Endothelin receptor A antagonism attenuates renal medullary blood flow impairment in endotoxemic pigs.

Background: Endothelin-1 is a potent endogenous vasoconstrictor that contributes to renal microcirculatory impairment during endotoxemia and sepsis. Here we investigated if the renal circulatory and metabolic effects of endothelin during endotoxemia are mediated through activation of endothelin-A receptors.

Methods And Findings: A randomized experimental study was performed with anesthetized and mechanically ventilated pigs subjected to Escherichia coli endotoxin infusion for five hours.

Immunomodulation by a combination of nitric oxide and glucocorticoids in a human endotoxin model.

Background: inflammatory reactions arise in reaction to a variety of pathogenic insults. The combination of inhaled nitric oxide (iNO) and glucocorticoids (GC) may attenuate endotoxin-induced inflammatory responses. It has been shown that the combination of iNO (30 p.

Endothelin-mediated gut microcirculatory dysfunction during porcine endotoxaemia.

Background: The potent vasoconstrictor endothelin-1 has been implicated in the pathogenesis of the microcirculatory dysfunction seen in sepsis. The mixed endothelin receptor antagonist tezosentan and the selective endothelin A-receptor antagonist TBC3711 were used to investigate the importance of the different endothelin receptors in modulating splanchnic regional blood flow and microvascular blood flow in endotoxaemia.

Methods: Eighteen anaesthetized pigs were i.

Adenosine infusion attenuates soluble RAGE in endotoxin-induced inflammation in human volunteers.

Aim: To evaluate possible anti-inflammatory effects of pre-treatment with adenosine in a human experimental inflammatory model.

Methods: The study design was double-blind, crossover, placebo-controlled and randomized. In the Intensive Care Unit of a university hospital, 16 healthy male volunteers were treated for 5.

The endothelin receptor antagonist tezosentan improves renal microcirculation in a porcine model of endotoxemic shock.

Background: Impaired renal microcirculation has been suggested as a factor contributing to the development of renal dysfunction in sepsis. This study was conducted to elucidate the role of endothelin-1 (ET-1)in mediating reductions in renal microcirculatory blood flow during endotoxemic shock.

Methods: A prospective, randomized, and experimental study was performed with 16 anesthetized and mechanically ventilated pigs.

Nitric oxide inhalation and glucocorticoids as combined treatment in human experimental endotoxemia.

Objective: Inhaled nitric oxide and glucocorticoids as a combination therapy may attenuate endotoxin-induced inflammatory responses in humans as indicated by levels of cytokines and clinical signs. Since other authors have shown that combined inhaled nitric oxide and steroids improved the histologic damage both in pulmonary and systemic organs in a porcine endotoxin model, we examined if an anti-inflammatory interaction could be demonstrated in humans.

Design: Double-blind, crossover, placebo-controlled randomized study.

Mixed endothelin receptor antagonism with tezosentan improves intestinal microcirculation in endotoxemic shock.

Background: Microcirculatory dysfunction is a common feature of sepsis. The potent vasoconstrictor endothelin (ET) is released in sepsis and endotoxemia, potentially contributing to sepsis-induced microcirculatory failure. In this study we tested the hypothesis that mixed ET receptor antagonism with tezosentan would improve splanchnic microcirculatory blood flow in acute porcine endotoxemia.

Effects of the dual endothelin receptor antagonist tezosentan and hypertonic saline/dextran on porcine endotoxin shock.

Aim: To evaluate the haemodynamic effects of the dual endothelin receptor antagonist tezosentan, both alone and combined with hypertonic saline/dextran (HSD), on porcine endotoxin shock, with focus on cardiopulmonary circulation. The effects on gas exchange and short-term survival were also studied.

Methods: A prospective, randomized experimental study was carried out.

Haemodynamic and metabolic effects of resuscitation with Ringer's ethyl pyruvate in the acute phase of porcine endotoxaemic shock.

Background: Ethyl pyruvate has been shown to possess anti-inflammatory and free radical scavenging properties. However, the haemodynamic effects of ethyl pyruvate have not been studied in detail. We investigated the systemic, regional and microcirculatory haemodynamic and metabolic effects of resuscitation with Ringer's ethyl pyruvate solution (REPS) vs.

Beneficial effects of hypertonic saline/dextran on early survival in porcine endotoxin shock.

Background: Hypertonic saline/dextran (HSD) has been shown to have beneficial effects in haemorrhagic shock. These effects, with improved haemodynamics and organ perfusion, would in theory also be of benefit in septic shock. However, this is less studied.

Dose-dependent effects of morphine on experimentally induced cutaneous pain in healthy volunteers.

This study examines the dose dependent analgesic effects of two doses of morphine and a single dose of alfentanil on experimentally induced cutaneous pain. In 16 healthy volunteers pain was induced by a skin burn injury and by continuous electrical skin stimulation. Mechanical pain thresholds (PT, von Frey filament), area of secondary hyperalgesia (SH) and 'wind-up like pain' upon repetitive stimulation (40-g load, 3Hz, 30s) were assessed.

Are there changes in leg vascular resistance during laparoscopic cholecystectomy with CO2 pneumoperitoneum?

Background: The prompt haemodynamic response to carbon dioxide insufflation during laparoscopic cholecystectomy suggests involvement of the sympathetic system. The aim of the present study was to examine if a change in vascular resistance in leg skeletal muscle could be an important mechanism behind the increased afterload. Furthermore, the arterio-venous differences of the catecholamines were measured in the leg before and during insufflation of carbon dioxide into the peritoneal cavity.

Is left ventricular diastolic function an independent marker of prognosis after acute myocardial infarction?

