Contractile dysfunction and abnormal Ca2+ modulation during postischemic reperfusion in rat heart.

Isolated adult rat hearts in an isovolumic nonworking Langendorff preparation were loaded with the Ca2+ indicator aequorin to investigate the effects of ischemic reperfusion on free intracellular Ca2+ concentration ([Ca2+]i) homeostasis and left ventricular (LV) contractile function. In three groups (each n = 8) that underwent 10, 20, and 30 min of ischemia, recovery of developed pressure amounted to, respectively, 63% [77 +/- 3 (SE) mmHg], 48% (56 +/- 4 mmHg), and 34% (43 +/- 4 mmHg) of preischemic control (122 +/- 5 mmHg) after 60 min of reperfusion. Diastolic pressure remained elevated at 40 +/- 4, 55 +/- 3, and 65 +/- 6 mmHg, respectively (preischemic control, 12 mmHg). During early reperfusion (0-20 min), the light transient demonstrated a prolonged time to 90% decline from peak light (t90L), which was paralleled by a delayed relaxation on the LV pressure tracing in the 10- and 20-min ischemia groups. After 60 min of reperfusion, the prolongation of t90L persisted in all groups (10-min ischemia, 89 +/- 2 ms; 20 min, 95 +/- 3 ms; 30 min, 96 +/- 2 ms; control, 82 +/- 2 ms; P < 0.05). In contrast, the LV pressure tracing was abbreviated beyond the preischemic control, indicating altered myofibrillar Ca2+ responsiveness. Diastolic [Ca2+]i was elevated after 60 min of reperfusion (10-min ischemia, 0.40 +/- 0.06 microM; 20 min, 0.48 +/- 0.04 microM; 30 min, 0.51 +/- 0.06 microM; control, 0.32 +/- 0.01 microM) and had a significant positive correlation with LV diastolic pressure (r = 0.79; P < 0.001). A positive correlation was also found for the amplitude of the Ca2+ transient and LV developed pressure (r = 0.53; P < 0.05). These findings suggest that postischemic contractile dysfunction is related to altered Ca2+ modulation with impaired [Ca2+]i homeostasis following moderate to severe reperfusion injury in the rat.