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.
Kokusho
Yasunori
Y
Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine, Seiryo-machi, Aoba-ku, Sendai, 980-8574, Japan.
Komaru
Tatsuya
T
Takeda
Satoru
S
Takahashi
Katsuaki
K
Koshida
Ryoji
R
Shirato
Kunio
K
Shimokawa
Hiroaki
H
D000818:Animals; D001681:Biological Assay; D001784:Blood Gas Analysis; D003326:Coronary Circulation / Q000502:physiology*; D003331:Coronary Vessels / Q000378:metabolism* / Q000503:physiopathology; D004285:Dogs; D005260:Female; D006861:Hydrogen Peroxide / Q000378:metabolism*; D007150:Immunohistochemistry; D008297:Male; D018613:Microscopy, Confocal; D009206:Myocardium / Q000378:metabolism*; D011817:Rabbits; D013610:Tachycardia / Q000378:metabolism / Q000503:physiopathology*; D014664:Vasodilation / Q000502:physiology*
D006861:Hydrogen Peroxide