Cardiac function and the proinflammatory cytokine response after recovery from cardiac arrest in swine.
Increased levels of cytokines have been reported after resuscitation from cardiac arrest. We hypothesized that proinflammatory cytokines, released in response to ischemia/reperfusion, increase following resuscitation and play a role in post-cardiac arrest myocardial dysfunction. Ventricular fibrillation (VF) was induced by coronary occlusion in 20 swine. After 7 min of VF, resuscitation was performed as per guidelines. Plasma levels of tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, and IL-6 were measured 15 min after the start of resuscitation in all animals and at intervals of 6 h in resuscitated animals. Intravascular pressures and cardiac output (CO) were also recorded. TNF-alpha abruptly increased after resuscitation, peaking at 15 min following return of spontaneous circulation, and declined to baseline levels after 3 h. IL-1beta increased more slowly, reaching a maximum 2 h after reperfusion. IL-6 concentrations were not significantly different from control values at any time point. Males demonstrated greater elevations of TNF-alpha and IL-1beta than females. Stroke work was significantly depressed at all time points with a nadir at 15-30 min after reperfusion, corresponding to the peak TNF-alpha values. The anti-TNF-alpha antibody infliximab attenuated the decrease in myocardial function observed 30 min after reperfusion. TNF-alpha increases during recovery from cardiac arrest are associated with depression of left ventricle (LV) function. The effect of TNF-alpha can be attenuated by anti-TNF-alpha antibodies.
Niemann
James T
JT
The David Geffen School of Medicine at UCLA, University of California-Los Angeles, CA, USA. jniemann@emedharbor.edu
Rosborough
John P
JP
Youngquist
Scott
S
Shah
Atman P
AP
Lewis
Roger J
RJ
Phan
Quynh T
QT
Filler
Scott G
SG
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D016207:Cytokines / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects / Q000276:immunology; D006323:Heart Arrest / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology; D018836:Inflammation Mediators / Q000378:metabolism; D000069285:Infliximab; D008297:Male; D023421:Models, Animal; D015427:Reperfusion Injury / Q000188:drug therapy / Q000276:immunology*; D012151:Resuscitation; D012737:Sex Factors; D013552:Swine; D016277:Ventricular Function, Left / Q000187:drug effects*
D000893:Anti-Inflammatory Agents; D000911:Antibodies, Monoclonal; D016207:Cytokines; D018836:Inflammation Mediators; D000069285:Infliximab