Bacterial lipopolysaccharide-stimulated release of tumor necrosis factor-α from the isolated rat heart: The effect of aprotinin and forskolin

William Mckinney, Walter H. Newman, Jerry G. Webb, Manuel R Castresana

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Aprotinin has been reported to reduce plasma levels of inflammatory cytokines associated with cardiopulmonary bypass (CPB). Because CPB is also associated with elevated levels of bacterial lipopolysaccharide (LPS) and LPS stimulates release of inflammatory cytokines from the heart we tested the hypothesis that aprotinin would inhibit cardiac release of tumor necrosis factor-α (TNF) provoked by LPS. Isolated rat hearts were perfused Langendorf style. After 30 minutes of equilibration LPS (100 ng/mL) was infused for 60 minutes. Timed samples of coronary effluent were collected at 0, 30, 60, 90,120, and 150 minutes after the initiation of LPS for the measurement of coronary flow and the determination of TNF and cyclic AMP. Other hearts were perfused with buffer containing aprotinin [137 kallikrein-inhibiting units (KIU)/mL or 250 KIU/mL] and then infused with LPS. An additional group received forskolin (10 μM) and LPS. In hearts perfused as controls with buffer alone no TNF was detected in the coronary effluent. In hearts perfused with LPS TNF was reliably detected in the coronary effluent at 60 minutes (606 ± 450 pg/min) and increased with time to a level of 1792 ± 650 pg/min at 150 minutes. The addition of aprotinin had no significant effect on LPS-stimulated TNF release. For instance in hearts perfused with 137 KIU/mL aprotinin LPS-stimulated release at 150 minutes was 2141 ± 732 pg/min and in hearts perfused with 250 KIU/mL LPS-stimulated TNF release was 2049 ± 789 pg/min. Forskolin administration was associated with release of cyclic AMP from the heart and completely inhibited LPS-stimulated TNF release. We conclude that LPS stimulated release of TNF from the heart. Adding aprotinin to the perfusion buffer in either high or low concentrations did not attenuate LPS-stimulated cytokine release. Elevating myocardial cyclic AMP with forskolin completely attenuated LPS-stimulated TNF release.

Original languageEnglish (US)
Pages (from-to)131-134
Number of pages4
JournalAmerican Surgeon
Volume69
Issue number2
StatePublished - Dec 1 2003
Externally publishedYes

Fingerprint

Aprotinin
Colforsin
Lipopolysaccharides
Tumor Necrosis Factor-alpha
Kallikreins
Cyclic AMP
Buffers
Cytokines
Cardiopulmonary Bypass

ASJC Scopus subject areas

  • Surgery

Cite this

Bacterial lipopolysaccharide-stimulated release of tumor necrosis factor-α from the isolated rat heart : The effect of aprotinin and forskolin. / Mckinney, William; Newman, Walter H.; Webb, Jerry G.; Castresana, Manuel R.

In: American Surgeon, Vol. 69, No. 2, 01.12.2003, p. 131-134.

Research output: Contribution to journalArticle

@article{e2f9c64fb3e646e181ea498f6c1344cb,
title = "Bacterial lipopolysaccharide-stimulated release of tumor necrosis factor-α from the isolated rat heart: The effect of aprotinin and forskolin",
abstract = "Aprotinin has been reported to reduce plasma levels of inflammatory cytokines associated with cardiopulmonary bypass (CPB). Because CPB is also associated with elevated levels of bacterial lipopolysaccharide (LPS) and LPS stimulates release of inflammatory cytokines from the heart we tested the hypothesis that aprotinin would inhibit cardiac release of tumor necrosis factor-α (TNF) provoked by LPS. Isolated rat hearts were perfused Langendorf style. After 30 minutes of equilibration LPS (100 ng/mL) was infused for 60 minutes. Timed samples of coronary effluent were collected at 0, 30, 60, 90,120, and 150 minutes after the initiation of LPS for the measurement of coronary flow and the determination of TNF and cyclic AMP. Other hearts were perfused with buffer containing aprotinin [137 kallikrein-inhibiting units (KIU)/mL or 250 KIU/mL] and then infused with LPS. An additional group received forskolin (10 μM) and LPS. In hearts perfused as controls with buffer alone no TNF was detected in the coronary effluent. In hearts perfused with LPS TNF was reliably detected in the coronary effluent at 60 minutes (606 ± 450 pg/min) and increased with time to a level of 1792 ± 650 pg/min at 150 minutes. The addition of aprotinin had no significant effect on LPS-stimulated TNF release. For instance in hearts perfused with 137 KIU/mL aprotinin LPS-stimulated release at 150 minutes was 2141 ± 732 pg/min and in hearts perfused with 250 KIU/mL LPS-stimulated TNF release was 2049 ± 789 pg/min. Forskolin administration was associated with release of cyclic AMP from the heart and completely inhibited LPS-stimulated TNF release. We conclude that LPS stimulated release of TNF from the heart. Adding aprotinin to the perfusion buffer in either high or low concentrations did not attenuate LPS-stimulated cytokine release. Elevating myocardial cyclic AMP with forskolin completely attenuated LPS-stimulated TNF release.",
author = "William Mckinney and Newman, {Walter H.} and Webb, {Jerry G.} and Castresana, {Manuel R}",
year = "2003",
month = "12",
day = "1",
language = "English (US)",
volume = "69",
pages = "131--134",
journal = "Handbook of Behavioral Neuroscience",
issn = "0003-1348",
publisher = "JAI Press",
number = "2",

}

TY - JOUR

T1 - Bacterial lipopolysaccharide-stimulated release of tumor necrosis factor-α from the isolated rat heart

T2 - The effect of aprotinin and forskolin

AU - Mckinney, William

AU - Newman, Walter H.

