Abstract P2034: Minimally-invasive Porcine Model for the Study of Cardiac Remodeling in Type 4 Cardiorenal Syndrome

Background: CKD is on the rise, and over half of patients die due to cardiac causes, usually HF. They present with HF not only due to volume overload, but also because of reno-cardiac interactions of unclear mechanisms termed type 4 cardiorenal syndrome (CRS4). In order to understand CRS4, we developed a pig model using minimally-invasive techniques. Methods: 4 female Yorkshire pigs had staged embolization of the renal arteries. Clot/contrast mix was injected by catheter until no flow was seen on angiography. Echo, pressure measurements, angiography, and urine and blood collection to monitor CKD and HF progression was done monthly. At 4 months, GFR and PV loop measurements were also taken, and tissues harvested. Results: BUN (11.3 ± 0.3 vs 5.3 ± 0.5 mg/dL, p < 0.01) and SCr (2.1 ± 0.2 vs 1.3 ±0.1 mg/dL, p<0.01) increased at the endpoint compared to controls, and GFR declined (6 ± 4 vs 124 ± 17 mL/min, p < 0.01). Kidneys showed diffuse fibrosis on trichrome staining. LV mass (136 ± 6 vs 106 ± 6 g, p < 0.05), EDP (16 ± 2 vs 9 ± 2 mmHg, p <0.05), aortic (146 ± 9 vs 96 ± 5 mmHg, p < 0.01) and pulmonary capillary wedge pressures (12 ± 1 vs 6 ± 1 mmHg, p < 0.01) and PA (22 ± 1 vs 16 ± 1 mmHg, p < 0.05) were increased. PV loop showed increased EDPVR slope (0.36 ± 0.03 vs 0.17 ± 0.03, p < 0.01) and Tau (48.9 ± 1.9 vs 36.3 ± 1.1 ms, p < 0.01). LV was fibrotic. Conclusions: Repetitive clot injection successfully induced CKD, seen by increased SCr and BUN, reduced GFR, and renal fibrosis. At 4 months, the heart was hypertrophic, fibrotic, and had PV relationships indicating development of HFpEF. Therefore, we have developed a successful minimally-invasive large animal model of CRS4 for future studies.