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

Pharmacology ◽  
1999 ◽  
Vol 59 (2) ◽  
pp. 95-105 ◽  
Author(s):  
Taku Taguchi ◽  
Wataru Uchida ◽  
Toichi Takenaka ◽  
Satoshi Takeo
Keyword(s):  
Infarct Size ◽  
Potassium Channel ◽  
Myocardial Infarct ◽  
Myocardial Infarct Size ◽  
Potassium Channel Opener ◽  
Channel Opener ◽  
Anesthetized Dogs ◽  
Experimental Myocardial Infarct

Activation of ATP-sensitive potassium channels lowers threshold for ischemic preconditioning in dogs

1994 ◽  
Vol 267 (5) ◽  
pp. H1888-H1894 ◽  
Author(s):  
Z. Yao ◽  
G. J. Gross
Keyword(s):  
Action Potential ◽  
Infarct Size ◽  
Potassium Channel ◽  
Ischemic Preconditioning ◽  
Myocardial Infarct ◽  
Myocardial Infarct Size ◽  
Potassium Channel Opener ◽  
Intracoronary Infusion ◽  
Anesthetized Dogs ◽  
Action Potential Shortening

The purpose of the present study was to determine whether enhanced activation of myocardial ATP-dependent potassium channels (KATP) with a potassium channel opener, bimakalim, can reduce the time necessary to produce the protective effect of ischemic preconditioning and to determine whether this effect is mediated via accelerating the rate of action potential shortening during preconditioning. Barbital-anesthetized dogs were subjected to 60 min of left anterior descending coronary artery (LAD) occlusion followed by 4 h of reperfusion. Ten minutes of preconditioning was found to markedly reduce myocardial infarct size from 30.6 +/- 4.7 to 7.1 +/- 2.6%. Subsequently, it was observed that either 3 min of LAD occlusion or a 3-min intracoronary infusion with 0.3 micrograms/min of bimakalim did not reduce myocardial infarct size. However, intracoronary infusion with bimakalim during the 3-min preconditioning period markedly reduced myocardial infarct size to a similar extent as that of ischemic preconditioning (12.2 +/- 1.9%). In addition, it was observed that bimakalim markedly accelerated the ischemia-induced shortening of the action potential during preconditioning. These results are the first to demonstrate that activation of KATP channels with a potassium channel opener reduces the threshold of time necessary to produce preconditioning in anesthetized dogs. These data also suggest that KATP channel activation may produce this effect by enhancing the rate of ischemic myocardial action potential shortening during preconditioning.

Isoflurane Mimics Ischemic Preconditioning via Activation of KATPChannels 

1997 ◽  
Vol 87 (2) ◽  
pp. 361-370 ◽  
Author(s):  
Judy R. Kersten ◽  
Todd J. Schmeling ◽  
Paul S. Pagel ◽  
Garrett J. Gross ◽  
David C. Warltier
Keyword(s):  
Infarct Size ◽  
Ischemic Preconditioning ◽  
Myocardial Infarct ◽  
Myocardial Infarct Size ◽  
Protective Effects ◽  
Hemodynamic Effects ◽  
Area At Risk ◽  
Triphenyltetrazolium Chloride ◽  
Anesthetized Dogs

Background The authors tested the hypothesis that isoflurane directly preconditions myocardium against infarction via activation of K(ATP) channels and that the protection afforded by isoflurane is associated with an acute memory phase similar to that of ischemic preconditioning. Methods Barbiturate-anesthetized dogs (n = 71) were instrumented for measurement of systemic hemodynamics. Myocardial infarct size was assessed by triphenyltetrazolium chloride staining. All dogs were subjected to a single prolonged (60 min) left anterior descending coronary artery (LAD) occlusion followed by 3 h of reperfusion. Ischemic preconditioning was produced by four 5-min LAD occlusions interspersed with 5-min periods of reperfusion before the prolonged LAD occlusion and reperfusion. The actions of isoflurane to decrease infarct size were examined in dogs receiving 1 minimum alveolar concentration (MAC) isoflurane that was discontinued 5 min before prolonged LAD occlusion. The interaction between isoflurane and ischemic preconditioning on infarct size was evaluated in dogs receiving isoflurane before and during preconditioning LAD occlusions and reperfusions. To test whether the cardioprotection produced by isoflurane can mimic the acute memory of ischemic preconditioning, isoflurane was discontinued 30 min before prolonged LAD occlusion and reperfusion. The mechanism of isoflurane-induced cardioprotection was evaluated in two final groups of dogs pretreated with glyburide in the presence or absence of isoflurane. Results Myocardial infarct size was 25.3 +/- 2.9% of the area at risk during control conditions. Isoflurane and ischemic preconditioning produced significant (P < 0.05) and equivalent reductions in infarct size (ischemic preconditioning alone, 9.6 +/- 2.0; isoflurane alone, 11.8 +/- 2.7; isoflurane and ischemic preconditioning, 5.1 +/- 1.9%). Isoflurane-induced reduction of infarct size also persisted 30 min after discontinuation of the anesthetic (13.9 +/- 1.5%), independent of hemodynamic effects during LAD occlusion. Glyburide alone had no effect on infarct size (28.3 +/- 3.9%), but it abolished the protective effects of isoflurane (27.1 +/- 4.6%). Conclusions Isoflurane directly preconditions myocardium against infarction via activation of K(ATP) channels in the absence of hemodynamic effects and exhibits acute memory of preconditioning in vivo.

