scholarly journals Methane inhalation reduces the systemic inflammatory response in a large animal model of extracorporeal circulation

2019 ◽  
Vol 56 (1) ◽  
pp. 135-142 ◽  
Author(s):  
Gábor Bari ◽  
Dániel Érces ◽  
Gabriella Varga ◽  
Szilárd Szűcs ◽  
Zoltán Varga ◽  
...  
Keyword(s):  
Extracorporeal Circulation ◽  
Whole Blood ◽  
Inflammatory Responses ◽  
Treated Group ◽  
Superoxide Production ◽  
Large Animal Model ◽  
Haemodynamic Monitoring ◽  
Relative Light Unit ◽  
Large Animal ◽  
Xanthine Oxidoreductase

Abstract OBJECTIVES Extracorporeal circulation induces cellular and humoral inflammatory reactions, thus possibly leading to detrimental secondary inflammatory responses. Previous data have demonstrated the bioactive potential of methane and confirmed its anti-inflammatory effects in model experiments. Our goal was to investigate the in vivo consequences of exogenous methane administration on extracorporeal circulation-induced inflammation. METHODS Two groups of anaesthetized Vietnamese minipigs (non-treated and methane treated, n = 5 each) were included. Standard central cannulation was performed, and extracorporeal circulation was maintained for 120 min without cardiac arrest or ischaemia, followed by an additional 120-min observation period with haemodynamic monitoring. In the methane-treated group, 2.5% v/v methane–normoxic air mixture was added to the oxygenator sweep gas. Blood samples through the central venous line and tissue biopsies from the heart, ileum and kidney were taken at the end point to determine the whole blood superoxide production (chemiluminometry) and the activity of xanthine-oxidoreductase and myeloperoxidase, with substrate-specific reactions. RESULTS Methane treatment resulted in significantly higher renal blood flow during the extracorporeal circulation period compared to the non-treated group (63.9 ± 16.4 vs 29.0 ± 9.3 ml/min). Whole blood superoxide production (548 ± 179 vs 1283 ± 193 Relative Light Unit (RLU)), ileal myeloperoxidase (2.23 ± 0.2 vs 3.26 ± 0.6 mU/(mg protein)) and cardiac (1.5 ± 0.6 vs 4.7 ± 2.5 pmol/min/mg), ileal (2.2 ± 0.6 vs 7.0 ± 3.4 pmol/min/mg) and renal (1.2 ± 0.8 vs 13.3 ± 8.0 pmol/min/mg) xanthine-oxidoreductase activity were significantly lower in the treated group. CONCLUSIONS The addition of bioactive gases, such as methane, through the oxygenator of the extracorporeal circuit represents a novel strategy to influence the inflammatory effects of extracorporeal perfusion in cardiac surgical procedures.

scholarly journals Extracorporeal circulation increases proliferation in the intestinal mucosa in a large animal model

2016 ◽  
Vol 64 (4) ◽  
pp. 1121-1133 ◽  
Author(s):  
Paula Rosalie Keschenau ◽  
Stefanie Ribbe ◽  
Miriam Tamm ◽  
Sebastiaan J. Hanssen ◽  
René Tolba ◽  
...  
Keyword(s):  
Animal Model ◽  
Intestinal Mucosa ◽  
Extracorporeal Circulation ◽  
Large Animal Model ◽  
Large Animal

Platelet-Targeted Expression of Coagulation Factor VIII (FVIII) Shows Efficacy for Using the Dog as a Large Animal Model for Gene Therapy of Hemophilia a

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 3525-3525 ◽  
Author(s):  
David A. Wilcox ◽  
Lily M. Du ◽  
Sandra L. Haberichter ◽  
Paula M. Jacobi ◽  
Juan Fang ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Bone Marrow ◽  
Animal Model ◽  
Whole Blood ◽  
Hemophilia A ◽  
Active Form ◽  
Biologically Active ◽  
Large Animal Model ◽  
Sublethal Dose ◽  
Large Animal

