TUMOR-NECROSIS-FACTOR-ALPHA, BUT NOT SEPTIC PLASMA DEPRESSES CARDIAC MYOFILAMENT CONTRACTION

Purpose: In sepsis, myocardial depression may be caused by mediators r eleased as part of the inflammatory reaction. Tumour necrosis factor a lpha (TNF-alpha) is one mediator that may contribute to this depressio n. In the present study we contrasted the effects of TNF-alpha and sep tic plasma fraction (SP) obtained from an E. coli model on contractile tension in intact and skinned canine ventricular trabecular (VT) prep arations. The objectives were to determine whether SP or TNF-alpha cou ld impair contractile tension at the level of the myofilaments, and to determine the extent to which TNF-alpha may account for myocardial de pression found in E. coli sepsis. Methods: Measurements of isometric t ensions were made after TNF-alpha and SP (10,000 to 30,000 MW fraction ) were added to respective intact or skinned canine VT preparations. I n the skinned preparation, trabeculae were chemically skinned with Tri ton X-100. Results: Septic plasma caused a decrease in contraction in the intact preparation compared with preseptic plasma(50 +/- 7 vs 33 /- 7%, P < 0.05), but had no effect in the skinned preparation. On the other hand, TNF-alpha (30 ng . ml(-1)) caused an approximately 50% re duction in tension (29 +/- 2 mg vs 16 +/-: 5 mg) in the skinned prepar ation (P < 0.05), but had no effect in the intact preparation. Conclus ion: These results suggest that TNF-alpha and SP act through different mechanisms. While SP requires an intact membrane, TNF-alpha impairs f unction by a direct effect on the myofilaments.