title: Effects of adding P38 mitogen-activated protein-kinase inhibitor to celsior solution in canine heart transplantation from non-heart-beating donors.
abstract: BACKGROUND
  The activation of p38 mitogen-activated protein kinase (MAPK) plays an important role in ischemia-reperfusion injury. This study evaluated the effects of p38 MAPK inhibition using FR167653, a novel p38 MAPK inhibitor, as an additive to Celsior solution in canine heart transplantation from non-heart-beating donors (NHBDs).
  
  
  METHODS
  Donor hearts were left in situ for 20 minutes after cardiac arrest, which was induced by rapid exsanguination. Twelve donor-recipient pairs of mongrel dogs were divided into two groups: the control and FR167653 (FR) groups (n=6 each). In both groups, the grafts were subjected to coronary flushing and immersed in Celsior solution for 4 hours with or without FR167653. Orthotopic heart transplantation was then performed. Cardiac output (CO), left ventricular pressure (LVP), and end-systolic maximal elastance (Emax) were measured 2 hours after weaning from cardiopulmonary bypass (CPB), and the hearts were then harvested for histopathologic study. The activation of p38 MAPK was evaluated in another 20 mongrel dogs.
  
  
  RESULTS
  In the FR group, CO, LVP recovery rate, and Emax were significantly (P<0.05) higher 2 hours after weaning from CPB, histopathologic damage was attenuated, and the activation of p38 MAPK was significantly (P<0.05) inhibited 10 minutes after reperfusion compared with the control group.
  
  
  CONCLUSIONS
  The addition of FR167653 to Celsior solution improved heart-graft viability, probably by way of the inhibition of p38 MAPK activation, which may attenuate ischemia-reperfusion injury in heart transplantation from NHBDs.
authors.affiliation: Second Department of Surgery, Gunma University Faculty of Medicine, Maebashi, Gunma, Japan.
authors.forename: Norimasa
authors.initials: N
authors.lastname: Koike
authors.forename: Izumi
authors.initials: I
authors.lastname: Takeyoshi
authors.forename: Shigeru
authors.initials: S
authors.lastname: Ohki
authors.forename: Masahiko
authors.initials: M
authors.lastname: Tokumine
authors.forename: Koshi
authors.initials: K
authors.lastname: Matsumoto
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Morishita
mesh_terms: D000818:Animals; D002314:Cardioplegic Solutions; D004187:Disaccharides; D004285:Dogs; D004573:Electrolytes; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005971:Glutamates; D005978:Glutathione; D006131:Growth Inhibitors / Q000494:pharmacology; D006321:Heart / Q000187:drug effects; D006323:Heart Arrest; D016027:Heart Transplantation / Q000502:physiology*; D006639:Histidine; D008353:Mannitol; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors*; D023421:Models, Animal; D017202:Myocardial Ischemia; D009206:Myocardium / Q000473:pathology; D011720:Pyrazoles / Q000494:pharmacology*; D011725:Pyridines / Q000494:pharmacology*; D015427:Reperfusion Injury / Q000517:prevention & control; D048051:p38 Mitogen-Activated Protein Kinases
chemical_list: D002314:Cardioplegic Solutions; C088453:Celsior; D004187:Disaccharides; D004573:Electrolytes; D004791:Enzyme Inhibitors; C104334:FR 167653; D005971:Glutamates; D006131:Growth Inhibitors; D011720:Pyrazoles; D011725:Pyridines; D008353:Mannitol; D006639:Histidine; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D005978:Glutathione