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https://hdl.handle.net/2440/9860
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dc.contributor.author | Peake, S. | - |
dc.contributor.author | Pierides, J. | - |
dc.contributor.author | Leppard, P. | - |
dc.contributor.author | Russ, G. | - |
dc.date.issued | 2002 | - |
dc.identifier.citation | Critical Care Medicine, 2002; 30(1):171-181 | - |
dc.identifier.issn | 0090-3493 | - |
dc.identifier.issn | 1530-0293 | - |
dc.identifier.uri | http://hdl.handle.net/2440/9860 | - |
dc.description.abstract | <h4>Objective</h4>To investigate the efficacy of an anti-ovine interleukin-1beta monoclonal antibody to ameliorate pathophysiological derangements and improve survival in an ovine model of gram-negative septic shock.<h4>Design</h4>Prospective, placebo-controlled, interventional study (24-hr study period).<h4>Setting</h4>University hospital animal research laboratory.<h4>Subjects</h4>Ten awake, mature female sheep.<h4>Interventions</h4>Seven milligrams per kilogram of intravenous anti-ovine interleukin-1beta immunoglobin G1 monoclonal antibody (anti-interleukin-1beta group, n = 5) or equivalent amount of protein (5% human albumin; control group, n = 5) was infused over 1 hr (time-zero minus 1 hr to time-zero) and followed by an intravenous LD100 live Escherichia coli infusion (time-zero to time-zero plus 1 hr). Normal saline, maintenance and boluses to maintain baseline filling pressures, and gentamicin, 3 mg/kg intravenous, at time-zero plus 2 and time-zero plus 13 hrs.<h4>Measurements and main results</h4>Hemodynamic and oxygen transport indexes as well as hematological, biochemical, cytokine (interleukin-1beta, tumor necrosis factor-alpha), and endotoxin measurements were performed at baseline (time-zero minus 1 hr), on completion of the monoclonal antibody/placebo (time-zero) and E. coli (time-zero plus 1 hr) infusions, and at multiple time points thereafter (time-zero plus 1.5 hrs to time-zero plus 24 hrs). Baseline data were not different between the treatment groups. From time-zero plus 1.5 hrs onward, in the anti-interleukin-1beta group, there was a sustained increase in mean arterial pressure, decreased peripheral vasodilation, and an attenuated metabolic acidosis, relative to the control group (p < or = .01, repeated-measures analysis of variance). Predicted percentage increases in mean arterial pressure and systemic vascular resistance index relative to the control group were 35% and 40%, respectively. Resuscitation fluid requirements were also decreased: anti-interleukin-1beta group, 4.1 +/- 2.9 mL x kg(-1) x hr(-1); control group, 10.6 +/- 1.8 mL x kg(-1) x hr(-1) (p < or = .01, Student's t-test). Survival was not different (anti-interleukin-1beta group, 40%; control group, 0%; p > .01, log-rank test).<h4>Conclusions</h4>Adjunctive therapy with anti-ovine interleukin-1beta monoclonal antibody in ovine gram-negative septic shock was associated with improved hemodynamic performance. However, the beneficial effects were incomplete and survival was not significantly improved. | - |
dc.language.iso | en | - |
dc.publisher | Lippincott Williams & Wilkins | - |
dc.source.uri | http://dx.doi.org/10.1097/00003246-200201000-00025 | - |
dc.subject | Animals | - |
dc.subject | Sheep | - |
dc.subject | Gram-Negative Bacterial Infections | - |
dc.subject | Escherichia coli Infections | - |
dc.subject | Shock, Septic | - |
dc.subject | Interleukin-1 | - |
dc.subject | Antibodies, Monoclonal | - |
dc.subject | Cytokines | - |
dc.subject | Prospective Studies | - |
dc.subject | Blood Pressure | - |
dc.subject | Vascular Resistance | - |
dc.subject | Vasodilation | - |
dc.subject | Female | - |
dc.title | Anti-ovine interleukin-1 beta monoclonal antibody immunotherapy in an ovine model of Gram-negative septic shock | - |
dc.type | Journal article | - |
dc.identifier.doi | 10.1097/00003246-200201000-00025 | - |
pubs.publication-status | Published | - |
dc.identifier.orcid | Peake, S. [0000-0001-6682-7973] | - |
Appears in Collections: | Aurora harvest 4 Medicine publications |
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