Mitochondrial dysfunction and biogenesis: do ICU patients die from mitochondrial failure?

Mitochondrial functions include production of energy, activation of programmed cell death, and a number of cell specific tasks, e.g., cell signaling, control of Ca2+ metabolism, and synthesis of a number of important biomolecules. As proper mitochondrial function is critical for normal performance and survival of cells, mitochondrial dysfunction often leads to pathological conditions resulting in various human diseases. Recently mitochondrial dysfunction has been linked to multiple organ failure (MOF) often leading to the death of critical care patients. However, there are two main reasons why this insight did not generate an adequate resonance in clinical settings. First, most data regarding mitochondrial dysfunction in organs susceptible to failure in critical care diseases (liver, kidney, heart, lung, intestine, brain) were collected using animal models. Second, there is no clear therapeutic strategy how acquired mitochondrial dysfunction can be improved. Only the benefit of such therapies will confirm the critical role of mitochondrial dysfunction in clinical settings. Here we summarized data on mitochondrial dysfunction obtained in diverse experimental systems, which are related to conditions seen in intensive care unit (ICU) patients. Particular attention is given to mechanisms that cause cell death and organ dysfunction and to prospective therapeutic strategies, directed to recover mitochondrial function. Collectively the data discussed in this review suggest that appropriate diagnosis and specific treatment of mitochondrial dysfunction in ICU patients may significantly improve the clinical outcome

Propofol administration to the fetal–maternal unit reduces cardiac oxidative stress in preterm lambs subjected to prenatal asphyxia and cardiac arrest

BACKGROUND: Little is known about the effects of propofol on oxidative stress and its effect on key structures of the contractile apparatus as the myosin light chain 2 (MLC2) and the p38MAPK survival pathway in the preterm heart. We hypothesized that propofol administration could attenuate the hypoxic myocardial injury after birth asphyxia. METHODS: Pregnant ewes were randomized to receive either propofol or isoflurane anesthesia. A total of 44 late-preterm lambs were subjected to in utero umbilical cord occlusion (UCO), resulting in asphyxia and cardiac arrest, or sham treatment. After emergency cesarean delivery, each fetus was resuscitated, mechanically ventilated, and supported under anesthesia for 8 h using the same anesthetic as the one received by its mother. RESULTS: At 8h after UCO, occurrence of reactive oxygen species and activation of inducible nitric oxide synthase in the heart were lower in association with propofol anesthesia than with isoflurane. This was accompanied by less degradation of MLC2 but higher p38MAPK level and in echocardiography with a trend toward a higher median left ventricular fractional shortening. CONCLUSION: The use of propofol resulted in less oxidative stress and was associated with less cytoskeletal damage of the contractile apparatus than the use of isoflurane anesthesia