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

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 myocar-dial 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 proinflamma-tory 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-a) expression but increased expression of granulocyte-macrophage colony-stimulating factor and nuclear fac-tor kappa-light-chain enhancer of activated B cells (NFkB). Following CABG, PGC1-a and NFkB expression returned to control whereas granulocyte-macrophage colony-stimulating factor, tumor necrosis factor -a, and interferon gamma remained increased.Conclusions: In porcine model of HM, increased NFkB expression, enhanced my-ofibroblasts, and collagen deposition along with decreased PGC1-a 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.

Automated summary

This study used a porcine model to investigate diastolic dysfunction in hibernating myocardium (HM) and the recovery with coronary artery bypass surgery (CABG). The results showed that diastolic peak filling rate was lower in HM compared with the control group, but there was partial recovery with CABG. Cardiac magnetic resonance imaging and histological examination supported these findings.