As compared with conventional therapy, the continuous intravenous infusion of epoprostenol produced symptomatic and hemodynamic improvement, as well as improved survival in patients with severe primary pulmonary hypertension.

In 120 patients with severe emphysema evaluated for participation in the National Emphysema Treatment Trial, pulmonary hemodynamics and ventricular function were assessed. Pulmonary function tests were (%predicted): FEV(1) = 27%; residual volume = 224.6%; diffusion capacity = 26.7%. In 90.8% of patients, end-expiratory pulmonary artery mean pressure was > 20 mm Hg; in 61.4%, end-expiratory wedge pressure was > 12 mm Hg. Cardiac index was normal. Mean pulmonary artery pressure correlated inversely with arterial PO(2), and severity of emphysema, and directly with wedge pressure. Multiple stepwise regression revealed that arterial PO(2) was not an independent predictor of mean pulmonary artery pressure. No correlation was found between indices of emphysema severity and PA pressures. Diastolic ventricular pressures were increased without evidence of systolic dysfunction. We conclude that (1) elevations of pulmonary vascular pressures are common, (2) pulmonary hypertension may be related to factors other than hypoxia, (3) pulmonary hypertension does not impair resting systemic O(2) delivery, and (4) elevated cardiac diastolic pressures do not represent systolic dysfunction.

The echocardiographic manifestations of severe primary pulmonary hypertension reflect abnormalities in hemodynamics and exercise capacity. Prostacyclin has beneficial effects on right heart structure and function that may contribute to the clinical improvement and prolonged survival observed with this drug.

Previously, we reported that In the Isolated perfused rabbit lung, red blood cells (RBCs) obtained from either rabbits or healthy humans were a required component of the perfusate to unmask evidence of nitric oxide (NO) participation in regulation of the pulmonary circulation. In addition, we found that mechanical deformation of rabbit and healthy human RBCs released ATP, a known agonist for enhanced NO synthesis. In contrast, RBCs obtained from patients with cystic fibrosis (CF) did not release ATP In response to mechanical deformation. The coexistence of airway disease and alveolar hypoxia In patients with CF precluded the drawing of conclusions relating a defect In RBC ATP release with the pulmonary hypertension associated with CF. Airway disease and alveolar hypoxia are not, however, features of primary pulmonary hypertension (PPH), a human condition of unknown etiology. We postulated that a defect In NO generation might contribute to the Increased pulmonary vascular resistance In PPH, and as a first step, we hypothesized that RBCs obtained from patients with PPH would not release ATP. In contrast to RBCs of healthy humans, when RBCs of PPH patients were passed through filters (average pore size 12, 8, or 5 101m), ATP was not released and the RBCs exhibited reduced deformabllity. Moreover, when incubated with the active cAMP analogue, Sp-cAMP (100 101M), an activator of the CF transmembrane conductance regulator, ATP was not released. These results demonstrate that RBCs obtained from patients with PPH fail to release ATP whether the stimulus Is mechanical or pharmacological. Thus, failure of RBCs to release ATP in patients with PPH might be a major pathogenetic factor that accounts for the heretofore unknown etiology of their pUlmonary hypertension.

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Improved ventilation and exercise capacity follows thoracoscopic lung volume reduction surgery (TLVRS) in patients with severe emphysema. This improvement could be related to changes in inspiratory and expiratory flows following surgery, with consequent improvement in dyspnea indices. Changes in inspiratory/expiratory flows at rest and exercise and their relation to subjective improvement in dyspnea after TLVRS are not well known. We studied 25 patients with severe emphysema who underwent unilateral TLVRS performed in well-defined zones with decreased perfusion in nuclear medicine lung scans. Early follow-up after surgery (4.2 +/- 0.8 mo) showed significant improvements in exercise tolerance: The distance covered over a 6 min walk test increased from 934 +/- 297 to 1,071 +/- 241 ft (p = 0.01). Exercise tolerance using a bicycle ergometer showed increased exercise endurance from 4.43 +/- 1.7 to 5.71 +/- 1.8 min (p < 0.001). The maximum workload tolerated increased from 37 +/- 19 to 52 +/- 21 W (p < 0.01) and VO2 max changed from 9.7 +/- 2 to 11.8 +/- 3 (ml.kg)/min (p < 0.01). This increment was achieved by generating significantly larger minute ventilation (VE), from 24 +/- 11 to 29 +/- 10 L/min, reached through larger tidal volumes (increasing from 951 +/- 330 to 1,145 +/- 367 ml), while maintaining the same maximum respiratory rates. Increased VE was also accompanied by significant increases in both average inspiratory and expiratory flows measured during exercise: from 0.89 +/- 0.41 L/s to 1.06 +/- 0.08 L/s, and from 0.77 +/- 0.37 to 0.90 +/- 0.32 L/s respectively (p < 0.01). The parallel increment in flows resulted in constant T1/Ttot relationship. These functional changes correlated with increased inspiratory flows at rest measured with pulmonary function tests (forced inspiratory volume in one s [FIV1], expiratory flows [FVC, FEV1], and increased maximum voluntary ventilation [MVV]) following the surgically induced reduction in residual volume (RV). These objective changes occurred parallel to improved dyspnea indices. The Baseline Focal Score was 3.36 +/- 1.47 and the Transition Focal Score was 6.12 +/- 0.7. The objectively measured variables at rest that best correlated with subjective improvement in dyspnea were the change in MVV, change in resting arterial PaO2, and change in FEV1 following TLVRS. Exercise variables did not have significant correlation with subjective markers indicating improvement in dyspnea, with the exception of the change in Dyspneic Index [(VE/MVV)100] at maximum exercise.