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

Pasupuleti, Latha V.; Cook, Kristin; Sifri, Ziad C.; Kotamarti, Srinath; Calderon, Gabriel M.; Alzate, Walter D.; Livingston, David H.; Mohr, Alicia M.

doi:10.1016/j.surg.2012.06.016

Cited by 9 publications

(21 citation statements)

References 25 publications

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“…Furthermore, our results are supported by similar observation in rats subjected to trauma/hemorrhagic shock where treatment with SR59230A and not with butoxamine or atenolol improved Hgb levels after seven days of treatment (45). In a separate sequential study, the authors observed an increase in Hgb levels with propranolol.…”

Section: Discussionsupporting

confidence: 88%

Discrete β-adrenergic mechanisms regulate early and late erythropoiesis in erythropoietin-resistant anemia

Hasan

Mosier

Szilágyi

et al. 2017

Surgery

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Background Anemia of critical illness is resistant to exogenous erythropoietin (Epo). pRBC transfusions being the only treatment option; despite related cost and morbidity, presses the need for alternate strategies. Erythrocyte development can be divided into Epo-dependent and Epo-independent stages. We have previously shown that Epo-dependent development is intact in burn patients and epo-independent early commitment stage is compromised, which is regulated by beta1/ beta2-adrenergic mechanisms. Utilizing scald burn injury model, we studied Epo-independent late maturation stages and the effect of beta1/beta2, beta-2, or beta-3 blockade in burn mediated Epo-resistant anemia. Methods Burn mice were randomized to receive daily injections of propranolol (non selective beta1/beta2 antagonist), Nadolol (long acting beta1/beta2 antagonist), Butoxamine (selective beta2 antagonist) or SR59230A (selective beta3 antagonist) for 6 days after burn. Total bone marrow (TBM) cells were characterized as non-erythroid cells; early and late erythroblasts; nucleated orthochromatic erythroblasts (Ortho-Es) and enucleated reticulocyte subsets using CD71, Ter119 and Syto-16 by flow cytometry. Multi potential progenitors were probed for MafB expressing cells. Results Although propranolol improved early and late erythroblasts, only butoxamine and SR59230A positively reflected in the peripheral blood Hgb and RBC counts. While burn impeded early commitment and late maturation stages; beta1/beta2 antagonism increased the early erythroblasts through commitment stages via beta2 specific MafB regulation. Beta3 antagonism was more effective in improving overall RBCs through late maturation stages. Conclusions Study unfolds novel beta2 and beta3 adrenergic mechanisms orchestrating erythropoietin resistant anemia after burn, which impedes both early commitment stage as well as late maturation stages respectively.

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Section: Discussionsupporting

confidence: 88%

Discrete β-adrenergic mechanisms regulate early and late erythropoiesis in erythropoietin-resistant anemia

Hasan

Mosier

Szilágyi

et al. 2017

Surgery

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“…HPC have been found within healing lungs as well as skin (34, 35). In addition, beta adrenergic receptors are found widely in fibroblasts, keratinocytes, endothelial cells, as well as HPC (36–38). In particular, the mobilization of HPC was shown to be mediated through beta 2 and 3 adrenergic receptors (38, 39).…”

Section: Discussionmentioning

confidence: 99%

“…In addition, beta adrenergic receptors are found widely in fibroblasts, keratinocytes, endothelial cells, as well as HPC (36–38). In particular, the mobilization of HPC was shown to be mediated through beta 2 and 3 adrenergic receptors (38, 39). In this study, the use of propranolol, a non-selective beta antagonist, decreased plasma G-CSF levels and the mobilization of HPC and it was hypothesized that reduced mobilization of HPC could worsen the healing of injured lung tissue.…”

Section: Discussionmentioning

confidence: 99%

Daily propranolol prevents prolonged mobilization of hematopoietic progenitor cells in a rat model of lung contusion, hemorrhagic shock, and chronic stress

