Does Beta Blockade Postinjury Prevent Bone Marrow Suppression?

Abstract

Trauma-induced hypercatecholaminemia negatively impacts bone marrow (BM) function by suppressing BM hematopoietic progenitor cell (HPC) growth and increasing HPC egress to injured tissue. Beta blockade (BB) given before tissue injury alone has been shown to reduce both HPC mobilization and restore HPC colony growth within the BM. In a clinically relevant model, this study examines the effect of BB given after both tissue injury and hemorrhagic shock (HS). Male Sprague-Dawley rats underwent lung contusion (LC) with a blast wave percussion. HS was achieved after LC by maintaining the mean arterial blood pressure 30 mm Hg to 35 mm Hg for 45 minutes. Propranolol (10 mg/kg) was given once the mean arterial blood pressure>80 mm Hg and subsequent doses were given daily (LC/HS/BB). One-day and 7-day postinjury, analysis of BM and lung tissue for the growth of HPCs, hematologic parameters, and histology of lung injury were performed. LC/HS significantly worsens BM CFU-E growth suppression (15±8 vs. 35±2) and increases CFU-E growth in injured tissue when compared with LC at 1 day and 7 days (33±5 vs. 22±9). The use of BB after LC/HS ameliorated BM suppression, the degree of anemia and HPC growth in the injured lung at 1 day and 7 days postinjury. Lung injury score shows that there was no worsening of lung healing with BB (LC/HS/BB 3.2±2 vs. LC/HS 3.8±0.8). In an injury and shock model, administration of propranolol immediately after resuscitation significantly reduced BM suppression, and the protective effect is maintained at 7 days with daily BB. Although BB appears to improve BM function by decreasing HPC mobilization to injured tissue, there was no worsening of lung healing. Therefore, the use of propranolol after trauma and resuscitation may minimize long-term BM suppression after injury with no adverse impact on healing.