133804-44-1

Na ⁺ /Ca ²⁺ exchanger

Caldaret (MCC-135) is demonstrated to restore Ca ²⁺ -ATPase activity of the sarcoplasmic reticulum (SR) isolated from the myocardium acutely exposed to ischemia and reperfusion in vitro.

Caldaret, an intracellular Ca ²⁺ handling modulator, limits infarct size of reperfused canine heart. The cardioprotective effect of Caldaret, a novel intracellular Ca ²⁺ handling modulator that acts through reverse-mode Na ⁺ /Ca ²⁺ exchanger inhibition and potential sarcoplasmic reticulum (SR) Ca ²⁺ uptake enhancement, against reperfusion injury is investigated. Intravenously infused Caldaret (3 or 30 microg/kg per hour) for 30 min at left circumflex (LCX)-reperfusion markedly reduces infarct size (by 51.3% or 71.9%, respectively). The amelioration of intracellular Ca ²⁺ handling dysfunction achieved by Caldaret leads to cardioprotective effects against reperfusion injury following prolonged ischemia. Caldaret (MCC-135) is a new potent compound with beneficial effects in heart failure. In diabetic rats, Caldaret decreases TR80 significantly without significant effect on developed tension (DT). Caldaret has minimal effects on SR Ca ²⁺ uptake in normal rats, that is observed as increased SR Ca ²⁺ uptake at uptake time of 20 and 30 s at the highest concentration of 10 μM. In diabetic rats, Caldaret increases SR Ca ²⁺ uptake all over the range of uptake time. Both initial rate of SR Ca ²⁺ uptake and the amount of Ca ²⁺ accumulated in the SR with longer uptake time are increased by Caldaret.