Abstract In order to develop a large animal model for platelet-targeted gene therapy of Hemophilia A, we transduced normal canine bone marrow with a lentivirus vector under the transcriptional control of integrin αIIb gene promoter driving expression of human BDD-FVIII. Bone marrow was collected from normal dogs and transduced in the presence of recombinant canine c-SCF, c-IL-6, human h-TPO, and h-flt-3/flk-2 ligand differentiation factor. Immunofluorescence analysis using antibodies against human FVIII, and the megakaryocyte-specific marker integrin αIIb revealed synthesis of FVIII within tissue cultured megakaryocytes derived from lentivirus transduced bone marrow cells. This result appeared similar to synthesis, trafficking and storage of FVIII trafficked to α-granules of the murine “small animal” model for hemophilia A and human megakaryoyctes in vitro. To examine the effect of FVIII expression in platelets, in vivo, FVIII-transduced canine bone marrow was xenotransplanted into immune-compromised “NOD-SCID” mice treated with a sublethal dose (350 cGy) of irradiation. Flow cytometric analysis using antibodies specific for canine glycoproteins Ibα and integrin αIibβ3 revealed that circulating canine platelets comprised approximately 20–30% of the total platelet population in whole blood isolated from the mice within four weeks after xenotransplant. Immunofluorescence confocal microscopy detected a punctuate staining for FVIII that co-localized with a platelet α–granule protein, P-selectin, within a subpopulation of canine platelets isolated from murine whole blood. In contrast, FVIII was not detected in platelets from control samples. In addition, chromogenic analysis of platelets isolated from mice transplanted with FVIII-transduced bone marrow demonstrated the presence of a biologically active form of FVIII, FVIII:C at 2 mU/ml/lysate of 1×108 platelets. These results indicate that canine megakaryocytes are able to synthesize and store a biologically active form of FVIII that can be retained within progeny platelets. We speculate that dogs affected with hemophilia A should serve as an ideal “large animal” model to test if FVIII can undergo regulated release from platelets following physiologic hemostatic response to vessel injury. This raises the possibility of developing a locally inducible secretory pool of FVIII in platelets of patients with Hemophilia A following autologous transplantation of FVIII-transduced hematopoietic stem cells.

DEVELOPMENT OF A LARGE ANIMAL MODEL OF OPIATE ADDICTION TO EVALUATE CARDIOVASCULAR FUNCTION.

Analgesia ◽  
1995 ◽  
Vol 1 (4) ◽  
pp. 598-602 ◽  
Author(s):  
L.D. Napier ◽  
Z. Mateo ◽  
D.A. Yoshishige ◽  
B.A. Barron ◽  
J.L. Caffrey
Keyword(s):  
Animal Model ◽  
Cardiovascular Function ◽  
Large Animal Model ◽  
Opiate Addiction ◽  
Large Animal

scholarly journals A novel large animal model of smoke inhalation-induced acute respiratory distress syndrome

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Premila D. Leiphrakpam ◽  
Hannah R. Weber ◽  
Andrea McCain ◽  
Roser Romaguera Matas ◽  
Ernesto Martinez Duarte ◽  
...  
Keyword(s):  
Animal Model ◽  
Acute Respiratory Distress Syndrome ◽  
Respiratory Distress Syndrome ◽  
Distress Syndrome ◽  
Inhalation Injury ◽  
Smoke Inhalation ◽  
Large Animal Model ◽  
Large Animal ◽  
X Ray ◽  
Chest X Ray

Abstract Background Acute respiratory distress syndrome (ARDS) is multifactorial and can result from sepsis, trauma, or pneumonia, amongst other primary pathologies. It is one of the major causes of death in critically ill patients with a reported mortality rate up to 45%. The present study focuses on the development of a large animal model of smoke inhalation-induced ARDS in an effort to provide the scientific community with a reliable, reproducible large animal model of isolated toxic inhalation injury-induced ARDS. Methods Animals (n = 21) were exposed to smoke under general anesthesia for 1 to 2 h (median smoke exposure = 0.5 to 1 L of oak wood smoke) after the ultrasound-guided placement of carotid, pulmonary, and femoral artery catheters. Peripheral oxygen saturation (SpO2), vital signs, and ventilator parameters were monitored throughout the procedure. Chest x-ray, carotid, femoral and pulmonary artery blood samples were collected before, during, and after smoke exposure. Animals were euthanized and lung tissue collected for analysis 48 h after smoke inhalation. Results Animals developed ARDS 48 h after smoke inhalation as reflected by a decrease in SpO2 by approximately 31%, PaO2/FiO2 ratio by approximately 208 (50%), and development of bilateral, diffuse infiltrates on chest x-ray. Study animals also demonstrated a significant increase in IL-6 level, lung tissue injury score and wet/dry ratio, as well as changes in other arterial blood gas (ABG) parameters. Conclusions This study reports, for the first time, a novel large animal model of isolated smoke inhalation-induced ARDS without confounding variables such as cutaneous burn injury. Use of this unique model may be of benefit in studying the pathophysiology of inhalation injury or for development of novel therapeutics.

