title: Vasopressin V1A receptors mediate the stabilization of intestinal mucosal oxygenation during hypercapnia in septic rats.
abstract: Microvascular oxygen saturation (μHBO2) plays an essential role in the development and outcome of sepsis. Hypercapnia (HC) improves the microvascular oxygenation of the mucosa in both healthy and septic animals. Vasopressin V1A receptor blockade prevents this positive effect under otherwise physiological conditions. The aim of this study was to investigate the effects and mechanisms of the vasopressin system during hypercapnia under septic conditions.
  
  
  
  80 rats were randomized into 8 groups (N=10). Colon ascendens stent peritonitis (CASP) or sham surgery was performed on 40 animals each to establish a moderate polymicrobial sepsis or sham control, respectively. 24h after sepsis induction the animals were subjected to 120min of volume-controlled and pressure-limited ventilation with either normocapnic (pCO2 35-45mmHg) or moderate hypercapnic (pCO2 of 65-75mmHg) ventilation targets. Animals received either vasopressin V1A receptor blockade (SR 49059, 1mgkg(-1) i.v.) or vehicle solution (dimethyl sulfoxide, 1%). Blood pressure, heart rate, pO2 and pCO2 were measured and microcirculatory oxygenation (μHBO2) and microcirculatory flow (μflow) were recorded using tissue reflectance spectrophotometry. Oxygen supply (μDO2) and consumption (μVO2) were calculated from intermittent blood gas analysis.
  
  
  
  In septic animals, μHBO2 declined during normocapnia (-11±10.3) but remained unchanged during hypercapnia. μHBO2 declined with vasopressin V1A receptor blockade both during normocapnia (-7.4±10.6) and hypercapnia (-9.2±9.8). Microcirculatory oxygen consumption was significantly reduced by hypercapnia in septic animals (-2.4·10(5) [AU]±2.4·10(5) [AU]). In sham animals, μHBO2 and μVO2 did not change.
  
  
  
  Vasopressin V1A receptors mediate the beneficial effects of hypercapnia on microcirculatory oxygenation during sepsis. The effects of vasopressin on μHBO2 might be related to decreased oxygen consumption during hypercapnia.
authors.affiliation: Department of Anesthesiology, University Hospital Duesseldorf, Moorenstrasse 5, 40225 Duesseldorf, Germany.
authors.forename: Sabrina
authors.initials: S
authors.lastname: Schöneborn
authors.affiliation: Department of Anesthesiology, University Hospital Duesseldorf, Moorenstrasse 5, 40225 Duesseldorf, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Vollmer
authors.affiliation: Department of Anesthesiology, University Hospital Duesseldorf, Moorenstrasse 5, 40225 Duesseldorf, Germany.
authors.forename: Franziska
authors.initials: F
authors.lastname: Barthel
authors.affiliation: Department of Anesthesiology, University Hospital Duesseldorf, Moorenstrasse 5, 40225 Duesseldorf, Germany.
authors.forename: Anna
authors.initials: A
authors.lastname: Herminghaus
authors.affiliation: Department of Anesthesiology, University Hospital Duesseldorf, Moorenstrasse 5, 40225 Duesseldorf, Germany.
authors.forename: Jan
authors.initials: J
authors.lastname: Schulz
authors.affiliation: Department of Anesthesiology, University Hospital Duesseldorf, Moorenstrasse 5, 40225 Duesseldorf, Germany.
authors.forename: Inge
authors.initials: I
authors.lastname: Bauer
authors.affiliation: Department of Anesthesiology, University Hospital Duesseldorf, Moorenstrasse 5, 40225 Duesseldorf, Germany. Electronic address: Christopher.Beck@bathildis.de.
authors.forename: Christopher
authors.initials: C
authors.lastname: Beck
authors.affiliation: Department of Anesthesiology, University Hospital Duesseldorf, Moorenstrasse 5, 40225 Duesseldorf, Germany.
authors.forename: Olaf
authors.initials: O
authors.lastname: Picker
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000097:blood; D004195:Disease Models, Animal; D006454:Hemoglobins / Q000378:metabolism; D006727:Hormone Antagonists / Q000494:pharmacology; D006935:Hypercapnia / Q000097:blood / Q000378:metabolism* / Q000503:physiopathology; D007413:Intestinal Mucosa / Q000098:blood supply* / Q000187:drug effects / Q000378:metabolism* / Q000382:microbiology; D008297:Male; D008833:Microcirculation; D010100:Oxygen / Q000097:blood*; D010101:Oxygen Consumption / Q000187:drug effects; D017208:Rats, Wistar; D017483:Receptors, Vasopressin / Q000187:drug effects / Q000378:metabolism*; D012039:Regional Blood Flow; D018805:Sepsis / Q000097:blood / Q000378:metabolism* / Q000382:microbiology / Q000503:physiopathology; D015398:Signal Transduction; D013152:Splanchnic Circulation; D013997:Time Factors; D014667:Vasopressins / Q000097:blood / Q000378:metabolism*
chemical_list: D015415:Biomarkers; D006454:Hemoglobins; D006727:Hormone Antagonists; D017483:Receptors, Vasopressin; C582098:V1a vasopressin receptor, rat; D014667:Vasopressins; D010100:Oxygen
keywords: Hypercapnia; Intestinal microcirculation; Sepsis; Vasopressin