Abstract
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.
Graphical abstract
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)To read this article in full you will need to make a payment
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Article info
Publication history
Published online: August 23, 2022
Accepted:
August 13,
2022
Received in revised form:
August 10,
2022
Received:
May 8,
2022
Footnotes
This work was supported by the VA Merit Review #I01 BX000760 (R.F.K.) and #I01 BX004146 (T.A.B.) from the United States Department of Veterans Affairs Biomedical Laboratory Research and Development. We also gratefully acknowledge the support of the University of Minnesota Lillehei Heart Institute.
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© 2022 Published by Elsevier Inc. on behalf of The American Association for Thoracic Surgery
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- Commentary: Myocardial relaxation mattersThe Journal of Thoracic and Cardiovascular SurgeryVol. 165Issue 6
- PreviewDespite 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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