Name: a rat carotid artery pressure-controlled segmental balloon injury with periadventitial therapeutic application
Uploaded: 2020-07-09T12:30:00
Description: Watch this Scientific Journal Video about A Rat Carotid Artery Pressure-Controlled Segmental Balloon Injury with Periadventitial Therapeutic Application at JoVE.com

N.E.B.는 국립 환경 보건 과학 연구소 (5T32ES007126-35, 2018)와 미국 심장 협회 전 박사 과정 펠로우십 (20PRE35120321)의 교육 보조금에 의해 지원되었습니다. E.S.M.B는 UNC 임상 및 번역 과학 상-K12 학자 프로그램(KL2TR002490, 2018),국립 심장, 폐 및 혈액 연구소(K01HL145354)가 부분적으로 지원하는 KL2 학자입니다. 저자는 LSFM을 지원한 UNC 현미경 서비스 연구소의 파블로 아리엘 박사에게 감사드립니다. 광시트 형광 현미경 검사는 현미경 서비스 실험실에서 수행되었다. 현미경 서비스 실험실, 병리학 및 실험실 의학의 학과는 UNC Lineberger 종합 암 센터에 P30 CA016086 암 센터 핵심 지원 교부금에 의해 부분적으로 지원됩니다.

여기에 설명 된 모든 방법은 채플 힐에서 노스 캐롤라이나 대학의 기관 동물 관리 및 사용위원회 (IACUC)에 의해 승인되었습니다.
1. 수술 전 절차
<ol><li>수술 기구를 살균합니다. 수술 전에 모든 수술 기구를 자동 클로브하십시오. 같은 날 여러 번 수술을 하는 경우, 드라이 비드 멸균제를 사용하여 수술 사이에 기기를 멸균하십시오.</li>
	<li>25% 물루론-127 젤 (멸균 증류수로 희?...

<ol>
	<li>American Heart Association. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Cardiovascular+Disease:+A+Costly+Burden+for+America,+Projections+Through+2035.">Cardiovascular Disease: A Costly Burden for America, Projections Through 2035.</a> American Heart Association CVD Burden Report. , (2017).</li><li>Singh, R. B., Mengi, S. A., Xu, Y. J., Arneja, A. S., Dhalla, N. S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Pathogenesis+of+atherosclerosis:+A+multifactorial+process.">Pathogenesis of atherosclerosis: A multifactorial process.</a> Experimental and Clinical Cardiology. 7 (1), 40-53 (2002).</li><li>Clowes, A. W., Reidy, M. A., Clowes, M. 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쥐 경동맥 풍선 부상은 가장 광범위하게 사용되고 연구 된 restenosis 동물 모델 중 하나입니다. 원래 풍선 상해 모델3과 변형 된 압력 제어 세그먼트 상해변화(10)는 인간에서도 발생하는 동맥 상해 반응의 많은 측면을 통보했으며, 몇 가지 제한사항은 피브린이 풍부한 혈전이 거의 발생하지 않으며 국소 염증은 콜레스테롤 토끼 또는 돼지 모델9,<...

