Mitochondrial Dysfunction in Sepsis: Evidence from Bacteraemic Baboons and Endotoxaemic Rabbits

Abstract

Mitochondria, that provide most of the ATP needed for cell work, and that play numerous specific functions in biosyntheses and degradations, as well as contributing to Ca2+ signaling, also play a key role in the pathway to cell death. Impairment of mitochondrial functions caused by mutations of mt-genome, and by acute processes, are responsible for numerous diseases. The involvement of impaired mitochondria in the pathogenesis of sepsis is discussed. By means of the skinned fiber technique and high resolution respirometry, we have detected significantly reduced rates of mitochondrial respiration in heart and skeletal muscle of endotoxaemic rabbits. Mitochondria from heart were more affected than those from skeletal muscle. Decreased respiration rates were accompanied by reduced activities of complex I + III of the respiratory chain. Endotoxin-caused impairment was also detectable at the level of the Langendorff perfused heart, where the coronary vascular resistance was significantly increased. For an investigation of the influence of bacteraemia on the mitochondrial respiratory chain, baboons were made septic by infusion of high and low amounts of E. coli. For complex I + III and II + III, a clear dose-dependent decrease was detectable and in animals which died in septic shock, a further decrease of enzyme activities in comparison to the controls were found. These results are discussed in the light of current knowledge on the role of mitochondria in cell pathology in respect to sepsis. In conclusion, we present evidence that mitochondrial function is disturbed during sepsis. Besides ischaemic and poison-induced disturbances of mitochondrial function, sepsis is a further example of an acute disease where impaired mitochondria have to be taken into account.

Cardiac Effects of Echinocandins in Endotoxemic Rats

“…Performing spectrophotometric measurements of rat left ventricular cardiac tissue after echinocandin treatment, we were not able to detect any altered mitochondrial enzyme activity (12). Previous studies on septic cardiomyopathy demonstrated the importance of mitochondrial dysfunction and reduced ATP generation (22,23). Moreover, studies using isolated cardiomyocytes found that endotoxins alter or suppress the L channel-dependent calcium flow, possibly through changes in autonomic regulation of this channel (24,25).…”

Function of the mitochondrial outer membrane as a diffusion barrier in health and diseases

“…Therefore these mitochondria are an excellent model for the study of AK-induced dynamic compartmentation within the IMS. In the presence of 10 yo (w/v) dextran M20 or BSA, approximately 64 yo of the maximal ADP flux from mt-AK to oxidative phosphorylation was not accessible to the extramitochondrial ADP scavenger pyruvate kinase [9,17,20,21]. In the absence of macromolecules this portion was only 34 yo [20,21].…”

“…Based on the experimental data it was possible to perform a simulation by means of a mathematical model, including diffusion terms [7,8]. Using such models diffusion rate constants six times lower than in the presence of dextran could be estimated (B. Korzeniewski and F. N. Gellerich, unpublished work).…”

“…If the C K system acts as an ADP shuttle mitochondrial and extramitochondrial C K must work in different directions. For thermodynamic reasons this requires a different metabolite pattern in both compartments [9]. T h e experimentally detected ADP concentration gradients are sufficient to realize this for an ADP shuttle [9].…”

Mitochondrial DNA Haplogroup R Confers a Genetic Risk Factor for Intrauterine Adhesion in Han Women Population

“…Focal ischemic/hypoxic changes have also been demonstrated in the endometrium of women with IUA [6]. Cellular oxygen delivery is well known to be most utilized by the mitochondria, which is the main intracellular energy source that is necessary for normal cellular function and metabolic homeostasis through oxidative phosphorylation [7]. It is suggested that the metabolic dysfunction of the mitochondria in endometrial cells may be an important factor that causes IUA.…”