Preservation of myofilament calcium responsiveness underlies protection

Objective: Whereas diminution of infarct size by ischemic preconditioning (IP) is well-accepted, protection against stunning is 21 controversial. Since stunning is characterized by decreased myofilament Ca 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 21 with fura-2 to measure intracellular calcium concentration ([Ca ] ) and developed force. Results: After 20 min of reperfusion, left i ventricular developed pressure decreased in stunned hearts to 6165% of control (P,0.01), whereas recovery was complete in the IP 21 21 hearts (9764%). Steady-state [Ca ] –force relationships revealed a decreased maximal Ca -activated force in stunned hearts relative to i 21 control, but no change in the IP group. The Ca 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.  1999 Elsevier Science B.V. All rights reserved.