Renal Medullary but Not Cerebral Hypoxia in a Large Animal Model of Heart Failure With Mildly Reduced Ejection Fraction

Background Chronic kidney disease and cognitive impairment are common in heart failure, but how changes in microcirculatory perfusion and oxygenation contribute to these complications remains unclear. We investigated how heart failure with mildly reduced ejection fraction (HFmrEF) affects renal and cerebral perfusion and oxygenation, renal blood flow (RBF), and renal function in adult female sheep ( Ovis aries , Linnaeus 1758). Methods HFmrEF was induced in Merino ewes ( n = 10) via progressive ligation of coronary artery branches. Sham‐operated controls ( n = 10) underwent thoracotomy without ligation. Three weeks later, fiber‐optic probes were implanted in the renal cortex, renal medulla, and frontal cerebral cortex to measure tissue perfusion and oxygenation. Transit‐time flow probes and vascular catheters enabled continuous assessment of systemic hemodynamics, left atrial pressure, and RBF. Bladder catheterization allowed urine output measurement, and plasma and urine samples were collected to calculate creatinine clearance. Systolic function was assessed by two‐dimensional echocardiography. Results Animals with HFmrEF exhibited reduced left ventricular ejection fraction (50.6% ± 1.4% vs. 77.8% ± 0.9%; p < 0.0001), elevated left atrial pressure (7.5 ± 0.9 vs. 3.3 ± 0.8 mmHg; p = 0.003), and clinical signs of heart failure. Renal medullary oxygenation was significantly reduced (41.4 ± 4.3 vs. 54.7 ± 2.7 mmHg; p = 0.02), while renal cortical and cerebral oxygenation were preserved. Systemic hemodynamics, RBF, and creatinine clearance were similar between groups. Conclusions In this large mammalian model of HFmrEF, selective renal medullary hypoxia occurred despite preserved renal function and systemic hemodynamics. These findings underscore the vulnerability of the renal medulla and support the need for early markers and interventions targeting renal microcirculation in heart failure.