scholarly journals Gynura procumbens Root Extract Ameliorates Ischemia-Induced Neuronal Damage in the Hippocampal CA1 Region by Reducing Neuroinflammation

Nutrients ◽  
2021 ◽  
Vol 13 (1) ◽  
pp. 181
Author(s):  
Woosuk Kim ◽  
Hyo Young Jung ◽  
Dae Young Yoo ◽  
Hyun Jung Kwon ◽  
Kyu Ri Hahn ◽  
...  
Keyword(s):  
Inflammatory Responses ◽  
Neuronal Damage ◽  
Ischemia Reperfusion ◽  
Treated Group ◽  
Biological Properties ◽  
Root Extract ◽  
Ischemic Damage ◽  
Neuroprotective Effects ◽  
Hippocampal Ca1 ◽  
Vehicle Treated Group

Gynura procumbens has been used in Southeast Asia for the treatment of hypertension, hyperglycemia, and skin problems induced by ultraviolet irradiation. Although considerable studies have reported the biological properties of Gynura procumbens root extract (GPE-R), there are no studies on the effects of GPE-R in brain damages, for example following brain ischemia. In the present study, we screened the neuroprotective effects of GPE-R against ischemic damage and neuroinflammation in the hippocampus based on behavioral, morphological, and biological approaches. Gerbils received oral administration of GPE-R (30 and 300 mg/kg) every day for three weeks and 2 h after the last administration, ischemic surgery was done by occlusion of both common carotid arteries for 5 min. Administration of 300 mg/kg GPE-R significantly reduced ischemia-induced locomotor hyperactivity 1 day after ischemia. Significantly more NeuN-positive neurons were observed in the hippocampal CA1 regions of 300 mg/kg GPE-R-treated animals compared to those in the vehicle-treated group 4 days after ischemia. Administration of GPE-R significantly reduced levels of pro-inflammatory cytokines such as interleukin-1β, -6, and tumor necrosis factor-α 6 h after ischemia/reperfusion. In addition, activated microglia were significantly decreased in the 300 mg/kg GPE-R-treated group four days after ischemia/reperfusion compared to the vehicle-treated group. These results suggest that GPE-R may be one of the possible agents to protect neurons from ischemic damage by reducing inflammatory responses.

scholarly journals Development of a porcine model of emergency resternotomy at a low-volume cardiac surgery centre

2020 ◽  
Vol 31 (6) ◽  
pp. 803-805
Author(s):  
Timothy M Guenther ◽  
Sarah A Chen ◽  
Joshua D Gustafson ◽  
Curtis J Wozniak ◽  
Bob Kiaii
Keyword(s):  
Intensive Care Unit ◽  
Cardiac Surgery ◽  
Porcine Model ◽  
Comfort Level ◽  
Large Animal Model ◽  
Large Animal ◽  
Training Environment ◽  
Life Saving ◽  
Simulation Scenario ◽  
Low Volume

Abstract Emergency resternotomy in the intensive care unit (ICU) is a rarely performed, yet potentially life-saving intervention. Success relies on recognition of a deteriorating clinical condition, timely deployment of equipment/personnel and rapid execution. Given how infrequently it is performed, we sought to develop a large animal model of resternotomy to prepare ICU nurses and technicians at our low-volume cardiac surgery military centre. A porcine model of resternotomy was developed at the end of an already-scheduled trauma lab. Participants worked their way through a pre-planned simulation scenario, culminating in the need for resternotomy. Pre-simulation surveys assessing knowledge and comfort level with aspects of resternotomy were compared to post-simulation surveys. Participants improved their knowledge of resternotomy by 20.4% (P < 0.0001; 14.7% for nurses and 26.9% for technicians). Improvements were seen in all aspects assessed relating to subjective comfort/preparedness of resternotomy. The model was an effective and realistic method to augment training of ICU staff about resternotomy. Costs associated with this model can be reduced when used in conjunction with large animal labs. This model should be used together with mannequin-based methods of resternotomy training to provide a realistic training environment and assessment of skills at capable institutions.

Sign in / Sign up

Export Citation Format

Share Document