Name: reproducible arterial denudation injury by infrarenal abdominal aortic clamping in a murine model
Uploaded: 2016-11-24T12:30:00.000+00:00
Duration: 8 min 33 s
Description: Watch this Scientific Journal Video about Reproducible Arterial Denudation Injury by Infrarenal Abdominal Aortic Clamping in a Murine Model at JoVE.com

이 작품은 MLIA에 건강 (HL130290)의 국립 연구소를 엘리와 재생 의학의 Edythe 넓은 센터에서 보조금 지원 ASS과 AIM, 필립 J. Whitcome 원정대는 AIM하기에 UCLA 교육 프로그램에 줄기 세포 연구하고 있었다.

참고 :이 프로토콜은 캘리포니아 로스 앤젤레스 대학에서 동물 연구위원회에 의해 승인되었습니다. 1. 수술 전 준비 및 마취 <ol><li> 절차 전반에 걸쳐 무균 기술을 준수해야합니다. </li><li> 증기 오토 클레이브를 사용하여 모든 수술 용품을 소독. </li><li> 이 수술하는 동안 시각화를위한 실체 현미경 하에서 적절한 온도 (37 °에 C) 및 장소에 따뜻하게 할 수 있도록 이전 마취 유도 가열 설치류 수술 플랫폼을 켭니다. </li><li> 마취 유도 챔버에 마우스를 위치시키고 1 L / min의 유속으로 4 % 이소 플루 란으로 유도한다. <ol><li> 조심스럽게 유도하는 동안 마우스의 호흡 속도 및 발바닥의 피부 색상을 모니터링 할 수 있습니다. </li><li> 호흡 속도의 둔화 후, 유도 챔버에서 마우스를 제거하고 2.5 %의 별도의 원추형 두부 및 유지 보수 이소 플루 란 농도 얼굴 수술 준비를위한 예열 패드에 배치합니다. </li><li> 마취의 적정성을 평가하기 위해 발가락 핀치를 수행합니다. </li></ol></li><li> 각막에 안과 연고를 적용하고 (5 ㎎ / ㎏) 피하 수술 전 카프로 펜을 관리 할 수 ​​있습니다. </li><li> 장소 마우스 부정사 사용 가위는 복부에서 머리를 제거합니다. </li><li> 멸균 거즈 패드에 적용되는 세 가지 포비돈 요오드의 교류 스크럽 70 % 이소 프로필 알코올로 수술 영역을 준비합니다. </li><li> 장소 마우스 원추형 두부에 얼굴 가열 설치류 수술 플랫폼에서 부정사 모든 사지를 확보하고 복부가 실체 현미경으로 볼 수 있도록 신중하게 위치 마우스입니다. </li><li> 준비된 외과 영역의 각 가장자리를 따라 멸균, 접착제 드레싱을 놓습니다. </li><li> 자발 호흡을 유지하면서 수술시 적절한 마취를 유지 이소 플루 란 농도를 적정. </li></ol> 2. Infrarenal 대동맥 클램핑 <ol><li> , 메스를 사용하여 approximatel을 시작 복부의 중간 선 아래 3cm의 절개를합니다칼 모양의 과정 열등 y를 0.5 cm. </li><li> 부드럽게 집게로 피부를 철회하고 잘 결합 조직을 잘라 미세 가위를 사용하여 복부 벽에서 떨어져 피부를 해부하다. </li><li> 근육 벽에 0.5 % bupivacaine을의 0.05-0.1 ml에 적용하고 복부 장기를 노출하는 복벽에 2cm 절개를합니다. <ol><li> 출혈은 복부 벽을 따라 발생하면 면봉으로 부드럽게 압력을 적용합니다. </li></ol></li><li> 부드럽게 식염수를 적신 면봉 어플리케이터를 사용하여 내장을 들어 올립니다. 참고 : 복강 외부의 따뜻한 멸균 식염수를 적신 거즈 스폰지에 jejunal과 회장 동맥과 장소에 외상을 피하기 위해주의해야합니다. <ol><li> 수분 손실을 방지하기 위해 다른 따뜻한, 멸균 식염수를 적신 거즈 스폰지로 장을 커버. </li></ol></li><li> 직장을 lateralize과 복막을 노출하는 트랙터를 놓습니다. </li><li> retroperitone의 시각화에 필요한 작은 거즈 패드를 배치UM 사용 횟수를 추적. </li><li> 오른쪽 신장의 열등한 극의 수준에서 대동맥에 retroperitonotomy는 측면하기 위해 날카로운 해부 집게를 사용합니다. 