title: Right Ventricular Pressure Overload and Pathophysiology of Growing Porcine Biomodel.
abstract: The primary objective was to create a clinically relevant model of right ventricular hypertension and to study right ventricular myocardial pathophysiology in growing organism. The secondary objective was to analyse the effect of oral enoximone (phosphodiesterase inhibitor) therapy on right ventricular haemodynamic parameters and myocardial changes in biomodel of right ventricular hypertension. The study included a total of 12 piglets of 42 days of age. Under general anaesthesia, pulmonary artery banding (PAB) was performed surgically to constrict the main pulmonary artery to about 70-80 % of its original dimension. The study presented two groups of animals labelled C (control animals with PAB; n = 8) and E (animals with PAB and oral administration of enoximone; n = 4). Direct pressure and echocardiographic measurements were taken during operation (time-1), and again at 40 days after surgery (time-2). The animals were killed, and tissue samples from the heart chambers were collected for quantitative morphological assessment. Statistical analysis was performed on all acquired data. At time-2, the median weight of animals doubled and the median systolic pressure gradient across the PAB increased (46.59 ± 15.87 mmHg vs. 20.29 ± 5.76 mmHg; p < 0.001). Changes in haemodynamic parameters were compatible with right ventricular diastolic dysfunction in all the animals. Apoptosis, tissue proliferation and fibrosis were identified in all the myocardial tissue samples. Right ventricular pressure overload leads to increased apoptosis of cardiac myocytes, proliferation and myocardial fibrosis. Our study did not show evidence of haemodynamic benefit or myocardial protective effect of oral enoximone treatment.
authors: Department of Pediatrics, Faculty of Medicine Pilsen and Faculty Hospital in Pilsen, Charles University in Prague, Alej Svobody 80, 304 60, Pilsen, Czech Republic. jikobr93@gmail.com.
authors: Jiri
authors: http://orcid.org/0000-0003-1050-3982
authors: J
authors: Kobr
authors: Royal Brompton Hospital, Royal Brompton and Harefield NHS Foundation Trust, Sydney Street, London, SW3 6NP, UK.
authors: Zdenek
authors: Z
authors: Slavik
authors: Royal Brompton Hospital, Royal Brompton and Harefield NHS Foundation Trust, Sydney Street, London, SW3 6NP, UK.
authors: Hideki
authors: H
authors: Uemura
authors: Royal Brompton Hospital, Royal Brompton and Harefield NHS Foundation Trust, Sydney Street, London, SW3 6NP, UK.
authors: Imran
authors: I
authors: Saeed
authors: Royal Brompton Hospital, Royal Brompton and Harefield NHS Foundation Trust, Sydney Street, London, SW3 6NP, UK.
authors: Anke
authors: A
authors: Furck
authors: Department of Pediatrics, Faculty of Medicine Pilsen and Faculty Hospital in Pilsen, Charles University in Prague, Alej Svobody 80, 304 60, Pilsen, Czech Republic.
authors: Katerina
authors: K
authors: Pizingerová
authors: Department of Pediatrics, Faculty of Medicine Pilsen and Faculty Hospital in Pilsen, Charles University in Prague, Alej Svobody 80, 304 60, Pilsen, Czech Republic.
authors: Jiri
authors: J
authors: Fremuth
authors: Department of Histology and Embryology and Biomedical Center, Faculty of Medicine in Pilsen, Charles University in Prague, Karlovarska 48, 301 66, Pilsen, Czech Republic.
authors: Zbynek
authors: Z
authors: Tonar
mesh_terms: D000818:Animals; D006352:Heart Ventricles; D006439:Hemodynamics; D009206:Myocardium; D013552:Swine; D018497:Ventricular Dysfunction, Right; D017725:Ventricular Pressure
keywords: Enoximone; Piglets; Pressure overload; Pulmonary hypertension