Background: In addition to clinical risk markers, indices of left ventricular (LV) systolic function are valuable prognostic markers after acute myocardial infarction (MI). Previous studies have also suggested that LV diastolic function may contribute with prognostic information. The present study assessed whether this assumption applies to a large population of patients with acute MI who underwent thrombolytic therapy.

The distribution of hyperaemia induced by skin burn injury is not correlated with the development of secondary punctate hyperalgesia.

Unlabelled: This study in 20 volunteers examines whether changes in cutaneous blood flow distribution (laser Doppler flow scanning, LDS) and visible flare correlate in time and in distribution with the development of secondary hyperalgesia (SH, punctate stimulation of a 45-g von Frey filament) induced by a superficial skin burn injury. Areas of LDS and flare were at their largest at 5 minutes after the burn injury (58 +/- 30 and 20 +/- 11 cm2, respectively), whereas the largest area of SH was seen after 60 minutes (50 +/- 45 cm2). Although the maximum areas of LDS and SH were of the same magnitude, the blood flow response was essentially abolished when the maximal SH area was noticed at 60 minutes.

The synergistic effect of combined treatment with systemic ketamine and morphine on experimentally induced windup-like pain in humans.

Unlabelled: In this study, we evaluated whether combined treatment with ketamine (KET), an N-methyl-D-aspartate receptor antagonist, and morphine (MO) results in positive analgesic effects. Eleven volunteers were exposed to a skin burn injury on the leg. The effects of IV KET (9 microg.

Bedside monitoring of coagulation activation after challenging healthy volunteers with intravenous endotoxin.

Introduction: In the intensive care, many patients are at risk of developing procoagulant changes leading to severe coagulopathy and disseminated intravascular coagulation (DIC). Close monitoring of the coagulation is therefore crucial. In this study, we assess a novel bedside instrument based on free oscillating rheometry, measuring the degree of coagulation activity as clotting onset time, COT.

Nicotinamide does not influence cytokines or exhaled NO in human experimental endotoxaemia.

This study examined the hypothesis that nicotinamide could attenuate endotoxin-induced inflammatory responses in humans as indicated by levels of cytokines and nitric oxide. Ten healthy male volunteers participated in a randomised, double-blind, cross-over design with regard to the effects of nicotinamide. The volunteers received orally 4 g nicotinamide or placebo at 14 h and at 2 h preceding the experiment (total dose of 8 g).

Complement activation, endothelin-1 and neuropeptide Y in relation to the cardiovascular response to endotoxin-induced systemic inflammation in healthy volunteers.

Background: Endotoxin is a major stimulus for triggering the host response in septicaemia. The pathophysiology of sepsis involves activation of the vascular endothelium and leukocytes, resulting in the release of various mediators, e.g.

Pharmacological modulation of experimental phasic and tonic muscle pain by morphine, alfentanil and ketamine in healthy volunteers.

Background: Muscle pain is a major clinical problem but the underlying mechanisms and its pharmacological modulation need further investigation. This study on 15 volunteers evaluates if two experimental muscle pain models are sensitive to micro -receptor agonists and to an N-methyl-D-aspartate (NMDA)-receptor antagonist.

Methods: In the left tibialis anterior, intramuscular electrical (IMES) pain thresholds were determined for single (SPTmuscle) and five (RPTmuscle) repeated stimuli.

Adenosine treatment attenuates cytokine interleukin-6 responses to endotoxin challenge in healthy volunteers.

Anti-inflammatory effects of adenosine were evaluated in two randomized, double-blind, placebo-controlled studies. In one study healthy male volunteers received no endotoxin (adenosine study, n = 10), in the other intravenous endotoxin (4 ng/kg, endotoxin study n = 11) was given. All subjects were treated with adenosine infusion (40 microg/kg/min) and placebo (saline) infusion in a crossover design.

Exhaled NO and plasma cGMP increase after endotoxin infusion in healthy volunteers.

Nitric oxide (NO) is believed to be involved in the pathophysiology of sepsis. This study evaluated the activity of the NO pathway in a human endotoxin model. At baseline and after endotoxin, on-line measurements of exhaled NO (eNO) were made using a chemiluminescence technique with a single-breath method.

Left ventricular function and cardiovascular events following adjuvant therapy with adenosine in acute myocardial infarction treated with thrombolysis, results of the ATTenuation by Adenosine of Cardiac Complications (ATTACC) study.

Background: Reperfusion therapy for acute myocardial infarction (AMI) reduces mortality but is also associated with reperfusion injury. The present study tested the hypothesis that adjuvant therapy with a low anti-inflammatory dose of adenosine might prevent reperfusion injury and preserve left ventricular function.

Methods: Six hundred and eight patients with ST-elevation AMI were randomised to receive infusions of adenosine (10 microg x kg(-1) x min(-1)) or placebo (saline) to be started with thrombolysis and maintained for 6 h.

A randomised double-blind evaluation of adenosine as adjunct to sufentanil in spinal labour analgesia.

Background: Intrathecal injection of sufentanil offers labour pain relief of short duration. This double-blind randomised study evaluates if the combination of adenosine to sufentanil could give relevant prolongation (40%) of the duration of sufentanil spinal analgesia.

Methods: Twenty-five healthy parturients requesting labour analgesia were included.

Differential release of matrix metalloproteinase-9 and nitric oxide following infusion of endotoxin to human volunteers.

Background: Roughly 400.000 cases of sepsis occur every year in the United States only and this is associated with a very high mortality. Bacterial lipopolysaccharide (LPS) triggers systemic inflammatory reactions in sepsis.