주 : 하대 정맥 또는 주변의 혈관을 손상하지 않도록주의하십시오. <ol><li> 퉁명스럽게 대동맥 떨어져 복막 조직을 해부하다 조심하면 하대 정맥 또는 주변의 혈관을 관통하지. </li></ol></li><li> 적어도 1 분, 또는 다른 지정된 시간 동안 대동맥을 통해 혈관 클램프를 배치하고 시각적으로 원위부 대동맥의 박동의 부족을 관찰하여 교합을 확인합니다. </li><li> 혈관 클램프를 제거하고 지혈을 확인합니다. 지혈 달성과 혈액의 활성 혈관 외 유출이 볼 수없는 경우 보장된다. <ol><li> 복강에 0.5 ㎖의 식염수를 추가하고 식염수가 점점 피가 섞인 될 경우 평가하여 혈관 외 유출을 확인합니다. 이것이 사실 인 경우, 1 분을 보장하기 위해 식염수 침지 어플리케이터를 사용하여 온화한 압력을 적용지혈. </li></ol></li><li> 복막의 시각화에 도움과 복부에 현장에서의 장을 대체 할 놓인 거즈 패드를 제거합니다. </li><li> 예열 멸균 식염수를 사용하여 복강 관개. </li></ol> 개복술과 피부 3. 폐쇄 <ol><li> 5-0 꼰, 흡수 단일 실행 봉합사를 사용하여 복벽 근육 층을 닫습니다. </li><li> 상처 클립 이후 다음 1-3 폴리머 접착제의 방울과의 긴밀한 피부는 접착제가 설정되면. </li></ol> 4. 복구 및 수술 후 평가 <ol><li> 새장 바닥에 음식과 물을 가열 패드에 복구 케이지에 마우스를 전송합니다. </li><li> 밀접하게 호흡 곤란의 징후 마우스를 모니터링 할 수 있습니다. 기관의 가이드 라인에 따라 수술 후 48 시간 동안 매일 카프로 펜 (5 ㎎ / ㎏)을 관리 할 수 ​​있습니다. <ol><li> 이 흉골 recum을 유지하기 위해 충분한 의식을 회복 할 때까지 무인 동물을 두지 마십시오bency. </li></ol></li><li> 음식과 물과의 정상 케이지에 마우스를 돌려줍니다. <ol><li> 완전히 회복 될 때까지 다른 동물의 회사에 수술을 한 동물을 반환하지 않습니다. </li></ol></li><li> 열개 대한 매일 상처를 평가하고 수술 후 14 일에 클립을 제거합니다. </li></ol> 5. 대동맥 박리 및 염색 <ol><li> 발가 벗김 부상 다음 관심있는 특정 시점을 기준으로 제사를 선택 마우스. </li><li> 이소 플루 란 흡입을 통해 마우스를 희생하고 즉시 혈관 평활근의 이완을 유발하는 5 mg을 메타 콜린 클로라이드로 주입. </li><li> 호흡 정지, 각막 반사와 운동 부족의 부족에 의한 사망 확인 후, 10 분 동안 왼쪽 심장 심실을 통해 100 mmHg로의 관류 압력 인산염 완충 생리 식염수에 4 % 파라 포름 알데히드로 관류. </li><li> 조심스럽게에서 그대로 복부 대동맥을 구분 해부 실체 현미경을 사용하여주변 조직. </li><li> 장골 분기에 신장 동맥과 꼬리에 대동맥 주동이를 가로로 쪼개다와 지느러미 표면을 따라 세로 절개를 통해 열었습니다. </li><li> 더 이상 2 시간 동안 최대 고정 용 내강면이 35mm 실리콘 코팅 접시 있지만 이상 12 시간에 평평 대동맥을 고정. 이어서, 조직 절편 어느 임베디드 또는 얼굴 전체 실장 EN 면역 세포에서 사용될 수있다. </li><li> 마운트는 공 초점 현미경 유리 슬라이드에 coverslip에 직면 내강면 대동맥 스테인드. </li></ol>

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저자는 공개 아무것도 없어.

때문에 이러한 풍선 혈관 성형술 및 혈관 스텐트 삽입술 등 경피적 중재에 동맥 발가 벗김 부상, 초기와 후기 혈관 혈전증과 재 협착 발생 및 재발 성 허혈성 사건 3,12에 기여한다. 흥미롭게도, 수술, 혈관 클램프는 또한 경피적 여부 13 열려있는 혈관 절차를받는 환자에게 문제의 범위를 확대하고, 동맥 삭박의 원인으로 관여한다. 손상된 내피 세포 형성 재 협착 및 혈전증 상당히 ?...

