Cytokines are not a requisite part of the pathophysiology leading to cardiac decompensation

An increase in circulating levels of proinflammatory cytokines has been pro posed as an important pathogenic factor contributing to cardiac injury duri ng chronic heart failure. To determine whether plasma levels of the cytokin es tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) increas e during pacing-induced heart failure, we paced the hearts of seven dogs at 210 beats/min for 3 weeks and at 240 beats/min for an additional week to i nduce severe clinical signs of cardiac decompensation. Hemodynamic measurem ents and blood samples from the aorta and coronary sinus (CS) were taken at control, at 3 weeks, and in end-stage failure. Decompensated heart failure occurred at 29 +/- 1.8 days, when left ventricular (LV) end-diastolic pres sure was 25 +/- 1.3 mmHg, LV systolic pressure was 92 +/- 4 mmHg, mean arte rial pressure was 77 +/- 3 mmHg, and dP/dt(max) was 1219 +/- 73 (all P < 0. 05 vs control). Arterial concentration of IL-6 was 12 +/- 4.0 U/ml at contr ol, 11 +/- 2.7 U/ml at 3 weeks, and 10 +/- 1.7 U/ml in end-stage failure (N S). At the same time points, IL-6 in CS plasma was 12 +/- 3.5, 13 +/- 2.8 a nd 11 +/- 2.4 U/ml, respectively (NS vs control and vs arterial concentrati ons). TNF-alpha did not reach detectable concentrations in arterial or CS b lood at any time. TNF-alpha and IL-6 concentrations did not increase in art erial blood, were not released in the CS from the heart during the developm ent of pacing-induced heart failure, and can not universally be implicated in the pathogenesis of ail forms of cardiac dysfunction. Our findings are c onsistent with other data from patients In which severe heart failure was n ot associated with Increased levels of circulating cytokines.