Effects of prostaglandin E1 and other vasodilator agents in pulmonary hypertension of scleroderma.

Sir, Guadagni et al. have recently reported the haemodynamic effects of prostacyclin in pulmonary hypertension. We report here the effects of prostaglandin Ei (PGEi) in the treatment of pulmonary hypertension in a patient with scleroderma.. A 25 year old woman with scleroderma was admitted to hospital in February 1980 for assessment of pulmonary hypertension. An open lung biopsy in January 1979 showed distinct changes in the small to medium sized muscular pulmonary arteries, with intimal fibrosis and medial hypertrophy. Neither plexiform lesions nor parenchymal fibrosis was found. In May 1979, the pulmonary arterial pressure was raised at 80/35 mmHg (mean 54 mmHg) and the pulmonary arteriolar resistance was 650 dynes s cm-5. An intravenous infusion ofnitroprusside at a dose of 6 ,ug/kg per min lowered pulmonary arterial pressure by 26% and pulmonary arteriolar resistance by 500/%. Phentolamine, 5 mg intravenously, produced a 20% reduction in pulmonary arterial pressure and 13% reduction in pulmonary arteriolar resistance. The patient was placed on oral phentolamine 250 mg daily in divided doses but developed progressive dyspnoea. On examination, the chest was normal. The jugular venous pressure was raised and a left parasternal heave was present. Skin over the fingers and toes was tight and bound down and multiple digital ulcerations were present. Telangiectasia were present on the face. Antinuclear factor was positive to a titre of 1/200. Right heart catheterisation was performed with a Swan-Ganz catheter. Cardiac output was assessed with the thermodilution technique using a bedside cardiac output computer (Edwards Laboratories). Diazoxide was given by bolus injection through the right atrial port. PGEi (Upjohn Company of Canada) was infused through the right atrial port for 10 minutes out of each hour for a total of 49 infusions. The initial dose was 1 ng/kg per min for 10 minutes increasing to a maximum tolerated level of 32 ng/kg per min for 10 minutes. The haemodynamic effects of PGEi were assessed just before the final infusion of 32 ng/kg per min and immediately after completion of this infusion. Between treatment with diazoxide and PGE1, haemodynamic measurements were allowed to return to baseline values. The right atrial pressure was 14 mmHg. Pulmonary arterial pressure was 75/34 mmHg (mean 51 mmHg), cardiac index 2-33 1/min per m2, and stroke index 23 ml/beat per M2. The catheter tip could not be made to flow into the wedged position and thus the total pulmonary resistance index was calculated instead of pulmonary arteriolar resistance. Diazoxide produced an increase in pulmonary arterial pressure to 85/39 mmHg (mean 60 mmHg) but a 24% decrease in systemic vascular resistance. PGE1 did not affect pulmonary arterial pressure, but just before the last infusion there had been a 23% increase in total pulmonary resistance index from 1751 dynes s cm-5 m-2 to 2153 dynes s cm-5 m-2 and a fall in stroke index of 22%. The failure of intravenous diazoxide to reduce pulmonary arterial pressure suggests progression to fixed pulmonary hypertension and may explain the lack of response to PGEi. This differs from the previous reports suggesting that prostaglandins may ameliorate haemodynamic measurements in pulmonary hypertension.1-4 On the other hand, studies in normal humans have also been variable, with PGE1 producing either a slight rise5 or fall6 in pulmonary arterial pressure or resistance. These results suggest that the effect of PGE1 on the pulmonary circulation in man remains to be clarified. M Baron, G Skrinskas, R Hyland, M B Urowitz, Rheumatic Disease Unit and the Department of Medicine, The Wellesley Hospital, University of Toronto, Toronto, Ontario, Canada.