Vasoactivity of Bovine Polymerized Hemoglobin (HBOC-201) in Swine With Traumatic Hemorrhagic Shock With and Without Brain Injury

BACKGROUND: Shenfu injection (SFI) is a traditional Chinese herbal medicine which has been clinically used for treatment of septic shock and cardiac shock. The aim of this study was to clarify effects of SFI on cerebral microcirculation and brain injury after hemorrhagic shock (HS). METHODS: Twenty-one domestic male Beijing Landrace pigs were randomly divided into three groups: SFI group (SFI, n = 8), saline group (SA, n = 8) or sham operation group (SO, n = 5). In the SFI group, animals were induced to HS by rapid bleeding to a mean arterial pressure of 40 mmHg within 10 minutes and maintained at 40±3 mmHg for 60 minutes. Volume resuscitation (shed blood and crystalloid) and SFI were given after 1 hour of HS. In the SA group, animals received the same dose of saline instead of SFI. In the SO group, the same surgical procedure was performed but without inducing HS and volume resuscitation. The cerebral microvascular flow index (MFI), nitric oxide synthase (NOS) expression, aquaporin-4 expression, interleukin-6, tumor necrosis factor-α (TNF-α) and ultrastructural of microvascular endothelia were measured. RESULTS: Compared with the SA group, SFI significantly improved cerebral MFI after HS. SFI up regulated cerebral endothelial NOS expression, but down regulated interleukin-6, TNF-α, inducible NOS and aquaporin-4 expression compared with the SA group. The cerebral microvascular endothelial injury and interstitial edema in the SFI group were lighter than those in the SA group. CONCLUSIONS: Combined application of SFI with volume resuscitation after HS can improve cerebral microcirculation and reduce brain injury.

Download Full-text

Resuscitation from hemorrhagic shock after traumatic brain injury with polymerized hemoglobin

Scientific Reports ◽

10.1038/s41598-021-81717-3 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Cynthia R. Muller ◽

Vasiliki Courelli ◽

Alfredo Lucas ◽

Alexander T. Williams ◽

Joyce B. Li ◽

...

Keyword(s):

Traumatic Brain Injury ◽

Brain Injury ◽

Hemorrhagic Shock ◽

Ischemia Reperfusion Injury ◽

Diastolic Pressure ◽

Ischemia Reperfusion ◽

Treatment Strategies ◽

Secondary Bleeding ◽

Additional Testing ◽

Systolic Blood Pressure Variability

AbstractTraumatic brain injury (TBI) is often accompanied by hemorrhage, and treatment of hemorrhagic shock (HS) after TBI is particularly challenging because the two therapeutic treatment strategies for TBI and HS often conflict. Ischemia/reperfusion injury from HS resuscitation can be exaggerated by TBI-induced loss of autoregulation. In HS resuscitation, the goal is to restore lost blood volume, while in the treatment of TBI the priority is focused on maintenance of adequate cerebral perfusion pressure and avoidance of secondary bleeding. In this study, we investigate the responses to resuscitation from severe HS after TBI in rats, using fresh blood, polymerized human hemoglobin (PolyhHb), and lactated Ringer’s (LR). Rats were subjected to TBI by pneumatic controlled cortical impact. Shortly after TBI, HS was induced by blood withdrawal to reduce mean arterial pressure (MAP) to 35–40 mmHg for 90 min before resuscitation. Resuscitation fluids were delivered to restore MAP to ~ 65 mmHg and animals were monitored for 120 min. Increased systolic blood pressure variability (SBPV) confirmed TBI-induced loss of autoregulation. MAP after resuscitation was significantly higher in the blood and PolyhHb groups compared to the LR group. Furthermore, blood and PolyhHb restored diastolic pressure, while this remained depressed for the LR group, indicating a loss of vascular tone. Lactate increased in all groups during HS, and only returned to baseline level in the blood reperfused group. The PolyhHb group possessed lower SBPV compared to LR and blood groups. Finally, sympathetic nervous system (SNS) modulation was higher for the LR group and lower for the PolyhHb group compared to the blood group after reperfusion. In conclusion, our results suggest that PolyhHb could be an alternative to blood for resuscitation from HS after TBI when blood is not available, assuming additional testing demonstrate similar favorable results. PolyhHb restored hemodynamics and oxygen delivery, without the logistical constraints of refrigerated blood.

Download Full-text

Hemostatic Resuscitation in Traumatic Hemorrhagic Shock: Case Report

Brazilian Journal of Anesthesiology (English Edition) ◽

10.1016/j.bjane.2012.03.006 ◽

2013 ◽

Vol 63 (1) ◽

pp. 99-102

Author(s):

José Osvaldo Barbosa Neto ◽

Marcos Fernando Breda de Moraes ◽

Ricardo Souza Nani ◽

Joel Avancini Rocha Filho ◽

Maria José Carvalho Carmona

Keyword(s):

Case Report ◽

Hemorrhagic Shock ◽

Hemostatic Resuscitation ◽

Traumatic Hemorrhagic Shock

Download Full-text

Traumatic brain injury may worsen clinical outcomes after prolonged partial resuscitative endovascular balloon occlusion of the aorta in severe hemorrhagic shock model

Journal of Trauma and Acute Care Surgery ◽

10.1097/ta.0000000000002149 ◽

2019 ◽

Vol 86 (3) ◽

pp. 415-423 ◽

Cited By ~ 5

Author(s):

Aaron M. Williams ◽

Umar F. Bhatti ◽

Isabel S. Dennahy ◽

Nathan J. Graham ◽

Vahagn C. Nikolian ◽

...

