Assessment of the charge selectivity of glomerular basement membrane using Ficoll sulfate.

The extent to which the glomerular basement membrane (GBM) contributes to the charge selectivity of the glomerular capillary wall has been controversial. To reexamine this issue, the size and charge selectivity of filters made from isolated rat GBM were assessed, using polydisperse Ficoll and Ficoll sulfate as test macromolecules. Ficoll sulfate, a novel tracer with spherical shape synthesized for this purpose, exhibited little or no binding to serum albumin, thereby avoiding a major difficulty that has been reported with dextran sulfate. The sieving coefficients of Ficoll sulfate were not different from those of Ficoll at physiological ionic strength, although the values for Ficoll sulfate were depressed at low ionic strength. These results confirm that the GBM possesses fixed negative charges but suggest that its charge density is insufficient to confer significant charge selectivity under physiological conditions, where electrostatic interactions are relatively well screened. The sieving coefficients of Ficoll sulfate and Ficoll were elevated significantly and by similar amounts when bovine serum albumin (BSA) was present in the retentate at 4 g/dl. This could be explained as the combined effect of two nonspecific physical factors, namely, the reduction in filtration velocity due to the osmotic pressure of BSA and the effect on macromolecular partitioning of repulsive solute-solute interactions. The view that BSA does not affect the intrinsic properties of the GBM is supported also by the absence of an effect on the hydraulic permeability of isolated GBM. The sieving coefficient of BSA was roughly half that of Ficoll or Ficoll sulfate of similar Stokes-Einstein radius. Given the finding of negligible charge selectivity, this difference may be attributed to the nonspherical shape of albumin. The results suggest that, to the extent that isolated GBM is similar to GBM in vivo, the charge selectivity of the glomerular capillary wall must be due to the endothelial and/or epithelial cell layers.

Plasma kinetics of digoxin in the cat.

The biological half-life of digoxin was 33.3 +/- 9.5 hours in 6 cats after a single IV injection. Longer half-lives were obtained after chronic oral administration, indicating that digoxin elimination is capacity-limited in the cat. The mean percentage of urinary excretion of digoxin after a single IV dose was 45% +/- 9.7% over a 10-day period. Toxic plasma concentrations ranged from 2.4 to 2.9 ng/ml, and 5 of 6 cats had clinical signs of toxicosis at concentrations greater than 2.6 ng/ml. Prolongation of the PQ interval was seen on the ECG at nontoxic plasma concentrations in 4 of 6 cats. The most striking ECG evidence of digoxin toxicosis was ST-segment elevation seen in 3 of the 6 cats.

Fibrinous pericarditis in the horse.

During a period of 18 months, between July 1978 and January 1980, 4 adult horses were referred to the New York State College of Veterinary Medicine with evidence of congestive heart failure. Characteristic clinical abnormalities included marked muffling of heart sounds, tachycardia, jugular vein distention, and peripheral edema. Treatment with antibiotics, diuretics, and anti-inflammatory drugs was unsuccessful, and all four died or were euthanatized and necropsied. At necropsy, there was marked distention of the pericardial sac with fluid, and thick layers of fibrin were deposited uniformly over the epicardium. In 3 cases, attempts to isolate bacteria and viruses from pericardial fluid were unsuccessful; in the 4th case, Actinobacillus equuli was isolated on culture of the pericardial fluid.