Cardiac dysfunction caused by factors released from endotoxin-activated macrophages.
This study was designed to evaluate the role of macrophages in cardiac dysfunction associated with endotoxemia or septic shock. Rat peritoneal macrophages were cultured on glass bead-carrier and placed in the perfusate stream of an isolated rat heart perfused according to the Langendorff technique. The heart was thus perfused with a Krebs solution exposed to macrophages stimulated with endotoxin. After 10-15 min of exposure, the macrophages released substance(s) that decreased left ventricular pressure (VP) 50-80% and coronary flow (CF) without significantly affecting heart rate or the ECG. In a separate study, macrophages were incubated with endotoxin and the incubate injected into the heart; a 20-30% reduction in VP and CF was observed. However, when macrophages were further stimulated with opsonized zymosan, 60-80% reductions in VP and CF were observed. Treatment with prostaglandin antagonists, leukotriene inhibitors, or trypsin did not significantly modify the activity of the material released from macrophages. Free radical scavengers (catalase and superoxide dismutase) reduced the activity of macrophage derived product by 15-20%. However, platelet-activating factor (PAF) antagonist prevented the action of macrophage mediators on the heart by approximately 58%. Heat inactivation destroyed activity released from the macrophages almost entirely. These findings may contribute to a better understanding of endotoxemia and endotoxin shock mechanisms.
Salari
H
H
Department of Medicine, University of British Columbia, Vancouver, Canada.
Walker
M J
MJ
D000818:Animals; D004731:Endotoxins / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects*; D066298:In Vitro Techniques; D008262:Macrophage Activation / Q000187:drug effects*; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D012772:Shock, Septic / Q000276:immunology* / Q000503:physiopathology; D013997:Time Factors
D004731:Endotoxins