title: Effects of alpha - and beta -adrenergic stimulation on hepatosplanchnic perfusion and oxygen extraction in endotoxic shock.
abstract: OBJECTIVE
  To examine the effects of adrenergic stimulation on hepatosplanchnic perfusion, oxygen extraction, and tumor necrosis factor-alpha production during endotoxic shock.
  
  
  METHODS
  In vivo, prospective, randomized, controlled, repeated-measures, experimental study.
  
  
  METHODS
  Experimental physiology laboratory in a university teaching hospital.
  
  
  METHODS
  Twenty-one anesthetized and mechanically ventilated dogs.
  
  
  METHODS
  An intrapericardial catheter was positioned. Catheters for blood sampling were inserted into the right femoral artery, hepatic vein, portal vein, and pulmonary artery. Ultrasonic flow probes were placed around the portal vein, the hepatic artery, the mesenteric artery, the left renal artery, and the left femoral artery. Animals received 2 mg/kg of Escherichia coli endotoxin, followed by fluid resuscitation. Seven dogs received intravenous isoproterenol (0.1 microg/kg x min(-1)), seven received phenylephrine (1 microg/kg x min(-1)), and seven served as controls. Thirty minutes later, cardiac tamponade was introduced to study organ perfusion and tissue oxygen extraction capabilities.
  
  
  RESULTS
  The isoproterenol group had a higher cardiac index and stroke index and lower systemic vascular resistance than the other groups. The phenylephrine group had a higher arterial pressure but a lower cardiac index than the isoproterenol group. The isoproterenol group had a higher hepatic artery blood flow than the other groups and a higher portal and mesenteric flow than the control group. Liver and gut mucosal blood flow was greater in the isoproterenol than in the phenylephrine group. The isoproterenol group had a lower global critical oxygen delivery than the other groups (8.8 +/- 1.3 vs. 13.1 +/- 2.0 (control) and 11.8 +/- 3.3 mL/kg x min(-1) (phenylephrine); both p < .05) and a higher liver critical oxygen extraction ratio than the control group. Isoproterenol tended to attenuate, but phenylephrine significantly increased, blood tumor necrosis factor levels.
  
  
  CONCLUSIONS
  During endotoxic shock, beta-stimulation can improve hepatosplanchnic perfusion and enhance tissue oxygen extraction capabilities, whereas alpha-stimulation does not. In addition, alpha-adrenergic stimulation can increase tumor necrosis factor levels.
authors.affiliation: Division of Respiratory Medicine, Mount Sinai Hospital, University of Toronto, Toronto, ON, Canada.
authors.forename: H
authors.initials: H
authors.lastname: Zhang
authors.forename: R
authors.initials: R
authors.lastname: De Jongh
authors.forename: D
authors.initials: D
authors.lastname: De Backer
authors.forename: S
authors.initials: S
authors.lastname: Cherkaoui
authors.forename: B
authors.initials: B
authors.lastname: Vray
authors.forename: J L
authors.initials: JL
authors.lastname: Vincent
mesh_terms: D000316:Adrenergic alpha-Agonists / Q000494:pharmacology / Q000627:therapeutic use*; D000318:Adrenergic beta-Agonists / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D001783:Blood Flow Velocity / Q000187:drug effects; D002302:Cardiac Output / Q000187:drug effects; D004195:Disease Models, Animal; D004285:Dogs; D004353:Drug Evaluation, Preclinical; D016903:Drug Monitoring; D005260:Female; D007413:Intestinal Mucosa / Q000098:blood supply; D007545:Isoproterenol / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D010101:Oxygen Consumption / Q000187:drug effects*; D010656:Phenylephrine / Q000494:pharmacology / Q000627:therapeutic use*; D011446:Prospective Studies; D011897:Random Allocation; D012772:Shock, Septic / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D013152:Splanchnic Circulation / Q000187:drug effects*; D013318:Stroke Volume / Q000187:drug effects; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000187:drug effects / Q000378:metabolism; D014655:Vascular Resistance / Q000187:drug effects
chemical_list: D000316:Adrenergic alpha-Agonists; D000318:Adrenergic beta-Agonists; D014409:Tumor Necrosis Factor-alpha; D010656:Phenylephrine; D007545:Isoproterenol