title: The Cardioprotective Effects of Late-Phase Remote Preconditioning of Trauma Depends on Neurogenic Pathways and the Activation of PKC and NF-κB (But Not iNOS) in Mice.
abstract: A superficial abdominal surgical incision elicits cardioprotection against cardiac ischemia-reperfusion (I/R) injury in mice. This process, called remote preconditioning of trauma (RPCT), has both an early and a late phase. Previous investigations have demonstrated that early RPCT reduces cardiac infarct size by 80% to 85%. We evaluated the cardioprotective and molecular mechanisms of late-phase RPCT in a murine I/R injury model.
  
  
  
  Wild-type mice, bradykinin (BK) 2 receptor knockout mice, 3M transgenic mice (nuclear factor κB [NF-κb] repressor inhibitor of nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor alpha [IκBα((S32A, S36A, Y42F))]), and inducible nitric oxide synthase (iNOS) knockout mice were analyzed using a previously established I/R injury model. A noninvasive abdominal surgical incision was made 24 hours prior to I/R injury and the infarct size was determined at 24 hours post-I/R injury.
  
  
  
  The results indicated that a strong cardioprotective effect occurred during late-phase RPCT (58.42% ± 1.89% sham vs 29.41% ± 4.00% late RPCT, mean area of the infarct divided by the mean area of the risk region; P ≤ .05; n = 10). Furthermore, pharmacological intervention revealed the involvement of neurogenic signaling in the beneficial effects of late RPCT via sensory and sympathetic thoracic nerves. Pharmacological experiments in transgenic mice-implicated BK receptors, β-adrenergic receptors, protein kinase C, and NF-κB but not iNOS signaling in the cardioprotective effects of late RPCT.
  
  
  
  Late RPCT significantly decreased myocardial infarct size via neurogenic transmission and various other signaling pathways. This protective mechanism differentiates late and early RPCT. This study describes a new cardiac I/R injury prevention method and refines the concept of RPCT.
authors.affiliation: Hand and Microsurgery Center, The Second Affiliated Hospital of Harbin Medical University, Harbin, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Song
authors.affiliation: Hand and Microsurgery Center, The Second Affiliated Hospital of Harbin Medical University, Harbin, China.
authors.forename: Y J
authors.initials: YJ
authors.lastname: Ye
authors.affiliation: Hand and Microsurgery Center, The Second Affiliated Hospital of Harbin Medical University, Harbin, China.
authors.forename: P W
authors.initials: PW
authors.lastname: Li
authors.affiliation: Hand and Microsurgery Center, The Second Affiliated Hospital of Harbin Medical University, Harbin, China.
authors.forename: Y L
authors.initials: YL
authors.lastname: Zhao
authors.affiliation: Hand and Microsurgery Center, The Second Affiliated Hospital of Harbin Medical University, Harbin, China.
authors.forename: Q
authors.initials: Q
authors.lastname: Miao
authors.affiliation: Hand and Microsurgery Center, The Second Affiliated Hospital of Harbin Medical University, Harbin, China.
authors.forename: D Y
authors.initials: DY
authors.lastname: Hou
authors.affiliation: Hand and Microsurgery Center, The Second Affiliated Hospital of Harbin Medical University, Harbin, China State-Province Key Laboratories of Biomedicine-Pharmaceutics, Harbin Medical University, Harbin, China Department of Molecular Pharmacology and Therapeutics, Stritch School of Medicine in Loyola University, Chicago, IL, USA xren1961@gmail.com chinarenxg@126.com.
authors.forename: X P
authors.initials: XP
authors.lastname: Ren
mesh_terms: D000005:Abdomen / Q000601:surgery*; D000818:Animals; D017209:Apoptosis; D004195:Disease Models, Animal; D004789:Enzyme Activation; D005260:Female; D020022:Genetic Predisposition to Disease; D008297:Male; D018345:Mice, Knockout; D009203:Myocardial Infarction / Q000201:enzymology / Q000473:pathology / Q000517:prevention & control*; D015428:Myocardial Reperfusion Injury / Q000201:enzymology / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D009206:Myocardium / Q000201:enzymology* / Q000473:pathology; D000072000:NF-KappaB Inhibitor alpha / Q000235:genetics / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D010641:Phenotype; D011493:Protein Kinase C / Q000378:metabolism*; D043782:Receptor, Bradykinin B2 / Q000172:deficiency / Q000235:genetics; D011943:Receptors, Adrenergic, beta / Q000378:metabolism; D011984:Sensory Receptor Cells / Q000378:metabolism; D009435:Synaptic Transmission; D013900:Thoracic Nerves / Q000378:metabolism / Q000503:physiopathology; D013997:Time Factors
chemical_list: D016328:NF-kappa B; C000606205:Nfkbia protein, mouse; D043782:Receptor, Bradykinin B2; D011943:Receptors, Adrenergic, beta; D000072000:NF-KappaB Inhibitor alpha; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; D011493:Protein Kinase C
keywords: cardioprotection; mechanism; myocardial ischemia reperfusion injury; remote nonischemic preconditioning; signal transduction