심혈관 질환(CVD)은 전 세계적으로 사망의 주요 원인으로 남아있다. 죽상 동맥 경화증은 대부분의 CVD 관련 이환율및 사망의 근본 원인입니다. 죽상 동맥 경화증은 좁은 루멘을 초래하는 동맥 내부의 플라크가 축적되어 장기및 탈구 조직에 적절한 혈액 관류를 방해합니다2. 심한 죽상 동맥 경화증 치료에 대 한 임상 개입 포함 풍선 혈관 성형술 또는 스텐트 배치 없이. 이 개입은 플라크의 사이트에 풍선 카테터를 진행하고, 동맥 벽에 플라크를 압축풍선을 팽창, 발광 영역을 확대 포함. 그러나 이 절차는 동맥 손상 반응을 시동하는 동맥을 손상시다3. 이 상해 반응의 장기간 활성화는 동맥 재분비, 또는 재협화, 신자극성 증식 및 혈관 리모델링에 이차로 이끌어 냅니다. 혈관 성형술 동안 친밀감 층은 즉각적인 혈소판 모집 및 국소 염증으로 이어지는 내피 세포의 탈모된다. 국시 신호는 혈관 원활한 근육 세포 (VSMC) 및 출현 섬유 아세포에 있는 현상 변을 유도합니다. 이것은 VSMC와 섬유아세포의 이주 및 증식으로 이끌어 내고, 신동성증식4,5로이끌어 냅니다. 순환 선조 세포 및 면역 세포는 또한 restenosis6의전반적인 부피에 기여한다. 해당되는 경우, 약물 용출 스텐트 (DES)는 restenosis7을억제하기위한 현재 표준이다. DES는 동맥 재내피화를 억제하지만, 따라서 늦은 스텐트 혈전증8을초래할 수 있는 프로 혈전환경을 조성한다. 따라서 동물 모델은 restenosis의 병리학을 이해하고, 개정 절차의 효능을 연장하기 위한 더 나은 치료 전략을 개발하기 위한 데 필수적입니다.
몇몇 크고 작은 동물 모형9는 이 병리학을 공부하기 위해 이용됩니다. 여기에는 동맥의 발광 측의 풍선 부상3,10 또는 와이어 부상11, 동맥 주위의 부분 결찰12 또는 커프배치(13)가 포함됩니다. 풍선과 와이어 부상은 혈관 성형술 후 임상적으로 발생하는 것을 모방하여 동맥의 내피 층을 디누드합니다. 특히, 풍선 부상 모델은 임상 설정(즉, 풍선 카테터)과 유사한 도구를 사용합니다. 쥐 동맥은 시판되는 풍선 카테터에 적합한 크기이기 때문에 풍선 부상은 쥐 모델에서 가장 잘 수행됩니다. 본원에서 우리는 압력 제어 세그먼트 동맥 손상, 쥐 경동맥 풍선 부상의 잘 확립, 변형 된 버전을 설명합니다. 이러한 압력 제어 접근법은 임상 혈관 성형술 절차를 밀접하게 모방하고 부상 후 2주 후에 재현 가능한 신자극성 증식형성을가능하게 한다14,15. 추가적으로, 이 압력 통제 동맥 상해는 수술16후에 2 주에 의하여 완전한 내피 층 복원결과. 이것은 클로즈에 의해 설명 된 원래 풍선 부상 모델을 직접 대조하며, 내피 층이 전체 커버리지3로돌아오지 않습니다.
수술 후, 치료는 여러 가지 접근을 통해 부상당한 동맥에 적용되거나 방향화 될 수 있습니다. 본 명세서에서 기재된 방법은 Pluronic 젤 용액에 내장된 작은 분자의 회림적 적용을 사용합니다. 구체적으로, 100μM 계피 알데히드의 용액을 25% 황토-F127 젤로 25% 발동하여 부상 직후 동맥에 적용하여 신자극 성 증식형성(15)을억제한다. Pluronic-F127은17에국소적으로 약물을 전달할 수 있는 무독성, 열 가역성 젤이다. 한편, 동맥 상해는 현지, 따라서 지방 행정은 오프 대상 효과를 최소화하면서 활성 원칙을 테스트 할 수 있습니다. 그럼에도 불구하고, 이 방법을 이용한 치료의 효과적인 전달은 사용되는 작은 분자 또는 생물학적 제제의 화학에 달려 있다.

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a rat carotid artery pressure-controlled segmental balloon injury with periadventitial therapeutic application

심혈 관 질환은 죽상 경화증으로 인해 전 세계적으로 사망과 장애의 주요 원인으로 남아 있습니다. 죽상 경화성 플라크는 동맥의 발광 표면적을 좁히어 장기및 탈조직에 대한 적절한 혈류를 줄입니다. 임상적으로, 풍선 혈관 성형술과 같은 변조 절차는 스텐트 배치의 유무에 관계없이 혈류를 회복하는 것을 목표로합니다. 이러한 절차는 플라크 부담을 줄여 혈류를 재확립하지만, 동맥 치유 반응을 시작하는 혈관 벽을 손상시킵니다. 장기간 치유 반응은 동맥 재결석을 일으키거나 다시 좁히며 궁극적으로 이러한 재혈관화 절차의 장기적인 성공을 제한합니다. 따라서, 전임상 동물 모델은 레스테노시스를 구동하는 병리학적 메커니즘을 분석하는 데 필수적이며, 새로운 치료 전략을 시험할 기회를 제공한다. Murine 모델은 대형 동물 모델보다 저렴하고 조작하기 쉽습니다. 풍선 또는 와이어 부상은 뮤린 모델에 사용되는 두 가지 일반적으로 허용되는 부상 양식입니다. 특히 풍선 상해 모델은 임상 혈관 성형술 절차를 모방하고 restenosis의 발달을 위한 동맥에 적당한 손상을 일으키는 원인이 됩니다. 본원에서 우리는 변형된 압력 조절 쥐 경동맥 풍선 상해 모형을 수행하고 조직학적으로 분석하기 위한 수술 세부 사항을 기술합니다. 추가적으로, 이 프로토콜은 치료의 현지 periadventitial 응용이 어떻게 신자극성 과대증을 억제하기 위하여 이용될 수 있는지 강조합니다. 마지막으로, 우리는 3 차원으로 동맥 상해를 화상 진찰하고 시각화하기위한 새로운 접근법으로 가벼운 시트 형광 현미경 검사를 제시합니다.

