Effect of endotoxin, dobutamine and dopamine on muscle mitochondrial respiration in vitro

Mitochondrial dysfunction may contribute to impaired oxygen metabolism during experimental and clinical sepsis. 1–5 In normal conditions, mitochondrial oxygen consumption is well coupled to ATP synthesis: electron transport through the respiratory chain complexes creates a proton gradient across the inner membrane, essential for final ATP synthesis. The efficiency of mitochondrial respiration is dependent on the function of the respiratory chain enzyme complexes and on the structural integrity of the inner mitochondrial membrane. It has been proposed that during endotoxemia, direct inhibition of complex I of the respiratory chain by nitric oxide4 and proton leak across the inner mitochondrial membrane 1 can contribute to impaired mitochondrial respiration and less efficient energy production. While the first mechanism indicates reduced oxygen consumption and ATP production, the latter mechanism implies oxygen use not related to energy production, and hence, reduced production of ATP per unit of oxygen consumed. Catecholamines are used to support hemodynamics in septic patients. While these drugs improve the supply of