Background-Exercise training in pulmonary arterial hypertension (PH) is a promising adjunct to medical treatment.However, it is still unclear whether training is beneficial for all PH patients. We hypothesized that right ventricular adaptation plays a pivotal role in the response to training. Methods and Results-Two different dosages of monocrotaline were used in rats to model stable PH with preserved cardiac output and progressive PH developing right heart failure. Two weeks after injection, PH was confirmed by echocardiography, and treadmill training was initiated. Rats were trained for 4 weeks unless manifest right heart failure developed earlier. At the end of the study protocol, all rats were functionally assessed by endurance testing, echocardiography, and invasive pressure measurements. Lungs and hearts were further analyzed in quantitative histomorphologic analyses. In stable PH, exercise training was well tolerated and markedly increased exercise endurance (from 25Ϯ3.9 to 62Ϯ3.9 minutes; PϽ0.001). Moreover, capillary density increased significantly (from 1.21Ϯ0.12 to 1.51Ϯ0.07 capillaries per cardiomyocyte; PϽ0.05). However, in progressive PH, exercise training worsened survival (hazard ratio, 2.7; 95% confidence interval, 1.1 to 14.2) and increased pulmonary vascular remodeling. In addition, training induced widespread leukocyte infiltration into the right ventricle (from 135Ϯ14 to 276Ϯ18 leukocytes per 1 mm 2 ; PϽ0.001). Conclusions-In our rat model, exercise training was found to be beneficial in stable PH but detrimental in progressive PH. Future studies are necessary to address the clinical implications of our findings. Key Words: capillaries Ⅲ exercise Ⅲ hypertension, pulmonary Ⅲ inflammation Ⅲ pulmonary heart disease P ulmonary arterial hypertension (PH) is characterized by progressive pulmonary vascular remodeling, which importantly increases right ventricular (RV) afterload, eventually leading to right heart failure and premature death. 1 Traditionally, PH patients were advised to limit physical activity because of risk of fatal cardiovascular compromise. 2 Clinical Perspective on p 49Recent developments, however, have challenged this view. 3 First, the prognosis of PH patients improved with the introduction of various potent PH-specific medications in the last decades. 4 Second, several studies have demonstrated beneficial effects of training in patients with chronic obstructive pulmonary disease and with congestive heart failure, and training was beneficial even for the most severely affected patients (GOLD IV, New York Heart Association class IV) often suffering from secondary PH. 5,6 Finally, in a recent clinical trial of 30 stable PH patients under optimized medical treatment, Mereles et al 7 reported marked improvement in exercise capacity and quality of life after exercise training.Although training might be a promising adjunct to medical treatment in PH, it remains to be elucidated whether exercise training is beneficial for all PH patients and what its effect is on RV function and remo...

In patients with idiopathic pulmonary arterial hypertension (iPAH), iron deficiency is common and has been associated with reduced exercise capacity and worse survival. Previous studies have shown beneficial effects of intravenous iron administration. In this study, we investigated the use of intravenous iron therapy in iron-deficient iPAH patients in terms of safety and effects on exercise capacity, and we studied whether altered exercise capacity resulted from changes in right ventricular (RV) function and skeletal muscle oxygen handling. Fifteen patients with iPAH and iron deficiency were included. Patients underwent a 6-minute walk test, cardiopulmonary exercise tests, cardiac magnetic resonance imaging, and a quadriceps muscle biopsy and completed a quality-of-life questionnaire before and 12 weeks after receiving a high dose of intravenous iron. The primary end point, 6-minute walk distance, was not significantly changed after 12 weeks (409 ± 110 m before vs. 428 ± 94 m after; P = 0.07). Secondary end points showed that intravenous iron administration was well tolerated and increased body iron stores in all patients. In addition, exercise endurance time (P < 0.001) and aerobic capacity (P < 0.001) increased significantly after iron therapy. This coincided with improved oxygen handling in quadriceps muscle cells, although cardiac function at rest and maximal V : O 2 were unchanged. Furthermore, iron treatment was associated with improved quality of life (P < 0.05). In conclusion, intravenous iron therapy in iron-deficient iPAH patients improves exercise endurance capacity. This could not be explained by improved RV function; however, increased quadriceps muscle oxygen handling may play a role. (Trial registration: ClinicalTrials.gov identifier NCT01288651)

Nebivolol could be a promising option for the management of PAH, improving endothelial dysfunction, pulmonary vascular remodeling, and right heart function. Until clinical studies are undertaken, however, routine use of β-blockers in PAH cannot be recommended.

The SU5416 combined with hypoxia (SuHx) rat model features angio-obliterative pulmonary hypertension resembling human pulmonary arterial hypertension. Despite increasing use of this model, a comprehensive haemodynamic characterisation in conscious rats has not been reported.We used telemetry to characterise haemodynamic responses in SuHx rats and associated these with serial histology.Right ventricular systolic pressure (RVSP) increased to a mean¡SD of 106¡7 mmHg in response to SuHx and decreased but remained elevated at 72¡8 mmHg upon return to normoxia. Hypoxia-only exposed rats showed a similar initial increase in RVSP, a lower maximum RVSP and near-normalisation of RVSP during subsequent normoxia. Progressive vascular remodelling consisted of a four-fold increase in intima thickness, while only minimal changes in media thickness were found. The circadian range in RVSP provided an accurate longitudinal estimate of vascular remodelling.In conclusion, in SuHx rats, re-exposure to normoxia leads to a partial decrease in pulmonary artery pressure, with persisting hypertension and pulmonary vascular remodelling characterised by progressive intima obstruction. @ERSpublications Telemetry studies can facilitate preclinical studies to further improve our understanding of drug actions in PAH