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.

Impact of Isolated Tricuspid Valve Repair on Right Ventricular Remodelling in an Adult Congenital Heart Disease Population

“…Echocardiography showed a reduction in RV dimensions (5.15 ± 1.2 vs 4.32 ± 1.16 cm; p  < 0.01), and RA area (44.7 ± 16.7 vs 26.7 ± 9.2 cm 2 ; p  < 0.01); this is most likely due to the effect of reduced RV pre-load. On the other hand, there was no significant change in RV function ( p  = 0.1); this is probably due to advanced structural modification of the RV which may have occurred before the time of the surgery (16). Therefore, the timing of surgery may be crucial to prevent damage to the RV and to achieve better results in the long term.…”

“…Among the cohort of ACHD patients, the RV has also been defined as “forgotten” (12), even though, in the last decade, increasing attention has been focussed on it, in an effort to avoid the adverse outcomes associated with its dysfunction and fibrosis (16). These include not only exercise limitation but also malignant ventricular arrhythmias (17).…”

Quantification of Biventricular Function and Morphology by Cardiac Magnetic Resonance Imaging in Mice with Pulmonary Artery Banding

“…This can be performed by a suture-banding (pulmonary artery banding, PAB) or a vascular clip around the pulmonary artery. PAB has been performed in several animal species, and cardiac dimensions and function have been studied in various ways, such as histology, transthoracic echocardiography (including speckle tracking), and heart catheterization 2,32,33,34,35,36,37,38,39,40 . PAB in small rodents, such as mice, is challenging.…”