Background and Purpose— Cerebral ischemia initiates cascades of pathological events such as edema, blood–brain barrier breakdown, and tissue degeneration. Thrombin activation is a key step in coagulation, and thrombin has recently been shown to mediate endothelial permeability and cellular toxicity in vitro. We examined the effect of thrombin on vasculature during ischemia in vivo. Methods— Focal ischemia was induced in adult Sprague-Dawley rats by occlusion of the middle cerebral artery for 4 hours followed by a short period of reperfusion. High-molecular-weight fluorescein isothiocyanate-dextran was injected before surgery to label the severe vascular disruption. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining was used to identify dying cells, which were quantified with manual counts. Intra-arterial thrombin or intravenous thrombin inhibitors were infused during ischemia and reperfusion. Results— Infusion of thrombin (3 U/kg) intra-arterially during ischemia greatly enlarged the volume of severe vascular disruption, as visualized by fluorescein isothiocyanate–dextran extravasation ( P <0.05). Thrombin also promoted blood–brain barrier leakage of IgG during ischemia. Vascular disruption was blocked by intravenous infusion of the direct thrombin inhibitor argatroban (1.69 mg/kg, P <0.05). Greater numbers of dying cells were found in regions of severe vascular disruption, and interventions that reduced vascular leakage also reduced the numbers of dying cells. Conclusions— Thrombin mediates severe vascular disruption during ischemia and thrombin inhibitors may partially ameliorate vascular disruption. Further work is needed to establish whether thrombin, entering parenchyma due to increased vascular permeability, augments neurotoxicity during ischemia.

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Intravenous Ig (IVIg) products are used in various medical conditions. Differences in excipients account for most adverse events (AE). Reports of complications including acute myocardial infarction (AMI) and acute renal failure (ARF) have emerged. Herein is described one institution's experience with IVIg-related complications. This study is a retrospective analysis of infusion-related AE that are associated with various IVIg products. Infusion-related AE were monitored during and after the administration of three IVIg products: Gamimune-N 10% (n ‫؍‬ 76), Polygam (n ‫؍‬ 105), and Carimune (n ‫؍‬ 98). AE segregated to specific IVIg products. No patients who received Gamimune-N experienced AMI or ARF. Five (4.7%) patients (P < 0.01) in the Polygam group experienced AMI. Eight (8.2%) patients (P < 0.0001) in the Carimune group developed ARF. IVIg was safe to give on hemodialysis. IVIg products differ in osmolality, pH, and sugar and sodium content; this results in specific AE. Polygam resulted in no ARF but an increase in AMI. Carimune products at 9% concentration resulted in an increase in ARF. Gamimune-N 10% and other IVIg products were frequently associated with headaches. Administration of IVIg to patients who are on hemodialysis seems to be safe and effective.