Pentoxifylline Decreases Pro‐Inflammatory Cytokines in Prolonged Heart Failure‐Induced Lung Injury

Understanding the mechanisms by which heart failure leads to fibrosis may suggest unique therapies to prevent this complication. We developed a rat model of increased left atrial pressure (LAP). In previous experiments we showed that elevated LAP leads to lung edema and fibrosis development, resulting in pulmonary dysfunction with decreased dynamic lung compliance. Furthermore, a significant increase in pro‐inflammatory cytokines, mainly TNF‐α was recorded at 4 and 7 days in BAL fluid in rats with elevated LAP. We investigated the down‐regulation of fibrosis development using pharmacologic interventions in vivo. Under isoflurane, a catheter was introduced into the left ventricle to record left ventricular end diastole pressure. A wire was introduced through the left ventricle to restrict left ventricular filling during cardiac diastole, causing an increase in LAP about 15–20 mm Hg. Group 1 received pentoxyfilline (PTX) in a dose of 1mg/kg/hr for 7 days, infused through an osmotic minipump whereas group 2 received saline. At day 7, rats were euthanized and lungs harvested. Our data show that in rats treated with PTX, lung fluid decreased significantly by 35% compared to non‐treated rats with elevated LAP. Our results suggest that PTX inhibits increases in TNF‐α by 80%, IL‐6 by 96% and IL‐8 by 85%. Our data indicate that PTX is a potent inhibitor of cytokines‐induced pulmonary injury in prolonged heart failure in rats.