Persistent diastolic dysfunction in chronically ischemic hearts following coronary artery bypass graft.
Autor: | Aggarwal R; Division of Cardiothoracic Surgery, Department of Surgery, University of Minnesota Medical School, Minneapolis, Minn., Qi SS; Division of Cardiothoracic Surgery, Department of Surgery, University of Minnesota Medical School, Minneapolis, Minn., So SW; Research Service, Minneapolis Veterans Affairs Health Care System, Minneapolis, Minn; Department of Neuroscience, University of Minnesota, Minneapolis, Minn; Center for Veterans Research and Education, Division of Cardiology and Cardiothoracic Surgery, Minneapolis, Minn., Swingen C; Division of Cardiothoracic Surgery, Department of Surgery, University of Minnesota Medical School, Minneapolis, Minn., Reyes CP; Division of Cardiothoracic Surgery, Department of Surgery, University of Minnesota Medical School, Minneapolis, Minn., Rose R; Division of Cardiothoracic Surgery, Department of Surgery, University of Minnesota Medical School, Minneapolis, Minn., Wright C; Division of Cardiothoracic Surgery, Department of Surgery, University of Minnesota Medical School, Minneapolis, Minn., Hocum Stone LL; Division of Cardiothoracic Surgery, Department of Surgery, University of Minnesota Medical School, Minneapolis, Minn., Nixon JP; Research Service, Minneapolis Veterans Affairs Health Care System, Minneapolis, Minn., McFalls EO; Division of Cardiology, Richmond VA Medical Center, Richmond, Va., Butterick TA; Department of Neuroscience, University of Minnesota, Minneapolis, Minn; Center for Veterans Research and Education, Division of Cardiology and Cardiothoracic Surgery, Minneapolis, Minn., Kelly RF; Division of Cardiothoracic Surgery, Department of Surgery, University of Minnesota Medical School, Minneapolis, Minn. Electronic address: kelly071@umn.edu. |
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Jazyk: | angličtina |
Zdroj: | The Journal of thoracic and cardiovascular surgery [J Thorac Cardiovasc Surg] 2023 Jun; Vol. 165 (6), pp. e269-e279. Date of Electronic Publication: 2022 Aug 24. |
DOI: | 10.1016/j.jtcvs.2022.08.010 |
Abstrakt: | Objective: A porcine model was used to study diastolic dysfunction in hibernating myocardium (HM) and recovery with coronary artery bypass surgery (CABG). Methods: HM was induced in Yorkshire-Landrace juvenile swine (n = 30) by placing a c-constrictor on left anterior descending artery causing chronic myocardial ischemia without infarction. At 12 weeks, animals developed the HM phenotype and were either killed humanely (HIB group; n = 11) or revascularized with CABG and allowed 4 weeks of recovery (HIB+CABG group; n = 19). Control pigs were matched for weight, age, and sex to the HIB group. Before the animals were killed humanely, cardiac magnetic resonance imaging (MRI) was done at rest and during a low-dose dobutamine infusion. Tissue was obtained for histologic and proinflammatory biomarker analyses. Results: Diastolic peak filling rate was lower in HIB compared with control (5.4 ± 0.7 vs 6.7 ± 1.4 respectively, P = .002), with near recovery with CABG (6.3 ± 0.8, P = .06). Cardiac MRI confirmed preserved global systolic function in all groups. Histology confirmed there was no transmural infarction but showed interstitial fibrosis in the endomysium in both the HIB and HIB+CABG groups compared with normal myocardium. Alpha-smooth muscle actin stain identified increased myofibroblasts in HM that were less apparent post-CABG. Cytokine and proteomic studies in HM showed decreased peroxisome proliferator-activator receptor gamma coactivator 1-alpha (PGC1-α) expression but increased expression of granulocyte-macrophage colony-stimulating factor and nuclear factor kappa-light-chain enhancer of activated B cells (NFκB). Following CABG, PGC1-α and NFκB expression returned to control whereas granulocyte-macrophage colony-stimulating factor, tumor necrosis factor-α, and interferon gamma remained increased. Conclusions: In porcine model of HM, increased NFκB expression, enhanced myofibroblasts, and collagen deposition along with decreased PGC1-α expression were observed, all of which tended toward normal with CABG. Estimates of impaired relaxation with MRI within HM during increased workload persisted despite CABG, suggesting a need for adjuvant therapies during revascularization. (Copyright © 2022. Published by Elsevier Inc.) |
Databáze: | MEDLINE |
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