Keyword(s):

Traumatic Brain Injury ◽

Brain Injury ◽

Hemorrhagic Shock ◽

Clinical Outcomes ◽

Balloon Occlusion ◽

Shock Model ◽

Endovascular Balloon Occlusion ◽

Hemorrhagic Shock Model

Download Full-text

THE LACK OF CONSISTENT DIASPIRIN CROSS-LINKED HEMOGLOBIN INFUSION BLOOD PRESSURE EFFECTS IN THE US AND EU TRAUMATIC HEMORRHAGIC SHOCK CLINICAL TRIALS

Shock ◽

10.1097/shk.0b013e3181ac482b ◽

2010 ◽

Vol 33 (2) ◽

pp. 123-133 ◽

Cited By ~ 6

Author(s):

Edward P. Sloan ◽

Nora B. Philbin ◽

Max D. Koenigsberg ◽

Weihua Gao

Keyword(s):

Blood Pressure ◽

Clinical Trials ◽

Hemorrhagic Shock ◽

Pressure Effects ◽

The Us ◽

Blood Pressure Effects ◽

Traumatic Hemorrhagic Shock

Download Full-text

Blood-Based Brain and Global Biomarker Changes after Combined Hypoxemia and Hemorrhagic Shock in a Rat Model of Penetrating Ballistic-Like Brain Injury

Neurotrauma Reports ◽

10.1089/neur.2021.0006 ◽

2021 ◽

Vol 2 (1) ◽

pp. 370-380

Author(s):

Xue Li ◽

Kevin Pierre ◽

Zhihui Yang ◽

Lynn Nguyen ◽

Gabrielle Johnson ◽

...

Keyword(s):

Brain Injury ◽

Hemorrhagic Shock ◽

Rat Model

Download Full-text

The calcilytic drug Calhex-231 ameliorates vascular hyporesponsiveness in traumatic hemorrhagic shock by inhibiting oxidative stress and mitochondrial fission

10.21203/rs.2.23868/v1 ◽

2020 ◽

Author(s):

Yan Lei ◽

Xiaoyong Peng ◽

Tao Li ◽

Liangming Liu ◽

Guangming Yang

Keyword(s):

Oxidative Stress ◽

Hemorrhagic Shock ◽

Vascular Reactivity ◽

Mitochondrial Fission ◽

Blood Perfusion ◽

Mitochondrial Fusion ◽

Vital Organ ◽

Animal Survival ◽

Traumatic Hemorrhagic Shock ◽

Mlc Phosphorylation

Abstract Background The calcium-sensing receptor (CaSR) plays a fundamental role in extracellular calcium homeostasis in humans. Surprisingly, CaSR is also expressed in non-homeostatic tissues and is involved in regulating diverse cellular functions. The objective of this study was to determine if Calhex-231 (Cal), a negative modulator of CaSR, may be beneficial in the treatment of traumatic hemorrhagic shock (THS) by improving cardiovascular function, and investigated its relationship to oxidative stress and the mitochondrial fusion-fission pathway. Methods Rats that had been subjected to traumatic hemorrhagic shock were used as models in this study. Hypoxia-treated vascular smooth muscle cells (VSMCs) were also used. The effects of Cal on cardiovascular function, animal survival, hemodynamic parameters, and vital organ function in THS rats were observed, and the relationship to oxidative stress and mitochondrial fusion-fission was investigated. Results Cal significantly improved hemodynamics, elevated blood pressure, increased vital organ blood perfusion and local oxygen supply, and markedly improved the survival outcomes of THS rats. Furthermore, Cal significantly improved vascular reactivity after THS, including the pressor response of THS rats to norepinephrine (NE), and also the contractile response of superior mesenteric arteries, mesenteric arterioles, and isolated VSMCs to NE. Cal also restored the THS-induced decrease in myosin light chain (MLC) phosphorylation, which is the principal mechanism responsible for VSMC contraction and vascular reactivity. Inhibition of MLC phosphorylation antagonized the Cal-induced restoration of vascular reactivity following THS. Cal decreased oxidative stress indexes and increased antioxidant enzyme levels in THS rats, and also reduced reactive oxygen species levels in hypoxic VSMCs. In addition, THS induced expression of mitochondrial fission proteins Drp1 and Fis1, and decreased expression of mitochondrial fusion protein Mfn1 in vascular tissues. Cal reduced expression of Drp1 and Fis1, but did not affect Mfn1 expression. In hypoxic VSMCs, Cal inhibited hypoxia-induced mitochondrial fragmentation and preserved mitochondrial morphology. Conclusions Calhex-231 exhibits outstanding potential for effective therapy of traumatic hemorrhagic shock, due to its ability to improve hemodynamics, increase vital organ blood perfusion, and markedly prolong animal survival. These beneficial effects result from its protection of vascular function via inhibition of oxidative stress and mitochondrial fission.

Download Full-text