The decrease in Ca2+ responsiveness of myofilaments in stunned myocardium implies that there may be structural changes in proteins composing the contractile machinery. To elucidate the lesion in stunned myocardium, isolated guinea pig hearts were subjected to global ischemia at 37°C and reperfused. SDS-PAGE revealed that the contents of desmin, α-actinin, and spectrin decreased in the myofibrillar fraction isolated from hearts reperfused after 60-minute ischemia compared with nonischemic control hearts. To examine the change of cytoskeletal proteins in stunned myocardium, immunohistochemical studies with antibodies against these proteins were performed after 15 minutes of ischemia. In stunned myocardium, the staining was largely intact, but there were some lesions where desmin was not stained and α-actinin and spectrin were only weakly identified. The percentage of normally stained areas in the myocardium (percent stained area), quantified by image processing, was significantly lower in stunned myocardium (79.6±3.6%, mean±SEM) than in nonischemic control myocardium (96.5±0.7%). Percent recovery of developed pressure significantly correlated with percent stained area (r=.82, P<.001). In hearts subjected to 15-minute ischemia but not reperfused, or in hearts reperfused with Ca2+ -free solution after 15- minute ischemia, staining by the antibodies remained intact, suggesting that the change of the cyloskeletal proteins is mediated by Ca2+ overload during reperfusion. In hearts treated with the protease inhibitor leupeptin (50 μmol/L) or calpain inhibitor I (100 μmol/L), both developed pressure and staining were well preserved. These results indicate that contractile dysfunction in stunned myocardium has a strong correlation with the disappearance of cytoskeletal proteins that may be mediated by a Ca2+- dependent intracellular protease activated during reperfusion. The disruption of cytoskeletal proteins is a possible mechanism for stunning, although it may be a secondary effect of protease activation.
- calpain inhibitor I
ASJC Scopus subject areas
- Cardiology and Cardiovascular Medicine