title: Oxygen transport and mitochondrial function in porcine septic shock, cardiogenic shock, and hypoxaemia.
abstract: BACKGROUND
  The relevance of tissue oxygenation in the pathogenesis of organ dysfunction during sepsis is controversial. We compared oxygen transport, lactate metabolism, and mitochondrial function in pigs with septic shock, cardiogenic shock, or hypoxic hypoxia.
  
  
  METHODS
  Thirty-two anaesthetized, ventilated pigs were randomized to faecal peritonitis (P), cardiac tamponade (CT), hypoxic hypoxia (HH) or controls. Systemic and regional blood flows, lactate, mitochondrial respiration, and tissue hypoxia-inducible factor 1 alpha (HIF-1α) were measured for 24 h.
  
  
  RESULTS
  Mortality was 50% in each intervention group. While systemic oxygen consumption (VO(2) ) was maintained in all groups, hepatic VO(2)  tended to decrease in CT [0.84 (0.5-1.3) vs. 0.42 (0.06-0.8)/ml/min/kg; P = 0.06]. In P, fractional hepatic, celiac trunk, and portal vein blood flows, and especially renal blood flow [by 46 (14-91)%; P = 0.001] decreased. In CT, renal blood flow [by 50.4 (23-81)%; P = 0.004] and in HH, superior mesenteric blood flow decreased [by 38.9 (16-100)%, P = 0.009]. Hepatic lactate influx increased > 100% in P and HH, and > 200% in CT (all P < 0.02). Hepatic lactate uptake remained unchanged in P and HH and converted to release in CT. Mitochondrial respiration remained normal. Muscle adenosine triphosphate (ATP) concentrations decreased in P (5.9 ± 1.4 μmol/g wt vs. 2.8 ± 2.7 μmol/g wt, P = 0.04). HIF-1α expression was not detectable in any group.
  
  
  CONCLUSIONS
  We conclude that despite shock and renal hypoperfusion, tissue hypoxia is not a major pathophysiological issue in early and established faecal peritonitis. The reasons for reduced skeletal muscle tissue ATP levels in the presence of well-preserved in-vitro muscle mitochondrial respiration should be further investigated.
authors.affiliation: Department of Intensive Care Medicine, Inselspital, Bern University Hospital, and University of Bern, Bern, Switzerland.
authors.forename: T
authors.initials: T
authors.lastname: Regueira
authors.forename: S
authors.initials: S
authors.lastname: Djafarzadeh
authors.forename: S
authors.initials: S
authors.lastname: Brandt
authors.forename: J
authors.initials: J
authors.lastname: Gorrasi
authors.forename: E
authors.initials: E
authors.lastname: Borotto
authors.forename: F
authors.initials: F
authors.lastname: Porta
authors.forename: J
authors.initials: J
authors.lastname: Takala
authors.forename: H
authors.initials: H
authors.lastname: Bracht
authors.forename: S
authors.initials: S
authors.lastname: Shaw
authors.forename: P M
authors.initials: PM
authors.lastname: Lepper
authors.forename: S M
authors.initials: SM
authors.lastname: Jakob
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D015687:Cell Hypoxia; D005260:Female; D006439:Hemodynamics; D000860:Hypoxia / Q000378:metabolism* / Q000503:physiopathology; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D007773:Lactates / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008297:Male; D008928:Mitochondria / Q000378:metabolism*; D008930:Mitochondria, Liver / Q000378:metabolism; D008931:Mitochondria, Muscle / Q000378:metabolism; D018482:Muscle, Skeletal / Q000378:metabolism; D010100:Oxygen / Q000378:metabolism*; D010101:Oxygen Consumption; D010538:Peritonitis / Q000150:complications / Q000503:physiopathology; D011897:Random Allocation; D012079:Renal Circulation; D012770:Shock, Cardiogenic / Q000378:metabolism* / Q000503:physiopathology; D012772:Shock, Septic / Q000209:etiology / Q000378:metabolism* / Q000503:physiopathology; D013152:Splanchnic Circulation; D034421:Sus scrofa; D013552:Swine
chemical_list: D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D007773:Lactates; D000255:Adenosine Triphosphate; D010100:Oxygen