그림 1은 이 수술을 수행하는 데 사용되는 모든 재료와 수술 도구를 보여줍니다. 헤마톡시린 & 에오신 (H&E) 2 주 부상 동맥 단면의 염색은 신자극증의 명확한 시각화를 허용합니다. 그림 2는 건강하고, 다치고, 취급된 동맥의 H&E 염색 동맥 단면의 대표적인 영상을 보여줍니다. 도 2는 또한 널리 사용되는 이미지 프로세싱 소프트웨어...

Watch this Scientific Journal Video about A Rat Carotid Artery Pressure-Controlled Segmental Balloon Injury with Periadventitial Therapeutic Application at JoVE.com

A Rat Carotid Artery Pressure-Controlled Segmental Balloon Injury with Periadventitial Therapeutic Application

쥐 경동맥 풍선 부상은 죽상 경화성 혈관에서 혈류를 복원하기 위해 수행 된 임상 혈관 성형술 절차를 모방합니다. 이 모델은 동맥 벽을 손상시키고 내피 세포의 친밀감 층을 비명하여 동맥 손상 반응을 유도하여 궁극적으로 리모델링 및 친밀한 과플라스틱 반응을 일으킵니다.

쥐 경동맥 압력 제어 세그먼트 풍선 부상 과식 치료 응용 프로그램

Cardiovascular disease remains the leading cause of death and disability worldwide, in part due to atherosclerosis. Atherosclerotic plaque narrows the ...

The pressure-controlled segmental carotid balloon injury. Is an experimental procedure used in the lab that mimics the balloon angioplasty revascularization procedure that is performed in human patients with severe atherosclerotic disease. It's used in the lab to study various aspects of the arterial injury response.This re-stenosis model is performed in a similar manner to balloon angioplasty in the clinical setting allowing a defined area of vascular injury and complete re endothelialization within two weeks of injury to be achieved. After performing all of the preoperative procedures, according to the university IACUC standards, confirm a lack of response to pedal reflex in an anesthetized adult rat. Place the rat under a dissecting microscope and use scissors to make a straight 1.5 to two centimeter superficial longitudinal skin incision along the neck line between the jaw bones.Make a second incision through the connective tissue under the skin until the muscle layer is exposed. And displace the salivary glands underneath the skin to access the muscle tissue. Insert closed scissor tips between the muscle layer and connective tissue and gently opened the scissors while pulling the skin upward to bluntly separate the connective tissue from the muscle.Dissect the sternohyoid and sternomastoid muscles longitudinally along the left side of the trachea until the omohyoid muscle which runs perpendicular to the two superficial muscles is observed. Use forceps to gently create a window separating the perpendicular omohyoid muscle from the longitudinal sternohyoid muscle running over the trachea. And reach the forceps under the omohyoid muscle to separate the sternohyoid and sternomastoid muscles to expose the common carotid artery.To isolate the common carotid artery, dissect the artery near the bifurcation until the internal and external carotid arteries are exposed. Using precut Proline sutures, ligate the superior thyroid and external carotid arteries near their respective bifurcations. Leaving the majority of the suture to one side of the nod and grabbing each suture with a curved hemostat.Finish dissecting around the internal carotid artery and reach the forceps under and around the artery. Use a non crushing vascular clamp to carefully clamp around the occipital artery with the internal carotid artery to achieve distal control without kinking the vessels. Dissect the common carotid artery proximal to the bifurcation, taking care to separate the vagus nerve from the artery.And reach forceps under and around the common carotid artery. Then use a non crushing vascular clamp to achieve proximal control, placing the clamp at least five millimeters from the bifurcation. To induce the balloon injury, maneuver the curved hemostats holding each litigated artery branch to expose the bifurcation between the external carotid artery and superior branch.Gently dissect the tissue at the bifurcation to clear the arteriotomy site as much as possible. And use microdissection scissors to make an arteriotomy incision between the external carotid artery and the superior branch. Take care to clear the site prior to inserting the micro scissors and to ensure that one blade of the micro scissors is fully within the artery before making the incision.Use a cotton swab to push all of the blood out of the common carotid artery and to clean up the arteriotomy site. Insert the uninflated balloon catheter through the arteriotomy by lifting the arteriotomy with forceps. And advance the balloon into the artery until the proximal end of the balloon is past the bifurcation.If the balloon does not easily advance into the common carotid, reposition the angle of the balloon before trying again. Tape the catheter to the anesthesia nose cone so the balloon does not slip out of the artery during the inflation. And slowly fill the balloon to five atmospheres of pressure.Leave the balloon in the artery for five minutes to induce the arterial injury before deflating and gently removing the balloon through the arteriotomy. Gently squeeze the clamp to flush out the artery. And ligate the external carotid artery proximal to the arteriotomy.Remove the clamps from the common and internal carotid arteries to restore blood flow. And apply 50 microliters of therapeutic gel periadventiatially along the left and right sides of the injured artery. Then use interrupted 4-0 or 6-0 Vicryl sutures to close the connective tissue.And close the skin with a running 4-0 nylon suture. Here, representative images of H and E stained arterial cross-sections of healthy, injured and treated arteries are shown. Using image J the perimeter of the neointima as well as the internal and external elastic lamina can be traced to quantify their respective areas.Light sheet fluorescence microscopy can also be used to visualize the entire region of injury along the length of the artery. The images can then be rendered using software for quantifying the intima-media ratio. Be sure to place the internal carotid clamps so as not to kink the common carotid and to completely clear the arteriotomy site before inserting the microdissection scissors.Many therapeutic approaches can be used at the end of surgery to attempt to mitigate the pathological response that is occurring within the carotid artery.

