Injection of isolated mitochondria during early reperfusion for cardioprotection
Injection of isolated mitochondria during early reperfusion for cardioprotection
复制标题
DOI：
10.1152/ajpheart.00567.2008
复制
发表时间：
2009-01-01
影响因子：
4.8
通讯作者：
Levitsky, Sidney
中科院分区：
文献类型：
--
作者：
McCully, James D.;Cowan, Douglas B.;Levitsky, Sidney
McCully JD，科万DB，Pacak CA，Toumpoulis IK，Dayalan H，Levitsky S.再灌注早期注射离体线粒体的心肌保护作用。Am J Physiol Heart Circ Physiol 296：H94-H105，2009.首次发表于2008年10月31日; doi：10.1152/ajpheart.00567.2008。- 以前，我们证明，缺血诱导线粒体损伤和功能障碍，在整个再灌注过程中持续存在，并对缺血后功能恢复和细胞活力产生负面影响。我们假设，从未受缺血影响的组织中分离出有呼吸能力的线粒体，然后在再灌注前注射到缺血区，将增强缺血后功能恢复并限制梗死面积。新西兰白色兔（n = 52）进行30分钟的平衡和30分钟的局部缺血（RI）诱导的左冠状动脉前降支结扎。在RI 29分钟时，RI区注射溶剂（假手术对照和RI溶剂）或含有从供体兔左心室组织（RI-Mito）分离的线粒体（7.7 x 10（6）+/- 1.5 x 10（6）/ml）的溶剂。结果表明，RI后30 min解除圈套器，再灌注120 min，RI组左室最大发展压和收缩期缩短率明显增加（P < 0.05，相对于RI-载体）分别为平衡值的75%和83%，相比之下，在再灌注120分钟时分别为57%和62%，在RI车辆的心脏。与RI-载体心脏相比，RI-Mito中肌酸激酶-MB、心肌肌钙蛋白I和相对于危险区域的梗死面积显著降低（P < 0.05）。共聚焦显微镜显示，注射的线粒体存在，并在再灌注120分钟后存活，并从心外膜分布到内膜下。这些结果表明，从未受缺血影响的组织中分离出有活力的呼吸能力线粒体，然后在再灌注前注射到缺血区，显著增强缺血后功能恢复和细胞活力。
McCully JD, Cowan DB, Pacak CA, Toumpoulis IK, Dayalan H, Levitsky S. Injection of isolated mitochondria during early reperfusion for cardioprotection. Am J Physiol Heart Circ Physiol 296: H94-H105, 2009. First published October 31, 2008; doi: 10.1152/ajpheart.00567.2008. - Previously, we demonstrated that ischemia induces mitochondrial damage and dysfunction that persist throughout reperfusion and impact negatively on postischemic functional recovery and cellular viability. We hypothesized that viable respiration-competent mitochondria, isolated from tissue unaffected by ischemia and then injected into the ischemic zone just before reperfusion, would enhance postischemic functional recovery and limit infarct size. New Zealand White rabbits (n = 52) were subjected to 30 min of equilibrium and 30 min of regional ischemia (RI) induced by snaring the left anterior descending coronary artery. At 29 min of RI, the RI zone was injected with vehicle (sham control and RI vehicle) or vehicle containing mitochondria (7.7 x 10(6) +/- 1.5 x 10(6)/ml) isolated from donor rabbit left ventricular tissue (RI-Mito). The snare was released at 30 min of RI, and the hearts were reperfused for 120 min. Our results show that left ventricular peak developed pressure and systolic shortening in RI-Mito hearts were significantly enhanced (P < 0.05 vs. RI-vehicle) to 75% and 83% of equilibrium value, respectively, at 120 min of reperfusion compared with 57% and 62%, respectively, in RI-vehicle hearts. Creatine kinase-MB, cardiac troponin I, and infarct size relative to area at risk were significantly decreased in RI-Mito compared with RI-vehicle hearts (P < 0.05). Confocal microscopy showed that injected mitochondria were present and viable after 120 min of reperfusion and were distributed from the epicardium to the subendocardium. These results demonstrate that viable respiration-competent mitochondria, isolated from tissue unaffected by ischemia and then injected into the ischemic zone just before reperfusion, significantly enhance postischemic functional recovery and cellular viability.