title: Cardiovascular response to acute and chronic endotoxemia in an awake, volume-resuscitated, canine model.
abstract: The cardiovascular response to endotoxemia was evaluated in an awake, intravascular volume-resuscitated canine model. The animals were chronically instrumented for ultrasonic crystal dimension analysis and pressure measurements of the left ventricle (LV), aorta, right atrium (RA), and pulmonary artery (PA) and for cardiac output (CO) measurement. Lipopolysaccharide (Escherichia coli 011:B4) (LPS) was administered intravenously either as an acute, high dose bolus (5 mg/kg; n = 5), a high dose bolus after complete beta-blockade with propranolol (n = 3), or a chronic, low dose infusion (5 micrograms/kg/h; n = 7). Relative to baseline values, cardiac contractility was increased after acute high dose LPS bolus, however this effect was negated by beta-blockade. Chronic, low dose LPS infusion produced an increase in cardiac contractility at 1 h, a return to baseline by 4 h, and maximal contractile depression by 24 h. No change was seen in LV compliance after the high dose LPS bolus. The LV end diastolic volume was decreased by the high dose LPS bolus. This change was blocked by propranolol administration. Chronic LPS administration was accompanied by a decrease in LV compliance and an increase in LV end diastolic volume. Other cardiovascular indices (heart rate, CO, systemic vascular resistance) changed in a fashion similar to human sepsis. These findings confirm that endotoxemia in conscious canine subjects causes changes in cardiovascular function similar to that seen in human and animal models of sepsis. This study also allows us to explain some of the discrepancies between earlier studies of human sepsis and animal models in which the appropriate clinical conditions and an intact neuro-endocrine axis were not maintained.
authors.affiliation: Department of Surgery, University of Minnesota, Minneapolis 55455, USA.
authors.forename: C S
authors.initials: CS
authors.lastname: Walvatne
authors.forename: A S
authors.initials: AS
authors.lastname: Johnson
authors.forename: L J
authors.initials: LJ
authors.lastname: Wojcik
authors.forename: F B
authors.initials: FB
authors.lastname: Cerra
mesh_terms: D000818:Animals; D002319:Cardiovascular System / Q000187:drug effects* / Q000503:physiopathology; D004285:Dogs; D004347:Drug Interactions; D006439:Hemodynamics / Q000187:drug effects; D008070:Lipopolysaccharides / Q000008:administration & dosage*; D011433:Propranolol / Q000494:pharmacology; D012772:Shock, Septic / Q000503:physiopathology*
chemical_list: D008070:Lipopolysaccharides; D011433:Propranolol