Meissner A, Morgan J P
Charles A. Dana Research Institute, Boston, Massachusetts.
Am J Physiol. 1995 Jan;268(1 Pt 2):H100-11. doi: 10.1152/ajpheart.1995.268.1.H100.
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.
将成年大鼠心脏分离出来，置于等容非工作状态的Langendorff装置中，加载钙离子指示剂水母发光蛋白，以研究缺血再灌注对细胞内游离钙离子浓度（[Ca2+]i）稳态及左心室（LV）收缩功能的影响。在三组实验中（每组n = 8），分别进行10、20和30分钟的缺血处理，再灌注60分钟后，左心室舒张末压恢复至缺血前对照值（122±5 mmHg）的比例分别为63% [77±3（SE）mmHg]、48%（56±4 mmHg）和34%（43±4 mmHg）。舒张压分别维持在40±4、55±3和65±6 mmHg（缺血前对照值为12 mmHg）。在再灌注早期（0 - 20分钟），发光信号从峰值衰减至90%所需时间（t90L）延长，10分钟和20分钟缺血组的左心室压力曲线舒张期延迟与之平行。再灌注60分钟后，所有组的t90L均持续延长（10分钟缺血组，89±2毫秒；20分钟缺血组，95±3毫秒；30分钟缺血组，96±2毫秒；对照组，82±2毫秒；P < 0.05）。相反，左心室压力曲线相较于缺血前对照值缩短，提示肌原纤维对钙离子的反应性改变。再灌注60分钟后，舒张期[Ca2+]i升高（10分钟缺血组，0.40±0.06微摩尔；20分钟缺血组，0.48±0.04微摩尔；30分钟缺血组，0.51±0.06微摩尔；对照组，0.32±0.01微摩尔），且与左心室舒张压呈显著正相关（r = 0.79；P < 0.001）。钙离子瞬变幅度与左心室舒张末压也呈正相关（r = 0.53；P < 0.05）。这些研究结果表明，大鼠在经历中度至重度再灌注损伤后，缺血后收缩功能障碍与钙离子调节改变及[Ca2+]i稳态受损有关。
