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Experimental evidence suggests that nitric oxide (NO) and hydrogen sulfide (H2S) signaling pathways are intimately intertwined, with mutual attenuation or potentiation of biological responses in the cardiovascular system and elsewhere. The chemical basis of this interaction is elusive. Moreover, polysulfides recently emerged as potential mediators of(More)
BACKGROUND Hepatic dysfunction and jaundice are traditionally viewed as late features of sepsis and portend poor outcomes. We hypothesized that changes in liver function occur early in the onset of sepsis, yet pass undetected by standard laboratory tests. METHODS AND FINDINGS In a long-term rat model of faecal peritonitis, biotransformation and(More)
Myocardial function is depressed in sepsis and is an important prognosticator in the human condition. Using echocardiography in a long-term fluid-resuscitated Wistar rat model of faecal peritonitis we investigated whether depressed myocardial function could be detected at an early stage of sepsis and, if so, whether the degree of depression could predict(More)
CT-3 (ajulemic acid) is a synthetic analogue of a metabolite of Delta9-tetrahydrocannabinol that has reported analgesic efficacy in neuropathic pain states in man. Here we show that CT-3 binds to human cannabinoid receptors in vitro, with high affinity at hCB1 (Ki 6 nM) and hCB2 (Ki 56 nM) receptors. In a functional GTP-gamma-S assay CT-3 was an agonist at(More)
OBJECTIVE To explore the hypothesis that beta-1 adrenoreceptor blockade may be protective through the attenuation of sympathetic hyperactivity and catecholaminergic inflammatory effects on cardiac and hepatic function. DESIGN Prospective, randomized, controlled study. SETTING Animal laboratory in a university medical center. SUBJECTS Male adult Wistar(More)
Sepsis affects both macro- and micro-circulatory transport of oxygen to tissues, causing regional hypoxia. However, this relationship is poorly characterized with respect to inter-organ variability, disease severity and the evolution to organ dysfunction. We hypothesized that an early circulatory insult precedes the development of organ dysfunction, and is(More)
OBJECTIVE To postulate reasons as to why the benefits seen with novel therapies in animal models of sepsis fail to translate to the clinical setting. DATA SOURCE MEDLINE searches and relevant book chapters. DATA SUMMARY Thousands of preclinical trials performed over more than five decades have failed to find more than a handful of drugs and techniques(More)
Standard resuscitation practice for shock states mandates use of high flow, high concentration oxygen. However, this may induce microvascular constriction and potentially impair regional oxygen delivery. We thus investigated the impact of varying inspired oxygen concentrations in a rat model of progressive haemorrhage. Tissue oxygen tension (the balance(More)
INTRODUCTION Delirium is a common occurrence in critically ill patients and is associated with an increase in morbidity and mortality. Septic patients with delirium may differ from a general critically ill population. The aim of this investigation was to study the relationship between systemic inflammation and the development of delirium in septic and(More)
The pathophysiology of sepsis-induced acute kidney injury remains poorly understood. As changes in renal perfusion and oxygenation have been shown, we aimed to study the short-term effects of endotoxemia on microvascular and interstitial oxygenation in the cortex and medulla, in conjunction with global and renal hemodynamics. In a 4-h rat model of(More)