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Regulator of G protein signaling (RGS) proteins are important modulators of cardiac function. We previously reported that disruption of interactions between RGS proteins and Gα_i2 protects the heart from ischemic injury. However, the ability of specific members of the RGS protein family to influence cardiac sensitivity to ischemic injury has not been previously explored. The goal of the present study was to determine how genetic deletion of specific RGS proteins influences myocardial sensitivity to ischemic injury.

Hearts from RGS1 knockout (RGS1^‐/‐), RGS2^‐/‐, RGS2^‐/‐ RGS4^‐/‐ double knockout, RGS5^‐/‐, and RGS6^‐/‐ mice, and their respective wildtype (^+/+) littermates were subjected to 30 min ischemia and 2 hours reperfusion using the Langendorff isolated heart model. Infarct sizes were measured by triphenyltetrazolium chloride staining.

RGS6^‐/‐ hearts had significantly larger …