During acute drug testing, aerosolized iloprost was more potent than inhaled NO as a pulmonary vasodilator in PPH at the doses used in this study.

Anxiety and depression are frequent in patients with PH and increase as the severity of disease progresses. Given the fact that safe and efficacious treatments of mental disorders are available, greater importance should be attached to the diagnosis and treatment of these conditions in patients with PH.

We conclude that the pathological rise of PASP in asymptomatic family members is linked to chromosome 2q31-32 and is probably an early sign of PPH. Therefore, stress Doppler echocardiography may be a useful tool to identify persons at risk for PPH even before pulmonary artery pressures at rest are elevated.

In patients with CHF, inspiratory muscle strength is reduced and emerges as a novel, independent predictor of prognosis. Because testing for Pi(max) is simple in clinical practice, it might serve as an additional factor to improve risk stratification and patient selection for cardiac transplantation.

The quantification of adenine nucleotides released from the heart is hampered by their rapid dephosphorylation to adenosine in the extracellular space catalyzed by highly active ectonucleotidases. To determine the total release of adenine nucleotides from isolated Langendorffperfused guinea pig hearts, ecto 5'-nucleotidase was effectively blocked by infusion of a4.-methylene-ADP (AOPCP, 50 ,M). Adenine nucleotides were measured in the coronary venous effluent by the luciferin-luciferase method after enzymatic rephosphorylation to ATP. In hearts perfused at a constant flow rate (10 ml/min) with normoxic buffer (95% 02,5% C02) the release+SEM of adenine nucleotides and adenosine was 0.06±0.01 (n=11) and 0.04+±0.01 (n=13) nmol/min. In the presence of AOPCP, the release of adenine nucleotides increased to 0.43 +0.04 nmol/min (n=9; p<0.05), whereas adenosine remained unchanged. Hypoxic perfusion (10% 02, 85% N2, 5% C02) caused a threefold increase in adenine nucleotide release but a 40-fold increase in adenosine. In contrast, global ischemia (30 seconds) caused adenine nucleotide and adenosine release to rise to similar values of 1.06±0.10 and 0.80+0.14 nmol/min (n=9). Stimulation of hearts with isoproterenol (4 nM) likewise increased the release of adenine nucleotides (0.50±0.04 nmol/min) and adenosine (0.87±0.21 nmol/min) (n=6). To determine the cellular source of adenine nucleotides released from the heart, the coronary endothelial adenine nucleotide pool was selectively prelabeled by [3H]adenosine. Global ischemia increased the specific radioactivity of released adenine nucleotides by 57%. The findings indicate that 1) adenine nucleotides and adenosine are released at the same order of magnitude from the well-oxygenated heart; 2) P-adrenergic stimulation and ischemia stimulate the release of adenine nucleotides and adenosine, both purines reaching vasoactive concentrations in the effluent perfusate; 3) during hypoxic perfusion only the release of adenosine is greatly enhanced; and 4) the coronary endothelium preferentially contributes to the ischemiainduced adenine nucleotide release. (Circulation Research 1991;68:797-806) In hearts adenosine is generally assumed to be formed intracellularly by dephosphorylation of adenine nucleotides' and by hydrolysis of S-adenosyl-L-homocysteine.2 Adenosine production is accelerated when the breakdown of energy-rich adenine nucleotides is increased, for example, by an imbalance in the myocardial supply-to-demand ratio for oxygen.34 After being formed, adenosine is thought to reach the extracellular space by facilitated diffusion5 to finally cause the adaptive changes in coronary blood flow.

Background: As there is controversy about changes in lung function in primary pulmonary hypertension (PPH), lung mechanics were assessed with a focus on expiratory airflow in relation to pulmonary haemodynamics. Methods: A cross sectional study was performed in 64 controls and 171 patients with PPH (117 women) of mean (SD) age 45 (13) years, pulmonary artery pressure (PAPmean) 57 (15) mm Hg, and pulmonary vascular resistance 1371 (644) dyne.s/cm

No abstract

Dyspnea and exercise limitation are common in patients with idiopathic pulmonary arterial hypertension (IPAH). Recently, a reduction in inspiratory and expiratory muscle strength has been observed in IPAH. However, it has not been investigated whether this respiratory muscle weakness might be part of a general muscle dysfunction as observed in congestive left heart failure. Therefore, in 24 consecutive IPAH patients (16 female; age 58.7+/-16.2; WHO class II-III; systolic pulmonary artery pressure during echocardiography at rest (sPAP) 65.0+/-20.6 mmHg, and 6-min-walk test (6-MWT) 473.6+/-127.7 m), the maximal isometric forearm muscle strength (best of three hand grip manoeuvres), maximal inspiratory and expiratory mouth occlusion pressures (Pimax, Pemax) were prospectively evaluated. The isometric forearm muscle strength was significantly lower in IPAH patients (281.7+/-102.6N) than in matched 24 healthy controls (397.1+/-116.8 N; p=0.03). In IPAH patients, there was a correlation between maximal isometric forearm muscle strength and 6-MWT (r=0.67; p=0.0007) and both, Pimax (r=0.69; p=0.0003) and Pemax (r=0.63; p=0.01), respectively. There was no correlation between forearm muscle strength and sPAP (r=0.30; p=0.16). The present skeletal muscle dysfunction is a novel finding in patients with IPAH. The correlation with respiratory muscle dysfunction and severity of disease might indicate a generalised "myopathy" in IPAH.