Fluid sparing effects of chemokine (C-C motif) receptor 1 and 2 antagonists during resuscitation from hemorrhagic shock in rat models

by Elizabeth A. Cook, Ololade Ogunsina, Xianlong Gao, Matthias Majetschak We described previously that the chemokine (C-C motif) receptor 1 (CCR1) and CCR2 antagonists BX471 and INCB3284 reduce fluid requirements during resuscitation after hemorrhage.

Their effects, however, have not been directly compared with each other and consequences of simultaneous blockade of CCR1/2 are unknown. Here we utilized rat (Sprague-Dawley) models of hemorrhagic shock to compare fluid sparing properties when administered individually or in combination and to assess effects on shock tolerance.

Series 1: rats were hemorrhaged to a mean arterial blood pressure (MAP) of 30 mmHg for 30 min, followed by blood pressure-directed fluid resuscitation for 6h. At t = 30 min, vehicle (n = 12), BX471 (0.5 µmol/kg, n = 9), INCB3284 (5 µmol/kg, n = 7), or BX471 (0.5 µmol/kg) plus INCB3284 (5 µmol/kg, n = 6) were injected.