scholarly journals Novel use of XSTAT 30 for mitigation of lethal non-compressible torso hemorrhage in swine

PLoS ONE ◽  
2020 ◽  
Vol 15 (11) ◽  
pp. e0241906
Author(s):  
Alicia M. Bonanno ◽  
Todd L. Graham ◽  
Lauren N. Wilson ◽  
James D. Ross
Keyword(s):  
Blood Product ◽  
Ischemia Reperfusion Injury ◽  
Damage Control ◽  
Ischemia Reperfusion ◽  
Survival Rates ◽  
Damage Control Surgery ◽  
Left Lobe ◽  
Adverse Outcomes ◽  
Significant Difference ◽  
Similar Survival

Background Management of Non-Compressible Torso Hemorrhage (NCTH) consists primarily of aortic occlusion which has significant adverse outcomes, including ischemia-reperfusion injury, in prolonged field care paradigms. One promising avenue for treatment is through use of RevMedx XSTAT 30™ (an FDA approved sponge-based dressing utilized for extremity wounds). We hypothesized that XSTAT 30™ would effectively mitigate NCTH during a prolonged pre-hospital period with correctable metabolic and physiologic derangements. Methods and findings Twenty-four male swine (53±2kg) were anesthetized, underwent line placement, and splenectomy. Animals then underwent laparoscopic transection of 70% of the left lobe of the liver with hemorrhage for a period of 10min. They were randomized into three groups: No intevention (CON), XSTAT 30™-Free Pellets (FP), and XSTAT 30™-Bagged Pellets (BP). Animals were observed for a pre-hospital period of 180min. At 180min, animals underwent damage control surgery (DCS), balanced blood product resuscitation and removal of pellets followed by an ICU period of 5 hours. Postoperative fluoroscopy was performed to identify remaining pellets or bags. Baseline physiologic and injury characteristics were similar. Survival rates were significantly higher in FP and BP (p<0.01) vs CON. DCS was significantly longer in FP in comparison to BP (p = 0.001). Two animals in the FP group had pellets discovered on fluoroscopy following DCS. There was no significant difference in blood product or pressor requirements between groups. End-ICU lactates trended to baseline in both FP and BP groups. Conclusions While these results are promising, further study will be required to better understand the role for XSTAT in the management of NCTH.

scholarly journals Exosomes Derived from CXCR4-Overexpressing BMSC Promoted Activation of Microvascular Endothelial Cells in Cerebral Ischemia/Reperfusion Injury

2020 ◽  
Vol 2020 ◽  
pp. 1-13
Author(s):  
Xutong Li ◽  
Ye Zhang ◽  
Yong Wang ◽  
Dan Zhao ◽  
Chengcheng Sun ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Reperfusion Injury ◽  
Vascular Function ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Tube Formation ◽  
Microvascular Endothelial Cells ◽  
Significant Difference ◽  
Microvascular Endothelial

Background. Ischemic stroke is a severe acute cerebrovascular disease which can be improved with neuroprotective therapies at an early stage. However, due to the lack of effective neuroprotective drugs, most stroke patients have varying degrees of long-term disability. In the present study, we investigated the role of exosomes derived from CXCR4-overexpressing BMSCs in restoring vascular function and neural repair after ischemic cerebral infarction. Methods. BMSCs were transfected with lentivirus encoded by CXCR4 (BMSCCXCR4). Exosomes derived from BMSCCXCR4 (ExoCXCR4) were isolated and characterized by transmission electron microscopy and dynamic light scattering. Western blot and qPCR were used to analyze the expression of CXCR4 in BMSCs and exosomes. The acute middle cerebral artery occlusion (MCAO) model was prepared, ExoCXCR4 were injected into the rats, and behavioral changes were analyzed. The role of ExoCXCR4 in promoting the proliferation and tube formation for angiogenesis and protecting brain endothelial cells was determined in vitro. Results. Compared with the control groups, the ExoCXCR4 group showed a significantly lower mNSS score at 7 d, 14 d, and 21 d after ischemia/reperfusion ( P < 0.05 ). The bEnd.3 cells in the ExoCXCR4 group have stronger proliferation ability than other groups ( P < 0.05 ), while the CXCR4 inhibitor can reduce this effect. Exosomes control (ExoCon) can significantly promote the migration of bEnd.3 cells ( P < 0.05 ), while there was no significant difference between the ExoCXCR4 and ExoCon groups ( P > 0.05 ). ExoCXCR4 can further promote the proliferation and tube formation for the angiogenesis of the endothelium compared with ExoCon group ( P < 0.05 ). In addition, cobalt chloride (COCl2) can increase the expression of β-catenin and Wnt-3, while ExoCon can reduce the expression of these proteins ( P < 0.05 ). ExoCXCR4 can further attenuate the activation of Wnt-3a/β-catenin pathway ( P < 0.05 ). Conclusions. In ischemia/reperfusion injury, ExoCXCR4 promoted the proliferation and tube formation of microvascular endothelial cells and play an antiapoptotic role via the Wnt-3a/β-catenin pathway.

