ABSTRACT
Systemic sclerosis [scleroderma] is a chronic debilitating disease that is caused by the occurrence of fibrotic changes and vascular abnormalities at various levels such as: Skin, lungs, kidneys or heart. Lung involvement in scleroderma is one of the leading causes of mortality in this disease. Sildenafil inhibits phosphodiesterase type 5, an enzyme that metabolizes cyclic guanosine monophosphate, thereby enhancing the cyclic guanosine monophosphate-mediated relaxation and growth inhibition of vascular smooth-muscle cells, including those in the lung. We hypothesized that chronic oral administration of the phosphodiesterase-5 inhibitor sildenafil could improve the pulmonary haemodynamics in Systemic sclerosis [Ssc] patients. To investigate the use of sildenafil, detect the effect of sildenafil on the left ventricular function and the pulmonary blood flow echocardiographic parameters and pulmonary functions in a series of SSc patients. Twenty three systemic sclerosis cases were selected for the study. All patients were subjected to clinical evaluation, laboratory investigations, plain chest X-ray, ECG, basal pulmonary function tests and basal echocardiographic assessment. One week of therapy with oral sildenafil 75mg/day in three divided doses was given to the patients, after which they were subjected to a second assessment of respiratory function tests and echocardiography. Sildenafil therapy resulted in the following changes: Mitral E/A was significantly increased [p<0.05]. This was further supported by a significant drop of the pre-ejection period [p<0.001] after using sildenafil. There was a significant rise in acceleration time and the ratio between it and ejection time in both aortic and pulmonary Doppler. Also there was a significant decrease in pulmonary artery diameter [p<0.001], maximal pulmonary flow velocity [p<0.001], pulmonary integral area under the curve [p<0.001] and mean acceleration [p=0.007]. Some ventricular contractility indices as the posterior wall excursion [p=0.001], inter-ventricular septal excursion [p=0.043], velocity of posterior wall excursion [p<0.001], velocity of interventricular septal excursion [p<0.001] showed statistically significant increase. The left ventricular internal dimensions and volume in diastole showed a significant drop [p=0.001, p=0.002 respectively], there was a significant increase in the interventricular septum thickness in systole and diastole [p<0.05] with a borderline significant increase in posterior wall thickness in systole [p=0.05]. Spirometric studies showed a statistically significant increase in FEV[25-75] after the use of sildenafil, [p<0.05] which denotes improvement of airway obstruction. Sildenafil improved left ventricular systolic and diastolic functions and may improve pulmonary blood flow in patients with systemic sclerosis. PDE-5 inhibitors are efficacious in scleroderma-associated pulmonary hypertension