{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T21:16:17Z","timestamp":1760217377760,"version":"build-2065373602"},"reference-count":72,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2015,3,25]],"date-time":"2015-03-25T00:00:00Z","timestamp":1427241600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Sepsis is associated with an increase in reactive oxygen species (ROS), however, the precise role of ROS in the septic process remains unknown. We hypothesized that treatment with EUK-134 (manganese-3-methoxy N,N'-bis(salicyclidene)ethylene-diamine chloride), a compound with superoxide dismutase and catalase activity, attenuates the vascular manifestations of sepsis in vivo. Pigs were instrumented to measure cardiac output and blood flow in renal, superior mesenteric and femoral arteries, and portal vein. Animals were treated with saline (control), lipopolysaccharide (LPS; 10 \u00b5g\u00b7kg\u22121\u00b7h\u22121), EUK-134, or EUK-134 plus LPS. Results show that an LPS-induced increase in pulmonary artery pressure (PAP) as well as a trend towards lower blood pressure (BP) were both attenuated by EUK-134. Renal blood flow decreased with LPS whereas superior mesenteric, portal and femoral flows did not change. Importantly, EUK-134 decreased the LPS-induced fall in renal blood flow and this was associated with a corresponding decrease in LPS-induced protein nitrotyrosinylation in the kidney. PO2, pH, base excess and systemic vascular resistance fell with LPS and were unaltered by EUK-134. EUK-134 also had no effect on LPS-associated increase in CO. Interestingly, EUK-134 alone resulted in higher CO, BP, PAP, mean circulatory filling pressure, and portal flow than controls. Taken together, these data support a protective role for EUK-134 in the renal circulation in sepsis.<\/jats:p>","DOI":"10.3390\/ijms16046801","type":"journal-article","created":{"date-parts":[[2015,3,25]],"date-time":"2015-03-25T11:53:17Z","timestamp":1427284397000},"page":"6801-6817","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Preservation of Renal Blood Flow by the Antioxidant EUK-134 in LPS-Treated Pigs"],"prefix":"10.3390","volume":"16","author":[{"given":"Sheldon","family":"Magder","sequence":"first","affiliation":[{"name":"Critical Care Division, Royal Victoria Hospital, 687 Pine Ave W, Montreal, QC H3A 1A1, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dimitrios","family":"Parthenis","sequence":"additional","affiliation":[{"name":"Vascular Surgery of Nikaia, Peiraeous 18454, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Imad","family":"Ghouleh","sequence":"additional","affiliation":[{"name":"Vascular Medicine Institute and Department of Pharmacology and Chemical Biology, University of Pittsburgh, Room E1228-2B, 200 Lothrop St, Pittsburgh, PA 15261, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2015,3,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1016\/j.immuni.2014.04.001","article-title":"Sepsis: Current dogma and new perspectives","volume":"40","author":"Deutschman","year":"2014","journal-title":"Immunity"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1699","DOI":"10.1056\/NEJMra043632","article-title":"Management of sepsis","volume":"355","author":"Russell","year":"2006","journal-title":"N. Engl. J. Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1173","DOI":"10.1016\/S0891-5849(02)00961-9","article-title":"Oxidative stress in septic shock and disseminated intravascular coagulation","volume":"33","author":"Salvemini","year":"2002","journal-title":"Free Radic. Biol. Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"2129","DOI":"10.1089\/ars.2013.5401","article-title":"Evaluation of vitamin C for adjuvant sepsis therapy","volume":"19","author":"Wilson","year":"2013","journal-title":"Antioxid. Redox Signal."},{"key":"ref_5","first-page":"222","article-title":"Clinical management of the cardiovascular failure in sepsis","volume":"11","author":"Scolletta","year":"2013","journal-title":"Curr. Vasc. Pharmacol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1770","DOI":"10.1097\/00003246-199311000-00029","article-title":"Free radicals and antioxidants in sepsis","volume":"21","author":"Goode","year":"1993","journal-title":"Crit. Care Med."},{"key":"ref_7","first-page":"292","article-title":"Effect of allopurinol and superoxide dismutase on survival rate in rats with sepsis","volume":"43","author":"Warner","year":"1986","journal-title":"Curr. Surg."