Is Na/Ca exchange during ischemia and reperfusion beneficial or detrimental?

Cytosolic calcium increases to approximately 3 μM after 15 min of global ischemia. Manipulations that attenuate this increase in cytosolic Ca²⁺ reduce myocyte death and dysfunction. The increase in cytosolic Ca²⁺ during ischemia is dependent on an increase in intracellular Na⁺, suggesting a role for Na/Ca exchange. Typical ischemic values for ionized intra- and extracellular Na⁺, Ca²⁺, and membrane potential are consistent with the Na/Ca exchanger operating near equilibrium during ischemia. Studies were undertaken using hearts from mice that overexpress the Na/Ca exchanger to determine if Na/Ca exchanger overexpression enhances or reduces ischemic injury. These studies suggest that overexpression of the Na/Ca exchanger enhances injury in males, but females are protected by a gender-related mechanism.