TY - JOUR
T1 - Anti-tumor necrosis factor-alpha improves myocardial recovery after ischemia and reperfusion
AU - Gurevitch, Jacob
AU - Frolkis, Inna
AU - Yuhas, Yael
AU - Lifschitz-Mercer, Beatriz
AU - Berger, Esther
AU - Paz, Yosef
AU - Matsa, Menachem
AU - Kramer, Amir
AU - Mohr, Rephael
N1 - Funding Information:
This study was supported by the Research Fund of the Department of Thoracic and Cardiovascular Surgery, Elias Sourasky–Tel-Aviv Medical Center.
PY - 1997/11/15
Y1 - 1997/11/15
N2 - Objectives. This study sought to assess the importance of locally released or paracrine myocardial tumor necrosis factor-alpha (TNF-alpha) in the evolution of postischemic myocardial dysfunction and to use immunohistochemical studies to localize TNF-alpha within the myocardium. Background. TNF-alpha is implicated as a systemic mediator in the development of myocardial ischemia-reperfusion injury by promoting leukocyte myocardial infiltration, and it has been shown to originate from noncardiac peripheral mononuclear cells. We have recently documented in a blood-free environment the release of TNF-alpha from the ischemic-reperfused myocardium. Methods. Isolated rat hearts undergoing 1 h of global cardioplegia-induced ischemia and 30 min of reperfusion were investigated with use of the modified Langendorff model. Hearts were randomly divided into three subgroups: group A, control group; and groups B and C, isolated hearts receiving cardioplegic solution containing monoclonal hamster antimurine TNF-alpha antibodies (group B) or hamster IgG (group C). Results. Significant amounts of TNF-alpha were detected in group A and group C effluent on 1 min of reperfusion (752 ± 212 and 958 ± 409 μmol/ml, respectively). However, in group B, TNF-alpha was below detectable levels. In this group, postischemic left ventricular peak systolic pressures, first derivative of the rise in left ventricular pressure (dP/dt(max), pressure-time integral, coronary flow and O2 consumption improved (analysis of variance [ANOVA] p < 0.0001 for all variables) compared with values in groups A and C; creatine kinase levels decreased (p < 0.005); and myocardial structure was preserved. Immunohistochemical staining localized TNF-alpha to cardiac myocytes and to endothelial cells. Conclusions. Anti-TNF-alpha neutralizes local TNF-alpha release from cardiac myocytes after ischemia and improves myocardial recovery during reperfusion, indicating that postischemic paracrine TNF-alpha release plays an active role in myocardial dysfunction.
AB - Objectives. This study sought to assess the importance of locally released or paracrine myocardial tumor necrosis factor-alpha (TNF-alpha) in the evolution of postischemic myocardial dysfunction and to use immunohistochemical studies to localize TNF-alpha within the myocardium. Background. TNF-alpha is implicated as a systemic mediator in the development of myocardial ischemia-reperfusion injury by promoting leukocyte myocardial infiltration, and it has been shown to originate from noncardiac peripheral mononuclear cells. We have recently documented in a blood-free environment the release of TNF-alpha from the ischemic-reperfused myocardium. Methods. Isolated rat hearts undergoing 1 h of global cardioplegia-induced ischemia and 30 min of reperfusion were investigated with use of the modified Langendorff model. Hearts were randomly divided into three subgroups: group A, control group; and groups B and C, isolated hearts receiving cardioplegic solution containing monoclonal hamster antimurine TNF-alpha antibodies (group B) or hamster IgG (group C). Results. Significant amounts of TNF-alpha were detected in group A and group C effluent on 1 min of reperfusion (752 ± 212 and 958 ± 409 μmol/ml, respectively). However, in group B, TNF-alpha was below detectable levels. In this group, postischemic left ventricular peak systolic pressures, first derivative of the rise in left ventricular pressure (dP/dt(max), pressure-time integral, coronary flow and O2 consumption improved (analysis of variance [ANOVA] p < 0.0001 for all variables) compared with values in groups A and C; creatine kinase levels decreased (p < 0.005); and myocardial structure was preserved. Immunohistochemical staining localized TNF-alpha to cardiac myocytes and to endothelial cells. Conclusions. Anti-TNF-alpha neutralizes local TNF-alpha release from cardiac myocytes after ischemia and improves myocardial recovery during reperfusion, indicating that postischemic paracrine TNF-alpha release plays an active role in myocardial dysfunction.
UR - http://www.scopus.com/inward/record.url?scp=0030689717&partnerID=8YFLogxK
U2 - 10.1016/S0735-1097(97)00328-8
DO - 10.1016/S0735-1097(97)00328-8
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AN - SCOPUS:0030689717
SN - 0735-1097
VL - 30
SP - 1554
EP - 1561
JO - Journal of the American College of Cardiology
JF - Journal of the American College of Cardiology
IS - 6
ER -