},{"key":"ref_8","first-page":"15","article-title":"Inhibition of lipid peroxidation improves survival rate of endotoxemic rats","volume":"21","author":"Kunimoto","year":"1987","journal-title":"Circ. Shock"},{"key":"ref_9","first-page":"913","article-title":"Protection by recombinant human superoxide dismutase in lethal rat endotoxemia","volume":"308","author":"Schneider","year":"1989","journal-title":"Prog. Clin. Biol. Res."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1240","DOI":"10.1164\/rccm.200410-1346OC","article-title":"Polyethylene glycol-superoxide dismutase prevents endotoxin-induced cardiac dysfunction","volume":"173","author":"Supinski","year":"2006","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1005","DOI":"10.1152\/jappl.1985.58.3.1005","article-title":"Potentiation of lung vascular response to endotoxin by superoxide dismutase","volume":"58","author":"Traber","year":"1985","journal-title":"J. Appl. Physiol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1526","DOI":"10.1152\/jappl.1987.63.4.1526","article-title":"Effect of polyethylene glycol-superoxide dismutase and catalase on endotoxemia in pigs","volume":"63","author":"Olson","year":"1987","journal-title":"J. Appl. Physiol."},{"key":"ref_13","first-page":"H954","article-title":"Evidence for lack of importance of oxygen free radicals in Escherichia coli endotoxemia in dogs","volume":"254","author":"Novotny","year":"1988","journal-title":"Am. J. Physiol."},{"key":"ref_14","first-page":"77","article-title":"Effect of antioxidants in experimental Escherichia coli septicemia","volume":"29","author":"Broner","year":"1989","journal-title":"Circ. Shock"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2426","DOI":"10.1152\/jappl.1987.63.6.2426","article-title":"Dimethylthiourea attenuates endotoxin-induced acute respiratory failure in pigs","volume":"63","author":"Olson","year":"1987","journal-title":"J. Appl. Physiol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1210","DOI":"10.1152\/jappl.1988.65.3.1210","article-title":"Catalase prevents prostanoid release and lung lipid peroxidation after endotoxemia in sheep","volume":"65","author":"Seekamp","year":"1988","journal-title":"J. Appl. Physiol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1159","DOI":"10.1073\/pnas.77.2.1159","article-title":"Free radicals and inflammation: Superoxide-dependent activation of a neutrophil chemotactic factor in plasma","volume":"77","author":"Petrone","year":"1980","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1772","DOI":"10.1172\/JCI111386","article-title":"Effect of N-acetylcysteine on the pulmonary response to endotoxin in the awake sheep and upon in vitro granulocyte function","volume":"73","author":"Bernard","year":"1984","journal-title":"J. Clin. Investig."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"798","DOI":"10.1016\/S0022-3565(25)12131-9","article-title":"EUK-8, a synthetic superoxide dismutase and catalase mimetic, ameliorates acute lung injury in endotoxemic swine","volume":"275","author":"Gonzalez","year":"1995","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1080","DOI":"10.1111\/resp.12363","article-title":"Intratracheal co-administration of antioxidants and ceftriaxone reduces pulmonary injury and mortality rate in an experimental model of sepsis","volume":"19","author":"Galvao","year":"2014","journal-title":"Respirology"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"L640","DOI":"10.1152\/ajplung.00097.2011","article-title":"N-acetylcysteine prevents pulmonary edema and acute kidney injury in rats with sepsis submitted to mechanical ventilation","volume":"302","author":"Campos","year":"2012","journal-title":"Am. J. Physiol. Lung Cell. Mol. Physiol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"2697","DOI":"10.1097\/00003246-200008000-00003","article-title":"Aminoethyl-isothiourea, a nitric oxide synthase inhibitor and oxygen radical scavenger, improves survival and counteracts hemodynamic deterioration in a porcine model of streptococcal shock","volume":"28","author":"Saetre","year":"2000","journal-title":"Crit. Care Med."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1243","DOI":"10.1161\/01.HYP.33.5.1243","article-title":"Role of increased production of superoxide anions by NAD(P)H oxidase and xanthine oxidase in prolonged endotoxemia","volume":"33","author":"Brandes","year":"1999","journal-title":"Hypertension"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"e108455","DOI":"10.1371\/journal.pone.0108455","article-title":"Adjuvant potential of selegiline in attenuating organ dysfunction in septic rats with peritonitis","volume":"9","author":"Tsao","year":"2014","journal-title":"PLoS ONE"},{"key":"ref_25","first-page":"580320","article-title":"Prophylactic antioxidant potential of gallic acid in murine model of sepsis","volume":"2014","author":"Maurya","year":"2014","journal-title":"Int. J. Inflamm."