Adult: Coronary: Basic Science| Volume 165, ISSUE 6, e269-e279, June 2023

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Persistent diastolic dysfunction in chronically ischemic hearts following coronary artery bypass graft

Published:August 23, 2022DOI:



      A porcine model was used to study diastolic dysfunction in hibernating myocardium (HM) and recovery with coronary artery bypass surgery (CABG).


      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.


      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.


      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.

      Graphical abstract

      Figure thumbnail fx1

      Key Words

      Abbreviations and Acronyms:

      CABG (coronary artery bypass graft), EDV (end-diastolic volume), EF (ejection fraction), GM-CSF (granulocyte-macrophage colony-stimulating factor), HM (hibernating myocardium), IFNγ (interferon gamma), IL (interleukin), LAD (left anterior descending), LIMA (left internal mammary artery), LV (left ventricular), MRI (magnetic resonance imaging), NFκB (nuclear factor kappa-light-chain enhancer of activated B cells), PFR (peak filling rate), PGC1-α (peroxisome proliferator-activator receptor gamma coactivator 1-alpha), SMA (smooth muscle actin), TGF-1β (transforming growth factor 1beta), TNFα (tumor necrosis factor alpha)
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      • Commentary: Myocardial relaxation matters
        The Journal of Thoracic and Cardiovascular SurgeryVol. 165Issue 6
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          Despite the performance of anatomically complete revascularization, recovery of myocardial function and regression of symptomatology following coronary artery bypass grafting (CABG) is often incomplete. This impaired recovery is often found to be related to diastolic dysfunction in the setting of significant recovery of systolic function and improvements in ejection fraction. Diastolic dysfunction after CABG associated with poor ventricular compliance as well as elevated left ventricular end-diastolic and pulmonary vascular pressures has been associated with adverse outcomes, including major adverse cardiac events and mortality, and thus remains a challenge to the efficacy of CABG.
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