Abdominal surgical incision induces remote preconditioning of trauma (RPCT) via activation of bradykinin receptors (BK2R) and the cytochrome P450 epoxygenase pathway in canine hearts. Cardiovasc Drugs Ther 2011 Dec;25(6):517-22
Date
07/26/2011Pubmed ID
21786213Pubmed Central ID
PMC3329256DOI
10.1007/s10557-011-6321-9Scopus ID
2-s2.0-83055194622 (requires institutional sign-in at Scopus site) 50 CitationsAbstract
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.
Author List
Gross GJ, Baker JE, Moore J, Falck JR, Nithipatikom KAuthor
John E. Baker PhD Professor in the Surgery department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
8,11,14-Eicosatrienoic AcidAbdomen
Animals
Bradykinin
Bradykinin B2 Receptor Antagonists
Coronary Circulation
Cytochrome P-450 Enzyme Inhibitors
Cytochrome P-450 Enzyme System
Disease Models, Animal
Dogs
Female
Hemodynamics
Ischemic Postconditioning
Ischemic Preconditioning, Myocardial
Male
Myocardial Infarction
Myocardial Reperfusion Injury
Myocardium
Receptor, Bradykinin B2
