Publication

Metabolic Resuscitation Strategies to Prevent Organ Dysfunction in Sepsis

Reitsema, 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 journalReview articleAcademicpeer-review

Copy link to clipboard

Documents

  • Metabolic Resuscitation Strategies to Prevent Organ Dysfunction in Sepsis

    Final publisher's version, 950 KB, PDF-document

    Request copy

DOI

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.

Original languageEnglish
Pages (from-to)134-152
Number of pages19
JournalAntioxidants & Redox Signaling
Volume31
Issue number2
Early online date23-Jan-2019
Publication statusPublished - 10-Jul-2019

    Keywords

  • 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

View graph of relations

ID: 76330550