Protective Effect of Shenfu Injection (参附注射液) on Vascular Endothelial Damage in a Porcine Model of Hemorrhagic Shock

2022 ◽  
Author(s):  
Ming-qing Zhang ◽  
Qiang Zhang ◽  
Wei Yuan ◽  
Jun-yuan Wu ◽  
Yong Liang ◽  
...  
Keyword(s):  
Protective Effect ◽  
Hemorrhagic Shock ◽  
Porcine Model ◽  
Endothelial Damage ◽  
Vascular Endothelial ◽  
Shenfu Injection

Protective effect of Shenfu on gut epithelium in a porcine model of hemorrhagic shock

2021 ◽  
pp. jim-2021-001939
Author(s):  
Yong Liang ◽  
Chunsheng Li ◽  
Wei Yuan ◽  
Junyuan Wu ◽  
Qiang Zhang ◽  
...  
Keyword(s):  
Blood Transfusion ◽  
Protective Effect ◽  
Hemorrhagic Shock ◽  
Porcine Model ◽  
Negative Control Group ◽  
Negative Control ◽  
Control Group ◽  
Necrosis Factor Alpha ◽  
Fatty Acid Binding ◽  
Gut Epithelium

This study aimed to explore the protective effect of Shenfu on the hemodynamics and gut integrity in a porcine model of hemorrhagic shock. Hemorrhagic shock was induced in 32 domestic pigs with a rapid bleeding via the arterial sheath to a mean arterial pressure of 40 mm Hg within 10 min. Animals with hemorrhagic shock were then randomly assigned into the negative control group (n=8), receiving neither blood transfusion nor drug treatment; the blood transfusion group, in which animals were given blood transfusion alone; the saline group, in which animals were blood transfused and resuscitated with saline (3 mL/kg); and the Shenfu group, in which animals received blood transfusion and resuscitation with Shenfu (3 mL/kg). Blood tumor necrosis factor-alpha (TNF-ɑ) and interleukin-6 were measured using ELISAs. Tissue levels of superoxide dismutase (SOD), malondialdehyde (MDA), Na+/K+-ATPase, Ca++ATPase, myeloperoxidase (MPO), and fatty acid binding protein 2 (FABP2) were determined using respective quantitation kits. Fluid resuscitation with Shenfu significantly improved HR, CI, and MAP of pig with hemorrhagic shock, which was accompanied with mitigation of tissue damages in intestinal epithelium. Blood TNF-ɑ was reduced in the Shenfu group. Bcl-2 and cleaved caspase-3 expression in intestinal tissues were elevated and decreased, respectively, in pigs treated with Shenfu. Notably, treatment with Shenfu suppressed oxidative stress markers MDA, MPO, and FABP2 in the intestine. Oppositely, SOD, Na+/K+-ATPase and Ca++ATPase levels in intestinal tissues were promoted by Shenfu treatment. Shenfu demonstrates significant protective effect on the hemodynamics and gut epithelium of pigs with hemorrhagic shock.

Protective Effect of Vitamin E on Immune Triggered, Granulocyte Mediated Endothelial Injury

1984 ◽  
Vol 51 (01) ◽  
pp. 089-092 ◽  
Author(s):  
M A Boogaerts ◽  
J Van de Broeck ◽  
H Deckmyn ◽  
C Roelant ◽  
J Vermylen ◽  
...  
Keyword(s):  
Vitamin E ◽  
Protective Effect ◽  
Umbilical Vein ◽  
Endothelial Damage ◽  
Endothelial Injury ◽  
Mediated Effects ◽  
Anti Oxidant ◽  
Endothelial Cell Cultures ◽  
Vitro Model