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1179","DOI":"10.1097\/00003246-199607000-00019","article-title":"Plasma antioxidant potential in severe sepsis: A comparison of survivors and nonsurvivors","volume":"24","author":"Cowley","year":"1996","journal-title":"Crit. Care Med."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"272","DOI":"10.1097\/00003246-200102000-00009","article-title":"N-acetylcysteine reduces respiratory burst but augments neutrophil phagocytosis in intensive care unit patients","volume":"29","author":"Heller","year":"2001","journal-title":"Crit. Care Med."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1907","DOI":"10.1164\/ajrccm.161.6.9903043","article-title":"The effect of glutathione and N-acetylcysteine on lipoperoxidative damage in patients with early septic shock","volume":"161","author":"Ortolani","year":"2000","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1378\/chest.105.1.190","article-title":"N-acetylcysteine enhances recovery from acute lung injury in man. A randomized, double-blind, placebo-controlled clinical study","volume":"105","author":"Suter","year":"1994","journal-title":"Chest"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"3799","DOI":"10.1097\/00003246-200012000-00006","article-title":"N-acetylcysteine increases liver blood flow and improves liver function in septic shock patients: Results of a prospective, randomized, double-blind study","volume":"28","author":"Rank","year":"2000","journal-title":"Crit. Care Med."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1378\/chest.112.1.164","article-title":"A trial of antioxidants N-acetylcysteine and procysteine in ARDS. The Antioxidant in ARDS Study Group","volume":"112","author":"Bernard","year":"1997","journal-title":"Chest"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"918","DOI":"10.1097\/00003246-199207000-00004","article-title":"Antioxidant treatment with N-acetylcysteine during adult respiratory distress syndrome: A prospective, randomized, placebo-controlled study","volume":"20","author":"Jepsen","year":"1992","journal-title":"Crit. Care Med."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"857","DOI":"10.1213\/01.ANE.0000133144.60584.F6","article-title":"The beneficial effects of antioxidant supplementation in enteral feeding in critically ill patients: A prospective, randomized, double-blind, placebo-controlled trial","volume":"99","author":"Crimi","year":"2004","journal-title":"Anesth. Analg."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1016\/j.biochi.2014.03.006","article-title":"Effects of levosimendan on mitochondrial function in patients with septic shock: A randomized trial","volume":"102","author":"Torraco","year":"2014","journal-title":"Biochimie"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1186\/cc9098","article-title":"Bench-to-bedside review: Targeting antioxidants to mitochondria in sepsis","volume":"14","author":"Galley","year":"2010","journal-title":"Crit. Care"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1016\/S0014-2999(03)01538-3","article-title":"A superoxide dismutase mimetic with catalase activity (EUK-8) reduces the organ injury in endotoxic shock","volume":"466","author":"McDonald","year":"2003","journal-title":"Eur. J. Pharmacol."},{"key":"ref_37","first-page":"BR1","article-title":"Superoxide dismutase mimetic with catalase activity, EUK-134, attenuates the multiple organ injury and dysfunction caused by endotoxin in the rat","volume":"8","author":"Bianca","year":"2002","journal-title":"Med. Sci. Monit."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"359","DOI":"10.2174\/187152011795677490","article-title":"Salen Mn complexes mitigate radiation injury in normal tissues","volume":"11","author":"Rosenthal","year":"2011","journal-title":"Anticancer Agents Med. Chem."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1159\/000076547","article-title":"EUK-134 reduces renal dysfunction and injury caused by oxidative and nitrosative stress of the kidney","volume":"24","author":"Chatterjee","year":"2004","journal-title":"Am. J. Nephrol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1664","DOI":"10.1097\/00007890-199612150-00022","article-title":"EUK-134, a synthetic superoxide dismutase and catalase mimetic, protects rat kidneys from ischemia-reperfusion-induced damage","volume":"62","author":"Gianello","year":"1996","journal-title":"Transplantation"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"9897","DOI":"10.1073\/pnas.96.17.9897","article-title":"EUK-134, a