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

Aggarwal, Rishav; Qi, Steven S.; So, Simon W.; Swingen, Cory; Reyes, Christina P.; Rose, Rebecca; Wright, Christin; Stone, Laura L. Hocum; Nixon, Joshua P.; McFalls, Edward O.; Butterick, Tammy A.; Kelly, Rosemary F.

doi:10.1016/j.jtcvs.2022.08.010

Cited by 3 publications

(7 citation statements)

References 29 publications

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“…In this study, we found that treatment with an allogeneic MSC-loaded patch during CABG dramatically improves diastolic function upon inotropic stimulation. We have previously presented our swine model of HIB, which recapitulates the clinical observations initially described by Rahimtoola et al, and found that diastolic function in HIB remains impaired despite revascularization with CABG [ 3 , 9 ]. While surgical revascularization with CABG can restore blood flow to previously ischemic myocardium and reduces long-term mortality, its role in preventing subsequent progression to diastolic heart failure is unknown [ 1 , 2 ].…”

Section: Discussionmentioning

confidence: 84%

“…We have previously characterized our swine model of HIB [ 40 ]. Please refer to Aggarwal et al for detailed methods [ 9 ]. Briefly, 51 juvenile female Yorkshire-Landrace swine were studied with the following groups: Control (n = 6), HIB (n = 17), CABG (n = 19), and CABG + MSC (n = 9).…”

Section: Methodsmentioning

confidence: 99%

“…The swine model of off-pump CABG has also been previously well characterized [ 13 ]. Refer to Aggarwal et al for detailed methods [ 9 ]. Briefly, at the end of 12 weeks after hibernation, pigs undergo general anesthesia.…”

Section: Methodsmentioning

confidence: 99%

“…Four weeks after revascularization, a second cardiac MRI was performed, followed by sacrifice. Refer to Aggarwal et al for detailed methods [ 9 ]. Briefly, pigs were anesthetized using general endotracheal anesthesia.…”

Section: Methodsmentioning

confidence: 99%

“…This model of HIB has allowed us to characterize the impairment in systolic function, measured by regional wall thickening (measured at the end diastole and end systole) and circumferential strain, that improves with revascularization [ 4 ]. Our model has shown impaired diastolic function, measured by the Peak Filling Rate (PFR), that only slightly improves with revascularization alone [ 9 ]. The proteomic profile of HIB is characterized by an upregulation of oxidative stress and inflammatory cytokines as well as the downregulation of mitochondrial and contractile proteins [ 10 , 11 ].…”

Section: Introductionmentioning

confidence: 99%

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An Adjuvant Stem Cell Patch with Coronary Artery Bypass Graft Surgery Improves Diastolic Recovery in Porcine Hibernating Myocardium

Aggarwal

Potel

Shao

et al. 2023

IJMS

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Diastolic dysfunction persists despite coronary artery bypass graft surgery (CABG) in patients with hibernating myocardium (HIB). We studied whether the adjunctive use of a mesenchymal stem cells (MSCs) patch during CABG improves diastolic function by reducing inflammation and fibrosis. HIB was induced in juvenile swine by placing a constrictor on the left anterior descending (LAD) artery, causing myocardial ischemia without infarction. At 12 weeks, CABG was performed using the left-internal-mammary-artery (LIMA)-to-LAD graft with or without placement of an epicardial vicryl patch embedded with MSCs, followed by four weeks of recovery. The animals underwent cardiac magnetic resonance imaging (MRI) prior to sacrifice, and tissue from septal and LAD regions were collected to assess for fibrosis and analyze mitochondrial and nuclear isolates. During low-dose dobutamine infusion, diastolic function was significantly reduced in HIB compared to the control, with significant improvement after CABG + MSC treatment. In HIB, we observed increased inflammation and fibrosis without transmural scarring, along with decreased peroxisome proliferator-activated receptor-gamma coactivator (PGC1α), which could be a possible mechanism underlying diastolic dysfunction. Improvement in PGC1α and diastolic function was noted with revascularization and MSCs, along with decreased inflammatory signaling and fibrosis. These findings suggest that adjuvant cell-based therapy during CABG may recover diastolic function by reducing oxidant stress–inflammatory signaling and myofibroblast presence in the myocardial tissue.

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