Reduction by ATP-Sensitive Potassium Channel Opener, YM934, of Experimental Myocardial Infarct Size in Anesthetized Dogs

Taguchi, Taku; Uchida, Wataru; Takenaka, Toichi; Takeo, Satoshi

doi:10.1159/000028309

Cited by 2 publications

(6 citation statements)

References 19 publications

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“…YM934, a pure ATP-sensitive potassium channel opener that selectively affects mitochondrial potassium channels, 3,4,15) was confirmed to decrease the LCx peripheral vascular resistance, increase the LCx coronary flow, and improve the recovery-interval of myocardial function following transient coronary occlusion with the LCx coronary stenosed. In contrast, NTG dilated the proximal conduit artery without changing the coronary flow or improving the recovery-time of myocardial function under the same study condition.…”

Section: Discussionmentioning

confidence: 97%

“…We used 0.3 µg/kg of YM934 in the present experiment, based on our preliminary study and previous studies reporting the effect of this dose on hemodynamic variables. 3,4,16) Higher doses of YM934 induce dose-dependent decreases in aortic pressure. The NTG dose, 3 µg/kg/min, was confirmed not to induce hypotension.…”

Section: Discussionmentioning

confidence: 99%

“…3,4,15) YM934 (prepared at Yamanouchi Pharmaceutical Co., Tokyo) was dissolved in saline containing 0.02% dimethyl sulfoxide and 0.02% (v/v) ethanol. NTG (Millisrol, Nippon-Kayaku Co., Tokyo) was dissolved in saline.…”

Section: Methodsmentioning

confidence: 99%

“…4) Clinical studies have yet to show any reduction in mortality in cardiovascular disease patients treated with nitrates [5][6][7][8][9] ; although nicorandil, a hybrid of K-ops and nitrates, has been confirmed to reduce cardiovascular events in patients with stable angina. 10) Nicorandil is reported to improve no-reflow phenomena during percutaneous coronary intervention, 11) improve recovery of left ventricular function, 11) and decrease infarction size.…”

mentioning

confidence: 99%

“…We compared the effect of YM934, a pure K-op, 3,4,15) with that of nitroglycerin (NTG) in a dog model of impaired coronary circulation similar to unstable angina. The circulatory impairment was induced by transiently interrupting coronary flow in the presence of a fixed coronary stenosis.…”

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confidence: 99%

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Comparison of the Effect of the ATP-Sensitive Potassium Channel Opener YM934 With That of Nitroglycerin on Impaired Coronary Circulation in Dogs

et al. 2005

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SUMMARYWe compared the effect of an ATP-sensitive potassium channel opener, YM934, with that of nitroglycerin (NTG) on impaired coronary circulation in dogs. Coronary stenosis was produced in 7 dogs by placing a hydraulic occluder around the proximal left circumflex coronary (LCx) artery and abolishing reactive hyperemia to compromise the LCx flow. The following parameters were measured: the aortic pressure, LCx flow velocity, LCx vessel diameter, LCx peripheral pressure, and segment length in the LCx area. Subsequently, we occluded the LCx artery for 15 seconds and measured the recovery-interval (time required for the segment shortening to return to the preocclusion value). The measurements were recorded under three study conditions: (1) at baseline without LCx stenosis; (2) with LCx stenosis under NTG infusion (3 µg/Kg/min); and (3) with LCx stenosis after intravenous administration of YM934 (0.3 µg/kg). The heart rate and aortic pressure were similar under the three study conditions. Mean LCx flow velocity and segment shortening did not significantly change either. However, LCx peripheral pressure decreased after the induction of stenosis (P < 0.05) and showed no response to either NTG or YM934. YM934 administration significantly increased LCx flow in the presence of LCx stenosis, (P < 0.05), whereas NTG infusion did not. YM934 significantly shortened the recovery-interval of the segment shortening after 15-sec LCx occlusion (P < 0.05), whereas NTG did not. These findings suggest that YM934 improves coronary blood flow and prevents myocardial ischemic damage in severely impaired coronary circulation. (Int Heart J 2005; 46: 501-512) Key words: ATP-sensitive potassium channel opener, Nitroglycerin, Coronary stenosis, Coronary flow, Myocardial function NITRATES and ATP-sensitive potassium channel openers (K-ops) are both effective in dilating coronary arteries and are used as agents to reduce myocardial ischemia in patients with ischemic heart disease. However, the cardiovascular From the

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Section: Discussionmentioning

confidence: 97%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Comparison of the Effect of the ATP-Sensitive Potassium Channel Opener YM934 With That of Nitroglycerin on Impaired Coronary Circulation in Dogs

et al. 2005

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Histamine H2 Receptor Antagonism by T-593: Studies on cAMP Generation in Hepa Cells Expressing Histamine H2 Receptor

Tashiro

Ono²,

Watanabe³

et al. 1999

Pharmacology

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Histamine H₂ receptor antagonism by T-593 was investigated in Hepa cells expressing canine histamine H₂ receptors. T-593 inhibited generation of cAMP in Hepa cells stimulated by 10^–5 mol/l histamine with an IC₅₀ value of 2.3 × 10^–6 mol/l, (S)-(–)-T-593, one of the enantiomers comprising racemic T-593, inhibited cAMP generation with an IC₅₀ value of 6.1 × 10^–7 mol/l. On the other hand, the other enantiomer (R)-(+)-T-593 exhibited only a negligible effect. Incubation of the cell with (S)-(–)-T-593 for 60 min depressed the maximal response of the concentration-response curve of histamine with a nonparallel rightward shift. The slope of a Schild plot was 1.27. In contrast, (S)-(–)-T-593 caused a parallel rightward shift of the curve, with a Schild plot slope that did not significantly differ from unity, by treating the cells for 15 min. The H₂ receptor-blocking action of (S)-(–)-T-593 remained almost unaffected after washing out the drug, whereas the effect of ranitidine was reversible after washing. These results suggest that T-593 possesses a time-dependent unsurmountable antagonistic action against histamine H₂ receptor. T-593 may interact with the histamine H₂ receptor molecule in a slowly associable and dissociable manner.

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Reduction by ATP-Sensitive Potassium Channel Opener, YM934, of Experimental Myocardial Infarct Size in Anesthetized Dogs

Cited by 2 publications

References 19 publications

<b>Comparison of the Effect of the ATP-Sensitive Potassium Channel Opener YM934 With That of Nitroglycerin on Impaired Coronary Circulation in Dogs</b>

<b>Comparison of the Effect of the ATP-Sensitive Potassium Channel Opener YM934 With That of Nitroglycerin on Impaired Coronary Circulation in Dogs</b>

Histamine H<sub>2</sub> Receptor Antagonism by T-593: Studies on cAMP Generation in Hepa Cells Expressing Histamine H<sub>2</sub> Receptor

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