scholarly journals Pharmacodynamics of Five Anthraquinones (Aloe-emodin, Emodin, Rhein, Chysophanol, and Physcion) and Reciprocal Pharmacokinetic Interaction in Rats with Cerebral Ischemia

Molecules ◽  
2019 ◽  
Vol 24 (10) ◽  
pp. 1898 ◽  
Author(s):  
Rong-Rong Li ◽  
Xue-Fang Liu ◽  
Su-Xiang Feng ◽  
Sheng-Nan Shu ◽  
Pei-Yang Wang ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Plasma Concentrations ◽  
Pharmacokinetic Parameters ◽  
Pharmacokinetic Studies ◽  
Plasma Exposure ◽  
Significant Difference ◽  
Aloe Emodin ◽  
Exposure Levels

(1) Background: Rhubarb anthraquinones—a class of components with neuroprotective function—can be used to alleviate cerebral ischemia reperfusion injury. (2) Methods: The three pharmacodynamic indicators are neurological function score, brain water content, and cerebral infarction area; UPLC-MS/MS was used in pharmacokinetic studies to detect plasma concentrations at different time points, and DAS software was used to calculate pharmacokinetic parameters in a noncompartmental model. (3) Results: The results showed that the pharmacodynamics and pharmacokinetics of one of the five anthraquinone aglycones could be modified by the other four anthraquinones, and the degree of interaction between different anthraquinones was different. The chrysophanol group showed the greatest reduction in pharmacodynamic indicators comparing with other four groups where the rats were administered one of the five anthraquinones, and there was no significant difference between the nimodipine group. While the Aloe-emodin + Physcion group showed the most obvious anti-ischemic effect among the groups where the subjects were administered two of the five anthraquinones simultaneously. Emodin, rhein, chrysophanol, and physcion all increase plasma exposure levels of aloe-emodin, while aloe-emodin lower their plasma exposure levels. (4) Conclusions: This experiment provides a certain preclinical basis for the study of anthraquinone aglycones against cerebral ischemia and a theoretical basis for the study of the mechanism of interaction between anthraquinones.

scholarly journals Hydrogen sulfide-mediated cardioprotection against ischemia reperfusion is linked to KATP channel for mitochondrial preservation but not for its distinct preference on interfibrillar mitochondria

2019 ◽  
Vol 14 (2) ◽  
pp. 107-115 ◽  
Author(s):  
Priyadharshini Chandrasekaran ◽  
Sriram Ravindran ◽  
Sri Rahavi Boovarahan ◽  
Gino A. Kurian
Keyword(s):  
Hydrogen Sulfide ◽  
Reperfusion Injury ◽  
Katp Channel ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Rat Hearts ◽  
Significant Difference ◽  
Interfibrillar Mitochondria ◽  
Subsarcolemmal Mitochondria

Hydrogen sulfide has been shown to protect  myocardium against ischemia-reperfusion injury by preserving interfibrillar mitochondria functional activi-ties than subsarcolemmal mitochondria. In this study, the role of the KATP channel in modulating the mitochondrial subpopulations during the cardioprotection mediated by NaSH (H2S donor) was investigated. Isolated rat hearts were treated with mitochondrial KATP channel closer glibenclamide (10 μM)/opener diazoxide (0.8 mM) via Langendorff perfusion apparatus before ischemia-reperfusion. The results showed that NaSH pre-conditioning in presence of glibenclamide significantly improved cardiac recovery without any significant difference between interfibrillar mitochondria and subsarcolemmal mitochondria.  In conclusion, targeting KATP channel may not be good option to target interfibrillar mitochondria/subsarcolemmal mitochondria against ischemia-reperfusion injury.

scholarly journals Gp91phox (NOX2) in Activated Microglia Exacerbates Neuronal Damage Induced by Oxygen Glucose Deprivation and Hyperglycemia in an in Vitro Model

2018 ◽  
Vol 50 (2) ◽  
pp. 783-797 ◽  
Author(s):  
Xianzhang Zeng ◽  
Hongliang Ren ◽  
Yana Zhu ◽  
Ruru Zhang ◽  
Xinxin Xue ◽  
...  
Keyword(s):  
Ischemia Reperfusion Injury ◽  
Neuronal Damage ◽  
Neuronal Survival ◽  
Ischemia Reperfusion ◽  
Survival Rates ◽  
Glucose Deprivation ◽  
Oxygen Glucose Deprivation ◽  
Sirna Transfection ◽  
Culture Model

