Pulmonary hypertension without heart failure causes cardiorenal syndrome in a porcine model

作者：Arthur Orieux, Chloé Samson, Laurence Piéroni, Sarah Drouin, Simon Dang Van, Tiffany Migeon, Perrine Frère, Dorothée Brunet, David Buob, Juliette Hadchouel, Julien Guihaire, Olaf Mercier, Pierre Galichon · 发表于：Scientific Reports · 年份：2023 · DOI：10.1038/s41598-023-36124-1 · 被引用次数：6 · 研究领域：Pulmonary Hypertension Research and Treatments、Liver Disease and Transplantation、Congenital Heart Disease Studies

Cardiorenal syndromes type 1 and 2 are complex disorders in which cardiac dysfunction leads to kidney dysfunction. However, the mechanisms remain incompletely explained, during pulmonary hypertension in particular. The objective of this study is to develop an original preclinical model of cardiorenal syndrome secondary to a pulmonary hypertension in piglets. Twelve 2-month-old Large White piglets were randomized in two groups: (1) induction of pulmonary hypertension by ligation of the left pulmonary artery and iterative embolizations of the right lower pulmonary artery, or (2) Sham interventions. We evaluated the cardiac function using right heart catheterization, echocardiography and measurement of biochemistry markers). Kidney was characterized using laboratory blood and urine tests, histological evaluation, immunostainings for renal damage and repair, and a longitudinal weekly assessment of the glomerular filtration rate using creatinine-based estimation and intravenous injection of an exogenous tracer on one piglet. At the end of the protocol (6 weeks), the mean pulmonary artery pressure (32 ± 10 vs. 13 ± 2 mmHg; p = 0.001), pulmonary vascular resistance (9.3 ± 4.7 vs. 2.5 ± 0.4 WU; p = 0.004) and central venous pressure were significantly higher in the pulmonary hypertension group while the cardiac index was not different. Piglets with pulmonary hypertension had higher troponin I. We found significant tubular damage and an increase in albuminuria in the pulmonary hyperte...