scholarly journals CP-060S, a novel cardioprotective drug, limits myocardial infarct size in anesthetized dogs

1997 ◽  
Vol 73 ◽  
pp. 233
Author(s):  
Yoshiyuki Suzuki ◽  
Kazuhiko Tamura ◽  
Michitaka Akima ◽  
Takaki Koga ◽  
Yuichiro Adachi ◽  
...  
Keyword(s):  
Infarct Size ◽  
Myocardial Infarct ◽  
Myocardial Infarct Size ◽  
Anesthetized Dogs ◽  
Cardioprotective Drug

scholarly journals Effects of the selective EET antagonist, 14,15-EEZE, on cardioprotection produced by exogenous or endogenous EETs in the canine heart

2008 ◽  
Vol 294 (6) ◽  
pp. H2838-H2844 ◽  
Author(s):  
Garrett J. Gross ◽  
Kathryn M. Gauthier ◽  
Jeannine Moore ◽  
John R. Falck ◽  
Bruce D. Hammock ◽  
...  
Keyword(s):  
Infarct Size ◽  
Potassium Channel ◽  
Low Dose ◽  
Myocardial Infarct ◽  
Specific Interaction ◽  
High Dose ◽  
Dodecanoic Acid ◽  
Myocardial Infarct Size ◽  
Canine Heart ◽  
Area At Risk

Previously, we demonstrated ( 17 ) that 11,12- and 14,15-epoxyeicosatrienoic acids (EETs) produce marked reductions in myocardial infarct size. Although it is assumed that this cardioprotective effect of the EETs is due to a specific interaction with a membrane-bound receptor, no evidence has indicated that novel EET antagonists selectively block the EET actions in dogs. Our goals were to investigate the effects of 11,12- and 14,15-EET, the soluble epoxide hydrolase inhibitor, 12-(3-adamantan-1-yl-ureido)-dodecanoic acid (AUDA), and the putative selective EET antagonist, 14,15-epoxyeicosa-5( Z)-enoic acid (14,15-EEZE), on infarct size of barbital anesthetized dogs subjected to 60 min of coronary artery occlusion and 3 h of reperfusion. Furthermore, the effect of 14,15-EEZE on the cardioprotective actions of the selective mitochondrial ATP-sensitive potassium channel opener diazoxide was investigated. Both 11,12- and 14,15-EET markedly reduced infarct size [expressed as a percentage of the area at risk (IS/AAR)] from 21.8 ± 1.6% (vehicle) to 8.7 ± 2.2 and 9.4 ± 1.3%, respectively. Similarly, AUDA significantly reduced IS/AAR from 21.8 ± 1.6 to 14.4 ± 1.2% (low dose) and 9.4 ± 1.8% (high dose), respectively. Interestingly, the combination of the low dose of AUDA with 14,15-EET reduced IS/AAR to 5.8 ± 1.6% ( P < 0.05), further than either drug alone. Diazoxide also reduced IS/AAR significantly (10.2 ± 1.9%). In contrast, 14,15-EEZE had no effect on IS/AAR by itself (21.0 ± 3.6%), but completely abolished the effect of 11,12-EET (17.8 ± 1.4%) and 14,15-EET (19.2 ± 2.4%) and AUDA (19.3 ± 1.6%), but not that of diazoxide (10.4 ± 1.4%). These results suggest that activation of the EET pathway, acting on a putative receptor, by exogenous EETs or indirectly by blocking EET metabolism, produced marked cardioprotection, and the combination of these two approaches resulted in a synergistic effect. These data also suggest that 14,15-EEZE is not blocking the mitochondrial ATP-sensitive potassium channel as a mechanism for antagonizing the cardioprotective effects of the EETs.

Determination of Experimental myocardial infarct size

1981 ◽  
Vol 6 (3) ◽  
pp. 199-210 ◽  
Author(s):  
David C. Warltier ◽  
Mark G. Zyvoloski ◽  
Garrett J. Gross ◽  
Harold F. Hardman ◽  
Harold L. Brooks
Keyword(s):  
Infarct Size ◽  
Myocardial Infarct ◽  
Myocardial Infarct Size ◽  
Experimental Myocardial Infarct

CP-060S, a Novel Cardioprotective Drug, Limits Myocardial Infarct Size in Anesthetized Dogs

1998 ◽  
Vol 31 (3) ◽  
pp. 400-407 ◽  
Author(s):  
Yoshiyuki Suzuki ◽  
Kazuhiko Tamura ◽  
Michitaka Akima ◽  
Yuichiro Adachi ◽  
Masanori Fukazawa ◽  
...  
Keyword(s):  
Infarct Size ◽  
Myocardial Infarct ◽  
Myocardial Infarct Size ◽  
Anesthetized Dogs ◽  
Cardioprotective Drug

Reduction of Myocardial Infarct Size by Trapidil in Anesthetized Dogs

1983 ◽  
Vol 5 (3) ◽  
pp. 499-505 ◽  
Author(s):  
K. Yamaguchi ◽  
K. Suzuki ◽  
T. Niho ◽  
M. Sato ◽  
C. Ito ◽  
...  
Keyword(s):  
Infarct Size ◽  
Myocardial Infarct ◽  
Myocardial Infarct Size ◽  
Anesthetized Dogs
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