• Tyler J Loftus, Kolenkode B Kannan, Juan C Mira, Scott C Brakenridge, Philip A Efron, and Alicia M Mohr.
• Department of Surgery and Sepsis and Critical Illness Research Center, University of Florida Health, Gainesville, Florida.
• Shock. 2020 Oct 1; 54 (4): 482-487.

BackgroundTrauma and hemorrhagic shock trigger mobilization of hematopoietic progenitor cells (HPC) from bone marrow to peripheral blood. Hepatocyte growth factor (HGF), tyrosine-protein kinase Met (c-Met), matrix metallopeptidase 9 (MMP-9), and corticosterone regulate this mobilization process. We hypothesized that beta-blockade with propranolol and sympathetic outflow inhibition with clonidine following trauma and chronic stress would decrease hematopoietic progenitor cell mobilization.MethodsSprague-Dawley rats were randomized to undergo three models of injury and stress: lung contusion, LC plus hemorrhagic shock (LCHS), or LCHS plus chronic restraint stress for 2 h daily (LCHS/CS). Propranolol and clonidine were administered by daily intraperitoneal injection until sacrifice on day seven. Bone marrow HGF, c-Met, and MMP-9 were measured by real-time PCR. Plasma corticosterone was measured by ELISA. Percentage HPC in peripheral blood was measured by flow cytometry.ResultsPropranolol and clonidine significantly decreased bone marrow MMP-9 expression, plasma corticosterone levels, and HPC mobilization, and significantly increased hemoglobin levels. HPC mobilization was greatest following LCHS/CS (5.4 ± 1.8) and was significantly decreased by propranolol (2.2 ± 0.9, P < 0.001) and clonidine (1.7 ± 0.5, P < 0.001). Hemoglobin (g/dL) was lowest following LCHS/CS (12.3 ± 1.2) and was significantly increased by propranolol (13.7 ± 0.4, P = 0.022) and clonidine (14.1 ± 1.1, P < 0.001).ConclusionsSevere injury was associated with increased bone marrow HGF, c-Met, and MMP-9, circulating corticosterone, HPC mobilization, and persistent anemia. Attenuating the neuroendocrine response to injury and stress with propranolol and clonidine reduced MMP-9 expression, corticosterone levels, HPC mobilization, and the degree of anemia.

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