Beat-to-beat evaluation of cardiac function in low-dose endotoxemia using a conscious sheep model.
The effects of very low doses of endotoxin (20 ng/kg/h for 8 h) were evaluated in a conscious sheep model in which introducers for catheters for monitoring pressure and ventricular dimensions had been previously inserted so that the studies could be performed without anesthesia and without a previous thoracotomy. Analog data was obtained at hourly intervals for 10 h and again at 24 h and was used to construct a beat-to-beat analysis of left ventricular performance. Only minimal effects were observed on heart rate, end diastolic pressure, arterial pressure, cardiac output, or cardiac work, although there was a significant rise in pulmonary artery pressure at 1 h of infusion. Despite the absence of changes in heart rate, preload, or afterload, maximal dp/dt decreased significantly by 4 h and remained decreased for the 10-h observation period; it returned to normal at 24 h. End systolic elastance decreased at 6 h and Pmax/EDV, a new indicator of performance, also decreased at 6 and 9 h. Thus, systolic performance decreased. Negative dp/dt did not change, but time for relaxation from 80% to 20% of peak ventricular pressure increased significantly at 5, 6, and 8 h. Plasma TNF-alpha was also measured and showed a significant rise at 2 h, but rapidly decreased thereafter. These results indicate an early depression of myocardial contractility and distensibility at doses of endotoxin insufficient to produce measurable effects on arterial pressure or cardiac output.
Abel
F L
FL
Department of Pharmacology and Physiology, University of South Carolina School of Medicine, Columbia, South Carolina 29208, USA.
Krösl
P
P
Redl
H
H
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D003243:Consciousness; D004195:Disease Models, Animal; D019446:Endotoxemia / Q000503:physiopathology*; D004926:Escherichia coli; D006321:Heart / Q000503:physiopathology*; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology*; D006439:Hemodynamics / Q000187:drug effects* / Q000502:physiology; D007700:Kinetics; D008070:Lipopolysaccharides / Q000633:toxicity*; D012756:Sheep; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D016277:Ventricular Function, Left / Q000187:drug effects
D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha