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Updated: Jul 20, 2026
An Intact Pericardium Ischemic Rodent Model
Published on: September 2, 2021
Cardiac ICAM-1 mediates leukocyte-dependent decreased ventricular contractility in endotoxemic mice
Ehsan Y Davani1, John H Boyd, Delbert R Dorscheid
1Critical Care Research Laboratories, St. Paul's Hospital, University of British Columbia, 1081 Burrard Street, Vancouver, BC, Canada V6Z 1Y6.
Insights
Systemic inflammation reduces heart contractility by increasing intercellular adhesion molecule-1 (ICAM-1) in cardiac cells. Blocking ICAM-1 in mice prevents this inflammatory effect on left ventricular function.
Area of Science:
- Cardiovascular Physiology
- Immunology
- Molecular Biology
Background:
- Intercellular Adhesion Molecule-1 (ICAM-1) on cardiomyocytes is known to reduce contractility in vitro.
- Systemic inflammation can impact cardiac function, but the specific mechanisms are not fully understood.
Purpose of the Study:
- To investigate the role of ICAM-1 signaling in mediating decreased left ventricular contractility during systemic inflammation in vivo.
- To determine if cardiac ICAM-1 expression is essential for inflammation-induced cardiac dysfunction.
Main Methods:
- Utilized C57B6 wild-type and ICAM-1 knock-out mice treated with lipopolysaccharide (LPS) to induce systemic inflammation.
- Measured left ventricular contractility using a volume-conductance micromanometer catheter.
- Employed chimeric mice with selective ICAM-1 deficiency in bone marrow-derived cells (M-) and/or heart (H-) to pinpoint ICAM-1's cellular source.
Main Results:
- LPS administration significantly increased cardiac ICAM-1 expression and reduced left ventricular contractility in wild-type mice.
- Leukocyte depletion via cyclophosphamide pretreatment abrogated the LPS-induced decline in contractility.
- ICAM-1 knock-out mice and chimeric mice lacking ICAM-1 in bone marrow-derived cells (M+/H-) showed no reduction in contractility after LPS exposure.
- Mice with cardiac ICAM-1 expression (M+/H+ and M-/H+) exhibited significant decreases in contractility, highlighting the role of cardiac ICAM-1.
Conclusions:
- Signaling through cardiac ICAM-1 is a critical mediator of leukocyte-dependent reductions in left ventricular contractility during endotoxemia.
- Targeting cardiac ICAM-1 may offer a therapeutic strategy to preserve cardiac function in inflammatory conditions.
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.
