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.

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.

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.

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.

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.

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.

Experimental pain by ischaemic contractions compared with pain by intramuscular infusions of adenosine and hypertonic saline.

Deep tissue pain can be related to reduced muscle blood flow, which comprises the metabolic demand under muscle work. The tissues and receptors involved in nociception after ischaemic muscle contractions are not known. The concentration of adenosine is increased after ischaemic contractions and might act as an algesic substance.

Systemic adenosine infusion: a new treatment modality to alleviate neuropathic pain.

Adenosine, an endogenous antinociceptive compound acting in the central nervous system, was infused intravenously (50-70 micrograms/kg/min) to 2 patients with peripheral neuropathic pain. In 1 subject, spontaneous pain was alleviated, and tactile allodynia was essentially relieved during 40 min of infusion. Allodynia to warmth and touch were abolished in the other subject.