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- W1987815859 abstract "433 Background: Impairment of mitochondrial function is a critical factor in limiting preservation times of the heart. In our study, the nature and extent of mitochondrial defects were determined in muscle fibers obtained from rat hearts after prolonged cold ischemia, transplantation and reperfusion. Methods: Rat hearts were subjected to 10 hours of cold preservation in UW or HTK solutions (4 °C), syngeneic heterotopic heart transplantation (60 min of second ischemia) and 24 hours of reperfusion. Cardiac performance was scored from 0 to 4 by palpation and microscopic observation of organ function. Subsequently, small amounts of tissue were sampled, yielding permeabilized myocardial fibers of 2-4 mg wet weight per assay of mitochondrial function (high-resolution respirometry; OROBOROS Oxygraph). Substrate/inhibitor titrations and a cytochrome c (cyt c) test were applied to localize mitochondrial defects. Results: Cardiac scores were obtained between 1 and 4. Rates of ADP-stimulated respiration (State 3) supported by glutamate/malate (complex I) were linearly related to heart scores. Respiratory control ratios (active/passive rates) declined with reduction in heart scores. Although a similar decline in rate was found for respiration supported by succinate (complex II) and TMPD/ascorbate (complex IV), these rates were restored nearly to control levels after cyt c addition. Stimulation by added cyt c was restricted to respiration downstream of complex I, and increased with progressive loss of heart performance. Conclusion: Impairment of mitochondrial function correlates closely with reduction of cardiac performance and is caused by a specific damage of respiratory complex I and cyt c release. Mitochondrial cyt c depletion could be restored by added cyt c. This indicates a damage of the outer mitochondrial membrane and points to the importance of apoptosis in cardiac ischemia/reperfusion injury. High-resolution respirometry with permeabilized cardiac fibers obtained from small biopsy samples, therefore, offers a qualitative and quantitative evaluation of ischemia/reperfusion injury and provides a potential viability test after heart preservation." @default.
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- W1987815859 date "1999-05-01" @default.
- W1987815859 modified "2023-09-27" @default.
- W1987815859 title "PRESERVATION/REPERFUSION INJURY IN THE RAT CARDIAC TRANSPLANT MODEL. II. MITOCHONDRIAL AND CARDIAC PERFORMANCE" @default.
- W1987815859 doi "https://doi.org/10.1097/00007890-199905150-00456" @default.
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