Role of prostacyclin in pulmonary hypertension

Date of Acceptance: 11/12/2014 This is an open access article distributed under the terms of the Creative Commons Attribution license CC BY-4.0, which permits unrestricted use, distribution and reproduction in any medium, provided the original work is properly cited.Prostacyclin is a powerful cardioprotective hormone released by the endothelium of all blood vessels. Prostacyclin exists in equilibrium with other vasoactive hormones and a disturbance in the balance of these factors leads to cardiovascular disease including pulmonary arterial hypertension. Since it’s discovery in the 1980s concerted efforts have been made to make the best therapeutic utility of prostacyclin, particularly in the treatment of pulmonary arterial hypertension. This has centred on working out the detailed pharmacology of prostacyclin and then synthesising new molecules based on its structure that are more stable or more easily tolerated. In addition, newer molecules have been developed that are not analogues of prostacyclin but that target the receptors that prostacyclin activates. Prostacyclin and related drugs have without doubt revolutionised the treatment and management of pulmonary arterial hypertension but are seriously limited by side effects within the systemic circulation. With the dawn of nanomedicine and targeted drug or stem cell delivery systems it will, in the very near future, be possible to make new formulations of prostacyclin that can evade the systemic circulation allowing for safe delivery to the pulmonary vessels. In this way, the full therapeutic potential of prostacyclin can be realised opening the possibility that pulmonary arterial hypertension will become, if not curable, a chronic manageable disease that is no longer fatal. This review discusses these and other issues relating to prostacyclin and its use in pulmonary arterial hypertensionPeer reviewedFinal Published versio

Clinical cardiac electrophysiologic evaluation of the positive inotropic agent, DPI 201-106

DPI 201-106 is a new positive inotropic agent. The cardiac electrophysiology of 16 patients was studied before and during DPI 201-106 administration (loading dose of intravenous DPI 201-106, 1·8 mg kg−1 h−1 administered over 10 min, followed by a maintenance dose of 0·2 mg kg−1 h−1). DPI 201-106 had no effect on the sinus node. The AH interval during fixed-rate atrial pacing became prolonged during DPI 201-106 infusion. There was a significant prolongation of the QT interval [QT (corrected), 417 ± 22 to 502 ± 35 ms, P<0·05; QT (atrial pacing at 600 ms), 374 ±17 to 419 ± 23 ms, P<0·05; QT (ventricular pacing at 600 ms), 409 ± 37 to 449 ± 30 ms, P<0·05]. The ventricular effective refractory period significantly prolonged during DPI 201-106 administration (242 ± 21 to 287 ± 56 ms, P < 0·05), but the supernormal-period duration decreased. The atrial effective refractory period was shortened in four patients and prolonged in one (261 ± 67 to 240 ± 53 ms, NS). The corrected atrial repolarization time (PTac) shortened significantly during DPI 210-106 infusion (479 ± 26 to 445 ± 22 ms at 20 min of the maintenance dose, P<0·05). Atrial fibrillation was initiated in five patients during DPI infusion, but no ventricular arrhythmia was provoked. These findings suggest that DPI 201-106 has novel differential electrophysiological effects on atria and ventricle

