| Abstrakt: |
We occluded the left anterior descending coronary artery of anesthetized, open-chest dogs, for 1 or 2 h. Some hearts were reperfused for 1 h after 1 h of ischemia. We isolated mitochondria from the central ischemic zone (CIZ) and a surrounding nonischemic zone (NIZ) of the left ventricle, and assayed HO production using a horseradish peroxidase-dual wavelength spectrophotometric technique. Mitochondria, studied in the absence of exogenous respiratory chain inhibitors, generated HO during State 4 respiration with succinate as the substrate. NIZ mitochondria in all groups produced ca. 1.5 nmols HO/min/mg protein (no significant differences between groups). The State 4 O consumption rates of NIZ mitochondria from hearts subjected to 1 h ischemia plus reperfusion, or 2 h of ischemia (ca. 30 nmols/min/mg) were significantly higher than that of NIZ mitochondria of hearts subjected to only 1 h of ischemia (23 nmols/min/mg). Thus, the ratio between HO produced and State 4 O consumption fell from 6.5% to 5%. Mitochondria from all CIZ samples had State 4 O consumption rates that were not different from corresponding NIZ values. However CIZ mitochondria of hearts subjected to 1 h ischemia without reperfusion produced less HO (1.1±0.1 nmols/min/mg), and had a slightly reduced HO/O ratio (4.4±0.7%), compared with their NIZ samples (1.5±0.1 nmols/min/mg; 5.3%). Reperfusion after 1 h of ischemia abolished these regional differences. The CIZ mitochondria from hearts subjected to 2 h ischemia produced only 0.75±0.22 nmols HO/min/mg (2.5% of State 4 O consumption). These values were 50% of corresponding NIZ values, and were significantly less than for any other group or tissue region. If similar phenomena occur in conscious animals subjected to incomplete regional ischemia, especially of relatively brief duration or if accompanied by reduced intracellular defenses against oxidants such as HO, they suggest that mitochondria persist as HO sources and so may contribute to the oxidant load and myocardial dysfunction. [ABSTRACT FROM AUTHOR] |
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