Disturbance of energy metabolism in acute septic cardiomyopathy: decreased activities of the complexes I and II of the mitochondrial respiratory chain and phosphofructokinase

Abstract

Acute septic cardiomyopathy accounts for about 10% of fatalities in sepsis and septic shock. Currently, therapy of septic cardiomyopathy is merely symptomatic. Causal therapeutic approaches could help reduce mortality. In the skeletal muscle of septic patients elevated oxygen partial pressures have been detected indicating a diminished oxygen consumption of mitochondria in sepsis. There is evidence that tumor necrosis factor α and interleukin 1 disturb mitochondrial function of cardiomyocytes in vitro. It was therefore assumed that mitochondrial function in septic cardiomyopathy may be disturbed. Ten key enzymes of energy metabolism were determined in vitro in myocardial tissue (removed post mortem) of septic and non-septic (sham) baboons under systemic anaesthesia, a standardised and hemodynamically well-characterised model of E coli sepsis. Measurements were performed spectrophotometrically and enzyme activities referred to non-collagen protein (NCP) (mU/g NCP, mean ± SEM). A newly developed principal component analysis of data was used to detect impaired enzyme pattern in myocardial specimen. Two sepsis protocols were compared: single challenge and multiple challenge (less E coli). A 50% reduction of the activity of complex II of the respiratory chain was found after single challenge (3.6 ± 0.6) in comparison to the multiple challenge group (7.3 ± 2.1, P < 0.05). The other enzymes were less affected. The activities of the complexes I and II and phosphofructokinase were significantly lowered after single challenge in the heart in lethal septic shock (I), in comparison to non-lethal septic shock (II) and to the sham animals *P < 0.05). The effects on cytochrome-c-oxidase, succinate dehydrogenase and complex III were essentially smaller, and citrate synthase was nearly unaffected. Similar changes were observed after multiple challenge protocol too.