TY - JOUR
T1 - Hydrogen peroxide derived from beating heart mediates coronary microvascular dilation during tachycardia
AU - Kokusho, Yasunori
AU - Komaru, Tatsuya
AU - Takeda, Satoru
AU - Takahashi, Katsuaki
AU - Koshida, Ryoji
AU - Shirato, Kunio
AU - Shimokawa, Hiroaki
PY - 2007/5
Y1 - 2007/5
N2 - 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.
AB - 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.
KW - Coronary circulation
KW - Myocardium
KW - Reactive oxygen species
KW - Tachycardia
KW - Vasodilation
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U2 - 10.1161/ATVBAHA.0000261570.85983.4f
DO - 10.1161/ATVBAHA.0000261570.85983.4f
M3 - Article
C2 - 17442897
AN - SCOPUS:34247341702
VL - 27
SP - 1057
EP - 1063
JO - Arteriosclerosis, Thrombosis, and Vascular Biology
JF - Arteriosclerosis, Thrombosis, and Vascular Biology
SN - 1079-5642
IS - 5
ER -