Recent development of rigors during infusion of urokinase: is it related to an endotoxin?

PURPOSE: This study was undertaken to determine the prevalence of rigors associated with the use of urokinase (UK) and to assay for the presence of an endotoxin in the UK solution. PATIENTS AND METHODS: Records of 75 patients who underwent 86 UK infusions between January 1988 and July 1992 were reviewed to evaluate for the development of UK-associated rigors. A modified chromogenic limulus amebocyte lysate (LAL) test was performed to determine the presence of endotoxin in four samples of UK from lots associated with rigors, one sample of UK not associated with rigors, sterile water, nonionic contrast medium, and ionic contrast medium. RESULTS: Between January 1, 1988, and July 10, 1990, 43 patients underwent 46 UK treatments (group 1) with no documented rigors (0% prevalence). In 45 of these 46 treatments, a standard, non-pulse-spray bolus of 75,000-500,000 IU of UK (mean dose, 182,222 IU) was used. Between July 11, 1990, and July 6, 1992, 38 patients underwent 40 UK treatments (group 2). In 33 of these 40 treatments, a standard bolus was given. Five patients received a pulse-spray bolus. The mean bolus was 213,768 IU (range, 100,000-500,000 IU). Eleven group 2 patients developed rigors (28% prevalence; P = .0005 vs group 1). The chromogenic LAL tests demonstrated no endotoxin in sterile water, nonionic contrast media, or ionic contrast media. Endotoxin was detected in small concentrations in the four samples of UK associated with rigors and in the UK sample not associated with rigors. CONCLUSION: The increase in the prevalence of rigors associated with the use of UK does not appear to be related to an endotoxin in UK, since the concentration of endotoxin detected is well below the threshold pyrogenic dose in humans.

Blood-brain barrier alterations in bacterial meningitis: development of an in vitro model and observations on the effects of lipopolysaccharide.

To further examine the effects of purified Haemophilus influenzae type b lipopolysaccharide (LPS) on blood-brain barrier permeability, we have developed an in vitro model of the BBB. Microvascular endothelial cells were isolated from rat cerebral cortices by enzymatic digestion, dextran centrifugation, and separation on percoll gradients. The cells were determined to be endothelial in origin by positive fluorescent staining for Factor VIII-related antigen and the ability to take up acetylated low density lipoproteins, and their cerebral origin by the formation of junctional complexes in vitro. Cells were seeded onto semipermeable polycarbonate filters and permeability assessed by measuring traversal of radioactive albumin across the monolayer. Treatment of the cells with LPS at concentrations of 1.0 microgram/ml and 0.1 microgram/ml for 4 h led to statistically significant increases in albumin permeability of 4.6% (P = 0.001) and 5.6% (P less than 0.001), respectively, without evidence of cell death as assessed by release of lactate dehydrogenase into the media. These results indicate that LPS significantly increases albumin permeability across a monolayer of cerebral microvascular endothelial cells in the absence of host inflammatory cells. Future studies on the effects of LPS on intracellular regulation will determine the mechanisms responsible for these alterations.