Antithrombin III is an important element of the endogenous thrombosis protection system. Congenital Anti-thrombin III deficiencies are associated with increased incidence of thrombo-embolisms. If Antithrombin III is determined at the time of operation, postoperative deficiencies resulting from an increased turnover rate can be identified. Determination of Antithrombin III is not suitable for prognosticating the occurrence of thrombo-embolic complications in isolated cases. Antithrombin III can be administered in the form of fresh frozen plasma (FFP), though it is also available as Antithrombin III concentrate. So far no investigations have been carried out to establish whether it is possible to improve thrombosis protection with or without heparin prophylaxis by concentrated Antithrombin III substitution.
Background and Purpose —Hypothermia reduces neuronal damage in animal stroke models. Whether hypothermia is neuroprotective in patients with acute stroke remains to be clarified. In this case-control study, we evaluated the feasibility and safety of inducing modest hypothermia by a surface cooling method in awake patients with acute stroke. Methods —We prospectively included 17 patients (cases) with stroke admitted within 12 hours from stoke onset (mean 3.25 hours). They were given hypothermic treatment for 6 hours by the “forced air” method, a surface cooling method that uses a cooling blanket with a flow of cool air (10°C). Pethidine was given to treat compensatory shivering. Cases were compared with 56 patients (controls) from the Copenhagen Stroke Study matched for age, gender, initial stroke severity, body temperature on admission, and time from stroke onset to admission. Blood cytology, biochemistry, ECGs, and body temperature were monitored during hypothermic treatment. Multiple regression analyses on outcome were performed to examine the safety of hypothermic therapy. Results —Body temperature decreased from t 0 =36.8°C to t 6 =35.5°C ( P <0.001), and hypothermia was present until 4 hours after therapy (t 0 =36.8°C versus t 10 =36.5°C; P =0.01). Mortality at 6 months after stroke was 12% in cases versus 23% in controls ( P =0.50). Final neurological impairment (Scandinavian Stroke Scale score at 6 months) was mean 42.4 points in cases versus 47.9 in controls ( P =0.21). Hypothermic therapy was not a predictor of poor outcome in the multivariate analyses. Conclusions —Modest hypothermia can be achieved in awake patients with acute stroke by surface cooling with the “forced air” method, in combination with pethidine to treat shivering. It was not associated with a poor outcome. We suggest a large, randomized clinical trial to test the possible beneficial effect of induced modest hypothermia in unselected patients with stroke.
The use of mechanical/physical devices for applying mild therapeutic hypothermia is the only proven neuroprotective treatment for survivors of out of hospital cardiac arrest. However, this type of therapy is cumbersome and associated with several side-effects. We investigated the feasibility of using a transient receptor potential vanilloid type 1 (TRPV1) agonist for obtaining drug-induced sustainable mild hypothermia. First, we screened a heterogeneous group of TRPV1 agonists and secondly we tested the hypothermic properties of a selected candidate by dose-response studies. Finally we tested the hypothermic properties in a large animal. The screening was in conscious rats, the dose-response experiments in conscious rats and in cynomologus monkeys, and the finally we tested the hypothermic properties in conscious young cattle (calves with a body weight as an adult human). The investigated TRPV1 agonists were administered by continuous intravenous infusion. Screening: Dihydrocapsaicin (DHC), a component of chili pepper, displayed a desirable hypothermic profile with regards to the duration, depth and control in conscious rats. Dose-response experiments: In both rats and cynomologus monkeys DHC caused a dose-dependent and immediate decrease in body temperature. Thus in rats, infusion of DHC at doses of 0.125, 0.25, 0.50, and 0.75 mg/kg/h caused a maximal ΔT (°C) as compared to vehicle control of -0.9, -1.5, -2.0, and -4.2 within approximately 1 hour until the 6 hour infusion was stopped. Finally, in calves the intravenous infusion of DHC was able to maintain mild hypothermia with ΔT > -3°C for more than 12 hours. Our data support the hypothesis that infusion of dihydrocapsaicin is a candidate for testing as a primary or adjunct method of inducing and maintaining therapeutic hypothermia.
