Metabolic Resuscitation Strategies to Prevent Organ Dysfunction in SepsisReitsema, V. A., Star, B. S., de Jager, V. D., van Meurs, M., Henning, R. H. & Bouma, H. R., 10-Jul-2019, In : Antioxidants & Redox Signaling. 31, 2, p. 134-152 19 p.
Research output: Contribution to journal › Review article › Academic › peer-review
Recent Advances: Mitochondrial dysfunction is emerging as a key process in the induction of organ dysfunction during sepsis, and metabolic resuscitation might reveal to be a novel cornerstone in the treatment of sepsis. Critical Issues: Here, we review novel strategies to maintain organ function in sepsis by precluding mitochondrial dysfunction by lowering energetic demand to allow preservation of adenosine triphosphate-levels, while reducing free radical generation. As the most common strategy to suppress metabolism, that is, cooling, does not reveal unequivocal beneficial effects and may even increase mortality, caloric restriction or modulation of energy-sensing pathways (i.e., sirtuins and AMP-activated protein kinase) may offer safe alternatives. Similar effects may be offered when mimicking hibernation by hydrogen sulfide (H2S). In addition H2S may also confer beneficial effects through upregulation of antioxidant mechanisms, similar to the other gasotransmitters nitric oxide and carbon monoxide, which display antioxidant and anti-inflammatory effects in sepsis. In addition, oxidative stress may be averted by systemic or mitochondria-targeted antioxidants, of which a wide range are able to lower inflammation, as well as reduce organ dysfunction and mortality from sepsis. Future Directions: Mitochondrial dysfunction plays a key role in the pathophysiology of sepsis. As a consequence, metabolic resuscitation might reveal to be a novel cornerstone in the treatment of sepsis.
|Number of pages||19|
|Journal||Antioxidants & Redox Signaling|
|Early online date||23-Jan-2019|
|Publication status||Published - 10-Jul-2019|
- sepsis, oxidative phosphorylation, metabolism, hypothermia, caloric restriction, hibernation, hydrogen sulfide, ALPHA-LIPOIC ACID, ACUTE KIDNEY INJURY, PERMEABLE RADICAL SCAVENGER, CARBON-MONOXIDE INHALATION, CRITICALLY-ILL PATIENTS, PROTEIN-KINASE PATHWAY, NITRIC-OXIDE, SEPTIC SHOCK, OXIDATIVE STRESS, RAT MODEL