Proinflammatory cytokines depress cardiac efficiency by a nitric oxide-dependent mechanism

factor-a, and interferon-g; Cytomix) depress myocardial con-tractile work partially by stimulating expression of inducible nitric oxide (NO) synthase (iNOS). Because NO and peroxyni-trite inhibit myocardial O2 consumption (MV̇O2), we exam-ined whether this mechanism contributes to reduced cardiac work. In control isolated working rat hearts, cardiac work was stable for 60 min, followed by a decline from 60 to 120 min, without change in MV̇O2. Cardiac efficiency (work/MV̇O2) was therefore reduced from 60 to 120 min. Cytomix shortened the onset (within 20–40 min) and enhanced the depression in cardiac work and efficiency and inhibited MV̇O2 after 80 min. Mercaptoethylguanidine (MEG), an iNOS inhibitor and per-oxynitrite scavenger, or the glucocorticoid dexamethasone (Dex) abolished the effects of Cytomix. iNOS expression was increased 10-fold by Cytomix and abolished by Dex but no