RECOMBINANT ENDOTOXIN-BINDING PROTEIN (RBPI(23)) ATTENUATES ENDOTOXIN-INDUCED CIRCULATORY CHANGES IN HUMANS

In the present study the protective effect of a recombinant endotoxin- binding protein rBPI(23) on the circulatory changes in experimental en dotoxemia in humans was investigated. In a controlled, blinded crossov er study, eight volunteers were challenged twice with an intravenous b olus injection of endotoxin (40 EU/kg body weight), and concurrently r eceived either rBPI(23) (1 mg/kg) or placebo (human serum albumin, 0.2 mg/kg). Hemodynamic parameters were obtained non-invasively by means of M-mode, two-dimensional, and Doppler echocardiography. rBPI(23) sig nificantly reduced indices of the endotoxin-induced hyperdynamic circu lation. rBPI(23) treatment significantly reduced increase in cardiac i ndex (P = 0.0156). rBPI(23) treatment diminished the endotoxin-induced decrease in systemic vascular resistance index (P = 0.0304). rBPI(23) did not prevent the endotoxin-induced rise in body temperature and sy stolic, diastolic and mean arterial pressure were not significantly di fferent in the rBPI(23)- and placebo-treatment arm. Both treatment per iods showed a small reduction in end diastolic and end systolic volume s. rBPI(23) treatment slightly reduced the increase in M-mode ejection fraction and fractional shortening. These results indicate that rBPI( 23) is capable of attenuating the potentially deleterious circulatory effects of endotoxin in humans. (C) 1995 Wiley-Liss, Inc.