Effects of the cardioselective KATP channel blocker HMR 1098 on cardiac function in isolated perfused working rat hearts and in anesthetized rats during ischemia and reperfusion

It has been argued that activation of KATP channels in the sarcolemmal membrane of heart muscle cells during ischemia provides an endogenous cardioprotective mechanism. In order to test whether the novel cardioselective KATP channel blocker HMR 1098 affects cardiac function during ischemia, experime...

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Bibliographic Details
Published in:Naunyn-Schmiedeberg's archives of pharmacology 2001-07, Vol.364 (1), p.33-41
Main Authors: Gögelein, H, Ruetten, H, Albus, U, Englert, H C, Busch, A E
Format: Article
Language:English
Subjects:
Anesthesia
Animals
Anti-Arrhythmia Agents - pharmacology
Benzamides - administration & dosage
Benzamides - pharmacology
Glyburide - pharmacology
Heart - drug effects
Heart - physiopathology
Hemodynamics - drug effects
In Vitro Techniques
Male
Models, Animal
Myocardial Contraction - drug effects
Myocardial Infarction
Myocardial Ischemia - physiopathology
Myocardial Reperfusion
Potassium - metabolism
Potassium Channel Blockers - pharmacology
Rats
Rats, Wistar
Sulfonamides - pharmacology
Thiourea - analogs & derivatives
Thiourea - pharmacology
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Summary:It has been argued that activation of KATP channels in the sarcolemmal membrane of heart muscle cells during ischemia provides an endogenous cardioprotective mechanism. In order to test whether the novel cardioselective KATP channel blocker HMR 1098 affects cardiac function during ischemia, experiments were performed in rat hearts during ischemia and reperfusion. Isolated perfused working rat hearts were subjected to 30 min of low-flow ischemia in which the coronary flow was reduced to 10% of its control value, followed by 30-min reperfusion. In the first set of experiments the hearts were electrically paced at 5 Hz throughout the entire protocol. At the end of the 30-min ischemic period the aortic flow had fallen to 44 +/- 2% (n=8) of its nonischemic value in vehicle-treated hearts, whereas in the presence of 0.3 micromol/l and 3 micromol/l HMR 1098 it had fallen to 29 +/- 7% (n=5, not significant) and 8 +/- 2% (n=12, P
ISSN:0028-1298
DOI:10.1007/s002100000391