혈전증과 재 협착은 혈관 풍선 성형술 및 1,2 스텐트 등 경피적 혈관 중재를 받아야 환자에서 심각한 초기와 후기 합병증이다. 몇 가지 전략은 이들 합병증, 특히 이중 항 혈소판 요법 및 약물 방출 스텐트를 해결하는데 이용되어왔다. 그러나, 약간의 초점은 혈전증과 재 협착, 내피 세포 커버리지 (삭박), 즉 손실의 근본 원인에 배치되었습니다. 삭박 손상으로 인해 혈관 벽에 기계적 외상 중재 방법의 불가피한 결과이다. 이 기계적 외상은 혈액 3 순환에 손상 및 기저막 및 혈관 평활근의 보호 내피 층과 노출이 제거 될 수 있습니다. 이 분야에서 내피 세포의 손실뿐만 아니라 혈소판 부착 및 후속 혈전증을 촉진하는 프로 혈전 성 및 염증성 환경을 조성하지만,LSO 마이그레이션 및 신생 내막 비후 및 재 협착 (4)에서 얻어진 혈관 평활근 세포의 증식을 자극한다. 이러한 합병증 및 관련 치료는 인간의 건강에 영향을 미칠 중요한 병적 상태, 특히 재발 성 허혈성 질환 및 출혈 이벤트로 이어집니다. 다시에 내피 상처 여백에서 무 결함 부상의 혈전증과 재 협착 (5) 예방에 가장 중요하다. 스텐트의 범위가 6,7 스트럿과 부검 결과 및 동물 모델을 효과적으로 혈전증의 감소 속도를 보여 주었다. 약물 방출 스텐트는 평활근의 증식과 신생 내막의 증식을 억제하여 재 협착의 비율을 감소 동맥 재 내피 세포 형성에 상당한 장애와 후기 혈전증 3의 증가 속도가 발생할 고안. 불행하게도, 재 내피 세포 형성을위한 메커니즘을 이해하는 것은 주로 AP의 부족에 의해 제한 느린 프로세스왔다propriate 동물 모델 (8). 혈관 손상에 따라 내피 세포와 혈관 평활근 세포의 역할을 이해하기위한 여러 동물 모델 7,9,10 생성되었다. 래트 경동맥 풍선 손상 모델은 가장 특징이 있으며, 총 세포 및 분자 수준에서 11 삭박 손상의 효과를 연구하기 위해 사용되었다. 그럼에도 불구하고, 우수한 생존율과 동맥 발가 벗김 부상의 높은 재현성 쥐 모델은 누락 훨씬 더 다양한 설정에서 혈관 재생을 규명 할 수 여러 유전자 변형 라인을 활용할 필요가있다. 이 원고는 재현하고 수행 간단 동맥 발가 벗김 부상의 쥐 모델을 제시한다. 접근 방식은 여러 유전자 변형 라인에서 최소한의 이환율과 사망률을 보이고있다. 이 때문에, 유전자 변형 마우스 라인의 다양한 숫자,이 모델로 사용될 수있다발가 벗김 부상 후 재 내피 세포 형성의 기초가되는 분자 메커니즘을 규명.

<table><tbody><tr><td>Zeiss Discovery.V12 Stereomicroscope</td><td>Zeiss</td><td>495037-9904-000</td><td></td></tr><tr><td>Rodent Heated Surgical Platform</td><td>Protech International</td><td>RES4000</td><td>Heated platform for body temperature maintenance with nosecone for anesthestic maintenance and on which surgical procedure is performed</td></tr><tr><td>Isoflurane</td><td>Henry Schein</td><td>50033</td><td>4% Induction; 2.5% Maintenance</td></tr><tr><td>Isoflurane Vaporizer</td><td>Summit Medical Equipment</td><td>470062</td><td></td></tr><tr><td>Stryker T/Pump Warm Water Recirculator</td><td>Kent Scientific</td><td>TP-700</td><td></td></tr><tr><td>Artifical Tears Lubricant Opthalmic Ointment</td><td>Akorn Animal Health</td><td>17478-162-35</td><td></td></tr><tr><td>Carprieve (Carprofen)</td><td>Norbrook Laboratories</td><td>NDC 55529-131-01</td><td></td></tr><tr><td>Oster&amp;trade; A5 Professional Animal Clipper</td><td>M.Schneider &amp;amp; Sons Inc.</td><td>78005010</td><td>Use with animal clipper size 40</td></tr><tr><td>Adjustable Wire Retractor</td><td>Fine Science Tools</td><td>17004-05</td><td></td></tr><tr><td>Schwartz Micro Serrefines - Sharp Bend</td><td>Fine&amp;nbsp;Science Tools</td><td>18052-03</td><td></td></tr><tr><td>Surgical Instruments</td><td>Fine Science Tools</td><td></td><td>sharp dissecting forceps, blunt forceps, fine scissors, spring scissors, hemostat</td></tr><tr><td>0.5% Marcaine</td><td>Hospira</td><td>0409-1610-50</td><td></td></tr><tr><td>5-0 Suture, Vicryl</td><td>Fisher Scientific</td><td>NC0189890</td><td>tapered needle</td></tr><tr><td>Vetbond</td><td>Fisher Scientific</td><td>NC0304169</td><td></td></tr><tr><td>Falcon&amp;reg; 35 mm Not TC-Treated Easy-Grip Style Bacteriological Petri Dish</td><td>Corning</td><td>351008</td><td></td></tr><tr><td>Sylgard 184 Silicone Elastomer Kit</td><td>Dow Corning</td><td>3097358-1004</td><td></td></tr><tr><td>Dissecting pins</td><td>Fisher Scientific</td><td>NC9681411</td><td></td></tr></tbody></table>