synthetic superoxide dismutase and catalase mimetic, prevents oxidative stress and attenuates kainate-induced neuropathology","volume":"96","author":"Rong","year":"1999","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"R470","DOI":"10.1152\/ajpregu.00371.2013","article-title":"EUK-134 ameliorates nNOS\u03bc translocation and skeletal muscle fiber atrophy during short-term mechanical unloading","volume":"306","author":"Lawler","year":"2014","journal-title":"Am. J. Physiol. Regul. Integr. Comp. Physiol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1159\/000327243","article-title":"Striatal neuroprotection from neonatal hypoxia-ischemia in piglets by antioxidant treatment with EUK-134 or edaravone","volume":"33","author":"Ni","year":"2011","journal-title":"Dev. Neurosci."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"486","DOI":"10.1097\/01.shk.0000054374.88889.37","article-title":"Superoxide production in the vasculature of lipopolysaccharide treated rats and pigs","volume":"19","author":"Javeshghani","year":"2003","journal-title":"Shock"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1097\/SHK.0b013e318157ebc8","article-title":"Nicotinamide adenine dinucleotide phosphate (reduced form) oxidase is important for LPS-induced endothelial cell activation","volume":"29","author":"Magder","year":"2008","journal-title":"Shock"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1097\/SHK.0b013e31824582e6","article-title":"NADPH oxidase-derived superoxide destabilizes lipopolysaccharide-induced interleukin 8 mRNA via p38, extracellular signal-regulated kinase mitogen-activated protein kinase, and the destabilizing factor tristetraprolin","volume":"37","author":"Magder","year":"2012","journal-title":"Shock"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"S4","DOI":"10.1186\/cc11502","article-title":"Supporting hemodynamics: What should we target? What treatments should we use?","volume":"17","author":"Gattinoni","year":"2013","journal-title":"Crit. Care"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1186\/2110-5820-1-35","article-title":"Clinical applicability of functional hemodynamic monitoring","volume":"1","author":"Garcia","year":"2011","journal-title":"Ann. Intensive Care"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"2630","DOI":"10.1097\/01.CCM.0000286399.21008.64","article-title":"Disorders of acid-base balance","volume":"35","author":"Kellum","year":"2007","journal-title":"Crit. Care Med."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1186\/cc7116","article-title":"Bench-to-bedside review: Ventilatory abnormalities in sepsis","volume":"13","author":"Magder","year":"2009","journal-title":"Crit. Care"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"304","DOI":"10.1097\/00024382-200116040-00013","article-title":"Presence of nitrotyrosine with minimal iNOS induction in LPS treated pigs","volume":"16","author":"Javeshghani","year":"2001","journal-title":"Shock"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1016\/S0883-9441(96)90026-X","article-title":"Circuit factors in the high cardiac output of sepsis","volume":"11","author":"Magder","year":"1996","journal-title":"J. Crit. Care"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1097\/00024382-200209000-00005","article-title":"Superoxide dismutase mimetics with catalase activity reduce the organ injury in hemorrhagic shock","volume":"18","author":"Izumi","year":"2002","journal-title":"Shock"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"853","DOI":"10.1152\/japplphysiol.00066.2011","article-title":"Peripheral vascular decoupling in porcine endotoxic shock","volume":"111","author":"Hatib","year":"2011","journal-title":"J. Appl. Physiol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1165\/ajrcmb.16.2.9032115","article-title":"Peroxynitrite causes energy depletion and increases permeability via activation of poly (ADP-ribose) synthetase in pulmonary epithelial cells","volume":"16","author":"Szabo","year":"1997","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1097\/00003246-199902000-00047","article-title":"Porcine endotoxaemic shock is associated with increased expired nitric oxide","volume":"27","author":"Mehta","year":"1999","journal-title":"Crit. Care Med."