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Translational model of vein graft failure following coronary artery bypass graft in atherosclerotic microswine

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Abstract

Objective

Vein graft failure is a major complication following coronary artery bypass graft surgery. There is no translational model to understand the molecular mechanisms underlying vein-graft failure. We established a clinically relevant bypass graft model to investigate the underlying pathophysiological mechanisms of vein-graft failure and identify molecular targets for novel therapies.

Methods

Six female Yucatan microswine fed with high cholesterol diet underwent off-pump bypass, using superficial epigastric vein graft, which was anastomosed to an internal mammary artery and distal left anterior descending artery. Vein-graft patency was examined 10-months after bypass surgery by echocardiography, coronary angiography, and optical coherence tomography followed by euthanasia. Coronary tissues were collected for histomorphometry studies.

Results

Atherosclerotic microswine were highly susceptible to sudden ventricular fibrillation with any cardiac intervention. Two out of six animals died during surgery due to ventricular fibrillation. Selection of the anesthetics and titration of their doses with careful use of inotropic drugs were the key to successful swine cardiac anesthesia. The hypotensive effects of amiodarone and the incidence of arrhythmia were avoided by the administration of magnesium sulfate. The vein-graft control tissue displayed intact endothelium with well-organized medial layer. The grafted vessels revealed complete occlusion and were covered with fibrous tissues. Expression of CD31 in the graft was irregular as the layers were not clearly defined due to fibrosis.

Conclusion

This model represents the clinical vein-graft failure and offers a novel platform to investigate the underlying molecular mechanisms of vein-graft disease and investigate novel therapeutic approaches to prevent its progression.

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Abbreviations

ABGS:

Arterial blood gases

ACS:

Activated clotted time

CABG:

Coronary artery bypass graft

CRT:

Capillary refill time

EKG:

Electrocardiogram

ETCO2 :

End tidal CO2

HDL:

High density lipoprotein

HFD:

High fat diet

IMA:

Internal mammary artery

LAD:

Left anterior descending artery

LDL :

Low density lipoprotein

OCT:

Optical coherence tomography

SEV:

Superficial epigastric vein

TG:

Triglycerides

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Acknowledgements

The authors acknowledge the support of several individuals during the initial stages of establishing the CABG model in swine. These individuals include: Gunasekar Palanikumar MBBS, Liang Mo MD, Jubing Zhang MD, Zefu Zhang MD, Marcus Balters MD, Ashok Kujur MSc, Michael J. Moulton MD, and several veterinary technicians.

Funding

The research work of DK Agrawal is supported by research grants R01HL 128063, R01 HL144125 and R01HL147662 from the National Institutes of Health, USA. The content of this review article is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

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Authors and Affiliations

  1. Department of Translational Research, Western University of Health Sciences, Pomona, CA, 91766, USA

    Mohamed M. Radwan, Finosh G. Thankam & Devendra K. Agrawal

  2. Department of Clinical and Translational Science, Creighton University School of Medicine, Omaha, NE, 68178, USA

    Mohamed M. Radwan, Finosh G. Thankam, Kouassi Tata Kouassi & Devendra K. Agrawal

  3. Division of Cardiothoracic Surgery, University of Nebraska Medical Center, Omaha, NE, 68198, USA

    Aleem Siddique

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Correspondence to Devendra K. Agrawal.

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Conflict of interest

All authors have read the journal’s policy on disclosure of potential conflicts of interest. Author E (DKA) has received grants from the National Institutes of Health. Other authors (MMR, AS, FGT, KTK) have no relevant affiliations or financial or non-financial involvement with any organization or entity with financial or non-financial interest or conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. All authors (MMR, AS, FGT, KTK, DKA) declare that they have no conflict of interest.

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All institutional and national guidelines for the care and use of laboratory animals were followed and approved by the appropriate institutional committees.

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Supplementary Information

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Supplementary file1 Video 1: OPCABG using SEV as a conduit; This approach was used in all six Yucatan microswine (MOV 18992 KB)

Supplementary file2 Video 2: Graft occlusion post-sacrifice after 10 months of CABG procedure. This is a representative of 4 Yucatan microswine (MOV 16735 KB)

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Radwan, M.M., Siddique, A., Thankam, F.G. et al. Translational model of vein graft failure following coronary artery bypass graft in atherosclerotic microswine. Gen Thorac Cardiovasc Surg 70, 445–454 (2022). https://doi.org/10.1007/s11748-021-01725-y

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