Clonidine reduces norepinephrine and improves bone marrow function in a rodent model of lung contusion, hemorrhagic shock, and chronic stress.

Abstract

BACKGROUND:

Propranolol has been shown previously to restore bone marrow function and improve anemia after lung contusion/hemorrhagic shock. We hypothesized that daily clonidine administration would inhibit central sympathetic outflow and restore bone marrow function in our rodent model of lung contusion/hemorrhagic shock with chronic stress.

METHODS:

Male Sprague-Dawley rats underwent 6 days of restraint stress after lung contusion/hemorrhagic shock during which the animals received clonidine (75 μg/kg) after the restraint stress. On postinjury day 7, we assessed urine norepinephrine, blood hemoglobin, plasma granulocyte colony stimulating factor, and peripheral blood mobilization of hematopoietic progenitor cells, as well as bone marrow cellularity and erythroid progenitor cell growth.

RESULTS:

The addition of clonidine to lung contusion/hemorrhagic shock with chronic restraint stress significantly decreased urine norepinephrine levels, improved bone marrow cellularity, restored erythroid progenitor colony growth, and improved hemoglobin (14.1 ± 0.6 vs 10.8 ± 0.6 g/dL). The addition of clonidine to lung contusion/hemorrhagic shock with chronic restraint stress significantly decreased hematopoietic progenitor cells mobilization and restored granulocyte colony stimulating factor levels.

CONCLUSION:

After lung contusion/hemorrhagic shock with chronic restraint stress, daily administration of clonidine restored bone marrow function and improved anemia. Alleviating chronic stress and decreasing norepinephrine is a key therapeutic target to improve bone marrow function after severe injury.

• Authors: Ines G Alamo, Kolenkode B Kannan, Harry Ramos, Tyler J Loftus, Philip A Efron, Alicia M Mohr
• Journal: Surgery (Surgery) Vol. 161 Issue 3 Pg. 795-802 (03 2017) ISSN: 1532-7361 [Electronic] United States
• PMID: 27742030 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
• Copyright: Copyright © 2016 Elsevier Inc. All rights reserved.

Chemical References

• Hemoglobins
• Sympatholytics
• Granulocyte Colony-Stimulating Factor
• Clonidine
• Norepinephrine

Topics

• Animals
• Bone Marrow (physiopathology)
• Chronic Disease
• Clonidine (therapeutic use)
• Contusions (blood, complications, therapy)
• Disease Models, Animal
• Granulocyte Colony-Stimulating Factor (blood)
• Hematopoietic Stem Cells (physiology)
• Hemoglobins (metabolism)
• Lung Injury (blood, complications, therapy)
• Male
• Norepinephrine (blood)
• Rats, Sprague-Dawley
• Shock, Hemorrhagic (blood, complications, therapy)
• Stress, Psychological (blood, complications, therapy)
• Sympatholytics (therapeutic use)