SummaryThe effect of alfa-tocopherol on the cell-cell interactions at the vessel wall were studied, using an in vitro model of human umbilical vein endothelial cell cultures (HUEC). Immune triggered granulocytes (PMN) will adhere to and damage HUEC and platelets enhance this PMN mediated endothelial injury. When HUEC are cultured in the presence of vitamin E, 51Cr-leakage induced by complement stimulated PMN is significantly decreased and the enhanced cytotoxicity by platelets is completely abolished (p <0.001).The inhibition of PMN induced endothelial injury is directly correlated to a diminished adherence of PMN to vitamin E- cultured HUEC (p <0.001), which may be mediated by an increase of both basal and stimulated endogenous prostacyclin (PGI2) from alfa-tocopherol-treated HUEC (p <0.025). The vitamin E-effect is abolished by incubation of HUEC with the irreversible cyclo-oxygenase inhibitor, acetylsalicylic acid, but the addition of exogenous PGI2 could not reproduce the vitamin E-mediated effects.We conclude that vitamin E exerts a protective effect on immune triggered endothelial damage, partly by increasing the endogenous anti-oxidant potential, partly by modulating intrinsic endothelial prostaglandin production. The failure to reproduce vitamin E-protection by exogenously added PGI2 may suggest additional, not yet elucidated vitamin E-effects on endothelial metabolism.

Protective Effect of Crocin on Liver Function and Survival in Rats With Traumatic Hemorrhagic Shock

2021 ◽  
Vol 261 ◽  
pp. 301-309
Author(s):  
Yang Liu ◽  
Caoyuan Yao ◽  
Yuan Wang ◽  
Xiaolin Liu ◽  
Shanggang Xu ◽  
...  
Keyword(s):  
Liver Function ◽  
Protective Effect ◽  
Hemorrhagic Shock ◽  
Traumatic Hemorrhagic Shock

Shenfu injection improves cerebral microcirculation and reduces brain injury in a porcine model of hemorrhagic shock; SFI reduces brain injury after hemorrhagic shock

2021 ◽  
pp. 1-11
Author(s):  
Junyuan Wu ◽  
Zhiwei Li ◽  
Wei Yuan ◽  
Qiang Zhang ◽  
Yong Liang ◽  
...  
Keyword(s):  
Brain Injury ◽  
Hemorrhagic Shock ◽  
Interleukin 6 ◽  
Aquaporin 4 ◽  
Flow Index ◽  
Sham Operation ◽  
Volume Resuscitation ◽  
Cerebral Microcirculation ◽  
Shenfu Injection ◽  
Tnf Α

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.

Abstract 135: Endothelial Dysfunction in Acute Graft-versus-host Disease After Allogeneic Hematopoietic Cell Transplantation. In vitro Evidence of the Protective Effect of Defibrotide

2016 ◽  
Vol 36 (suppl_1) ◽  
Author(s):  
Enrique Mir ◽  
Marta Palomo ◽  
Enric Carreras ◽  
Maribel Diaz-Ricart ◽  
Montse Rovira ◽  
...  
Keyword(s):  
Endothelial Dysfunction ◽  
Protective Effect ◽  
Cell Transplantation ◽  
Graft Versus Host Disease ◽  
Hematopoietic Cell Transplantation ◽  
Endothelial Damage ◽  
Hematopoietic Cell ◽  
Graft Versus Host ◽  
Acute Graft

