Cardiac ICAM-1 mediates leukocyte-dependent decreased ventricular contractility in endotoxemic mice.

TitleCardiac ICAM-1 mediates leukocyte-dependent decreased ventricular contractility in endotoxemic mice.
Publication TypeJournal Article
Year of Publication2006
AuthorsDavani, EY, Boyd, JH, Dorscheid, DR, Wang, Y, Meredith, A, Chau, E, Singhera, GK, Walley, KR
JournalCardiovasc Res
Date Published2006 Oct 1
KeywordsAnimals, Cyclophosphamide, Extracellular Fluid, Fibrinogen, Gene Expression, Intercellular Adhesion Molecule-1, Leukocyte Count, Leukocytes, Lipopolysaccharides, Mice, Mice, Inbred C57BL, Mice, Knockout, Myocardium, Sepsis, Signal Transduction, Ventricular Dysfunction, Left

OBJECTIVE: Binding of ICAM-1 expressed on cardiomyocytes decreases cardiomyocyte contractility in vitro by altering the intracellular Ca2+ transient. We tested the hypothesis that signaling via ICAM-1 contributes to decreased left ventricular contractility in an in vivo model of systemic inflammation.

METHODS: C57B6 wild-type mice and ICAM-1 knock-out mice were treated with intraperitoneal lipopolysaccharide (LPS) then left ventricular contractility was measured 6 h later using a volume-conductance micromanometer catheter. We repeated this experiment in chimeric mice lacking ICAM-1 expression in bone marrow-derived cells (M-) and/or lacking ICAM-1 expression in the heart and other tissues (H-).

RESULTS: In C57B6 wild-type mice LPS injection significantly increased cardiac ICAM-1 expression and decreased in vivo measures of left ventricular contractility (end-systolic elastance, Ees decreased 58 +/- 4%, p < 0.05, [dP/dtmax]/EDV decreased 60 +/- 6%, p < 0.05). Cyclophosphamide pretreatment to decrease leukocyte count prevented the LPS-induced decrease in contractility. In ICAM-1 knock-out mice LPS did not decrease any measure of contractility. LPS did not decrease left ventricular contractility in M+/H- mice but decreased contractility in M+/H+ and M-/H+ mice to the same extent as in C57B6 wild-type mice implicating the importance of cardiac ICAM-1.

CONCLUSIONS: We conclude that signaling via cardiac ICAM-1 is necessary to mediate leukocyte-dependent decreases of left ventricular contractility in endotoxemic mice.

Alternate JournalCardiovasc. Res.
PubMed ID16934241