Background/Aims: Peri-operative cerebral ischemia reperfusion injury is one of the most serious peri-operative complications that can be aggravated in patients with diabetes. A previous study showed that microglia NOX2 (a NADPH oxidase enzyme) may play an important role in this process. Here, we investigated whether increased microglial derived gp91phox, also known as NOX2, reduced oxygen glucose deprivation (OGD) after induction of hyperglycemia (HG). Methods: A rat neuronal-microglial in vitro co-culture model was used to determine the effects of gp91phox knockdown on OGD after HG using six treatment groups: A rat microglia and neuron co-culture model was established and divided into the following six groups: high glucose + scrambled siRNA transfection (HG, n = 5); HG + gp91phoxsiRNA transfection (HG-gp91siRNA, n = 5); oxygen glucose deprivation + scrambled siRNA transfection (OGD, n = 5); OGD + gp91phoxsiRNA transfection (OGD-gp91siRNA, n = 5); HG + OGD + scrambled siRNA transfection (HG-OGD, n = 5); and HG + OGD + gp91phoxsiRNA transfection (HG-OGD-gp91siRNA, n = 5). The neuronal survival rate was measured by the MTT assay, while western blotting was used to determine gp91phox expression. Microglial derived ROS and neuronal apoptosis rates were analyzed by flow cytometry. Finally, the secretion of cytokines, including IL-6, IL-8, TNF-α, and 8-iso-PGF2α was determined using an ELISA kit. Results: Neuronal survival rates were significantly decreased by HG and OGD, while knockdown of gp91phox reversed these rates. ROS production and cytokine secretion were also significantly increased by HG and OGD but were significantly inhibited by knockdown of gp91phoxsiRNA. Conclusion: Knockdown of gp91phoxsiRNA significantly reduced oxidative stress and the inflammatory response, and alleviated neuronal damage after HG and OGD treatment in a rat neuronal-microglial co-culture model.

Relaxin protects against renal ischemia-reperfusion injury

2013 ◽  
Vol 305 (8) ◽  
pp. F1169-F1176 ◽  
Author(s):  
Takuya Yoshida ◽  
Hiromichi Kumagai ◽  
Tetsuya Kohsaka ◽  
Naoki Ikegaya
Keyword(s):  
Structural Damage ◽  
Ischemia Reperfusion Injury ◽  
Apoptotic Cell ◽  
Ischemia Reperfusion ◽  
Kidney Injury ◽  
Renal Ischemia ◽  
Male Rats ◽  
Semiquantitative Assessment ◽  
Cell Counts ◽  
Significant Difference

Relaxin, a pregnancy hormone, has antiapoptotic and anti-inflammatory properties. The aim of this study was to determine the effects of relaxin on ischemia-reperfusion (IR)-induced acute kidney injury. Male rats underwent unilateral nephrectomy and contralateral renal IR (45 min of renal pedicle clamping). Rats were divided into three groups: 1) sham group, 2) IR group, and 3) IR-RLX group (rats treated with relaxin before ischemia). In this group, relaxin was infused at 500 ng/h via subcutaneous osmotic minipump for 24 h beginning 2 h before renal ischemia. At 24 h after reperfusion, renal function was assessed and kidneys were removed for analysis. There was no significant difference in blood pressure among the three groups. IR increased plasma levels of creatinine and urea nitrogen, and relaxin provided protection against the increases in these two parameters. Relaxin significantly decreased plasma TNF-α levels and renal TNF receptor 1 mRNA expression, compared with the IR group. Semiquantitative assessment of the histological lesions showed marked structural damage in IR rats compared with the IR-RLX rats. RLX significantly reduced apoptotic cell counts compared with the IR group. Overexpression of caspase-3 observed in the IR kidneys was reduced in the IR-RLX group. The results demonstrated that relaxin provided protection against IR-induced renal injury by reducing apoptosis and inflammation.

scholarly journals Influence of Gender on Ischemia-Reperfusion Injury in Lungs in an Animal Model

2016 ◽  
pp. 953-958 ◽  
Author(s):  
H. MRAZKOVA ◽  
R. LISCHKE ◽  
J. HERGET
Keyword(s):  
Animal Model ◽  
Lung Transplantation ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ex Vivo ◽  
Ischemia Reperfusion ◽  
Treatment Options ◽  
Subsequent Treatment ◽  
Organ Systems ◽  
Significant Difference

