title: Direct protective effects of dexmedetomidine against myocardial ischemia-reperfusion injury in anesthetized pigs.
abstract: Systemic administration of α2-adrenergic agonists has been shown to protect ischemic myocardium, but the direct effects on ischemia-reperfused myocardium have not yet been clarified. This study was carried out to determine the effects of intracoronary dexmedetomidine (DEX) on the myocardial ischemia-reperfusion injury in anesthetized pigs. In open-chest pigs, the left anterior descending coronary artery was perfused through an extracorporeal circuit from the carotid artery. They received intracoronary infusion of DEX at a rate of 1 ng · mL(-1) (group LD, n = 9), 10 ng · mL(-1) (group MD, n = 9), or 100 ng · mL(-1) (group HD, n = 9) of coronary blood flow or vehicle (group C, n = 12) for 30 min before ischemia. Myocardial stunning was produced by 12-min ischemia of the perfused area of left anterior descending coronary artery and 90-min reperfusion. The effect on reperfusion-induced arrhythmias was evaluated using the incidence of ventricular tachycardia or fibrillation after reperfusion. Regional myocardial contractility was evaluated with segment shortening (%SS). Dexmedetomidine significantly reduced the incidence of reperfusion-induced ventricular arrhythmias. Dexmedetomidine significantly improved the recovery of percentage segment shortening at 90 min after reperfusion (32.6% ± 3.1% in group C, 58.2% ± 2.1% in group LD, 61.1% ± 1.8% in group MD, and 72.0% ± 2.0% in group HD). Dexmedetomidine suppressed the increase in plasma norepinephrine concentration after reperfusion. The results indicate that DEX would exert the protective effect against ischemia-reperfusion injury by the direct action on the myocardium, which is not mediated through the central nervous system.
authors.affiliation: Department of Anesthesiology, Nagasaki University School of Medicine, Nagasaki, Japan.
authors.forename: Osamu
authors.initials: O
authors.lastname: Yoshitomi
authors.forename: Sungsam
authors.initials: S
authors.lastname: Cho
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Hara
authors.forename: Itsuko
authors.initials: I
authors.lastname: Shibata
authors.forename: Takuji
authors.initials: T
authors.lastname: Maekawa
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Ureshino
authors.forename: Koji
authors.initials: K
authors.lastname: Sumikawa
mesh_terms: D058647:Adrenergic alpha-2 Receptor Agonists / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000209:etiology / Q000517:prevention & control; D002316:Cardiotonic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D003326:Coronary Circulation / Q000187:drug effects; D020927:Dexmedetomidine / Q000494:pharmacology / Q000627:therapeutic use*; D004353:Drug Evaluation, Preclinical / Q000379:methods; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D015425:Myocardial Reperfusion / Q000009:adverse effects; D015428:Myocardial Reperfusion Injury / Q000097:blood / Q000517:prevention & control*; D017682:Myocardial Stunning / Q000097:blood / Q000517:prevention & control; D009638:Norepinephrine / Q000097:blood; D034421:Sus scrofa
chemical_list: D058647:Adrenergic alpha-2 Receptor Agonists; D002316:Cardiotonic Agents; D020927:Dexmedetomidine; D009638:Norepinephrine