Abstract

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/dt_max]/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.