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Am J Physiol Heart Circ Physiol 277: H253-H260, 1999;
0363-6135/99 $5.00
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Vol. 277, Issue 1, H253-H260, July 1999

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

Matthew G. Simms and Keith R. Walley

University of British Columbia Pulmonary Research Laboratory, St. Paul's Hospital, Vancouver, British Columbia, Canada V6Z 1Y6

Macrophages are found in the heart as part of the inflammatory response. To determine whether macrophages could contribute to myocardial dysfunction, rat ventricular myocytes were isolated and cocultured with elicited peritoneal macrophages in media containing tumor necrosis factor-alpha (TNF-alpha ), interleukin (IL)-1beta , or endotoxin for 4 h. Cardiac myocytes were electrically stimulated, and fractional shortening was determined using videomicroscopy. When myocytes alone or myocytes in coculture with macrophages separated by a membrane were challenged with TNF-alpha , lipopolysaccharide, or IL-1, fractional shortening did not decrease. When macrophages were allowed to contact myocytes, fractional shortening decreased from 20.1 ± 0.9% in unchallenged macrophage-myocyte cocultures to 15.5 ± 0.9, 16.3 ± 0.8, and 15.8 ± 0.6% when challenged for 4 h with TNF-alpha , endotoxin, or IL-1beta , respectively (P < 0.05). Myocytes had a mean adherence of 4.2 ± 0.2 macrophages after TNF-alpha challenge compared with 2.6 ± 0.3 for controls (P < 0.05). The number of adherent macrophages was associated with the decrease in fractional shortening. Anti-intercellular adhesion molecule-1 (ICAM-1) reduced macrophage adherence and prevented the decrease in fractional shortening. This decrease was also prevented by desferoxamine, superoxide dismutase, and nitro-L-arginine methyl ester. This suggests that activated macrophages adhere to myocytes via ICAM-1, and adherent macrophages decrease their contractile function via TNF-alpha , oxygen free radicals, and nitric oxide.

ischemia-reperfusion; sepsis; tumor necrosis factor-alpha ; intercellular adhesion molecule-1


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