Elevated tumor necrosis factor-alpha and interleukin-6 in myocardium and serum of malfunctioning donor hearts

Myocardial dysfunction is a common and important problem in donor hearts. The mechanisms responsible remain unclear. We have studied the cytokines tumor necrosis factor (TNF)-alpha and interleukin-6 (IL-6) in the myocardium and serum from donors with myocardial dysfunction (unused donors) and compar...

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Veröffentlicht in:Circulation (New York, N.Y.) N.Y.), 2000-11, Vol.102 (19 Suppl 3), p.III352-III358
Hauptverfasser: Birks, E J, Burton, P B, Owen, V, Mullen, A J, Hunt, D, Banner, N R, Barton, P J, Yacoub, M H
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container_end_page III358
container_issue 19 Suppl 3
container_start_page III352
container_title Circulation (New York, N.Y.)
container_volume 102
creator Birks, E J
Burton, P B
Owen, V
Mullen, A J
Hunt, D
Banner, N R
Barton, P J
Yacoub, M H
description Myocardial dysfunction is a common and important problem in donor hearts. The mechanisms responsible remain unclear. We have studied the cytokines tumor necrosis factor (TNF)-alpha and interleukin-6 (IL-6) in the myocardium and serum from donors with myocardial dysfunction (unused donors) and compared them with donors with good ventricular function (used donors) and patients with advanced heart failure (HF). Clinical details and ventricular function were assessed in 46 donors (31 used, 15 unused). Real-time reverse transcription-polymerase chain reaction, Western blotting, and immunocytochemistry were performed on myocardium and immunoassays on serum. TNF-alpha mRNA was 1.6-fold higher in unused than in used donors (P:
doi_str_mv 10.1161/circ.102.suppl_3.III-352
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The mechanisms responsible remain unclear. We have studied the cytokines tumor necrosis factor (TNF)-alpha and interleukin-6 (IL-6) in the myocardium and serum from donors with myocardial dysfunction (unused donors) and compared them with donors with good ventricular function (used donors) and patients with advanced heart failure (HF). Clinical details and ventricular function were assessed in 46 donors (31 used, 15 unused). Real-time reverse transcription-polymerase chain reaction, Western blotting, and immunocytochemistry were performed on myocardium and immunoassays on serum. TNF-alpha mRNA was 1.6-fold higher in unused than in used donors (P:<0.005) and 1.74-fold higher than in 36 patients with HF. IL-6 mRNA was 2.4-fold higher in unused than in used donors (P:<0.0001) and 4.67-fold higher than in HF (P:<0.0001). Western blotting showed higher TNF-alpha in unused (218. 3+/-6.4, n=4 versus 187.3+/-5.4, n=3 OD units) than used donors (P:<0.05). TNF-alpha expression was localized to cardiac myocytes. Serum TNF-alpha was higher in unused (8.72+/-1.3 pg/mL, n=13) than in used (6.12+/-0.8 pg/mL, n=25, P:<0.05) donors and HF (4.0+/-0.4 pg/mL, n=17, P:<0.005). Serum TNF-alpha receptors did not differ between unused (4.3+/-0.8 and 8.6+/-1.6 ng/mL, n=10) and used (3. 5+/-0.4 and 6.5+/-1.1 ng/mL, n=24) donors. There was a trend for higher serum IL-6 in unused (16.5+/-2.9 pg/mL, n=9) compared with used (13.9+/-1.6 pg/mL, n=26, P:=NS) donors. This study documented an increase in the expression of TNF-alpha and IL-6 in the myocardium of all donor hearts that was more marked in the dysfunctional (unused) donor hearts. This was accompanied by similar changes in the serum. 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The mechanisms responsible remain unclear. We have studied the cytokines tumor necrosis factor (TNF)-alpha and interleukin-6 (IL-6) in the myocardium and serum from donors with myocardial dysfunction (unused donors) and compared them with donors with good ventricular function (used donors) and patients with advanced heart failure (HF). Clinical details and ventricular function were assessed in 46 donors (31 used, 15 unused). Real-time reverse transcription-polymerase chain reaction, Western blotting, and immunocytochemistry were performed on myocardium and immunoassays on serum. TNF-alpha mRNA was 1.6-fold higher in unused than in used donors (P:<0.005) and 1.74-fold higher than in 36 patients with HF. IL-6 mRNA was 2.4-fold higher in unused than in used donors (P:<0.0001) and 4.67-fold higher than in HF (P:<0.0001). Western blotting showed higher TNF-alpha in unused (218. 3+/-6.4, n=4 versus 187.3+/-5.4, n=3 OD units) than used donors (P:<0.05). 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The mechanisms responsible remain unclear. We have studied the cytokines tumor necrosis factor (TNF)-alpha and interleukin-6 (IL-6) in the myocardium and serum from donors with myocardial dysfunction (unused donors) and compared them with donors with good ventricular function (used donors) and patients with advanced heart failure (HF). Clinical details and ventricular function were assessed in 46 donors (31 used, 15 unused). Real-time reverse transcription-polymerase chain reaction, Western blotting, and immunocytochemistry were performed on myocardium and immunoassays on serum. TNF-alpha mRNA was 1.6-fold higher in unused than in used donors (P:<0.005) and 1.74-fold higher than in 36 patients with HF. IL-6 mRNA was 2.4-fold higher in unused than in used donors (P:<0.0001) and 4.67-fold higher than in HF (P:<0.0001). Western blotting showed higher TNF-alpha in unused (218. 3+/-6.4, n=4 versus 187.3+/-5.4, n=3 OD units) than used donors (P:<0.05). TNF-alpha expression was localized to cardiac myocytes. Serum TNF-alpha was higher in unused (8.72+/-1.3 pg/mL, n=13) than in used (6.12+/-0.8 pg/mL, n=25, P:<0.05) donors and HF (4.0+/-0.4 pg/mL, n=17, P:<0.005). Serum TNF-alpha receptors did not differ between unused (4.3+/-0.8 and 8.6+/-1.6 ng/mL, n=10) and used (3. 5+/-0.4 and 6.5+/-1.1 ng/mL, n=24) donors. There was a trend for higher serum IL-6 in unused (16.5+/-2.9 pg/mL, n=9) compared with used (13.9+/-1.6 pg/mL, n=26, P:=NS) donors. This study documented an increase in the expression of TNF-alpha and IL-6 in the myocardium of all donor hearts that was more marked in the dysfunctional (unused) donor hearts. This was accompanied by similar changes in the serum. This might have important therapeutic implications.]]></abstract><cop>United States</cop><pmid>11082413</pmid><doi>10.1161/circ.102.suppl_3.III-352</doi></addata></record>
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source MEDLINE; American Heart Association Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Journals@Ovid Ovid Autoload
subjects Adult
Biomarkers - blood
Blotting, Western
Female
Heart - physiopathology
Heart Transplantation - standards
Humans
Immunohistochemistry
Interleukin-6 - genetics
Interleukin-6 - metabolism
Male
Middle Aged
Myocardium - metabolism
Reverse Transcriptase Polymerase Chain Reaction
RNA, Messenger - metabolism
Tissue Donors - classification
Tumor Necrosis Factor-alpha - genetics
Tumor Necrosis Factor-alpha - metabolism
Ventricular Dysfunction - blood
Ventricular Dysfunction - diagnosis
title Elevated tumor necrosis factor-alpha and interleukin-6 in myocardium and serum of malfunctioning donor hearts
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