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Hypometabolism in Endotoxic Shock Reflects a Thermoregulatory Response and Occurs Independently of Circulatory Hypoxia
Author(s) -
Steiner Alexandre,
Corrigan Joshua,
Fonseca Monique,
Flatow Elizabeth,
Lewis Kevin,
Brito Camila
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.lb690
Subject(s) - hypoxia (environmental) , circulatory system , hypothermia , thermoregulation , septic shock , lipopolysaccharide , shock (circulatory) , endocrinology , circulatory failure , nad+ kinase , medicine , oxygen , biology , chemistry , biochemistry , sepsis , organic chemistry , enzyme
Oxygen utilization (VO 2 ) is thought to fall in the late stages of septic shock because of mitochondrial dysfunction, circulatory hypoxia or both. However, the applicability of this conceptual framework to early septic shock is unclear. We investigated this matter in a rat model of lipopolysaccharide (LPS)‐induced shock (endotoxic shock). A novel experimental preparation was devised to simultaneously monitor oxygen delivery (DO 2 ) and VO 2 in rats whose thermoregulation had not been disrupted by anesthetics. Using a β 3 ‐adrenergic agonist known to activate brown adipocytes, we found no evidence of metabolic impairment between 20 and 150 min post‐LPS. In spite of that, VO 2 fell early in the LPS‐challenged rats, and such a fall in VO 2 seemed to be driving a decrease in body temperature. The fall in VO 2 was not preceded by any fall in cardiac output or DO 2 . Furthermore, no imbalance between VO 2 and DO 2 were encountered, and an analysis of NAD + /NADH ratios provided no indication of tissue hypoxia. Only when hypometabolism and hypothermia were prevented by exposure to a warm environment did an imbalance in the DO 2 /VO 2 ratio become evident, and such an imbalance was associated with tissue hypoxia (reduction in NAD + /NADH ratio). It is concluded that reduced VO 2 in early endotoxic shock (i) results from neither metabolic failure nor circulatory hypoxia, (ii) reflects a thermoregulatory adjustment, and (iii) serves as preemptive strategy to avoid hypoxia. Clinical data and conduct should be reexamined in light of these new findings. Funding FAPESP, AHA & CNPq.