Exercise and hypoxia unmask pulmonary vascular disease and right ventricular dysfunction in a 10-to 12-week-old swine model of neonatal oxidative injury

Steenhorst, Jarno J.; Hirsch, Alexander; Verzijl, Annemarie; Wielopolski, Piotr; De Wijs-Meijler, Daphne; Duncker, Dirk J.; Reiss, Irwin K. M. und Merkus, Daphne (2022): Exercise and hypoxia unmask pulmonary vascular disease and right ventricular dysfunction in a 10-to 12-week-old swine model of neonatal oxidative injury. In: Journal of Physiology, Bd. 600, Nr. 17: S. 3931-3950

Abstract

Prematurely born young adults who experienced neonatal oxidative injury (NOI) of the lungs have increased incidence of cardiovascular disease. Here, we investigated the long-term effects cif NOI on cardiopulmonary function in piglets at the age of 10-12 weeks. To induce NOI, term-horn piglets (1.81 +/- 0.06 kg) were exposed to hypoxia (10-12% F-1O2), within 2 days after birth, and maintained for 4 weeks or until symptoms of heart failure developed (range 16-28 days), while SHAM piglets were normoxia raised. Following recovery weeks), NOI piglets were surgically instrumented to measure haemodynamics during hypoxic-challenge testing (HCT) and exercise with modulation of the nitric-oxide system. During exercise, NOI piglets showed a normal increase in cardiac index, but an exaggerated increase in pulmonary artery pressure and a blunted increase in left atrial pressure - suggesting left atrial under-filling - consistent with an elevated pulmonary vascular resistance (PVR), which correlated with the duration of hypoxia exposure. Moreover, hypoxia duration correlated inversely with stroke volume (SV) during exercise. Nitric oxide synthase inhibition and HCT resulted in an exaggerated increase in PVR, while the PVR reduction by phosphodiesterase-5 inhibition was enhanced in NOI compared to SHAM piglets. Finally, within the NOI piglet group, prolonged duration of hypoxia was associated with a better maintenance of SV during HCT, likely due to the increase in RV mass. In conclusion, duration of neonatal hypoxia appears an important determinant of alterations in cardiopulmonary function that persist further into life. These changes encompass both pulmonary vascular and cardiac responses to hypoxia and exercise.

• Dokumententyp: Zeitschriftenartikel
• Fakultät: Medizin
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• ISSN: 0022-3751
• Sprache: Englisch