Medical College of Wisconsin
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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



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Scopus ID

2-s2.0-83055194622   44 Citations


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 K


John E. Baker PhD Professor in the Surgery department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

8,11,14-Eicosatrienoic Acid
Bradykinin B2 Receptor Antagonists
Coronary Circulation
Cytochrome P-450 Enzyme Inhibitors
Cytochrome P-450 Enzyme System
Disease Models, Animal
Ischemic Postconditioning
Ischemic Preconditioning, Myocardial
Myocardial Infarction
Myocardial Reperfusion Injury
Receptor, Bradykinin B2
jenkins-FCD Prod-482 91ad8a360b6da540234915ea01ff80e38bfdb40a