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). Calda ret 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.
