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Summary

In this protocol, novel pig vein bypass grafting was performed through a small incision in the left chest wall without cardiopulmonary bypass. A postoperative pathology study was done, which showed intimal thickening.

Abstract

Venous graft disease (VGD) is the leading cause of coronary artery bypass graft (CABG) failure. Large animal models of CABG-VGD are needed for the investigation of disease mechanisms and the development of therapeutic strategies.

To perform the surgery, we enter the cardiac chamber through the third intercostal space and carefully dissect the internal mammary vein and immerse it in normal saline. The right main coronary artery is then treated for ischemia. The target vessel is incised, a shunt plug is placed, and the distal end of the graft vein is anastomosed. The ascending aorta is partially blocked, and the proximal end of the graft vein is anastomosed after perforation. The graft vein is checked for patency, and the proximal right coronary artery is ligated.

CABG surgery is performed in minipigs to harvest the left internal mammary vein for its use as a vascular graft. Serum biochemical tests are used to evaluate the physiological status of the animals after surgery. Ultrasound examination shows that the proximal, middle, and distal end of the graft vessel are unobstructed. In the surgical model, turbulent blood flow in the graft is observed upon histological examination after the CABG surgery, and venous graft stenosis associated with intimal hyperplasia is observed in the graft. The study here provides detailed surgical procedures for the establishment of a repeatable CABG-induced VGD model.

Introduction

Although coronary heart disease mortality has declined significantly in recent years, half of middle-aged adults in the United States develop ischemic heart-related symptoms each year, and one-third of older adults die from coronary heart disease1. Coronary artery bypass grafting (CABG) is an effective surgical modality to improve myocardial ischemia, and more importantly, it is an irreplaceable surgical modality for the treatment of multivessel coronary artery disease2. Over time, however, vascular grafts develop inflammation, intimal hyperplasia, and progressive atherosclerosis, which is known to lead to vein graft fai....

Protocol

The procedures for the care and use of laboratory animals were approved by the Institutional Animal Care and Use Committee of the Guangdong Laboratory Animals Monitoring Institute. All experiments were conducted in accordance with the Guide for the Care and Use of Laboratory Animals (8th Ed., 2011, National Research Council, USA). The surgical procedure is shown in Figure 1.

1. Preoperative preparation of animals

  1. Randomly divide 10 3-m.......

Representative Results

BMI and serum biochemical indices
The BMI between the sham and VGD groups was not significantly different (sham vs. VGD, 22.05 kg/cm2 ± 0.46 kg/cm2 vs. 21.14 kg/cm2 ± 0.39 kg/cm2, p = 0.46). The serum biochemical results are listed in Table 1. Statistically significant changes between the groups were found in four biochemical indexes, including aspartate aminotransferase (AST, sham vs. VGD, 25.25 IU/L ± 1.88 I.......

Discussion

In this study, we described in detail the protocol for animal selection, instrument preparation, surgical procedures, and post-operative evaluation when developing a CABG-induced VGD model. We performed ultrasonic examination of the venous graft before and after CABG surgery and histological examination of the graft 30 days after the surgery. The blood flow in the internal mammary vein was normal before the CABG surgery, while retrograde flow was observed in the graft of the internal mammary vein. Compared with the sham .......

Acknowledgements

The authors thank Guangdong Laboratory Animals Monitoring Institute for technical support, animal care, and sample collection. They also thank Shenzhen Mindray Bio-Medical Electronics Co., Ltd, for technical support in the ultrasonic examination. This work was supported by Guangdong Science and Technology Program, China, and Jinan University Central Universities Basic Scientific Research Business Expenses Project (2017A020215076, 2008A08003, and 21621409).

....

Materials

NameCompanyCatalog NumberComments
Aortic PunchMedtronic Inc. , America3.0mm, 3.5mm, 4.0mmUsed for proximal coronary bridge anastomosis
Automatic biochemical analyzerIDEXX Laboratories, Inc. AmericaCatalyst One
Cardiac coronary artery bypass grafting instrument kitLANDANGER, France
Cardiogram monitorShenzhen Mindray Bio-Medical Electronics Co, LtdMEC-1000
Coronary ShuntAXIUS OF-1500, OF-2500, OF-3000The product temporarily blocks the coronary artery during arteriotomy to reduce the amount of bleeding in the surgical field and provide blood flow to the distal end during anastomosis.  The Axius shunt plug is not an implant and should be removed prior to completion of the anastomosis.  
DefibrillatorMEDIANAMediana D500
DiazepamNanguo pharmaceutical Co. LTD, Guangdong, ChinaH37023039 Narcotic inducer
Disposable manual electric knifeCovidien, AmericaE2516H
Electric negative pressure suction machineShanghai Baojia Medical Instrument Co, LtdYX932D
EsmololGuangzhou Wanzheng Pharmaceutical Co. LTDH20055990Emergency drugs
Ice machine Local suppliers, Guangzhou, China
Lidocaine Chengdu First Pharmaceutical Co. LTDH51021662Emergency drugs
Luxtec headlight systemLuxtec, AmericaAX-1375-BIFUsed for lighting fine parts during operation
Medical operation magnifier (glasses)Germany Lista co, LTDSuperVu Galilean 3.5×Used for fine site operation during operation
Multi-function high-frequency electrotomeShanghai Hutong Electronics Co, LtdGD350-B
Nitrogen canisterLocal suppliers, Guangzhou, China
Nonabsorbable surgical suture (polypropylene suture)Johnson & Johnson, America6-0, 7-0Used to suture blood vessels.
Nonabsorbable suture (cotton thread)Covidien, America1-0Used for skin and muscle tissue tugging
Open heart surgery instrument kitShanghai Medical Instrument (Group) Co., LTD
Propofol injectionXi 'an Libang Pharmaceutical Co. LTDH19990282Anesthetic sedative
RefrigeratorLocal suppliers, Guangzhou, China
Respiratory anesthesia machine for animalShenzhen Reward Life Technology Co, Ltd, ChinaR620-S1
Semi-occlusion clampXinhua Surgical Instrument Co., Ltd.ZL1701RBTemporarily cut off the aortic flow
vecuronium bromideRichter, Hungary JX20090127Muscle relaxant
Veterinary ultrasound system Royal Philips, NetherlandsCX50
ZoletilVirbac, FranceZoletil 50 Animal narcotic

References

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