Histologic Lesions Associated with Intravenous Infusions of Large Volumes of Isotonic Saline Solution in Rats for 30 Days

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Abstract
The objective of this study was to characterize the changes associated with intravenous infusions of large volumes of isotonic saline solution in rats so that effects of the infusion process could be more easily distinguished from effects of test articles. Male Sprague-Dawley rats weighing approximately 225-275 g at the beginning of the study were given intravenous infusions of isotonic saline solution once daily for 30 consecutive days at dosages of 40 or 80 ml/kg body weight. Saline solution was administered through catheters placed in the caudal veins of the tail according to one of the following regimens: 80 ml/kg at 0.25 ml/min; 80 ml/kg at 0.5 ml/min; 80 ml/kg at 1.0 ml/min; and 40 ml/kg at 1.0 ml/min. Control rats were catheterized but not administered intravenous fluids. One day following the last treatment, all rats were necropsied and major organs were collected in 10% formalin. Histologic lesions associated with treatment included increased incidence and severity of pulmonary periarterial infiltrates of eosinophils, multifocal pulmonary inflammation, pulmonary granulomas that often contained hairshaft fragments, endothelial hypertrophy and hyperplasia within pulmonary arterial vessels, and pulmonary arterial medial thickening. Infiltrates of eosinophils around small pulmonary arteries were more severe in rats given intravenous infusions than in untreated rats and were more severe in rats given isotonic saline at the 80-ml/kg dosage than at the 40-ml/kg dosage. The severity of periarterial infiltrates of eosinophils increased with increasing infusion rates in rats that received 80 ml/kg isotonic saline. Pulmonary granulomas and multifocal pulmonary inflammation were observed in more rats that received intravenous saline than in control rats, but their incidences did not appear to vary with the volume or rate of infusion. Multifocal endothelial hypertrophy and hyperplasia occurred in most rats given isotonic saline solution at all volumes and rates, but not in untreated control rats. Inflammatory lesions in the tail near the injection site were considered sequellae of catheter insertion that, in some instances, may have been exacerbated by intravenous saline infusion. There were no lesions in other organs that were attributable to intravenous infusions of isotonic saline solution.