LAUSR

The use of a low dose of rtPA by Hinds et al. (40% of the usual lytic dose, 0.15 mg/kg and after 0.3 mg/kg, 9–12 kg juvenile baboons) could be, in part, responsible for the absence of difference observed. Indeed, the injection of rtPA in humans is composed of a bolus (10% of the total dose), which neutralizes the inhibitor of rtPA, and then an intravenous continuous injection lasting 60 min. By using a reduced dose, Hinds et al. would not have neutralized the rtPA inhibitor thus leading to an impaired thrombolysis compared to the result obtained by Petit et al. Another point, considering the use of a reduced dosage of rtPA, is that, in vivo, endothelial cells are secreting tPA during ischemia. This phenomenon may promote the efficacy of a reduced dose of rtPA, but was absent in the ex vivo model used by Hinds et al. It may be then interesting to evaluate the potential of a reduced dose of rtPA with taking into account these two potentials reasons of failure and modifying the scheme of use of rtPA in future research. Sincerely,