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 Ca(2+)-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.
Pérez
N G
NG
Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Marbán
E
E
Cingolani
H E
HE
D008841:Actin Cytoskeleton / Q000378:metabolism*; D000704:Analysis of Variance; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D066298:In Vitro Techniques; D007424:Intracellular Fluid / Q000378:metabolism; D019157:Ischemic Preconditioning, Myocardial; D008297:Male; D008954:Models, Biological; D017202:Myocardial Ischemia / Q000378:metabolism*; D010477:Perfusion; D051381:Rats; D011919:Rats, Inbred Strains
D002118:Calcium