Increase in myofilament separation in the "stunned" myocardium

This study explores the effects of ischemic reperfusion injury on the radial separation distance between thick and thin myofilaments. The left anterior descending coronary artery was occluded for 5 mins and reperfused for 10 mins twelve times repetitively in 6 dogs. At the end of a final 90 min reperfusion period, the hearts were fixed by perfusion with glutaraldehyde, and subepicardial and subendocardial tissue from both normal and ischemic areas were prepared for transmission electron microscopy. Quantitative analysis of inter-filament distance (IFD) was performed on micrographs of transverse sections. The center-to-center IFD was calculated from the numerical density of thick filaments at the A band level using a hexagonal array conversion formula. Sarcomere length was measured on micrographs of longitudinal sections. The results showed that center-to-center thick IFD in the stunned subendocardium was 43.9 ± 0.8 nm which was significantly greater than the control distance of 40.6 ± 0.4 nm (P<0.001) from normal zone tissue. Thick IFD in the subepicardium was also significantly different: 43.4 ± 0.6 nm in the stunned tissue as compared with 39.0 ± 0.7 nm in the non-ischemic tissue (P<0.001). Sarcomere length in the normally perfused subendocardium was 2.01 ± 0.07 μm and was increased to 2.20 ± 0.08 μm in the stunned subendocardium (P<0.005). Sarcomere length in the normal and the stunned subepicardium was also different: 2.02 ± 0.04 vs. 2.10 ± 0.09 μm (P<0.005). The significant increase in spatial separation between the contractile filaments may affect optimal cross-bridge force generation at the molecular level. Myocardial performance in stunned myocardium is likely to be affected by these geometric alterations. The longer "unstressed" sarcomere lengths in stunned myocardium are suggestive of cytoskeletal abnormalities in the post-ischemic myocardium.