title: Abdominal surgical incision induces remote preconditioning of trauma (RPCT) via activation of bradykinin receptors (BK2R) and the cytochrome P450 epoxygenase pathway in canine hearts.
abstract: OBJECTIVE
  Recently, a novel observation was made in which nonischemic trauma at a site remote from the heart produced by a transverse abdominal incision resulted in a marked reduction of infarct size (IS) in the mouse heart via activation of sensory nerve fibers in the skin and subsequent activation of bradykinin 2 receptors (BK2R). This phenomenon was termed remote preconditioning of trauma (RPCT). Since RPCT may have potential clinical implications we attempted to confirm these findings in a large animal model, the dog. The epoxyeicosatrienoic acids (EETs) have also recently been shown to be antinociceptive and have been shown to mimic ischemic preconditioning (IPC) and postconditioning (POC) in dogs, therefore, we tested the role of the EETs in RPCT.
  
  
  METHODS
  Anesthetized adult mongrel dogs of either sex were subjected to 60 min of left anterior descending (LAD) coronary artery occlusion followed by 3 h of reperfusion. In all groups except the controls (no slit), a transverse slit (9 cm) was applied to the abdominal wall of the dog being careful to only slit the skin. Subsequently, 15 min after the slit the heart was subjected to the ischemia/reperfusion protocol.
  
  
  RESULTS
  In the control dogs, the IS as a percent of the area at risk (AAR) was 22.5 ± 2.4%, whereas in the dogs subjected to the slit alone the IS/AAR was reduced to 9.2 ± 1.2% (*P < 0.01). The BR2R blocker, HOE 140 (50 ug/kg, iv) given 10 min prior to the slit, completely abolished the protective effects of RCPT as did pretreatment with 14,15-EEZE, a putative EET receptor blocker or pretreatment with the selective EET synthesis inhibitor, MSPPOH.
  
  
  CONCLUSIONS
  These results suggest that BK and the EETs share cardioprotective properties in a large animal model of RPCT.
authors.affiliation: Department of Pharmacology and Toxicology, Medical College of Wisconsin, Milwaukee, USA. ggross@mcw.edu
authors.forename: Garrett J
authors.initials: GJ
authors.lastname: Gross
authors.forename: John E
authors.initials: JE
authors.lastname: Baker
authors.forename: Jeannine
authors.initials: J
authors.lastname: Moore
authors.forename: John R
authors.initials: JR
authors.lastname: Falck
authors.forename: Kasem
authors.initials: K
authors.lastname: Nithipatikom
mesh_terms: D015126:8,11,14-Eicosatrienoic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D000005:Abdomen / Q000601:surgery*; D000818:Animals; D001920:Bradykinin / Q000031:analogs & derivatives / Q000494:pharmacology; D065094:Bradykinin B2 Receptor Antagonists; D003326:Coronary Circulation / Q000187:drug effects; D065607:Cytochrome P-450 Enzyme Inhibitors; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D004195:Disease Models, Animal; D004285:Dogs; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D057775:Ischemic Postconditioning / Q000379:methods; D019157:Ischemic Preconditioning, Myocardial / Q000379:methods*; D008297:Male; D009203:Myocardial Infarction / Q000201:enzymology / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D015428:Myocardial Reperfusion Injury / Q000201:enzymology / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control; D009206:Myocardium / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D043782:Receptor, Bradykinin B2 / Q000378:metabolism*
chemical_list: D065094:Bradykinin B2 Receptor Antagonists; D065607:Cytochrome P-450 Enzyme Inhibitors; D043782:Receptor, Bradykinin B2; C065679:icatibant; D003577:Cytochrome P-450 Enzyme System; C067407:14,15-episulfide eicosatrienoic acid; D015126:8,11,14-Eicosatrienoic Acid; D001920:Bradykinin