Research

JoVE Journal

Medicine

Pressure Controlled Ventilation to Induce Acute Lung Injury in Mice

마우스의 급성 폐 상해를 유발하는 압력 제어 환기

Murine models are extensively used to investigate acute injuries of different organs systems (1-34). Acute lung injury (ALI), which occurs with prolonged ...

연구

의학

Catheterization of the Carotid Artery and Jugular Vein to Perform Hemodynamic Measures, Infusions and Blood Sampling in a Conscious Rat Model

경동맥과 경정맥의 도관은 의식 쥐 모델에서, 혼합 및 혈액 샘플링을 혈역학 적 조치를 수행하는

The success of a small animal model to study critical illness is, in part, dependent on the ability of the model to simulate the human condition. ...

Carotid Artery Infusions for Pharmacokinetic and Pharmacodynamic Analysis of Taxanes in Mice

마우스의 탁산의 약동학 및 약력 학적 분석을위한 경동맥 팅크

When proposing the use of a drug, drug combination, or drug delivery into a novel system, one must assess the pharmacokinetics of the drug in the study ...

Vascular Balloon Injury and Intraluminal Administration in Rat Carotid Artery

쥐 경동맥의 혈관 풍선 부상과 관내 관리

The carotid artery balloon injury model in rats has been well established for over two decades. It remains an important method to study the molecular and ...

Murine Model of Femoral Artery Wire Injury with Implantation of a Perivascular Drug Delivery Patch

혈관 주위 약물 전달 패치의 주입과 대퇴 동맥 와이어 부상의 쥐 모델

Percutaneous interventions including balloon angioplasty and stenting have been used to restore blood flow in vessels with occlusive vascular disease. ...

Performing Permanent Distal Middle Cerebral with Common Carotid Artery Occlusion in Aged Rats to Study Cortical Ischemia with Sustained Disability

세 쥐의 경동맥 폐색으로 영구 말초 중간 대뇌을 수행하면 두피 허혈 지속적인 장애를 연구하는

Stroke typically occurs in elderly people with a range of comorbidities including carotid (or other arterial) atherosclerosis, high blood pressure, ...

A Rat Carotid Balloon Injury Model to Test Anti-vascular Remodeling Therapeutics

생쥐 경동맥 풍선 손상 모델은 반대로 혈관 리모델링의 치료를 테스트하는

The rat carotid balloon injury is a well-established surgical model that has been used to study arterial remodeling and vascular cell proliferation. It is ...

Method of Direct Segmental Intra-hepatic Delivery Using a Rat Liver Hilar Clamp Model

쥐 간 문부 클램프 모델을 사용하여 직접 분절 인트라 간 납품 방법

Major hepatic surgery with inflow occlusion, and liver transplantation, necessitate a period of warm ischemia, and a period of reperfusion leading to ...

The Rabbit Model of Accelerated Atherosclerosis: A Methodological Perspective of the Iliac Artery Balloon Injury

가속된 동맥 경화의 토끼 모델: 장 골 동맥 풍선 상해의 방법 론 적 관점

Acute coronary syndrome resulting from coronary occlusion following atherosclerotic plaque development and rupture is the leading cause of death in the ...

In Vivo Gene Transfer to the Rabbit Common Carotid Artery Endothelium

In Vivo Gene Transfer to the Rabbit Common Carotid Artery Endothelium

Vivo에서 토끼 일반적인 경 동맥 내 피에 유전자 이동

The goal of this method is to introduce a transgene into the endothelium of isolated segments of both rabbit common carotid arteries. The method achieves ...