As with other organ transplants even lung transplantation raises the question of the possibility of the influence of gender on ischemia-reperfusion injury. This is a current topic especially for increasingly utilized method of lung transplantation from non-heart-beating donors, where reperfusion preceded by a period of warm and cold ischemia with subsequent treatment options for lung graft reperfusion. For measurements we used our laboratory previously created and validated animal model for ex vivo lung transplantation. As with other organ systems of our monitoring resulted protective effect of female sex on ischemia reperfusion lung injury. In two of the three parameters that were monitored, we found a significant difference. In females, higher oxygen transfer ability after reperfusion was manifested as well as lower perfusion pressure (vascular compliance). Conversely, weight gain (the development of pulmonary edema) in males was not significant difference from the females. These conclusions could cause further studies leading to influence the selection of appropriate donor grafts.

scholarly journals Curcumin prevents renal oxidative stress and tissue damage induced by renal ischemia/reperfusion in rats

2018 ◽  
Vol 5 (10) ◽  
pp. 3192
Author(s):  
Nazile Erturk ◽  
Hulya Elbe ◽  
Zumrut Dogan ◽  
Serdar Aktas ◽  
Savas Demirbilek ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Renal Tissue ◽  
Renal Ischemia ◽  
Normal Morphology ◽  
Treatment Groups ◽  
Significant Difference ◽  
Intraperitoneal Dose ◽  
Dose Dependent

Background: There is increasing evidence to suggest that curcumin has antioxidant efficacy in renal ischemia reperfusion injury (IRI). However, it has not been investigated whether this effect is dose-dependent or not.  The aim of this study is to investigate the dose-dependent effect of curcumin on renal IRI in an experimental rat model.Methods: The rats (n=32) were separated into four groups: sham, I/R, I/R+CUR-50, I/R+CUR-100. Rats were subjected to renal ischemia by clamping bilateral renal pedicles for 60 min, and then reperfused for 3 h. Animals in treatment groups received 50 mg/kg/day and 100 mg/kg/day curcumin orally for 5 days before IRI, respectively. MDA, GSH, SOD, and CAT activities were determined in renal tissue. Renal tissue also evaluated histopathologically for mean histopathological damage score.Results: The mean MDA levels in the I/R+CUR-50 and I/R+CUR-100 groups were significantly decreased when compared with the I/R group (p=0.038 and p=0.016, respectively). SOD, CAT and GSH levels of all treatment groups were significantly increased in comparison to that of I/R group (p<0.05, for all). No statistically significant difference between treatment groups were detected (p>0.05). In histological examination, the rats treated with curcumin had nearly normal morphology of the kidney.Conclusions: Curcumin significantly ameliorates the damage of renal IRI by its antioxidant activity. We detected the highest intraperitoneal dose of curcumin reduced the IRI induced oxidative stress as 50 mg/kg per day.

scholarly journals Rolling in P-selectin-deficient mice is reduced but not eliminated in the dorsal skin

Blood ◽  
1995 ◽  
Vol 86 (9) ◽  
pp. 3487-3492 ◽  
Author(s):  
S Yamada ◽  
TN Mayadas ◽  
F Yuan ◽  
DD Wagner ◽  
RO Hynes ◽  
...  
Keyword(s):  
Shear Rate ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Dorsal Skin ◽  
Wild Type ◽  
Significant Difference ◽  
Deficient Mice

P-selectin-mediated rolling is believed to be important in the recruitment of leukocytes to tissue after ischemia-reperfusion injury. The dorsal skin chamber was used to examine differences in the rolling and stable adhesion of circulating leukocytes in subcutaneous (SC) vessels of P-selectin-deficient and age-matched wild-type mice, both under basal conditions and after ischemia-reperfusion. Rolling in the postcapillary venules in SC tissue of P-selectin-deficient mice was significantly lower than that in wild-type mice under the basal conditions and post-ischemia-reperfusion (P < .05), but was not eliminated by the deletion of the P-selectin gene. No significant difference between P-selectin-deficient and wild-type mice in shear rate or leukocyte-endothelial adhesion was observed up to 24 hours after ischemia-reperfusion. These results show that P-selectin-mediated rolling is not a prerequisite for ischemia-reperfusion-induced leukocyte-endothelial adhesion in the skin.

