Mitochondrial dysfunction during different sepsis forms

Background: Sepsis-induced multiple organ failure is the major cause of mortality and morbidity in critically ill patients. The precise mechanisms by which this dysfunction is caused remain to be elucidated. Because ATP production by mitochondrial oxidative phosphorylation accounts for more than 90% of total oxygen consumption, we postulated that mitochondrial dysfunction results in organ failure, possibly due to nitric oxide, which is known to inhibit mitochondrial respiration in vitro and is produced in excess in sepsis. Methods: We did skeletal muscle biopsies on 25 septic patients within 24 h of admission to intensive care. The biopsy samples were analyzed for myosin heavy chains (MHC), isoform gene transcript levels using a real-time PCR technique, respiratory-chain activity and ATP production (complex V) using a real-time QPCR technique for mitochondrial enzyme gene transcript levels citrate synthase (CS), cytochrome C oxidase I-III, NADH and UCPs 2-3. Results: The gene transcription of myosin fiber types I, IIa and citrate synthase (complex V) was significant higher in skeletal muscle biopsy of septic survivors, and demonstrated lower insulin sensitivity using HOMA test. Severity of septic shock ( SAPS II) found to be higher in critically ill patients. Conclusion: In critically ill patients, we found an association between the type of myosin fiber and ATPase gene transcription and insulin resistance that relate to organ failure and eventual outcome. These data implicate bioenergetic failure as an important pathophysiological mechanism underlying multiple organ dysfunction.