Activated macrophages decrease rat cardiac myocyte contractility : importance of ICAM-1 dependent adhesion

Macrophages are found in the heart as part of the inflammatory response. Our goal was to determine whether macrophages could contribute to myocardial dysfunction. Rat ventricular myocytes were isolated using a collagenase perfusion system and cultured for 24 hours. Then myocytes were co-cultured with elicited peritoneal macrophages in media alone or in media containing TNFα IL-1β or endotoxin for 4 hours. Myocytes were electrically stimulated and fractional shortening was determined using videomicroscopy. When myocytes alone were challenged with TNFα, or LPS, fractional shortening did not decrease. When macrophages were prevented from adhering to myocytes by well inserts, TNFα and LPS did not have an effect. Fractional shortening of myocytes decreased from 20.3 ± 1.1% in unchallenged macrophage-myocyte co-cultures, without inserts, to 15.3 ± 1.1% and 15.1 ±1.8% when challenged for 4 hours with TNFα or endotoxin respectively (p<0.05). After 4 hours, the challenged myocytes had a mean adherence of 4.2 ± 0.2 macrophages compared to 2.6 ± 0.3 for controls (p