The development of hirudin as an antithrombotic drug

Experimental studies of ocular inflammation induced by endotoxin have been performed almost exclusively in rabbits. Although the rat has been considered refractory to both the systemic and local effects of endotoxin, the present study has shown that intravitreal injection of endotoxin evoked a characteristic acute inflammatory response which was reproducible and dose-dependent. In addition, a consensual ocular response in the control eye occurred which was less severe but also dose-dependent. Preliminary investigations support the view that consensual responses of this nature may be mediated by a nervous reflex are mechanism. Sequential histological analysis revealed a marked polymorphonuclear cell infiltration of most ocular tissues in the early stages, while mononuclear cells predominated after 3 days. Widespread intravascular microthrombi were also observed, particularly in the ciliary vessels. Recovery, however, was usually complete by 7 days.

Endotoxin-induced uveitis in the rat

Studies on the catabolism and distribution of fibrinogen in rats. Application of the iodogen® labelling technique

Summary. A prospective, randomized, controlled trial to examine the effects of antithrombin supplementation on mortality, coagulation and renal function has been carried out on 132 intensive care patients. Antithrombin activity was measured in all patients on admission to the intensive care unit (ICU). Patients with an antithrombin activity of less than 70% were randomized to either receive antithrombin replacement or to act as controls. Antithrombin activity was maintained above 70% in the treated patients throughout their stay on ICU. Ninety-three patients had an antithrombin activity of less than 70% and 35 received replacement therapy. Patients with antithrombin activity below 70% remained on the ICU significantly longer and had a significantly higher mortality rate than patients with antithrombin activity above 70%. Antithrombin supplementation neither reduced mortality nor shortened the intensive care stay. Fifty patients with reduced antithrombin activity remained on the ICU for at least 4 days, 25 received antithrombin and 25 acted as controls; coagulation parameters and renal function have been monitored in these patients. Fibrinogen concentration and platelet count were unaffected by antithrombin replacement. Antithrombin supplementation did not appear to reduce the incidence of impaired renal function in sepsis, trauma and postoperative patients. The creatinine clearance fell below 20 ml/min in eight patients in the no-treatment arm while by comparison only three patients in the treatment arm developed impaired renal function. Our study does not demonstrate a clear role for the use of antithrombin supplementation in intensive care, however the finding that antithrombin reduced renal impairment is encouraging and a larger study to confirm this finding is at present underway.

A pilot study of antithrombin replacement in intensive care management: the effects on mortality, coagulation and renal function

/pdf/studies-on-the-catabolism-and-distribution-of-fibrinogen-in-xkgzekr7cd.pdf

Studies On The Catabolism And Distribution Of Fibrinogen In Rats. Application Of The IodogenR Labelling Technique

Induction of disseminated intravascular coagulation by endotoxin and saline loading in rats. I. The influence on fibrinogen turnover and plasma parameters.

Induction of disseminated intravascular coagulation by endotoxin and saline loading in rats II. Fibrin deposition and removal.

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Induction of disseminated intravascular coagulation by endotoxin and saline loading in rats. I. The influence on fibrinogen turnover and plasma parameters.

Induction of disseminated intravascular coagulation by endotoxin and saline loading in rats II. Fibrin deposition and removal.