Plasma Lipocalin-2 and Echocardiographic Indices After Isolated Right Pulmonary Artery Ligation in Rats: Associations with Right Ventricular Systolic Pressure and Histologic Remodeling

Isolated right pulmonary artery ligation redirects flow to the contralateral lung. We tested whether adding plasma lipocalin-2 (LCN2) to echocardiography improves discrimination between ligation and sham operation. Male Sprague–Dawley rats undergoing ligation or sham operation (n = 16 each) were assessed at postoperative weeks 4, 8, or 12 by echocardiography, right-heart catheterization, histology, and LCN2 immunoassay. Leave-one-out ridge-logistic regression compared echocardiographic models with and without LCN2. The models distinguish ligation from sham and do not grade pulmonary hypertension. At week 4, LCN2, right ventricular systolic pressure, medial wall thickness percentage, and collagen volume fraction differed between groups; echocardiographic indices did not differ significantly. This is between-group separation in different animals, not earlier detection within one animal. The area under the curve (AUC) was 0.914 (95% confidence interval [CI] 0.798–0.992) without LCN2 and 0.945 (0.847–1.000) with LCN2, a nonsignificant increase (ΔAUC +0.031; 95% CI 0.000–0.089; p = 0.174). The supported increments were in integrated discrimination (0.061; 95% CI 0.031–0.095) and continuous prediction of right ventricular systolic pressure (leave-one-out R2 0.819 to 0.847). The in-sample nested change in R2 was 0.028 (95% CI 0.0008–0.087; false-discovery-rate q = 0.004). These internal results establish neither residual severity grading nor replacement of right-heart catheterization.