Abstract| Volume 177, ISSUE 1, P47, August 2013

Sympathetic reinnervation and arrhythmia prevention following cardiac ischemia-reperfusion injury

      Sympathetic axons fail to regenerate into infarcted myocardium after cardiac ischemia-reperfusion (I-R) injury, which is surprising due to well documented sympathetic regeneration into other tissues. Sympathetic denervation of the heart is also associated with increased risk for ventricular arrhythmias and sudden cardiac death. We found that the inhibitory extra cellular matrix component, chondroitin sulfate proteoglycans (CSPGs), were present in the infarct after I-R. Protein tyrosine phosphatase receptor sigma (PTPRS) was recently identified as a receptor for CSPGs. To test directly if infarct-derived CSPGs prevented cardiac reinnervation, we carried out ischemia-reperfusion in ptprs-/- and ptprs+/- mice. Cardiac infarcts in ptprs-/- mice were hyperinnervated, while infarcts in ptprs+/- littermates were denervated, confirming that CSPGs prevent sympathetic reinnervation of the cardiac scar after I-R. Electrical properties of ptprs+/- and ptprs-/- mice were also examined following I-R using optical mapping. In addition to denervation of the infarct, ptprs+/- mice exhibit several indicators of rhythm instability, including calcium alternans during normal pacing and calcium elevation in response to isoproterenol. Reinnervated ptprs-/- mice, however exhibited normal calcium dynamics. Additionally, conscious, ambulatory ptprs-/- mice following I-R were less susceptible isoproterenol induced ventricular arrhythmias, as assessed by ECG telemetry. These results suggest that reinnervation of the heart after I-R injury stabilizes calcium handling and reduces the likelihood of ventricular arrhythmias.
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