Preservation of myofilament calcium responsiveness underlies protection against myocardial stunning by ischemic preconditioning

Objective: Whereas diminution of infarct size by ischemic preconditioning (IP) is well-accepted, protection against stunning is controversial. Since stunning is characterized by decreased myofilament Ca²⁺ responsiveness, we investigated whether IP would preserve myofilament responsiveness in a model of stunning. Methods: Rat hearts were retrogradely perfused with Krebs-Henseleit (K-H) solution for 20 min and then subjected to 20 min of no-flow global ischemia, followed by 20 min of reperfusion in the absence (stunning) or in the presence (IP) of a previous 5-min period of ischemia followed by 15 min of reperfusion. A group of hearts perfused under non-ischemic conditions served as control. Thin ventricular trabeculae were dissected from each of the experimental groups and loaded with fura-2 to measure intracellular calcium concentration ([Ca²⁺](i)) and developed force. Results: After 20 min of reperfusion, left ventricular developed pressure decreased in stunned hearts to 61±5% of control (P<0.01), whereas recovery was complete in the IP hearts (97±4%). Steady-state [Ca²⁺](i)- force relationships revealed a decreased maximal Ca²⁺-activated force in stunned hearts relative to control, but no change in the IP group. The Ca²⁺ required for 50% activation increased in stunning but not in IP. Conclusions: These results show that the decrease in myofilament responsiveness that characterizes stunning is prevented by ischemic preconditioning.