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Vascular cell adhesion molecule--1 expression is obligatory for endotoxin-induced myocardial neutrophil accumulation and contractile dysfunction. Surgery 2001 Aug;130(2):319-25



Pubmed ID




Scopus ID

2-s2.0-0034902654   36 Citations


BACKGROUND: Sepsis-induced cardiac dysfunction occurs commonly in critically ill patients and is associated with high mortality rates. Neutrophils play a central role in sepsis-induced lung and liver injury; however, the mechanism of sepsis-induced cardiac dysfunction remains unclear. Vascular cell adhesion molecule-1 (VCAM-1) has been implicated in neutrophil-mediated liver injury during endotoxemia and is also expressed in myocardium. The purposes of this study were to examine the temporal relationship of myocardial VCAM-1 expression with neutrophil accumulation during endotoxemia and to determine whether VCAM-1 mediates neutrophil accumulation and cardiac dysfunction during endotoxemia.

METHODS: Mice were subjected to lipopolysaccharide (LPS; 0.5 mg/kg, intraperitoneally). Myocardial VCAM-1 expression and neutrophil accumulation were determined by immunofluorescence staining. Cardiac performance with or without VCAM-1 blocking antibody (5 mg/kg, intravenously) was determined by the Langendorff technique.

RESULTS: LPS caused a time-dependent increase in both myocardial VCAM-1 expression and neutrophil accumulation. At 6 hours after LPS, the immunofluorescent intensity for VCAM-1 increased from 2.5 +/- 0.6 x 10(6) in saline solution controls to 19.9 +/- 3.5 x 10(6) (P <.05, analysis of variance), and neutrophil count increased from 2.4 +/- 1.7/mm(2) in saline solution controls to 13.0 +/- 2.5/mm(2) (P <.05). Left ventricular developed pressure was decreased maximally at 6 hours after LPS compared with saline solution controls (29.1 +/- 1.1 mm Hg vs 53.1 +/- 3.9 mm Hg; P <.05). Treatment with VCAM-1 monoclonal antibody abrogated both myocardial neutrophil accumulation and cardiac dysfunction during endotoxemia.

CONCLUSIONS: LPS-induced myocardial dysfunction is associated with increased expression of VCAM-1 and with neutrophil accumulation. Blockade of VCAM-1 abrogates myocardial neutrophil accumulation and preserves cardiac function during endotoxemia, which supports a role for VCAM-1 as a therapeutic target for myocardial protection during sepsis.

Author List

Raeburn CD, Calkins CM, Zimmerman MA, Song Y, Ao L, Banerjee A, Meng X, Harken AH


Casey Matthew Calkins MD Professor in the Surgery department at Medical College of Wisconsin
Michael A. Zimmerman MD, FACS Professor in the Surgery department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Fluorescent Antibody Technique
Mice, Inbred C57BL
Myocardial Contraction
Vascular Cell Adhesion Molecule-1
Ventricular Function, Left
jenkins-FCD Prod-486 e3098984f26de787f5ecab75090d0a28e7f4f7c0