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"685","DOI":"10.1038\/sj.bjp.0702604","article-title":"Protective effects of a superoxide dismutase mimetic and peroxynitrite decomposition catalysts in endotoxin-induced intestinal damage","volume":"127","author":"Salvemini","year":"1999","journal-title":"Br. J. Pharmacol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"412","DOI":"10.1164\/ajrccm.165.3.2103028","article-title":"Molecular characterization of a superoxide-generating NAD(P)H oxidase in the ventilatory muscles","volume":"165","author":"Javesghani","year":"2002","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1097\/00024382-200116030-00011","article-title":"Regional changes in constitutive nitric oxide synthase and the hemodynamic consequences of its inhibition in lipopolysaccharide-treated pigs","volume":"16","author":"Javeshghani","year":"2001","journal-title":"Shock"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"4549","DOI":"10.1021\/jm020207y","article-title":"Salen-manganese complexes as catalytic scavengers of hydrogen peroxide and cytoprotective agents: Structure-activity relationship studies","volume":"45","author":"Doctrow","year":"2002","journal-title":"J. Med. Chem."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"2224","DOI":"10.1097\/01.CCM.0000227646.98423.98","article-title":"Central venous pressure: A useful but not so simple measurement","volume":"34","author":"Magder","year":"2006","journal-title":"Crit. Care Med."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1378\/chest.07-2331","article-title":"Does central venous pressure predict fluid responsiveness? A systematic review of the literature and the tale of seven mares","volume":"134","author":"Marik","year":"2008","journal-title":"Chest"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1271","DOI":"10.1016\/j.freeradbiomed.2011.06.011","article-title":"Oxidases and peroxidases in cardiovascular and lung disease: New concepts in reactive oxygen species signaling","volume":"51","author":"Khoo","year":"2011","journal-title":"Free Radic. Biol. Med."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1152\/physrev.00044.2005","article-title":"The NOX family of ROS-generating NADPH oxidases: Physiology and pathophysiology","volume":"87","author":"Bedard","year":"2007","journal-title":"Physiol. Rev."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"659","DOI":"10.1161\/01.RES.61.5.659","article-title":"Group B streptococcal sepsis in the piglet: Effects of fluid therapy on venous return, organ edema, and organ blood flow","volume":"61","author":"Bressack","year":"1987","journal-title":"Circ. Res."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1802","DOI":"10.1152\/jappl.1985.59.6.1802","article-title":"Distribution of respiratory muscle and organ blood flow during endotoxic shock in dogs","volume":"59","author":"Hussain","year":"1985","journal-title":"J. Appl. Physiol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1093\/cvr\/18.4.195","article-title":"Distribution of cardiac output, oxygen consumption and lactate production in canine endotoxin shock","volume":"18","author":"Bronsveld","year":"1984","journal-title":"Cardiovasc Res."},{"key":"ref_68","first-page":"R331","article-title":"Cardiac output and redistribution of organ blood flow in hypermetabolic sepsis","volume":"246","author":"Lang","year":"1984","journal-title":"Am. J. Physiol."},{"key":"ref_69","first-page":"H291","article-title":"Effect of vasopressors on organ blood flow during endotoxin shock in pigs","volume":"252","author":"Breslow","year":"1987","journal-title":"Am. J. Physiol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"777","DOI":"10.1161\/01.RES.24.6.777","article-title":"Endotoxin-induced regional circulatory changes in the unanesthetized monkey","volume":"24","author":"Wyler","year":"1969","journal-title":"Circ. Res."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"1296","DOI":"10.1097\/00003246-199309000-00011","article-title":"Regional blood flow and oxygen transport in septic shock","volume":"21","author":"Ruokonen","year":"1993","journal-title":"Crit. Care Med."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1152\/jappl.1991.70.1.77","article-title":"Chemical activation of thin-fiber phrenic afferents. 2. Cardiovascular responses","volume":"70","author":"Hussain","year":"1991","journal-title":"J. Appl. Physiol."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/16\/4\/6801\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T20:43:55Z","timestamp":1760215435000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/16\/4\/6801"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,3,25]]},"references-count":72,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2015,4]]}},"alternative-id":["ijms16046801"],"URL":"https:\/\/doi.org\/10.3390\/ijms16046801","relation":{},"ISSN":["1422-0067"],"issn-type":[{"type":"electronic","value":"1422-0067"}],"subject":[],"published":{"date-parts":[[2015,3,25]]}}}