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Milrinone-Induced Postconditioning Requires Activation of Mitochondrial Ca2+-sensitive Potassium (mBKCa) Channels
- Source :
- Journal of cardiothoracic and vascular anesthesia, 32(5), 2142-2148. W.B. Saunders Ltd
- Publication Year :
- 2018
-
Abstract
- Cardioprotection by postconditioning requires activation of mitochondrial large-conductance Ca2+-sensitive potassium (mBKCa) channels. The involvement of these channels in milrinone-induced postconditioning is unknown. The authors determined whether cardioprotection by milrinone-induced postconditioning involves activation of mBKCa channels in the rat heart in vitro. Randomized, prospective, blinded laboratory investigation. Experimental laboratory. Male Wistar rats. Hearts of male Wistar rats were randomized, placed on a Langendorff system, and perfused with Krebs-Henseleit buffer at a constant pressure of 80 mmHg. All hearts were subjected to 33 minutes of global ischemia and 60 minutes of reperfusion. At the onset of reperfusion, hearts were perfused with different concentrations of milrinone (0.3-100 μM) for determination of a dose-effect curve. In a second set of experiments, 3 μM milrinone was administered in combination with the mBKCa channel inhibitor paxilline (1 μM). Infarct size was determined by triphenyltetrazoliumchloride staining. In control animals, infarct size was 37 ± 7%. Milrinone at a concentration of 3 μM reduced infarct size to 22 ± 7% (p < 0.05 v control). Higher milrinone concentrations did not confer stronger protection. Paxilline completely blocked milrinone-induced cardioprotection whereas paxilline alone had no effect on infarct size. This study shows that activation of mBKCa channels plays a pivotal role in milrinone-induced postconditioning
- Subjects :
- 0301 basic medicine
Cardioprotection
business.industry
Potassium
Ischemia
chemistry.chemical_element
030204 cardiovascular system & hematology
Pharmacology
medicine.disease
Infarct size
03 medical and health sciences
chemistry.chemical_compound
030104 developmental biology
0302 clinical medicine
Anesthesiology and Pain Medicine
chemistry
Medicine
Milrinone
Myocardial infarction
Paxilline
Cardiology and Cardiovascular Medicine
business
Reperfusion injury
medicine.drug
Subjects
Details
- Language :
- English
- ISSN :
- 10530770
- Volume :
- 32
- Issue :
- 5
- Database :
- OpenAIRE
- Journal :
- Journal of cardiothoracic and vascular anesthesia
- Accession number :
- edsair.doi.dedup.....cb56f18a5081af63a03c2de199420bc6