Abstract 251: Comparison of Ischemia-Reperfusion Injury in Langendorff-Prepared Hearts From Zucker Diabetic Fatty and Lean Rats

Circulation ◽  
2018 ◽  
Vol 138 (Suppl_2) ◽  
Author(s):  
William J Cleveland ◽  
Claudius Balzer ◽  
Michele M Salzman ◽  
Matthias L Riess
Keyword(s):  
Ischemia Reperfusion Injury ◽  
Heart Function ◽  
Ischemia Reperfusion ◽  
Left Ventricular Pressure ◽  
Left Ventricular ◽  
Zdf Rat ◽  
Mitochondrial Redox State ◽  
Significant Difference ◽  
Before And After ◽  
Zdf Rats

Introduction: The Zucker Diabetic Fatty (ZDF) rat is a relevant model for assessing ischemia-reperfusion (IR) injury, due to it having comorbidities associated with a higher risk for cardiac arrest and poorer outcomes following cardiopulmonary resuscitation in humans. Hypothesis: Based on previous studies in the literature, we hypothesize that ZDF rats would have similar outcomes to lean rats subjected to IR when accounting for perfusion buffer osmolarity. Methods: ZDF (n=4) and lean control (n=6) rats were anesthetized with pentobarbital, intubated, and mechanically ventilated and monitored for 3-hours, with blood glucose (BG) readings taken before and after ventilation. They were then decapitated and a thoracotomy performed to isolate the Langendorff-prepared hearts. Krebs buffer with the osmolarity adjusted to each rat’s BG level using glucose was used to perfuse the hearts. Following a 20-minute stabilization period, the hearts were subjected to a 30-minute period of global no-flow ischemia followed by 120-minutes of reperfusion. Spontaneous heart rate, isovolumetric left ventricular pressure (LVP), and mitochondrial redox state were measured continuously. Data are mean ± SD. Statistics: two-tailed t-test, p<0.05 Results: There was no significant difference in average body weight between the two groups; however, ZDF rats showed significantly higher BG levels (504±52 vs 174±14 mg/dl) than their lean littermates. ZDF rats had a greater percent change from baseline systolic LVP upon reperfusion than lean rats (133±33.3 vs 84.9±16.5 %), with the lean rats never returning to baseline. Diastolic contracture occurred more in lean rats during ischemia, but trended towards a lower contracture during reperfusion. No significant difference was seen in developed LVP, rate pressure products, or mitochondrial redox states, although lean rats trended towards better diastolic contractility and relaxation. Conclusion: Lean rats showed marginally better outcomes in heart function than their ZDF littermates. Future studies will focus on potential mechanisms of Type 2 diabetes that may exacerbate IR injuries.

Electro-acupuncture on Nei Guan and Bai Hui: How Does It Affect GRP78 and Caspase-12 Gene Expression in Rats with Ischemia-Reperfusion Injury

2015 ◽  
Vol 3 (1) ◽  
pp. 65-69
Author(s):  
Jing Shen ◽  
Xiao-Ming Lei ◽  
Yang Song ◽  
Xing Tan ◽  
Qin Liu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Reperfusion Injury ◽  
Mrna Expression ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Statistical Significance ◽  
Tunel Staining ◽  
Caspase 12 ◽  
Significant Difference ◽  
Operation Group

Abstract Objective: To observe the effects of electro-acupuncture (EA) on GRP78 and Caspase-12 gene expression in rats with ischemia- reperfusion injury (IRI) by stimulation on Nei Guan (PC6) and Bai Hui (GV20) points, so that to understand whether or not the protective effects of acupuncture is related to endocytoplasmic reticulum (ER) stressapoptosis passage. Methods: 50 rats were randomly assigned to five groups (10 in each group): normal control(A), pseudo-operation(B), operation(C), Edaravone(D) and EA(E). The ischemia/reperfusion model of middle cerebral artery occlusion (MCAO) was established by suture embolic method. TUNEL staining method was employed to measure the apoptosis index of nerve cells in rats. Real-time polymerase chain reaction (RT-PCR) was employed to measure the mRNA expression of GRP78 and Caspase-12. Results: Compared with normal group and pseudo-operation group, the apoptosis indexes and mRNA expression of GRP78 and Caspase-12 in operation group, Edaravone group and EA group were increased, with statistical significance（P＜0.05 or P＜0.01）; compared with operation group, the apoptosis indexes and Caspase-12 mRNA expression in Edaravone group and EA group were decreased（P＜0.05 or P＜0.01）, but GRP78 mRNA expression were increased（P＜0.01）; there were no significant difference between Edaravone group and EA group on the above indexes（P＞0.05). Conclusion: Acupuncture on Nei Guan and Bai Hui points could effectively suppress the nerve cell apoptosis in cerebral ischemia. The underlying mechanism might be related to upregulation of the ERS-protective GRP78 expression and downregulation of apoptosis-promotion Caspase-12 expression.

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