reproducible arterial denudation injury by infrarenal abdominal aortic clamping in a murine model

경피적 혈관 중재 균일 이후 혈전증과 재 협착을 초래할 동맥 발가 벗김 부상을 초래할. 이러한 합병증은 상처 마진 내에 재에 내피 세포의 손상에 기인한다. 그러나 재에 내피 세포의 세포 및 분자 메커니즘을 정의 할 남아있다. 동맥 발가 벗김 후 재 내피 세포 형성을 연구하는 여러 동물 모델을 사용할 수 있지만, 몇 가지 때문에 수술 제한 마우스로 수행됩니다. 이 형질 전환 마우스를 이용 라인 재에 내피 세포의 처리로 특정 유전자의 기여도를 조사 할 수있는 기회를 약화시킨다. 여기서는 외부 혈관 클램프를 사용하여 infrarenal 복부 대동맥에서 동맥 삭박 부상의 재현성 뮤린 모델을 만들기위한 단계별 프로토콜을 제시한다. 피브리노겐과 β-catenin이에 대한 부상 대동맥의 면역 세포 화학 염색 프로 혈전 표면의 노출을 보여각각 그대로 내피 세포의 국경을 거라고. 여기에 제시된 방법은 트랜스 제닉 마우스 모델에서 동맥 삭박 부상을 부과하기위한 고유 실제 공구를 생성 속도의 우수한 생존율 및 상대 기술 용이성의 이점을 갖는다. 이 방법을 사용하여, 연구자는 정상 또는 병리 적 조건하에 재에 내피 세포의 메카니즘을 해명 할 수있다.

85 마우스는 infrarenal 복부 대동맥 클램핑이 보고서에 기술 된 생존 수술 기법을 겪었다. 생존율은 85.9 %였다. 수술 합병증은 장 출혈과 큰 혈관 천공, 5.9 %와 3.5 %의 사망률의 결과로 각각 (표 1) 포함. 마취에서 회복 한 후, 마우스는 일반적으로 걸어 열등한 사지에 허혈성 손상의 징후를 표시하지 않습니다. 어떤 체중 감소 또는 식욕의 부족은 언급되지 않았다. <...

Watch this Scientific Journal Video about Reproducible Arterial Denudation Injury by Infrarenal Abdominal Aortic Clamping in a Murine Model at JoVE.com

Reproducible Arterial Denudation Injury by Infrarenal Abdominal Aortic Clamping in a Murine Model

동맥 발가 벗김 부상 다음 재에 내피 세포의 세포 및 분자 메커니즘을 이해하는 것은 혈전증과 동맥의 재 협착을 방지하는 가장 중요하다. 여기에서 우리는 infrarenal 복부 대동맥의 재현 동맥 발가 벗김 부상에 대한 프로토콜을 설명합니다. 절차는 마우스 모델을 사용하여 내피 세포 재생을 조절하는 기전을 연구하기 위해 개발되었다.

