Intensive Care Med (2004) 30:1175–1181 DOI 10.1007/s00134-003-2138-8
Francesco Imperatore Salvatore Cuzzocrea Carlo Luongo Giovanni Liguori Antonella Scafuro Antonella De Angelis Francesco Rossi Achille P. Caputi Amelia Filippelli
Received: 30 May 2003 Accepted: 12 December 2003 Published online: 12 February 2004 Springer-Verlag 2004
An editorial regarding this article can be found in the same issue (http://dx.doi.org/ 10.1007/s00134-004-2211-y) F. Imperatore · C. Luongo · A. Scafuro · A. De Angelis · F. Rossi · A. Filippelli Department of Experimental Medicine, Faculty of Medicine, Section of Pharmacology “L. Donatelli”, Second University of Naples, Naples, Italy S. Cuzzocrea ()) · A. P. Caputi Department of Clinical and Experimental Medicine and Pharmacology, School of Medicine, Torre Biologica–Policlinico Universitario, Via C. ValeriaUniversity of Messina, 98100 Gazzi, Messina, Italy e-mail:
[email protected] Tel.: +39-090-2213644 Fax: +39-090-2213300
EXPERIMENTAL
Hyperbaric oxygen therapy prevents vascular derangement during zymosan-induced multiple-organ-failure syndrome
Abstract Objective: This study investigated the effects of hyperbaric oxygen (HBO) therapy on the cardiovascular alteration (e.g. mean arterial pressure, vascular reactivity of thoracic aorta rings changes) caused by zymosan in rats. Design: Rats. Setting: University research laboratory. Intervention and measurements: We investigated the effects of HBO therapy (2 ATA at the fourth and eleventh hours after study onset) on the cardiovascular alteration caused by zymosan (500 mg/kg, administered i.p. as a suspension in saline) in rats. Cardiovascular alterations were assessed 18 h after administration of zymosan and/or HBO therapy. Results: Treatment of rats with HBO therapy attenuated the vasoplegic response to zymosan. In fact, the analysis of arterial pressure curves revealed no signs of vasoplegic shock. The aorta rings of animals treated with zymosan and HBO had a significantly increased contraction to
Introduction Multiple-organ-failure syndrome (MOFS) represents a formidable problem in many areas of clinical practice, afflicting more than 1% of hospital patients and leading in approximately 40% of cases to circulatory failure or septic shock. Mortality rises from 7% for patients with systemic inflammation response syndrome to 50–90% for those with septic shock, and it is usually attributable to MOFS [1]. Recently, investigators have focused their attention on circulatory failure associated with MOFS and its related condition hoping that the pathogenesis of
norepinephrine (NE) and endothelin-1 (ET-1) and dilation to acetylcholine (ACh) compared with the zymosan group. The HBO therapy also attenuated the increase of malondialdehyde (MDA) levels caused by zymosan in the aorta. Immunohistochemical analysis for nitrotyrosine and for iNOS revealed positive staining in the aorta from zymosantreated rats. The degree of staining for nitrotyrosine and iNOS was markedly reduced in tissue sections obtained from zymosan-rats treated with HBO therapy. Conclusion: This study provides the first evidence that HBO therapy attenuates the degree of zymosan-induced cardiovascular derangement in the rat. Keywords Zymosan-induced shock · Hyperbaric oxygen therapy · Vascular reactivity · Malondialdeyde · Nitrotyrosine · iNOS
MOFS might be elucidated [2]. In MOFS the presence of endotoxin and early inflammatory cytokines [tumour necrosis factor-alpha (TNF-a), interleukin-1 (IL-1)] results in endothelial cell activation and disruption. Probably, in vascular bed, the disordered production of mediators, produced by endothelial cells, results in MOFS. Endothelial cells are responsible for vascular tone, supply thromboresistance and they determine the extent to which the vasculature is permeable to cells and molecules through the synthesis and release of a wide variety of substances. In fact, pro-thrombotic, pro-inflammatory and vasoactive mediators are released in sepsis,
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including nitric oxide (NO), endothelins (ETs) and products of cyclo-oxygenase metabolism [3]. A new experimental model of MOFS, induced by the intraperitoneal administration of zymosan, has been codified by several studies. Zymosan, a cell wall component of the yeast Saccharomyces cerevisiae, is an inflammatory agent [4]. It is a nonbacterial, nonendotoxic agent that produces acute peritonitis and MOFS characterized by functional and structural changes in liver, kidney and intestine [5]. Recent reports have demonstrated the key role of some mediators, such as NO and TNF-a, in the development of zymosan-induced MOFS [6, 7]. Moreover, it has been demonstrated that zymosan-induced MOFS causes significant changes of vascular reactivity [6]. Our previous study showed the efficacy of hyperbaric oxygen (HBO) therapy in the treatment of zymosaninduced MOFS, resulting in a significant reduction of mortality, loss of body weight, and secretion of involved mediators [8]. Hyperbaric oxygenation is an important treatment given to various groups of patients exposed to pathological situations (i.e. carbon monoxide exposure) [9]. Recent papers report the use of HBO in critically ill patients treated for life-threatening disorders such as shock [10, 11]. Moreover, some authors have reported that HBO changes vascular reactivity [12]. Therefore, the aim of this study was to evaluate the effect of HBO exposure on vascular reactivity changes induced by zymosan MOFS model.
Materials and methods Animals Sprague-Dawley male rats weighing 250–300 g were used. The animals were housed in compliance with Good Laboratory Practice (GLP) for the protection of experimentally used animals (Italian Ministry of Health Decree no. 116/92) as well as with the European Economic Community regulation (O.J. of European Community Law 358/1, 18/12/1986). The animals were housed at constant temperature: 21€1C; relative humidity: 60%; regular alternation light–dark: light 7 a.m. to 7 p.m. water and food ad libitum. Zymosan-induced MOFS Animals were randomly divided into four groups (ten rats for each group). The first group of animals were treated with 3 ml of saline solution (0.9% NaCl) by intraperitoneal route and served as control group; the second group received intraperitoneally zymosan (500 mg/Kg) in 3 ml of saline solution. The third group of rats received zymosan (500 mg/kg by intraperitoneal route) and HBO (2 ATA) at fourth and eleventh hours after zymosan-induced shock. The fourth one was subjected to HBO exposure at fourth and eleventh hours after saline solution administration.
HBO treatment The HBO exposure was carried out in a cylindrical steel chamber (40-cm diameter65-cm length, Galeazzi, La Spezia, Italy) with thick glass windows allowing for direct observation of animals during the treatment. Before pressurization, 100% medical oxygen was flushed through the chamber for 5 min to displace the room air. Oxygen pressure was then increased at a constant rate to reach a pressure of 2 ATA in 4 min. The animals have been treated with 60min compression. The chamber was constantly ventilated at a rate of 4 l/min to avoid carbon dioxide accumulation during pressurization. Gases were analyzed and O2 concentration was >99% (Taylor Servomex OA272 Oxygen Analyzer, Italy) while carbon dioxide was
