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Abstract

Objective

To determine whether a detergent can prevent most of the early effects of IV infusion with Escherichia coli endotoxin (< 100 ng/kg of body weight) in horses: marked pulmonary hypertension, acute leukopenia, and fever.

Animals

8 healthy adult horses (4 male, 4 female), 415 to 615 kg.

Design and Procedure

Control and detergent experiments were performed in each horse while it was awake but sedated. In control experiments, 10 to 100 ng of E coli endotoxin/kg was given. In detergent experiments, 100 mg of detergent/kg was given 1 hour before injecting endotoxin, similar to the control experiments.

Results

In control experiments, pulmonary arterial pressure increased transiently over 40 minutes by 33 ± 8 mm of Hg (mean ± SD; P < 0.001), then returned to baseline. Circulating leukocytes decreased to 47 ± 19% (P < 0.02) of baseline by 1 hour after endotoxin, then increased above baseline by 6 hours. Rectal temperature increased by 0.7 ± 0.4 C (P < 0.01). In detergent experiments, the increase in pulmonary arterial pressure was much less than that in the control experiments (8 ± 7 mm of Hg; P < 0.001). Circulating leukocytes did not decrease, and the increase in rectal temperature after endotoxin was blocked.

Conclusions

This attenuation of the response to endotoxin may occur because the normal steps in the response of pulmonary intravascular macrophages (ie, endocytosis of endotoxin and subsequent release of inflammatory mediators) are altered by the detergent. This low-technology, inexpensive, and safe treatment could be an important new clinical tool for veterinarians in combating endotoxemia. (Am J Vet Res 1996;57:1063–1066)

Free access
in American Journal of Veterinary Research

Summary

Seven horses (4 anesthetized and 3 awake) and 2 ponies (anesthetized) were studied to evaluate the high sensitivity of the pulmonary circulation of the horse to various blood-borne particles, and to establish the presence of intravascular macrophages in the lung. Pulmonary and systemic pressures and cardiac output before and during particle injection were measured in some animals. An anesthetized foal had a large increase in pulmonary arterial pressure (32 and 34 mm of Hg) within 1 minute of IV administration of small test doses of radioactively labeled liposomes (2.5 μmol/kg of body weight) or a 1% suspension of blue pigment (0.3 ml/kg), respectively. Quantitative real-time gamma camera imaging of the foal revealed high retention of the labeled liposomes during the first pass through the lungs; retention persisted throughout the experiment. Postmortem analysis revealed 55 and 47% lung retention of liposomes and blue pigment, respectively. The 2 anesthetized ponies had increased pulmonary artery pressure of 34 ± 7 mm of Hg, decreased cardiac output, and 42% lung retention after administration of 1% blue pigment (0.2 ml/kg), whereas 3 awake horses had increased pressure of 28 ± 9 mm of Hg after 1.8 × 108 (1.8-μm-diameter) latex microspheres/kg. None of the injected particles caused vascular obstruction, and they do not cause pulmonary vascular reactivity in species that lack pulmonary intravascular macrophages. Finally, 3 horses (1 anesthetized and 2 awake) were infused Iv with small doses of the blue pigment, and their lungs were perfusion-fixed to identify specific labeling of the pulmonary intravascular macrophages. These cells were fully differentiated macrophages, contained blue pigment in phagocytes, and were tightly adherent to the pulmonary capillary endothelium. At this time, horses (order Perissodactyla) are the only species outside the mammalian order Artiodactyla (sheep, pig, cattle) documented to have reactive intravascular macrophages. Compared with other species, low doses of particles induced marked hemodynamic responses; horses appear to be more sensitive to IV administered particles than are other species studied.

Free access
in American Journal of Veterinary Research