TRANSITIONAL VACUOLE FORMATION FOLLOWING A BOLUS INFUSION OF PEG-HEMOGLOBIN IN THE RAT

This study was designed to assess the morphological effects of a bolus infusion of PEG-hemoglobin on the heart, lung, liver, spleen and kidn ey of laboratory rats. Of particular interest was the determination of PEG-hemoglobin's potential to form vacuoles in the tissues and whethe r these were transitory and article specific. One hundred ten female S prague-Dawley rats were used in this study. The first experiment deter mined whether vacuole formation was test article specific by infusing either stroma-free bovine hemoglobin, PEG-hemoglobin, bovine serum alb umin, PEG-bovine serum albumin or free PEG. The second experiment asse ssed the transitory nature of vacuolization. In both experiments, unco nscious rats received an intravenous top-loading (bolus) injection of test article via the tail vein. Rats were sacrificed at various time p oints following administration and had their tissues examined for the presence of vacuoles by light microscope morphological examination and iron staining. Formation of vacuoles appeared to be test article spec ific with only prolonged circulating, high solute test articles produc ing vacuoles. These vacuoles appeared dose responsive and transitory i n nature. The vacuolization found was non-toxic and believed to be due to the known effect of lysosomal overloading following the phagocytos is of vascularly persistent high solute test articles.