부산대학교 도서관

Introduction: Inhaled pulmonary vasodilators (iPVD) help prevent right heart failure (RHF) by lowering PVR after surgery. However, variable change in PVR is seen in response to iPVD. As metabolism is central to cardiomyocyte function, we evaluated the role of right ventricular (RV) myocardial metabolism in iPVD response heterogeneity.Hypothesis: We previously identified plasma metabolic biomarkers as potential reporters of response heterogeneity and posited here that these key metabolites change in parallel with changes in RV phenotypes.Methods: We evaluated 63 LVAD or heart transplant recipients with precapillary pulmonary hypertension before surgery from a recent randomized trial (INSPIRE-FLO, NCT03081052). All participants received iPVD after heart-lung bypass through postoperative day 1 (pod 1). Targeted profiling of > 500 metabolites (MxP® Quant 500, Biocrates) was performed in baseline and pod 1 plasma, and in RV free-wall full-thickness biopsies from LVAD recipients. Principal components analysis (PCA) was used for metabolite dimensionality reduction. Generalized linear models were used to assess the association of percent change (%Δ) in metabolite factors with (1) %Δ PVR (baseline to pod1); (2) responder, PVR < 3 Wood U vs. non-responder, PVR ≥ 3 Wood U, on pod 1); (3) RHF after surgery.Results: PCA identified 21 factors with 204 metabolites clustering in biologically consistent pathways. Of these, %Δ in factor 8 (glycine and eight glycerophospholipids, GPs) were positively correlated with %Δ PVR (P < 0.05). There was a trend for association in %Δ in factors 1 and 12 (ceramides, other GPs, amino acids: glutamate, aspartate, alanine, glutamine) and %Δ PVR (both P < 0.10, negatively correlated). There was a trend for association in %Δ in factor 7 (long chain acylcarnitines) and subsequent RHF (P = 0.08, positively correlated). No metabolites were associated with responder status. Plasma levels of select metabolites in factors 1 and 12 were positively correlated with RV myocardial levels (P < 0.05), suggesting a myocardial source.Conclusions: Leveraging a unique clinical trial cohort, we identified substrates of amino acid and fatty acid mitochondrial ß-oxidation metabolism in RV myocardium that may serve as biomarkers of metabolism in RHF.