Aims: 

The cardioprotectiveeffects of estrogens may be recognized by their beneficial influence on cardiac intracellular calcium(Ca²⁺_i) handling. However, literature data supporting this hypothesis are scarce. We aimed to show a relationship between ovariectomy and Ca²⁺_i-cycling and detect its effects on ischemic tolerance.

Methods: 

Isolated Langendorff-perfused hearts of ovariectomized (OVX) and control female rats were studied 10 weeks after operation. A subset of the animals received estrogen replacement therapy (ERT) (estradiol propionate 450 mg/bwkg/week im.). Left ventricular pressure, coronary flow, and, using Indo-1, surface fluorometry Ca²⁺_i-transients were recorded. Hearts were exposed to 30 min global ischemia followed by 30 min reperfusion.

Results: 

Hemodynamic performance of isolated hearts was similar in all studied groups under resting conditions. Analysis of Ca²⁺_i-transients revealed depressed Ca²⁺ sequestration in the OVX group which was restored by ERT. Lower ischemia tolerance following OVX was evidenced by more pronounced ischemic contracture and slower restitution of contractile/lusitropic function during reperfusion. Ca²⁺_i-handling of OVX hearts was characterized by higher [Ca²⁺_i]duringischemia. The onset of reperfusion resulted in a sudden elevation of basal [Ca²⁺_i]. In hearts of OVX rats basal [Ca²⁺_i] increase was higher and restitution of the rate of Ca²⁺ release and sequestration was slower during reperfusion. Depressed ischemic tolerance of OVX hearts was restored by ERT regarding both hemodynamic and Ca²⁺_i-handling parameters.

Conclusion: 

Ovariectomy produced depressed cardiac Ca²⁺_i-cycling which aggravated the impairment of Ca²⁺_i-handling during ischemia/reperfusion contributing to lower cardiac ischemia tolerance. Consequently, estrogens may exert their cardioprotective effects by protecting cardiac Ca²⁺_i-homeostasis.

Support: 

OTKA grant 68502