Propranolol attenuates hemorrhage and accelerates wound healing in severely burned adults

Ali, Arham; Herndon, David N.; Mamachen, Ashish; Hasan, Samir; Andersen, Clark R.; Grogans, Ro Jon; Brewer, Jordan L.; Lee, Jong O.; Heffernan, Jamie; Suman, Oscar E.; Finnerty, Celeste C.

doi:10.1186/s13054-015-0913-x

Cited by 66 publications

(72 citation statements)

References 29 publications

(29 reference statements)

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“…The latter may be positively influenced due to the additional angionetic effects of β-blockers [25]. Most of these effects were detected after oral or systemic application, respectively [9, 10]. In serum equivalent applications they seemed to have less influence on keratinocytes and fibroblasts.…”

Section: Discussionmentioning

confidence: 99%

Side Effects of Frequently Used Antihypertensive Drugs on Wound Healing in vitro

Besser

Terberger

Bachmann

et al. 2019

Skin Pharmacol Physiol

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Background: The number of patients who has a daily intake of antihypertensive drugs is rising, due to an also rising prevalence of lifestyle diseases. Interestingly, knowledge about effects of these drugs in terms of wound healing is low. Objective: Based on a few differing studies, the idea arose that antihypertensives may have side effects on wound healing. Methods: Five antihypertensive drugs from different substance classes (metoprolol, amlodipine, ramipril, hydrochlorothiazide, candesartan) were investigated, in terms of possible impacts on cell metabolism and migration of human skin fibroblasts and keratinocytes. Additionally, histological and immunohistochemical analyses were performed in a 3-dimensional (3D) wound model addressing the influence on regeneration processes, such as cell migration, metabolic activity, apoptosis and epidermal thickness. Results: Hydrochlorothiazide and ramipril exerted inhibiting effects in nearly all analyses, interestingly, in serum equivalent doses. In contrast, candesartan and amlodipine induced slight positive effects in 2D as well as in 3D models. The previously described positive effects of β-blockers could only partially be confirmed by metoprolol. Antihypertensive drugs affected fibroblasts more than keratinocytes – whether positively or negatively. Conclusion: Antihypertensive drugs have an influence on keratinocytes and fibroblasts; they are not neutral. Candesartan has the most positive effects on skin cells. For angiotensin-converting enzyme inhibitors and thiazide diuretics, wound healing in a 3D model is delayed. β-Receptor blockers seem to improve wound healing to a small extent just like calcium channel blockers. These results should be evaluated in a clinical trial to verify their clinical relevance.

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Section: Discussionmentioning

confidence: 99%

Side Effects of Frequently Used Antihypertensive Drugs on Wound Healing in vitro

Besser

Terberger

Bachmann

et al. 2019

Skin Pharmacol Physiol

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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%

“…Further study demonstrating the importance of propranolol dosing in wound healing was done by Zhang et al (42) who demonstrated that propranolol infusion at 1 mg/kg/hr in rabbits (significantly less than the 50 mg/kg doses in rabbits) did not negatively impact wound reepithelialization. Clinically most relevant, in adult burn patients that received an average of 3 mg/kg/day of propranolol there was an associated improvement in donor site healing time (36). …”

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

Bible

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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“…(93, 94) There have been several studies in burn patients demonstrating that propranolol improves wound healing, decreases cardiac work, and reduces metabolic demands without causing significant arterial hypotension or metabolic dysregulation. (95–97) Rodent models have provided the pathophysiologic basis for these clinical advances. Stress response pathways, including p38 MAPK, JNK, and NF-κB, are activated by scald burn injury and have been effectively blocked with propranolol.…”

Section: Burns and Wound Healingmentioning

confidence: 99%

β-Blockade use for Traumatic Injuries and Immunomodulation

Loftus

Efron

Moldawer

et al. 2016

Shock

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Sympathetic nervous system activation and catecholamine release are important events following injury and infection. The nature and timing of different pathophysiologic insults have significant effects on adrenergic pathways, inflammatory mediators, and the host response. Beta adrenergic receptor blockers (β-blockers) are commonly used for treatment of cardiovascular disease but recent data suggests that the metabolic and immunomodulatory effects of β-blockers can expand their use. β-blocker therapy can reduce sympathetic activation and hypermetabolism as well as modify glucose homeostasis and cytokine expression. It is the purpose of this review to examine either the biologic basis for proposed mechanisms or to describe current available clinical evidence for the use of β-blockers in traumatic brain injury (TBI), spinal cord injury (SCI), hemorrhagic shock, acute traumatic coagulopathy, erythropoietic dysfunction, metabolic dysfunction, pulmonary dysfunction, burns, immunomodulation, and sepsis.

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Propranolol attenuates hemorrhage and accelerates wound healing in severely burned adults

Cited by 66 publications

References 29 publications

Side Effects of Frequently Used Antihypertensive Drugs on Wound Healing in vitro

Side Effects of Frequently Used Antihypertensive Drugs on Wound Healing in vitro

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

β-Blockade use for Traumatic Injuries and Immunomodulation

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