Miyamae M, Camacho S A, Weiner M W, Figueredo V M
Department of Medicine (Cardiology), San Francisco General Hospital, California, USA.
Am J Physiol. 1996 Nov;271(5 Pt 2):H2145-53. doi: 10.1152/ajpheart.1996.271.5.H2145.
Intracellular calcium overload has been implicated in postischemic reperfusion injury. In myocytes, mitochondrial free calcium concentration ([Ca2+]m), not cytosolic free calcium concentration ([Ca2+]c), overload is related to reoxygenation injury. We tested the hypothesis that [Ca2+]m, not [Ca2+]c, overload is an important mediator of reperfusion injury in whole hearts. [Ca2+]m and [Ca2+]c were assessed using indo 1 fluorescence in isolated rat hearts subjected to 45 min of ischemia and 20 min of reperfusion. Ruthenium red (RR), a selective inhibitor of mitochondrial calcium uptake at 0.025 microM, attenuated the increase of [Ca2+]m (4% RR vs. 57% control) over preischemic levels (230 +/- 10 nM) but did not affect the increase of systolic [Ca2+]c (990 +/- 100 nM RR vs. 1,010 +/- 130 nM control). This was associated with improved recovery of left ventricular developed pressure (61% RR vs. 37% control) and attenuation of the increase of diastolic pressure (34 mmHg RR vs. 47 mmHg control). Contractile recovery was related to the degree of [Ca2+]m overload in both control and RR hearts (r2 = 0.47, P = 0.001). This study is the first to demonstrate that [Ca2+]m, and not [Ca2+]c, overload is related to reperfusion injury in intact beating hearts.
细胞内钙超载与缺血后再灌注损伤有关。在心肌细胞中，线粒体游离钙浓度（[Ca2+]m）而非胞质游离钙浓度（[Ca2+]c）超载与再氧合损伤有关。我们检验了这样一个假设，即[Ca2+]m而非[Ca2+]c超载是全心再灌注损伤的重要介质。在经历45分钟缺血和20分钟再灌注的离体大鼠心脏中，使用吲哚1荧光法评估[Ca2+]m和[Ca2+]c。钌红（RR）是一种0.025微摩尔的线粒体钙摄取选择性抑制剂，可减弱[Ca2+]m相对于缺血前水平（230±10纳摩尔）的升高（RR组为4%，对照组为57%），但不影响收缩期[Ca2+]c的升高（RR组为990±100纳摩尔，对照组为1010±130纳摩尔）。这与左心室舒张末压恢复改善（RR组为61%，对照组为37%）以及舒张压升高减弱（RR组为34毫米汞柱，对照组为47毫米汞柱）相关。在对照组和RR组心脏中收缩功能恢复均与[Ca2+]m超载程度相关（r2 = 0.47，P = 0.001）。本研究首次证明，在完整跳动的心脏中，[Ca2+]m而非[Ca2+]c超载与再灌注损伤有关。
