TY - JOUR
T1 - Administration of a tumor necrosis factor inhibitor at the time of myocardial infarction attenuates subsequent ventricular remodeling
AU - Berry, Mark F.
AU - Woo, Y. Joseph
AU - Pirolli, Timothy J.
AU - Bish, Lawrence T.
AU - Moise, Mireille A.
AU - Burdick, Jeffrey W.
AU - Morine, Kevin J.
AU - Jayasankar, Vasant
AU - Gardner, Timothy J.
AU - Sweeney, H. Lee
N1 - Funding Information:
This work was supported by grants HL07281201 (YJW), HL59407 (HLS), and HL007843 (MFB) from the National Heart Lung Blood Institute, National Institutes of Health (Bethesda, MD).
PY - 2004/9
Y1 - 2004/9
N2 - Tumor necrosis factor (TNF) causes myocardial extracellular matrix remodeling and fibrosis in myocardial infarction and chronic heart failure models. Pre-clinical and clinical trials of TNF inhibition in chronic heart failure have shown conflicting results. This study examined the effects of the administration of a TNF inhibitor immediately after myocardial infarction on the development of heart failure. Lewis rats underwent coronary artery ligation and then received either intravenous etanercept (n = 14), a soluble dimerized TNF receptor that inhibits TNF, or saline as control (n = 13). Leukocyte infiltration into the infarct borderzone was evaluated 4 days post-ligation in 7 animals (etanercept = 4, control = 3). After 6 weeks, the following parameters were evaluated in the remaining animals: cardiac function with a pressure-volume conductance catheter, left ventricular (LV) geometry, and borderzone collagenase activity. Etanercept rats had significantly less borderzone leukocyte infiltration 4 days post-infarction than controls (10.7 ± 0.5 vs 18.0, ±2.0 cells/high power field; p < 0.05). At 6 weeks, TNF inhibition resulted in significantly reduced borderzone collagenase activity (110 ± 30 vs 470 ± 140 activity units; p < 0.05) and increased LV wall thickness (2.1 ± 0.1 vs 1.8 ± 0.1 mm, p < 0.05). Etanercept rats had better systolic function as measured by maximum LV pressure (84 ± 3 mm Hg vs 68 ± 5 mm Hg, p < 0.05) and the maximum change in left ventricular pressure over time (maximum dP/dt) (3,110 ± 230 vs 2,260 ± 190 mm Hg/sec, p < 0.05), and better diastolic function as measured by minimum dP/dt (-3,060 ± 240 vs -1,860 ± 230 mm Hg/sec; p < 0.05) and the relaxation time constant (14.6 ± 0.6 vs 17.9 ± 1.2 msec; p < 0.05). TNF inhibition after infarction reduced leukocyte infiltration and extracellular matrix turnover and preserved cardiac function.
AB - Tumor necrosis factor (TNF) causes myocardial extracellular matrix remodeling and fibrosis in myocardial infarction and chronic heart failure models. Pre-clinical and clinical trials of TNF inhibition in chronic heart failure have shown conflicting results. This study examined the effects of the administration of a TNF inhibitor immediately after myocardial infarction on the development of heart failure. Lewis rats underwent coronary artery ligation and then received either intravenous etanercept (n = 14), a soluble dimerized TNF receptor that inhibits TNF, or saline as control (n = 13). Leukocyte infiltration into the infarct borderzone was evaluated 4 days post-ligation in 7 animals (etanercept = 4, control = 3). After 6 weeks, the following parameters were evaluated in the remaining animals: cardiac function with a pressure-volume conductance catheter, left ventricular (LV) geometry, and borderzone collagenase activity. Etanercept rats had significantly less borderzone leukocyte infiltration 4 days post-infarction than controls (10.7 ± 0.5 vs 18.0, ±2.0 cells/high power field; p < 0.05). At 6 weeks, TNF inhibition resulted in significantly reduced borderzone collagenase activity (110 ± 30 vs 470 ± 140 activity units; p < 0.05) and increased LV wall thickness (2.1 ± 0.1 vs 1.8 ± 0.1 mm, p < 0.05). Etanercept rats had better systolic function as measured by maximum LV pressure (84 ± 3 mm Hg vs 68 ± 5 mm Hg, p < 0.05) and the maximum change in left ventricular pressure over time (maximum dP/dt) (3,110 ± 230 vs 2,260 ± 190 mm Hg/sec, p < 0.05), and better diastolic function as measured by minimum dP/dt (-3,060 ± 240 vs -1,860 ± 230 mm Hg/sec; p < 0.05) and the relaxation time constant (14.6 ± 0.6 vs 17.9 ± 1.2 msec; p < 0.05). TNF inhibition after infarction reduced leukocyte infiltration and extracellular matrix turnover and preserved cardiac function.
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U2 - 10.1016/j.healun.2004.06.021
DO - 10.1016/j.healun.2004.06.021
M3 - Article
C2 - 15454172
AN - SCOPUS:5144223764
SN - 1053-2498
VL - 23
SP - 1061
EP - 1068
JO - Journal of Heart and Lung Transplantation
JF - Journal of Heart and Lung Transplantation
IS - 9
ER -