Abdominal Surgical Incision Induces Remote Preconditioning of Trauma (RPCT) via Activation of Bradykinin Receptors (BK2R) and the Cytochrome P450 Epoxygenase Pathway in Canine Hearts

• Published in: Cardiovascular drugs and therapy 2011-12, Vol.25 (6), p.517-522
• Main Authors: Gross, Garrett J., Baker, John E., Moore, Jeannine, Falck, John R., Nithipatikom, Kasem
• Format: Article
• Language: English
• Subjects: 8,11,14-Eicosatrienoic Acid - analogs & derivatives; 8,11,14-Eicosatrienoic Acid - pharmacology; Abdomen - surgery; Animals; Biological and medical sciences; Bradykinin - analogs & derivatives; Bradykinin - pharmacology; Bradykinin B2 Receptor Antagonists; Cardiology; Cardiovascular system; Coronary Circulation - drug effects; Cytochrome P-450 Enzyme Inhibitors; Cytochrome P-450 Enzyme System - metabolism; Disease Models, Animal; Dogs; Female; Hemodynamics - drug effects; Ischemic Postconditioning - methods; Ischemic Preconditioning, Myocardial - methods; Male; Medical sciences; Medicine; Medicine & Public Health; Myocardial Infarction - enzymology; Myocardial Infarction - metabolism; Myocardial Infarction - pathology; Myocardial Infarction - prevention & control; Myocardial Reperfusion Injury - enzymology; Myocardial Reperfusion Injury - metabolism; Myocardial Reperfusion Injury - pathology; Myocardial Reperfusion Injury - prevention & control; Myocardium - enzymology; Myocardium - metabolism; Myocardium - pathology; Pharmacology. Drug treatments; Receptor, Bradykinin B2 - metabolism
• ISSN: 0920-3206; 1573-7241
• DOI: 10.1007/s10557-011-6321-9

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