Does selective beta-1 blockade provide bone marrow protection after trauma/ hemorrhagic shock?

Numerous clinical studies have evaluated the effects of beta blockade in cardiac, general, vascular and trauma surgery subpopulations with varying results. Lindenauer et al. (1) recently showed that the use of perioperative beta-blocker therapy is associated with a reduced risk of in-hospital death among high-risk patients undergoing major noncardiac surgery but was of no benefit in low-risk patients. This retrospective database analysis does not specify the type of beta blocker or the effectiveness of dosing but draws their conclusion on the basis of timing of beta blockade administration. The Metoprolol after Vascular Surgery trial was a prospective, double blind randomized control trial studying the effects of metoprolol (selective B1 blocker) on cardiac risk in patients undergoing abdominal aortic surgery or major lower extremity revascularization operations. Yang et al. (2) showed that metoprolol was not effective in reducing either 30 day or 6 month postoperative cardiac events in vascular patients. In a retrospective study of trauma patients, Arbabi et al. (3), found that the use of beta blockade before or after injury was associated with decreased mortality. This retrospective study in trauma patients does not specify the type of beta blockade used, however, they advocate the benefits of the drug being its cardioprotective effects, decreased myocardial oxygen demands, and decreased cerebral oxygen requirements in head injury (3). A decrease in heart rate (HR) has been shown to be cardioprotective after myocardial infarction and may also be beneficial after a severe traumatic injury and it associated systemic inflammatory response. A significant increase in catecholamines secondary to the stress response to injury has been shown to be associated with bone marrow (BM) dysfunction (4). This BM dysfunction is prolonged and lasts for up to 14 days after injury and manifests clinically as increased susceptibility to infection and persistent anemia (5, 6). The need for multiple transfusions further contributes to the morbidity and mortality following their severe injuries (7, 8). The post-injury hypercatecholamine state has been shown to suppress BM function in a dose-dependent manner (9, 10). Previously we have demonstrated that the administration of non-selective beta blockade with propranolol, both before and after injury, restored BM function (11, 12). The BM protective effects of propranolol have been shown to be dose-dependent (12). It remains unclear if the beneficial effects of non-selective beta blockade given after trauma are via an overall cardiovascular protective effect or an immunomodulatory effect, or both. Understanding the mechanism of beta blockade protection of BM is important to the development of effective treatment modalities in the clinical setting. Thus, the aim of this study is to more clearly define the role of the specific beta adrenergic receptors (B1, B2, B3) in BM protection following trauma and hemorrhagic shock (HS) and to determine if a cardiovascular effect is necessary for BM protection.