Effects of two different dosing regimens of terlipressin on organ functions in ovine endotoxemia

Lange, Matthias; Ertmer, Christian; Rehberg, Sebastian; Morelli, Andrea; Köhler, Gabriele; Kampmeier, Tim; Aken, Hugo Van; Westphal, Martin

doi:10.1007/s00011-010-0299-9

Cited by 21 publications

(17 citation statements)

References 34 publications

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“…Sheep have been used widely to study a variety of disorders related to human disease (Petersson et al , 2002; Petersson et al , 2004; Soehnlein et al , 2010), including inflammatory conditions in both adult and fetal sheep (Hagberg et al , 2002; Mallard et al , 2003; Collins et al , 2010; Hillman et al , 2010; Lange et al , 2010; Shah et al , 2010; Soehnlein et al , 2010; Rehberg et al , 2011). Monoclonal antibodies (mAbs) specific for ovine IL-1 β and IL-6 have been generated (Rothel et al , 1997; McWaters et al , 2000).…”

Section: Introductionmentioning

confidence: 99%

In-vitro Validation of Cytokine Neutralizing Antibodies by Testing with Ovine Mononuclear Splenocytes

Chen

Threlkeld

Cummings

et al. 2013

Journal of Comparative Pathology

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Summary Cytokines have gained increasing attention as therapeutic targets in inflammation-related disorders and inflammatory conditions have been investigated in sheep. Monoclonal antibodies (mAbs) specific for the ovine pro-inflammatory cytokines, interleukin (IL)-1β and IL-6 could be used to study the effects of blocking pro-inflammatory cytokines in sheep. Ovine-specific IL-1β and IL-6 proteins and mAbs specific for these molecules were produced and the ability of the mAbs to neutralize the proteins was tested in cultures of ovine splenic mononuclear cells. Expression of nuclear factor (NF)-κβ and signal transducer and activator of transcription (STAT)-3 was evaluated by western blotting and densitometric quantification. Treatment with purified IL-1β and IL-6 proteins increased NF-κβ (P <0.001) and STAT-3 P <0.01) expression,(respectively, in cell culture. Treatment with these proteins that were pre-incubated with IL-1β and IL-6 mAbs attenuated (P <0.01) these effects. These results confirm the bioactivity of ovine IL-1β and IL-6 proteins and neutralizing capacity of anti-ovine-IL-1β and -IL-6 mAbs in vitro. These mAbs could be used to investigate anti-inflammatory strategies for attenuation of the effects of these pro-inflammatory cytokines in sheep.

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Section: Introductionmentioning

confidence: 99%

In-vitro Validation of Cytokine Neutralizing Antibodies by Testing with Ovine Mononuclear Splenocytes

Chen

Threlkeld

Cummings

et al. 2013

Journal of Comparative Pathology

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“…Other notable changes include improved gas exchange, decreased levels of myeloperoxidase (MPO) and lung 3-nitrotyrosine (65). There was also an overall improvement in pulmonary function suggesting that blocking nitric oxide-peroxynitrite pathway may ameliorate some effects of septic shock (65).The ovine model of sepsis and septic shock has made important contributions in the areas of cardiovascular (66) and pulmonary research as well as in determining the efficacy of fluids (58) and therapeutic agents (67), such as anticoagulants (68) and recombinant human protein C (69) to improve sepsis outcomes.…”

Section: Ovine Models Of Sepsismentioning

confidence: 99%

Experimental Sepsis Models

Mai¹,

Khan²,

Liaw³

et al. 2012

Sepsis - An Ongoing and Significant Challenge

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The CLP model of intra-abdominal sepsis was introduced by Wichterman, Baue, and Chaudry in 1980. The group published an insightful review of previous models and introduced a novel sepsis model still widely regarded as the gold standard for modelling polymicrobial sepsis today-the cecal ligation and puncture (CLP) model. Rats were fasted, Experimental Sepsis Models 37 their cecum was ligated distal to the ileocecal valve, the antimesenteric cecal surface was punctured twice with an 18G ½ needle, and received subcutaneous saline post-operatively. This model induced polymicrobial infection (blood cultures positive for Escherichia coli, Streptococcus bovis, Proteus mirabilis, Enterococcus, and Bacteroides fragilis) and bacteremia (peritoneal cavity fluid positive for the above microbes as well as Streptococcus viridians and Clostridium sporogenes) and a 70% mortality rate. Mildly ill rats sacrificed 10 hours following CLP demonstrated the early hyperdynamic phase of sepsis (increased blood flow to organs, hyperinsulinemia, and hyperglycemia) while rats sacrificed 16-24 hours post-operative represented a hypodynamic late septic state (decreased blood flow to organs, hypoinsulinemia, hypoglycemia, and high serum lactate levels) (3). The results of this model correlate with clinical sepsis conditions as patients who are initially normotensive, show an increase in cardiac output, have low peripheral resistance, and increased total oxygen consumption, conditions which reverse in late septic shock (3).Multiple aspects of the CLP procedure address the complex, of the clinical course of sepsis. CLP induces polymicrobial infection of the peritoneum with a localized infectious focus, release of bacteria and endotoxic molecular components of pathogens (pathogen-associated molecular patterns or PAMPs) into normally sterile areas in the host, and subsequent translocation of enteric bacteria into the bloodstream, modelling the stages of intraabdominal clinical sepsis (3). Under anaesthesia, the cecum is exposed and trauma is induced via a midline skin laparotomy and blunt dissection of the peritoneum to exteriorize the cecum. Avoiding damage to the mesenteric vessels, the cecum is ligated with suture distal to the ileocecal valve, punctured once or twice (through-and-though) from the mesenteric to anti-mesenteric direction halfway between the ligation and cecal end, and aspirated for trapped gasses (3). A small amount of fecal content is extruded to allow for patency of the puncture(s) and continuous flow of feces post-operatively. The cecum is returned into the peritoneal cavity taking care not to spread fecal content on the incision and the peritoneum and abdomen are closed separately with sutures (11).

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“…(8)(9)(10) Vasopressin is a potent vasopressor with extended purposes in the treatment of severe trauma, septic shock, cardiac diseases and during cardiopulmonary resuscitation. (11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22) In addition, a few researchers have found that vasopressin is absorbed well via the mucosa of the airway and alveoli. (23)(24)(25) The combination of a LMA and vasopressin could be a practical management tool in pre-hospital settings.…”

Section: Introductionmentioning

confidence: 99%

The feasibility of vasopressin administration via laryngeal mask airway using a porcine model

Chen

Liao

Hsu

et al. 2016

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Effects of two different dosing regimens of terlipressin on organ functions in ovine endotoxemia

Abstract: Continuous infusion of low-dose terlipressin preserved several surrogate parameters of organ function better than intermittent bolus injections in sheep with systemic inflammation.

Cited by 21 publications

References 34 publications

In-vitro Validation of Cytokine Neutralizing Antibodies by Testing with Ovine Mononuclear Splenocytes

In-vitro Validation of Cytokine Neutralizing Antibodies by Testing with Ovine Mononuclear Splenocytes

Experimental Sepsis Models

The feasibility of vasopressin administration via laryngeal mask airway using a porcine model

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