Sepsis impairs microvascular autoregulation and delays capillary response within hypoxic capillaries

• Published in: Critical care (London, England) England), 2015-11, Vol.19 (389), p.389-389, Article 389
• Main Authors: Bateman, Ryon M, Sharpe, Michael D, Jagger, Justin E, Ellis, Christopher G
• Format: Article
• Language: English
• Subjects: Analysis; Animals; Bands; Blood; Capillaries - abnormalities; Capillaries - microbiology; Capillaries - physiology; Capillaries - physiopathology; Care and treatment; Complications and side effects; Critical care; Erythrocytes; Erythrocytes - pathology; Heart; Homeostasis - physiology; Hypoxia; Hypoxia - physiopathology; Influence; Metabolism; Metabolites; Microcirculation; Microcirculation - physiology; Microvessels - abnormalities; Microvessels - physiopathology; Models, Animal; Muscle proteins; Muscles; Musculoskeletal system; Nitrates; Nitric oxide; Oxygen - blood; Oxygen Consumption - physiology; Rats; Rodents; Scholarships & fellowships; Sepsis; Sepsis - complications; Sepsis - physiopathology; Signal transduction
• ISSN: 1364-8535; 1466-609X; 1364-8535; 1366-609X
• DOI: 10.1186/s13054-015-1102-7

The microcirculation supplies oxygen (O2) and nutrients to all cells with the red blood cell (RBC) acting as both a deliverer and sensor of O2. In sepsis, a proinflammatory disease with microvascular complications, small blood vessel alterations are associated with multi-organ dysfunction and poor septic patient outcome. We hypothesized that microvascular autoregulation-existing at three levels: over the entire capillary network, within a capillary and within the erythrocyte-was impaired during onset of sepsis. This study had three objectives: 1) measure capillary response time within hypoxic capillaries, 2) test the null hypothesis that RBC O2-dependent adenosine triphosphate (ATP) efflux was not altered by sepsis and 3) develop a framework of a pathophysiological model. This was an animal study, comparing sepsis with control, set in a university laboratory. Acute hypotensive sepsis was studied using cecal ligation and perforation (CLP) with a 6-hour end-point. Rat hindlimb skeletal muscle microcirculation was imaged, and capillary RBC supply rate (SR = RBC/s), RBC hemoglobin O2 saturation (SO2) and O2 supply rate (qO2 = pLO2/s) were quantified. Arterial NOx (nitrite + nitrate) and RBC O2-dependent ATP efflux were measured using a nitric oxide (NO) analyzer and gas exchanger, respectively. Sepsis increased capillary stopped-flow (p = 0.001) and increased plasma lactate (p