Fluorescein-labeled dextran concentration is increased in BAL fluid after ANTU-induced edema in rats

Several methodologies have been developed to assess alveolocapillary membrane permeability in acute lung injury. The purpose of this study was to determine the reliability of FITC-dextran compared with radioactive tracers to assess lung permeability alterations. After intraperitoneal administration of α-naphthylthiourea (ANTU, 50 mg/kg) or DMSO-ANTU vehicle, the animals were euthanized and their lungs were studied in an isolated-lung preparation. FITC-dextran or radiolabeled tracers were added to the perfusate. At 2 h the bronchoalveolar lavage (BAL) fluid from the ANTU group showed a significantly greater amount of fluorescence in the supernatant after centrifugation of BAL fluid compared with the DMSO group. Consistent results were observed with the radioactive tracers: there was an increase in extravascular albumin space and extravascular lung water compared with the control group. No cleavage of the FITC from the dextran molecule was evident by chromatography comparing samples recovered from the BAL fluid to the pure FITC-dextran molecule. In conclusion, measurement of FITC-dextran in the supernatant of BAL fluid after intravascular administration is a reliable method of assessing lung permeability changes in vivo and ex vivo.

THE EFFECTS OF SINGLE LARGE INFUSIONS OF VARIOUS DEXTRAN SOLUTIONS ON HYPOVOLEMIC DOGS

Standardized bleeding procedures were carried out on anesthetized dogs. Some animals received no therapy, some infusions of saline, and some received dextran infusions at times that varied from immediately to three and one-half hours after hemorrhage. With no therapy, one of eight animals survived; with saline infusions, 4 of 13 survived; and with dextran 23 of 24 dogs survived. There was often wound bleeding after dextran; this was not seen in saline treated animals but dextran treated animals recovered rapidly and no other ill-effects were noted. Dextran infusions were quantitatively retained in the circulation for an appreciable time and the volume and pressure of the circulating fluid were effectively restored and maintained. The amount of dextran excreted in urine was inversely related to the mean molecular weight of the infused material and the quantity excreted was the same as that observed in normal animals. The rate of disappearance of dextran by other than the renal route did not vary with the mean molecular weight, and indicated that the dextran molecule is catabolized at from 4.9 to 8.6 mgm./hr./kgm. body weight. About 50% of total plasma proteins of animals was lost by the hemorrhage and was replaced, after dextran infusions, within four days. There was no evidence, after dextran infusions, of dextran storage in kidney, spleen, or liver.

THE EFFECTS OF SINGLE LARGE INFUSIONS OF VARIOUS DEXTRAN SOLUTIONS ON HYPOVOLEMIC DOGS

Standardized bleeding procedures were carried out on anesthetized dogs. Some animals received no therapy, some infusions of saline, and some received dextran infusions at times that varied from immediately to three and one-half hours after hemorrhage. With no therapy, one of eight animals survived; with saline infusions, 4 of 13 survived; and with dextran 23 of 24 dogs survived. There was often wound bleeding after dextran; this was not seen in saline treated animals but dextran treated animals recovered rapidly and no other ill-effects were noted. Dextran infusions were quantitatively retained in the circulation for an appreciable time and the volume and pressure of the circulating fluid were effectively restored and maintained. The amount of dextran excreted in urine was inversely related to the mean molecular weight of the infused material and the quantity excreted was the same as that observed in normal animals. The rate of disappearance of dextran by other than the renal route did not vary with the mean molecular weight, and indicated that the dextran molecule is catabolized at from 4.9 to 8.6 mgm./hr./kgm. body weight. About 50% of total plasma proteins of animals was lost by the hemorrhage and was replaced, after dextran infusions, within four days. There was no evidence, after dextran infusions, of dextran storage in kidney, spleen, or liver.