Haemolysis and artifactual lung damage induced by an euthanasia agent

The artifactual development of endothelial necrosis, pulmonary congestion, and oedema that has been reported in dogs, cats, and monkeys when the animals were killed with 1-1.5 ml/kg body weight of the euthanasia agent T-61 was reproduced in adult ewes of the merino breed. This species also exhibited a marked pulmonary congestion with intra-alveolar haemorrhages, septal oedema, and a diffuse cellular damage of the alveolar septa when the recommended dose of 0.3 ml/kg body weight was administered after forcing blood flow through one lung by clamping the contralateral hilum. The red coloration of the damaged lung areas may be due to haemolysis, another aspect of T-61 induced cell damage in this species. The degree of haemolysis increases with increasing blood concentration of the agent and approximates complete haemolysis at a T-61 blood concentration of 5%. The blood concentration dependent degree of haemolysis in sheep suggests a similar relationship between blood concentration of the agent and degree of pulmonary tissue damage.     

Pulmonary hemodynamics and tissue damage after one lung infusion of Pseudomonas aeruginosa in sheep.

The relative roles of hematogenous mediators and direct bacterial toxicity due to phagocytosis by pulmonary intravascular macrophages were determined by selective bacterial infusion into the left pulmonary artery and comparison of right and left lungs at 24 h. Chronically instrumented sheep received 15-min pulmonary arterial infusions of live Pseudomonas aeruginosa (0.35-2.9 x 10(9), n = 6) or saline (n = 5). The saline group demonstrated stable cardiopulmonary function over time. Left lung blood flow, measured by Doppler flow probe, decreased 15 min into the bacterial infusion, with a concomitant sevenfold increase in left lung pulmonary vascular resistance index. The right lung pulmonary vascular resistance index doubled at 1 h, in association with increased plasma thromboxane B2 levels. An increase in cardiac index and decrease in systemic vascular resistance occurred at 12 h. The wet-to-dry weight ratio of the Pseudomonas-infused left lung was increased compared with that of the sham-infused lung. The tissue count of neutrophils in the lungs was doubled in both sides, but neutrophils on the left were more degranulated. The left lung tissue damage was caused by direct bacterial toxicity, including activation of phagocytic cells. Hematogenous mediators induced pulmonary and systemic hemodynamic changes and right lung neutrophil sequestration, but they did not damage the noninfused lung.