Abdominal surgical incision induces remote preconditioning of trauma (RPCT) via activation of bradykinin receptors (BK2R) and the cytochrome P450 epoxygenase pathway in canine hearts

Garrett J. Gross, John E. Baker, Jeannine Moore, J R Falck, Kasem Nithipatikom

Research output: Contribution to journalArticle

43 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)517-522
Number of pages6
JournalCardiovascular Drugs and Therapy
Volume25
Issue number6
DOIs
StatePublished - Dec 2011

Fingerprint

Bradykinin Receptors
Cytochrome P-450 Enzyme System
Canidae
Dogs
Wounds and Injuries
Reperfusion
Animal Models
Ischemic Postconditioning
Abdominal Muscles
Ischemic Preconditioning
Skin
Coronary Occlusion
Abdominal Wall
Nerve Fibers
Surgical Wound
Coronary Vessels
Ischemia
Observation
Control Groups
Acids

Keywords

  • Bradykinin
  • Epoxyeicosatrienoic acids
  • Infarct size
  • Remote preconditioning

ASJC Scopus subject areas

  • Pharmacology (medical)
  • Cardiology and Cardiovascular Medicine
  • Pharmacology

Cite this

Abdominal surgical incision induces remote preconditioning of trauma (RPCT) via activation of bradykinin receptors (BK2R) and the cytochrome P450 epoxygenase pathway in canine hearts. / Gross, Garrett J.; Baker, John E.; Moore, Jeannine; Falck, J R; Nithipatikom, Kasem.

In: Cardiovascular Drugs and Therapy, Vol. 25, No. 6, 12.2011, p. 517-522.

Research output: Contribution to journalArticle

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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.",
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