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Effect of ischemia-reperfusion on heart mitochondria from hyperthyroid rats
Paola Venditti1, Claudio Agnisola, Sergio Di Meo
1Dipartimento di Fisiologia Generale ed Ambientale, Università di Napoli, V. Mezzocannone 8, Napoli, Italy.
Objective:
We investigated the effect of hyperthyroidism on the functional response of mitochondria to ischemia-reperfusion and its relationship with changes in mitochondrial susceptibility to stress conditions.
Methods:
Hyperthyroidism was elicited by ten daily intraperitoneal injections of T3 (10 microg/100 g body weight). Mitochondria were isolated at 3000xg (M3) from homogenates of hearts perfused by the Langendorff technique after either 25 min reperfusion following 20 min ischemia or 45 min perfusion (controls). Rates of O2 consumption and H2O2 release with complex II-linked substrate, capacity to remove H2O2, extent of oxidative damage, levels of liposoluble antioxidants, such as ubiquinols and vitamin E, and susceptibility to Ca2+ -induced swelling were determined.
Results:
During reperfusion, hyperthyroid hearts displayed a significant tachycardia together with a low functional recovery. In comparison to the respective controls, mitochondria from both euthyroid and hyperthyroid hearts subjected to ischemia-reperfusion protocol exhibited decreases in the rate of O2 consumption, capacity to remove H2O2, and concentration of antioxidants, and increases in the rate of H2O2 release, concentration of hydroperoxides and protein-bound carbonyls, and susceptibility to Ca2+ -induced swelling. Such changes were higher in mitochondria from hyperthyroid hearts. The increase in the protein percent content and cytochrome oxidase activity of a mitochondrial fraction isolated at 8000xg (M8) from hyperthyroid hearts after reperfusion, suggests that the decline of mitochondrial respiration of M3 fraction could be due to the degradation of the oldest, mature mitochondria endowed of high oxidative capacity, but low antioxidant capacity, which would be lost by heavy mitochondrial fraction and recovered in the light fraction.
Conclusions:
The higher susceptibility to ischemia-reperfusion of the heart from hyperthyroid animals is associated with a significant increase in mitochondrial dysfunction.