Peripheral nociception associated with surgical incision elicits remote nonischemic cardioprotection via neurogenic activation of protein kinase c signaling

Jones, W. Keith, et al. "Peripheral nociception associated with surgical incision elicits remote nonischemic cardioprotection via neurogenic activation of protein kinase C signaling." Circulation 120.11 suppl 1 (2009): S1-S9.

Ischemia reperfusion injury associated with myocardial infarction is a major contributor to cardiovascular related death.  Unfortunately, the only treatment we have for cardiac ischemia, is reperfusion of oxygen to the ischemic tissue, which in itself can also lead to cell death.  Importantly, ischemic preconditioning (IPC) has been shown to limit the damaged induced by ischemia/reperfusion and act as a cardioprotectant.  However, IPC is somewhat impractical in a clinical setting in terms of feasibility.  This study was able to show that a preconditioned non-ischemic remote trauma was also able to induce cardioprotection through neurogenic mechanisms.  Specifically they were able to show that stimulation of pain receptors located in the skin activated an antidromic spinal reflex, which in turn activated cardiac sympathetic nerves via calcitonin gene-related peptide (CGRP).  CGRP then induced NE and Bradykinin release, stimulating beta-AR and BK2R.  Activation of these receptors then caused an upregulation of PKC-epsilon (mediator of cardioprotection) and a down regulation of PKC-delta (mediator of cell-death via necrosis).  They believe that one of the cardioprotective effects of PKC-epsilon is the activation of mitochondrial Katp channels, which when inhibited attenuated the cardioprotective effects.  Conclusively, this study may provide to be extremely important clinically due to the ease and efficiency of the remote preconditioning of trauma on reducing I/R injury following an MI.

~JI