HEDONIC AND EUDAIMONIC VALUES IN SPORT PARTICIPATION OF THE YOUTH

Straipsnyje pristatomas tyrimas, kurio tikslas – pristatyti sporte dalyvaujančio jaunimo hedonines ir eudemonines vertybių preferencijas. Tyrime dalyvavo 345 mokiniai, kurių amžius: 16-18 metų. Anketą sudarė S. H. Schwartz vertybių klausimynas, klausimai apie sociodemografines charakteristikas, informacija apie aktyvumą sporte ir lūkesčius sportinės karjeros atžvilgiu. Rezultatai atskeidė, kad eudemoninės vertybės yra labiau išreikštos merginų tarpe nei vaikinų. Antra, sportinėje veikloje dalyvaujančiųjų vertybės yra išreikštos labiau nei tarp sportinėje veikloje nedalyvaujančių. Be to, dalyvavimas sportinėje veikloje siejamas tiek su eudemoninėmis, tiek su hedoninėmis vertybėmis. Galiausiai, jaunimo sportinės karjeros lūkesčiai yra susiję su asmeniniu augimu ir vystymusi (eudemoninis požiūris), taip pat pasiekimais ir pripažinimu (hedoninis požiūris).The aim of this study is to present the hedonic and eudaimonic value preferences for the youth Lithuanian participants and non-participants in sport. Participants of this study were 345 school children, 16–18 years of age. Self-report questionnaire consisted of S. H. Schwartz’s Value Survey, questions about socio-demographic characteristics, information about activity in sports and questions about expectations of the career in sport. The results revealed that eudaimonic values are more expressed in females than males. Secondly, young people that are participating in sports have more strongly expressed values compared to non-participants, and also, engagement in sport’s ac-tivities is driven by both – eudaimonic and hedonic values. Finally, expectations of young people’s career in sport are associated with personal growth and development (the eudemonic approach), as well as achievement and recognition (the hedonic approach). The implications for interventions are discussed

Pulmonary vascular effects of sildenafil on the development of chronic pulmonary hypertension in the ovine fetus

We investigated the pulmonary vascular effects of prophylactic use of sildenafil, a specific phosphodiesterase-5 inhibitor, in late-gestation fetal lambs with chronic pulmonary hypertension. Fetal lambs were operated on at 129 ñ 1 days gestation (term = 147 days). Ductus arteriosus (DA) was compressed for 8 days to cause chronic pulmonary hypertension. Fetuses were treated with sildenafil (24 mg/day) or saline. Pulmonary vascular responses to increase in shear stress and in fetal Pa O2 were studied at, respectively, day 4 and 6 . Percent wall thickness of small pulmonary arteries (%WT) and the right ventricle-to-left ventricle plus septum ratio (RVH) were measured after completion of the study. In the control group, DA compression increased PA pressure (48 ñ 5 to 72 ñ 8 mmHg, P < 0.01) and pulmonary vascular resistance (PVR) (0.62 ñ 0.08 to 1.15 ñ 0.11 mmHgúml-1úmin-1, P < 0.05). Similar increase in PAP was observed in the sildenafil group, but PVR did not change significantly (0.54 ñ 0.06 to 0.64 ñ 0.09 mmHgúml-1úmin-1). Acute DA compression, after brief decompression, elevated PVR 25% in controls and decreased PVR 35% in the sildenafil group. Increased fetal PaO2 did not change PVR in controls but decreased PVR 60% in the sildenafil group. %WT and RVH were not different between groups. Prophylactic sildenafil treatment prevents the rise in pulmonary vascular tone and altered vasoreactivity caused by DA compression in fetal lambs. These results support the hypothesis that elevated PDE5 activity is involved in the consequences of chronic pulmonary hypertension in the perinatal lung

Potential long-term effects of SARS-CoV-2 infection on the pulmonary vasculature: a global perspective.

The lungs are the primary target of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, with severe hypoxia being the cause of death in the most critical cases. Coronavirus disease 2019 (COVID-19) is extremely heterogeneous in terms of severity, clinical phenotype and, importantly, global distribution. Although the majority of affected patients recover from the acute infection, many continue to suffer from late sequelae affecting various organs, including the lungs. The role of the pulmonary vascular system during the acute and chronic stages of COVID-19 has not been adequately studied. A thorough understanding of the origins and dynamic behaviour of the SARS-CoV-2 virus and the potential causes of heterogeneity in COVID-19 is essential for anticipating and treating the disease, in both the acute and the chronic stages, including the development of chronic pulmonary hypertension. Both COVID-19 and chronic pulmonary hypertension have assumed global dimensions, with potential complex interactions. In this Review, we present an update on the origins and behaviour of the SARS-CoV-2 virus and discuss the potential causes of the heterogeneity of COVID-19. In addition, we summarize the pathobiology of COVID-19, with an emphasis on the role of the pulmonary vasculature, both in the acute stage and in terms of the potential for developing chronic pulmonary hypertension. We hope that the information presented in this Review will help in the development of strategies for the prevention and treatment of the continuing COVID-19 pandemic