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Pasupuleti

Gore

et al. 2015

Surgery

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Introduction Propranolol has been shown previously to decrease the mobilization of hematopoietic progenitor cells (HPC) after acute injury in rodent models; however, this acute injury model does not reflect the prolonged period of critical illness after severe trauma. Using our novel lung contusion/hemorrhagic shock/chronic restraint stress model, we hypothesize that daily propranolol (Prop) administration will decrease prolonged mobilization of HPC without worsening lung healing. Methods Male Sprague-Dawley rats underwent six days of restraint stress after undergoing lung contusion or lung contusion/hemorrhagic shock. Restraint stress consisted of a daily two hour period of restraint interrupted every 30 minutes by alarms and repositioning. Each day after the period of restraint stress, the rats received intraperitoneal propranolol (10mg/kg). On day seven, peripheral blood was analyzed for granulocyte-colony stimulating factor (G-CSF) and stromal cell-derived factor 1 (SDF-1) via ELISA and for mobilization of HPC using c-kit and CD71 flow cytometry. The lungs were examined histologically to grade injury. Results Seven days after lung contusion and lung contusion/hemorrhagic shock, the addition of chronic restraint stress significantly increased the mobilization of HPC, which was associated with persistently increased levels of G-CSF and increased lung injury scores. The addition of propranolol to lung contusion/chronic restraint stress and lung contusion/hemorrhagic shock/chronic restraint stress models significantly decreased HPC mobilization and restored G-CSF levels to that of naïve animals without worsening lung injury scores. Conclusions Daily propranolol administration after both lung contusion and lung contusion/hemorrhagic shock subjected to chronic restraint stress decreased the prolonged mobilization of HPC from the bone marrow and decreased plasma G-CSF levels. Despite the decrease in mobilization of HPC, lung healing did not worsen. Alleviating chronic stress with propranolol may be a future therapeutic target to improve healing after severe injury.

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“…Our previous work demonstrated that the use of atenolol at 10 mg/kg for 7 days following LCHS produced a cardiovascular response and effectively reduced heart rate by 10% but this was not associated with BM protection. 20 Atenolol use while associated with a reduction in heart rate was not associated with a change in mean arterial pressure, so the shock state was not propagated by the use of β1B. 20 …”

Section: Discussionmentioning

confidence: 99%

Do all β-blockers attenuate the excess hematopoietic progenitor cell mobilization from the bone marrow following trauma/hemorrhagic shock?

Pasupuleti

Cook

Sifri

et al. 2014

Journal of Trauma and Acute Care Surgery

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BACKGROUND Severe injury results in increased mobilization of hematopoietic progenitor cells (HPC) from the bone marrow (BM) to sites of injury, which may contribute to persistent BM dysfunction after trauma. Norepinephrine is a known inducer of HPC mobilization, and nonselective β-blockade with propranolol has been shown to decrease mobilization after trauma and hemorrhagic shock (HS). This study will determine the role of selective β-adrenergic receptor blockade in HPC mobilization in a combined model of lung contusion (LC) and HS. METHODS Male Sprague-Dawley rats were subjected to LC, followed by 45 minutes of HS. Animals were then randomized to receive atenolol (LCHS + β1B), butoxamine (LCHS + β2B), or SR59230A (LCHS + β3B) immediately after resuscitation and daily for 6 days. Control groups were composed of naive animals. BM cellularity, %HPCs in peripheral blood, and plasma granulocyte-colony stimulating factor levels were assessed at 3 hours and 7 days. Systemic plasma-mediated effects were evaluated in vitro by assessment of BM HPC growth. Injured lung tissue was graded histologically by a blinded reader. RESULTS The use of β2B or β3B following LCHS restored BM cellularity and significantly decreased HPC mobilization. In contrast, β1B had no effect on HPC mobilization. Only β3B significantly reduced plasma G-CSF levels. When evaluating the plasma systemic effects, both β2B and β3B significantly improved BM HPC growth as compared with LCHS alone. The use of β2 and β3 blockade did not affect lung injury scores. CONCLUSION Both β2 and β3 blockade can prevent excess HPC mobilization and BM dysfunction when given after trauma and HS, and the effects seem to be mediated systemically, without adverse effects on subsequent healing. Only treatment with β3 blockade reduced plasma G-CSF levels, suggesting different mechanisms for adrenergic-induced G-CSF release and mobilization of HPCs. This study adds to the evidence that therapeutic strategies that reduce the exaggerated sympathetic stimulation after severe injury are beneficial and reduce BM dysfunction.

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

Cited by 9 publications

References 25 publications

Discrete β-adrenergic mechanisms regulate early and late erythropoiesis in erythropoietin-resistant anemia

Discrete β-adrenergic mechanisms regulate early and late erythropoiesis in erythropoietin-resistant anemia

Daily propranolol prevents prolonged mobilization of hematopoietic progenitor cells in a rat model of lung contusion, hemorrhagic shock, and chronic stress

Do all β-blockers attenuate the excess hematopoietic progenitor cell mobilization from the bone marrow following trauma/hemorrhagic shock?

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