Injection of isolated mitochondria during early reperfusion for cardioprotection
- 1 January 2009
- journal article
- research article
- Published by American Physiological Society in American Journal of Physiology-Heart and Circulatory Physiology
- Vol. 296 (1), H94-H105
- https://doi.org/10.1152/ajpheart.00567.2008
Abstract
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 × 106± 1.5 × 106/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.Keywords
This publication has 44 references indexed in Scilit:
- Redox signaling triggers protection during the reperfusion rather than the ischemic phase of preconditioningBasic Research in Cardiology, 2008
- Redox signaling at reperfusion is required for protection from ischemic preconditioning but not from a direct PKC activatorBasic Research in Cardiology, 2007
- Survival and maturation of human embryonic stem cell-derived cardiomyocytes in rat heartsJournal of Molecular and Cellular Cardiology, 2007
- Age- and Gender-Related Differences in Mitochondrial Oxygen Consumption and Calcium With Cardioplegia and DiazoxideThe Annals of Thoracic Surgery, 2007
- Mitochondrial Ion ChannelsAnnual Review of Physiology, 2007
- Reduction and Redistribution of Gap and Adherens Junction Proteins After Ischemia and ReperfusionThe Annals of Thoracic Surgery, 2006
- Age- and Gender-Related Differences in Ischemia/Reperfusion Injury and Cardioprotection: Effects of DiazoxideThe Annals of Thoracic Surgery, 2006
- The Release of Cytochrome c from Mitochondria: A Primary Site for Bcl-2 Regulation of ApoptosisScience, 1997
- An Evaluation of the Measurement of the Activities of Complexes I-IV in the Respiratory Chain of Human Skeletal Muscle MitochondriaBiochemical Medicine and Metabolic Biology, 1994
- Cardioplegia with Adenosine and Adenosine Triphosphate in the Isolated Guinea Pig Heart.Japanese Heart Journal, 1992