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.

Background: 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.
Methods: 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.
Results: 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.
Conclusion: 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.
(© The Author(s) 2015.)