Mitochondrial Dysfunction Is Induced by Cardiac Pressure Overload

Pressure overload induced by ascending transaortic constriction was examined to evaluate cytoprotection with cytidine-5´-diphosphatecoline (CDP-choline) targeting oxidative stress and mitochondrial function. Male Wistar rats pre-treated with citicoline or a vehicle showed a decrease in mean arterial pressure (56.16 ± 10.08 vs. 60.55 ± 8.70 mmHg, respectively) with ascending transaortic constriction (AAC). After 60 min of hypotension, arterial blood gases, hepatic, renal, and inflammatory markers were measured together with oxidative stress, oxygen consumption, and the activity of the respiratory chain. Pressure-overloaded animals developed a marked elevation in blood lactate with a fall in pH values and a significant increase in urea nitrogen, creatinine, and lactate dehydrogenase (LDH); no changes were seen in hepatic transaminases, interleukins IL-1β, IL-6, and tumor necrosis factor α (TNFα), whereas IL-10 increased. In contrast, under a 60.55 ± 8.70 mmHg fall in blood pressure, preconditioning induced a moderate lactate elevation with a minor decrease in pH compared to the group without preconditioning. Urea nitrogen, creatinine, and LDH were elevated, whereas aspartate aminotransferase (AST)increased only in the pre-treated group; IL-1β, IL-6, and TNFα did not change, and IL-10 increased. Oxidative stress in the heart, liver, and kidney mitochondria was related to dysregulation of oxidative phosphorylation, associated with a loss of complex III and complex IV activity. Thus, CDP-choline attenuated the heart damage caused by pressure overload by reducing oxidative stress and maintaining mitochondrial function.