title: Effects of pimobendan and EGIS 9377, cardiotonic agents, and OG-VI, a nucleoside-nucleotide mixture, administered during reperfusion after ischemia on stunned myocardium in dogs.
abstract: BACKGROUND
  Pimobendan is a so-called calcium sensitizer that exerts a positive inotropic action. EGIS 9377 is synthesized as a calcium sensitizer. OG-VI is a nucleoside-nucleotide mixture that ameliorates the myocardial dysfunction (myocardial stunning) after ischemia.
  
  
  OBJECTIVE
  To determine whether administration of these agents after the onset of reperfusion after ischemia improves the condition of stunned myocardium.
  
  
  METHODS
  Dogs anesthetized with pentobarbital were subjected to 20 min ligation of left anterior descending coronary artery and then 60 min reperfusion. The corresponding vehicle, 0.3 and 1 mg/kg pimobendan, or 1 and 3 mg/kg EGIS 9377 was injected intravenously 30 min after the onset of reperfusion. Saline solution or 1.2 mumol/kg per min OG-VI was infused for 30 min, starting 30 min after the reperfusion. Shortening of myocardial segment was measured by sonomicrometry. The tissue levels of energy and carbohydrate metabolites in the 60 min-reperfused hearts were determined.
  
  
  RESULTS
  Shortening of myocardial segments significantly decreased during ischemia, and returned toward preischemic level after reperfusion for all groups, although the contractile dysfunction still remained. Injections and infusion of pimobendan, EGIS 9377, and OG-VI after the onset of reperfusion ameliorated the contractile dysfunction. Systemic vascular resistance was decreased by administrations of pimobendan and OG-VI. The levels of high-energy phosphates in 60 min-reperfused heart were not changed by either treatment.
  
  
  CONCLUSIONS
  Administration of pimobendan, EGIS 9377, and OG-VI ameliorate the myocardial contractile dysfunction after ischemia even when these agents are administered after the onset of reperfusion. The increase in contractile function due to these agents did not worsen the myocardial energy balance.
authors.affiliation: Department of Surgery II, Kochi Medical School, Nankoku, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Fukutomi
authors.forename: K
authors.initials: K
authors.lastname: Satoh
authors.forename: S
authors.initials: S
authors.lastname: Ogoshi
authors.forename: K
authors.initials: K
authors.lastname: Ichihara
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002316:Cardiotonic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004285:Dogs; D006321:Heart / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D009025:Morpholines / Q000494:pharmacology / Q000627:therapeutic use*; D015425:Myocardial Reperfusion; D017682:Myocardial Stunning / Q000188:drug therapy* / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism; D009705:Nucleosides / Q000494:pharmacology / Q000627:therapeutic use*; D009711:Nucleotides / Q000494:pharmacology / Q000627:therapeutic use*; D011724:Pyridazines / Q000494:pharmacology / Q000627:therapeutic use*; D011743:Pyrimidines / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: C403498:2-(1-methylthio)-5-(2-morpholinoethylamino)-8,9-dihydro-7H-thiopyrano(3,2-d)(1,2,4)triazolo(1,5-a)pyrimidine; D002316:Cardiotonic Agents; D009025:Morpholines; D009705:Nucleosides; D009711:Nucleotides; C087081:OG-VI solution; D011724:Pyridazines; D011743:Pyrimidines; C041648:pimobendan; D000255:Adenosine Triphosphate