The effect of mimicking prepartum concentration of estradiol-17 beta on the inflammatory response to endotoxin in gilts was studied. The study was performed in a split-litter design and comprised 5 pairs of littermates. A catheter was inserted into the jugular vein 2 days prior to the start of the study. In each pair, 1 littermate was treated IM with 2.5 mg of estradiol-17 beta/75 kg of body weight, and the other littermate was given peanut oil IM as a control. The day after treatment, all gilts were challenge-exposed with a Salmonella typhimurium-derived endotoxin (1 microgram/kg, IV) and the inflammatory response to challenge exposure was monitored. There was no effect of estradiol treatment on the transient clinical signs of endotoxemia or on the increase in rectal temperature. The increase in blood concentrations of prostaglandin F2 alpha, metabolite and cortisol after endotoxin challenge exposure was not affected by estradiol. Decrease in number of circulating blood mononuclear cells and polymorphonuclear leukocytes was not changed by estradiol treatment. Taken together, mimicking prepartum concentration of estradiol did not affect either the magnitude or the kinetics of the inflammatory response to endotoxin in gilts. Relevance of these findings to development of endotoxin-mediated diseases, such as the postpartum agalactia syndrome, needs further study.

Polymyxin B and an antiserum against an Re mutant Salmonella typhimurium were evaluated for protective effect in an equine model of endotoxemia. Six 3- to 5-month-old foals were given endotoxin (0.25 micrograms/kg of body weight) IV after no pretreatment, or pretreatment with polymyxin B (6,000 U/kg, IV) or S typhimurium antiserum (1.5 ml/kg, IV). When given without pretreatment, endotoxin caused transient recumbency and increases in rectal temperature, and heart and respiratory rates. In addition, leukopenia and increases in circulating tumor necrosis factor (TNF) and interleukin 6 (IL-6) activities were detected. Compared with results obtained when endotoxin was given alone, pretreatment with polymyxin B resulted in significantly (P < 0.05) lower maximal plasma TNF and IL-6 activities, and significantly lower rectal temperature and respiratory rate. In contrast, compared with effects of endotoxin given without pretreatment, use of antiserum was associated with significantly (P < 0.05) higher respiratory rate, maximal plasma IL-6 activity, and total TNF response (as determined by areas under curves of plasma TNF vs time). These results indicate that polymyxin B may have potential as a treatment for equine endotoxemia. Salmonella typhimurium antiserum had no positive effect in this model, and, under certain conditions, may exacerbate the actions of endotoxin.

Effects of endotoxemia on left ventricular contractility and systemic hemodynamics were determined in pentobarbital-anesthetized swine. A multielectrode conductance (volume) catheter and a high-fidelity pressure transducer catheter were passed retrograde into the left ventricle to continuously measure pressure and volume. End-systolic pressure-volume relationships were determined during transient (8 to 10 s) caudal vena caval balloon occlusion. Lactated Ringer's solution was administered at a rate sufficient to maintain left ventricular end-diastolic pressure > 6 mm of Hg. Following baseline measurements, Escherichia coli endotoxin (O55-B5) was infused IV at 2.5 micrograms/kg of body weight/h for 3 hours. Left ventricular end-systolic elastance (Ees), the slope of the end-systolic pressure-volume relationship; end-systolic elastance normalized for left ventricular end-diastolic volume (Ees norm); the rate of increase of left ventricular pressure (dP/dtmax); and preload recruitable stroke work (PRSW, stroke work-to-end-diastolic volume relationship) did not change in endotoxemic swine, compared with baseline measurements or with values from control (physiologic saline solution-treated) swine. Left ventricular pressures and volumes had marked pig-to-pig variability in the control and endotoxin-treated groups. Determination of Ees, Ees norm, and PRSW was further confounded by development of frequent premature ventricular contractions during caudal vena caval balloon occlusion. Endotoxin significantly (P < 0.05) decreased left ventricular end-diastolic pressure, compared with that in control swine, and significantly (P < 0.01) decreased left ventricular end-diastolic volume, compared with baseline. Endotoxin decreased cardiac index and arterial blood pressure, whereas heart rate, central venous pressure, and mean pulmonary arterial pressure increased. Endotoxin did not decrease myocardial contractility, as measured by Ees, Ees norm, dP/dtmax, or PRSW in anesthetized swine.