Intensive care medicine experimental
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Intensive Care Med Exp · Nov 2018
Fluid sparing and norepinephrine use in a rat model of resuscitated haemorrhagic shock: end-organ impact.
Haemostasis and correction of hypovolemia are the pillars of early haemorrhage shock (HS) management. Vasopressors, which are not recommended as first-line therapy, are an alternative to aggressive fluid resuscitation, but data informing the risks and benefits of vasopressor therapy as fluid-sparing strategy is lacking. We aimed to study its impact on end organs, in the setting of a haemodynamic response to the initial volume resuscitation. ⋯ Organ resuscitation after controlled HS can be assured with lesser fluid administration followed by vasopressors administration, without signs of dysoxia or worse evolution. Limiting fluid administration could benefit the brain and seems not to have a negative impact on the lung or kidney.
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Intensive Care Med Exp · Oct 2018
Cystathionine-γ-lyase expression is associated with mitochondrial respiration during sepsis-induced acute kidney injury in swine with atherosclerosis.
Sepsis is associated with disturbed glucose metabolism and reduced mitochondrial activity and biogenesis, ultimately leading to multiple organ dysfunction, e.g., acute kidney injury (AKI). Cystathionine-γ-lyase (CSE), the major cardiovascular source of endogenous H2S release, is implicated in the regulation of glucose metabolism and mitochondrial activity through a PGC1α-dependent mechanism, and critical for kidney function. Atherosclerosis is associated with mitochondrial dysfunction and reduced CSE expression. Thus, the aim of this post hoc study was to test the hypothesis whether there is an interplay between CSE expression and kidney dysfunction, mitochondrial activity, and oxidative/nitrosative stress in porcine septic AKI with underlying coronary artery disease. ⋯ Sepsis-induced AKI is associated with disturbed mitochondrial respiration and biogenesis, which may be aggravated by oxidative and nitrosative stress. Our results confirm previous data in murine septic shock and porcine hemorrhage and resuscitation on the crucial role of CSE for barrier integrity and kidney function.
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Intensive Care Med Exp · Oct 2018
Interaction of the hydrogen sulfide system with the oxytocin system in the injured mouse heart.
Both the hydrogen sulfide/cystathionine-γ-lyase (H2S/CSE) and oxytocin/oxytocin receptor (OT/OTR) systems have been reported to be cardioprotective. H2S can stimulate OT release, thereby affecting blood volume and pressure regulation. Systemic hyper-inflammation after blunt chest trauma is enhanced in cigarette smoke (CS)-exposed CSE-/- mice compared to wildtype (WT). CS increases myometrial OTR expression, but to this point, no data are available on the effects CS exposure on the cardiac OT/OTR system. Since a contusion of the thorax (Txt) can cause myocardial injury, the aim of this post hoc study was to investigate the effects of CSE-/- and exogenous administration of GYY4137 (a slow release H2S releasing compound) on OTR expression in the heart, after acute on chronic disease, of CS exposed mice undergoing Txt. ⋯ This study suggests that cardiac CSE regulates cardiac OTR expression, and this effect might play a role in the regulation of cardiovascular function.
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Intensive Care Med Exp · Aug 2018
ReviewMinimum quality threshold in pre-clinical sepsis studies (MQTiPSS): an international expert consensus initiative for improvement of animal modeling in sepsis.
Pre-clinical animal studies precede the majority of clinical trials. While the clinical definitions of sepsis and recommended treatments are regularly updated, a systematic review of pre-clinical models of sepsis has not been done and clear modeling guidelines are lacking. ⋯ We believe that these recommendations and considerations will serve to bring a level of standardization to pre-clinical models of sepsis and ultimately improve translation of pre-clinical findings. These guideline points are proposed as "best practices" for animal models of sepsis that should be implemented. In order to encourage its wide dissemination, this article is freely accessible in Shock, Infection and Intensive Care Medicine Experimental.
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Intensive Care Med Exp · Aug 2018
A mathematical model of CO2, O2 and N2 exchange during venovenous extracorporeal membrane oxygenation.
Venovenous extracorporeal membrane oxygenation (vv-ECMO) is an effective treatment for severe respiratory failure. The interaction between the cardiorespiratory system and the oxygenator can be explored with mathematical models. Understanding the physiology will help the clinician optimise therapy. As others have examined O2 exchange, the main focus of this study was on CO2 exchange. ⋯ This mathematical model of gas exchange during vv-ECMO found that the main determinants of PaCO2 during vv-ECMO were pulmonary shunt fraction, metabolic CO2 production, gas flow to the oxygenator and extracorporeal circuit recirculation.