Reduced mitochondrial Ca2+ loading and improved functional recovery after ischemia-reperfusion injury in old vs. young guinea pig hearts.
Reduced mitochondrial Ca2+ loading and improved functional recovery after ischemia-reperfusion injury in old vs. young guinea pig hearts.
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与年轻豚鼠心脏相比，减少了线粒体 Ca2 负荷并改善了缺血再灌注损伤后的功能恢复。
DOI：
10.1152/ajpheart.00533.2011
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发表时间：
2012
期刊：
影响因子：
--
通讯作者：
Stowe,DavidF
中科院分区：
文献类型：
--
作者：
Rhodes,SamhitaS;Camara,AmadouKS;Heisner,JamesS;Riess,MatthiasL;Aldakkak,Mohammed;Stowe,DavidF
氧化损伤和胞浆 Ca2+ 浓度 ([Ca2+]cyto) 处理受损与心肌缺血再灌注 (I/R) 损伤后线粒体 [Ca2+] ([Ca2+]mito) 过载和功能恢复抑制相关。我们假设与年轻豚鼠的心脏相比，老年豚鼠的心脏在 I/R 损伤后表现出 [Ca2+] 线粒体处理受损、功能恢复较差以及氧化状态更严重。分离年轻（~4 周）和年老（>52 周）豚鼠的心脏，并用 Krebs-Ringer 溶液（37°C 下 2.1 mM Ca2+ 浓度）灌注。用球囊测量左心室压力（LVP，mmHg），并使用靠在左心室游离壁上的光纤探针通过荧光测量NADH、[Ca2+]mito(nM)和[Ca2+]细胞(nM)。基线 (BL) 测量后，心脏进行 30 分钟整体缺血和 120 分钟再灌注 (REP)。在老年心脏与年轻心脏中，我们发现： 1) 梗塞面积百分比较低（27 ± 9 vs. 57 ± 2）； 2) REP 10 分钟（57 ± 11 vs. 29 ± 2）和 60 分钟（55 ± 10 vs. 32 ± 2）时的 LVP（收缩压-舒张压）较高； 3) REP 10 和 60 分钟时舒张 LVP 较低（6 ± 3 vs. 29 ± 4 和 3 ± 3 vs. 21 ± 4 mmHg）； 4) 缺血期间平均[Ca2+]细胞较高（837 ± 39 vs. 541 ± 39），但[Ca2+]mitow 较低（545 ± 62 vs. 975 ± 38）； 5) REP 10 和 60 分钟时 [Ca2+]mitow 较低（129 ± 2 对比 293 ± 23 和 122 ± 2 对比 234 ± 15）； 6) 减少对多巴胺和地高辛的正性肌力反应； 7) 两组的 NADH 在缺血期间均升高，而在 REP 期间低于 BL。与我们提出的假设相反，与年轻心脏相比，老年心脏在 I/R 损伤后表现出 [Ca2+]mito 减少、梗死减少和基础机械功能改善；由于年龄的不同，氧化还原状态没有差异。在该模型中，尽管老年心脏与年轻心脏缺血期间[Ca2+]细胞负荷较高，但与衰老相关的保护可能与I/R损伤后有限的[Ca2+]线粒体负荷有关。
Oxidative damage and impaired cytosolic Ca2+concentration ([Ca2+]cyto) handling are associated with mitochondrial [Ca2+] ([Ca2+]mito) overload and depressed functional recovery after cardiac ischemia-reperfusion (I/R) injury. We hypothesized that hearts from old guinea pigs would demonstrate impaired [Ca2+]mitohandling, poor functional recovery, and a more oxidized state after I/R injury compared with hearts from young guinea pigs. Hearts from young (∼4 wk) and old (>52 wk) guinea pigs were isolated and perfused with Krebs-Ringer solution (2.1 mM Ca2+concentration at 37°C). Left ventricular pressure (LVP, mmHg) was measured with a balloon, and NADH, [Ca2+]mito(nM), and [Ca2+]cyto(nM) were measured by fluorescence with a fiber optic probe placed against the left ventricular free wall. After baseline (BL) measurements, hearts were subjected to 30 min global ischemia and 120 min reperfusion (REP). In old vs. young hearts we found: 1) percent infarct size was lower (27 ± 9 vs. 57 ± 2); 2) developed LVP (systolic-diastolic) was higher at 10 min (57 ± 11 vs. 29 ± 2) and 60 min (55 ± 10 vs. 32 ± 2) REP; 3) diastolic LVP was lower at 10 and 60 min REP (6 ± 3 vs. 29 ± 4 and 3 ± 3 vs. 21 ± 4 mmHg); 4) mean [Ca2+]cytowas higher during ischemia (837 ± 39 vs. 541 ± 39), but [Ca2+]mitowas lower (545 ± 62 vs. 975 ± 38); 5) [Ca2+]mitowas lower at 10 and 60 min REP (129 ± 2 vs. 293 ± 23 and 122 ± 2 vs. 234 ± 15); 6) reduced inotropic responses to dopamine and digoxin; and 7) NADH was elevated during ischemia in both groups and lower than BL during REP. Contrary to our stated hypotheses, old hearts showed reduced [Ca2+]mito, decreased infarction, and improved basal mechanical function after I/R injury compared with young hearts; no differences were noted in redox state due to age. In this model, aging-associated protection may be linked to limited [Ca2+]mitoloading after I/R injury despite higher [Ca2+]cytoload during ischemia in old vs. young hearts.
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影响因子：
5
作者：
Gabel, Scott A;Walker, Vickie R;Murphy, Elizabeth
通讯作者：
Murphy, Elizabeth
心脏保护与衰老
影响因子：
2.9
作者：
Y. Shim
通讯作者：
Y. Shim
完整心脏全缺血后 [Na( )](i)、室室 [Ca(2 )] 和 NADH 的变化以及功能障碍。
DOI：
10.1152/ajpheart.2001.280.1.h280
发表时间：
2001
期刊：
American journal of physiology. Heart and circulatory physiology
影响因子：
--
作者：
Varadarajan,SG;An,J;Novalija,E;Smart,SC;Stowe,DF
通讯作者：
Stowe,DF
肌球蛋白组成的年龄依赖性变化与豚鼠心脏收缩经济性的增强相关
DOI：
--
发表时间：
1998
期刊：
Journal of Physiology
影响因子：
--
作者：
J. Velden;A. Moorman;G. Stienen
通讯作者：
G. Stienen
DOI：
--
发表时间：
1994-12
期刊：
The Journal of laboratory and clinical medicine
影响因子：
--
作者：
E. Lesnefsky;D. Gallo;Jian-wen Ye;T. Whittingham;W. Lust
通讯作者：
E. Lesnefsky;D. Gallo;Jian-wen Ye;T. Whittingham;W. Lust