AU - Webb, Jerry G.

AU - Castresana, Manuel R

PY - 2003/12/1

Y1 - 2003/12/1

N2 - Aprotinin has been reported to reduce plasma levels of inflammatory cytokines associated with cardiopulmonary bypass (CPB). Because CPB is also associated with elevated levels of bacterial lipopolysaccharide (LPS) and LPS stimulates release of inflammatory cytokines from the heart we tested the hypothesis that aprotinin would inhibit cardiac release of tumor necrosis factor-α (TNF) provoked by LPS. Isolated rat hearts were perfused Langendorf style. After 30 minutes of equilibration LPS (100 ng/mL) was infused for 60 minutes. Timed samples of coronary effluent were collected at 0, 30, 60, 90,120, and 150 minutes after the initiation of LPS for the measurement of coronary flow and the determination of TNF and cyclic AMP. Other hearts were perfused with buffer containing aprotinin [137 kallikrein-inhibiting units (KIU)/mL or 250 KIU/mL] and then infused with LPS. An additional group received forskolin (10 μM) and LPS. In hearts perfused as controls with buffer alone no TNF was detected in the coronary effluent. In hearts perfused with LPS TNF was reliably detected in the coronary effluent at 60 minutes (606 ± 450 pg/min) and increased with time to a level of 1792 ± 650 pg/min at 150 minutes. The addition of aprotinin had no significant effect on LPS-stimulated TNF release. For instance in hearts perfused with 137 KIU/mL aprotinin LPS-stimulated release at 150 minutes was 2141 ± 732 pg/min and in hearts perfused with 250 KIU/mL LPS-stimulated TNF release was 2049 ± 789 pg/min. Forskolin administration was associated with release of cyclic AMP from the heart and completely inhibited LPS-stimulated TNF release. We conclude that LPS stimulated release of TNF from the heart. Adding aprotinin to the perfusion buffer in either high or low concentrations did not attenuate LPS-stimulated cytokine release. Elevating myocardial cyclic AMP with forskolin completely attenuated LPS-stimulated TNF release.

AB - Aprotinin has been reported to reduce plasma levels of inflammatory cytokines associated with cardiopulmonary bypass (CPB). Because CPB is also associated with elevated levels of bacterial lipopolysaccharide (LPS) and LPS stimulates release of inflammatory cytokines from the heart we tested the hypothesis that aprotinin would inhibit cardiac release of tumor necrosis factor-α (TNF) provoked by LPS. Isolated rat hearts were perfused Langendorf style. After 30 minutes of equilibration LPS (100 ng/mL) was infused for 60 minutes. Timed samples of coronary effluent were collected at 0, 30, 60, 90,120, and 150 minutes after the initiation of LPS for the measurement of coronary flow and the determination of TNF and cyclic AMP. Other hearts were perfused with buffer containing aprotinin [137 kallikrein-inhibiting units (KIU)/mL or 250 KIU/mL] and then infused with LPS. An additional group received forskolin (10 μM) and LPS. In hearts perfused as controls with buffer alone no TNF was detected in the coronary effluent. In hearts perfused with LPS TNF was reliably detected in the coronary effluent at 60 minutes (606 ± 450 pg/min) and increased with time to a level of 1792 ± 650 pg/min at 150 minutes. The addition of aprotinin had no significant effect on LPS-stimulated TNF release. For instance in hearts perfused with 137 KIU/mL aprotinin LPS-stimulated release at 150 minutes was 2141 ± 732 pg/min and in hearts perfused with 250 KIU/mL LPS-stimulated TNF release was 2049 ± 789 pg/min. Forskolin administration was associated with release of cyclic AMP from the heart and completely inhibited LPS-stimulated TNF release. We conclude that LPS stimulated release of TNF from the heart. Adding aprotinin to the perfusion buffer in either high or low concentrations did not attenuate LPS-stimulated cytokine release. Elevating myocardial cyclic AMP with forskolin completely attenuated LPS-stimulated TNF release.

UR - http://www.scopus.com/inward/record.url?scp=0037313767&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0037313767&partnerID=8YFLogxK

M3 - Article

C2 - 12641353

AN - SCOPUS:0037313767

VL - 69

SP - 131

EP - 134

JO - Handbook of Behavioral Neuroscience

JF - Handbook of Behavioral Neuroscience

SN - 0003-1348

IS - 2

ER -