Document Detail


TNF-α blockade improves early post-resuscitation survival and hemodynamics in a swine model of ischemic ventricular fibrillation.
MedLine Citation:
PMID:  22683946     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
AIM OF THE STUDY: Inflammatory cytokines have been implicated in the pathophysiology of post cardiac arrest syndrome, including myocardial dysfunction and hypotension, often leading to multi-organ system dysfunction and death. We hypothesized that administration of infliximab after return of spontaneous circulation (ROSC) would ameliorate hypotension and myocardial dysfunction and prolong survival.
METHODS: Domestic swine were anesthetized and instrumented. Balloon occlusion of the LAD coronary artery just distal to the first septal perforator was performed and VF followed spontaneously in all animals. After 7 min, chest compressions, defibrillation, and standard ACLS resuscitation was performed. Animals achieving ROSC (N=32) were randomized to receive infliximab (5 mg/kg, n=16) or vehicle (250 mL normal saline, n=16) immediately post-ROSC and survival and hemodynamics were monitored for 3 h.
RESULTS: There were no differences in prearrest hemodynamic variables, TNF-α levels, or resuscitation variables between groups. Both groups demonstrated a time dependent decline in mean arterial pressure (MAP) and stroke work (SW) post-ROSC with a nadir at 1 h followed by recovery over hours 2 and 3. This decline was blunted in infliximab-treated swine (1-h between group difference in MAP 21 mm Hg, 95% CI 3-38 mm Hg and SW 6.7 gm-m, 95% CI 0.4-13 at 1 h). Left ventricular systolic dp/dt fell in the vehicle group (-437 mm Hg/s, 95% CI -183 to -690) but did not in the infliximab group. Tau rose only in the vehicle group (44 ms, 95% CI 1-87). Short-term survival was higher in the infliximab group (Kaplan-Meier p=0.022).
CONCLUSIONS: Blockade of TNF-α in the immediate post-ROSC period improved survival and hemodynamic parameters in this swine model of ischemic VF.
Authors:
James T Niemann; Scott T Youngquist; Atman P Shah; Joseph L Thomas; John P Rosborough
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2012-06-07
Journal Detail:
Title:  Resuscitation     Volume:  84     ISSN:  1873-1570     ISO Abbreviation:  Resuscitation     Publication Date:  2013 Jan 
Date Detail:
Created Date:  2012-12-24     Completed Date:  2013-07-08     Revised Date:  2014-01-09    
Medline Journal Info:
Nlm Unique ID:  0332173     Medline TA:  Resuscitation     Country:  Ireland    
Other Details:
Languages:  eng     Pagination:  103-7     Citation Subset:  IM    
Copyright Information:
Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.
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MeSH Terms
Descriptor/Qualifier:
Animals
Antibodies, Monoclonal / pharmacology*
Cardiopulmonary Resuscitation / methods*
Disease Models, Animal
Hemodynamics
Random Allocation
Survival Rate
Swine
Tumor Necrosis Factor-alpha / analysis,  antagonists & inhibitors*
Ventricular Fibrillation / therapy*
Grant Support
ID/Acronym/Agency:
R01 HL076671/HL/NHLBI NIH HHS; R01 HL076671/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Antibodies, Monoclonal; 0/Tumor Necrosis Factor-alpha; 0/infliximab
Comments/Corrections

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