Acute Graft-Versus-Host Disease (aGVHD) is the most common early complication after allogeneic Hematopoietic Cell Transplantation (allo-HCT). We demonstrated endothelial dysfunction (ED) in association with allo-HCT. According to this data, aGVHD has been linked to an inflammatory process that may affect the endothelium. To investigate the differential degree of endothelial damage in patients developing or not aGVHD, to identify potential biomarkers, and to explore the protective effect of defibrotide (DF) in this scenario. DF has orphan designation for GVHD prevention. Patients blood samples were collected before allo-HCT, at day 0, and every week till day 28 after HCT. Plasma proteins (sTNFR1, sVCAM-1, VWF and ADAMTS-13) were measured as biomarkers of ED in individual samples from patients developing (GVHD, n=24), or not (NoGVHD, n=13), aGVHD. In in vitro assays, endothelial cells (EC) in culture were exposed to media containing pooled sera from patients to evaluate changes in the: a) expression of VCAM-1 and ICAM-1 on cell surfaces; b) presence of VWF on the extracellular matrix (ECM) and c) reactivity of the ECM towards platelets, under flow. The effect of DF was explored in the in vitro experiments by previous exposure of the EC (for 24h) followed by continuous incubation (100 μg/ml, added every 24h). Levels of sTNFRI, sVCAM-1 and VWF in samples from group GVHD were significantly higher than in NoGVHD (increases of 100, 37 and 150% respectively, at diagnose, p<0.01). ADAMTS-13 activity and VWF levels were inversely related. In in vitro studies, cell surface expression of VCAM-1 and ICAM-1, presence of VWF and platelet adhesion on the ECM in response to GVHD samples were always superior (increases vs NoGVHD of 80, 40, 100 and 21%, respectively, at diagnose). In vitro exposure of EC to DF attenuated signs of endothelial injury reducing significantly (p<0.05) the expression of VCAM-1, ICAM-1 and VWF (reductions of 22, 30 and 30%, respectively) in the GVHD condition. Our results demonstrate endothelial damage in association with aGVHD, as evidenced by elevated plasma levels of several biomarkers. The in vitro approach showed a marked proinflammatory and prothrombotic phenotype in association with aGVHD, which could be significantly prevented by defibrotide.

Abstract 12836: Low-Intensity Pulsed Ultrasound Ameliorates Left Ventricular Dysfunction in a Porcine Model of Chronic Myocardial Ischemia -Potential Involvement of Mechanotransduction

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Tomohiko Shindo ◽  
Kenta Ito ◽  
Kenichiro Hanawa ◽  
Kentaro Aizawa ◽  
Takashi Shiroto ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Porcine Model ◽  
Left Ventricular ◽  
Control Group ◽  
Β1 Integrin ◽  
Vascular Endothelial ◽  
Pulsed Ultrasound ◽  
Caveolin 1 ◽  
Low Intensity Pulsed Ultrasound ◽  
Chronic Myocardial Ischemia

Purpose: Despite recent progress in the management of ischemic heart disease (IHD), the number of patients with severe IHD is increasing. In this study, we aimed to develop low-intensity pulsed ultrasound (LIPUS) therapy for the treatment of IHD and to elucidate the underlying molecular mechanisms for the LIPUS-induced angiogenesis. Methods and Results: We first confirmed that the LIPUS up-regulated mRNA expression of vascular endothelial growth factor (VEGF) with a peak at 32-cycle in cultured human vascular endothelial cells (HUVECs). Then, we examined the in vivo effects of LIPUS in a porcine model of chronic myocardial ischemia with reduced left ventricular ejection fraction (LVEF) (n=28). The heart was treated with either sham or LIPUS (32-cycle, 20 min) at 3 different short axis levels (n=14 each). Four weeks after the therapy, LVEF was significantly improved in the LIPUS group (46±4 to 57±5%, P<0.05), whereas it remained unchanged in the control group. Capillary density and regional myocardial blood flow in the ischemic region were also increased in the LIPUS group but not in the control group. The protein expressions of VEGF, eNOS and bFGF in the ischemic area were enhanced in the LIPUS group compared with the control group. To further examine the signaling pathways responsible for the LIPUS-induced angiogenesis, HUVECs were transfected with siRNA or scrambled siRNA of either β1 integrin or caveolin-1. Knockdown of either β1 integrin or caveolin-1 with siRNA suppressed the LIPUS-induced up-regulation of VEGF. siRNA-mediated suppression of either focal adhesion kinase (FAK) or Fyn also inhibited the LIPUS-induced up-regulation of VEGF. Knockdown of these molecules with siRNA was confirmed with real-time PCR. Conclusions: These results suggest that the LIPUS therapy is promising as a new, non-invasive therapy for IHD and that β1 integrin and caveolin-1 may be involved in underlying molecular mechanisms for the beneficial effects of the LIPUS.

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