쥐 모델에서 Infrarenal 복부 대동맥 클램핑에 의해 재현 동맥 발가 벗김 부상

Percutaneous vascular interventions uniformly result in arterial denudation injuries that subsequently lead to thrombosis and restenosis. These ...

reproducible-arterial-denudation-injury-infrarenal-abdominal-aortic

Research

JoVE Journal

Medicine

9.2K 조회수.  University of California, Los Angeles.  동맥 발가 벗김 부상 다음 재에 내피 세포의 세포 및 분자 메커니즘을 이해하는 것은 혈전증과 동맥의 재 협착을 방지하는 가장 중요하다. 여기에서 우리는 infrarenal 복부 대동맥의 재현 동맥 발가 벗김 부상에 대한 프로토콜을 설명합니다. 절차는 마우스 모델을 사용하여 내피 세포 재생을 조절하는 기전을 연구하기 위해 개발되었다. 

비디오: Reproducible Arterial Denudation Injury by Infrarenal Abdominal Aortic Clamping in a Murine Model

Use of a Hanging-weight System for Isolated Renal Artery Occlusion

In hospitalized patients, over 50% of cases of acute kidney injury (AKI) are caused by renal ischemia 1-3. A recent study of hospitalized patients revealed that only a mild increase in serum creatinine levels (0.3 to 0.4 mg/dl) is associated with a 70% greater risk of death than in persons without any increase 1. Along these lines, surgical procedures requiring cross-clamping of the aorta and renal vessels are associated with a renal failure rates of up to 30% 4. Similarly, AKI after cardiac surgery occurs in over 10% of patients under normal circumstances and is associated with dramatic increases in mortality. AKI are also common complications after liver transplantation. At least 8-17% of patients end up requiring renal replacement therapy 5. Moreover, delayed graft function due to tubule cell injury during kidney transplantation is frequently related to ischemia-associated AKI 6. Moreover, AKI occurs in approximately 20% of patients suffering from sepsis 6.The occurrence of AKI is associated with dramatic increases of morbidity and mortality 1. Therapeutic approaches are very limited and the majority of interventional trials in AKI have failed in humans. Therefore, additional therapeutic modalities to prevent renal injury from ischemia are urgently needed 3, 7-9. 
To elucidate mechanisms of renal injury due to ischemia and possible therapeutic strategies murine models are intensively required 7-13. Mouse models provide the possibility of utilizing different genetic models including gene-targeted mice and tissue specific gene-targeted mice (cre-flox system). However, murine renal ischemia is technically challenging and experimental details significantly influence results. We performed a systematic evaluation of a novel model for isolated renal artery occlusion in mice, which specifically avoids the use of clamping or suturing the renal pedicle 14. This model requires a nephrectomy of the right kidney since ischemia can be only performed in one kidney due to the experimental setting. In fact, by using a hanging-weight system, the renal artery is only instrumented once throughout the surgical procedure. In addition, no venous or urethral obstruction occurs with this technique. We could demonstrate time-dose-dependent and highly reproducible renal injury with ischemia by measuring serum creatinine. Moreover, when comparing this new model with conventional clamping of the whole pedicle, renal protection by ischemic preconditioning is more profound and more reliable. Therefore his new technique might be useful for other researchers who are working in the field of acute kidney injury.

A precise murine model for acute kidney injury (AKI) due to ischemia is an important tool to investigate acute kidney injury and possibly find therapeutic tools to treat renal injury. The hanging weight system offers a tool for immediate and reliable renal artery occlusion and reperfusion without causing renal congestion.

절연 신장 동맥 폐색에 대한 한깅 - 무게 시스템의 사용

In hospitalized patients, over 50% of cases of acute kidney injury (AKI) are caused by renal ischemia 1-3. A recent study of hospitalized patients ...

연구

의학

A New Murine Model of Endovascular Aortic Aneurysm Repair

Endovascular aneurysm exclusion is a validated technique to prevent aneurysm rupture. Long-term results highlight technique limitations and new aspects of Abdominal aortic aneurysm (AAA) pathophysiology. There is no abdominal aortic aneurysm endograft exclusion model cheap and reproducible, which would allow deep investigations of AAA before and after treatment. We hereby describe how to induce, and then to exclude with a covered coronary stentgraft an abdominal aortic aneurysm in a rat. The well known elastase induced AAA model was first reported in 19901 in a rat, then described in mice2. Elastin degradation leads to dilation of the aorta with inflammatory infiltration of the abdominal wall and intra luminal thrombus, matching with human AAA. Endovascular exclusion with small covered stentgraft is then performed, excluding any interactions between circulating blood and the aneurysm thrombus. Appropriate exclusion and stentgraft patency is confirmed before euthanasia by an angiography thought the left carotid artery. Partial control of elastase diffusion makes aneurysm shape different for each animal. It is difficult to create an aneurysm, which will allow an appropriate length of aorta below the aneurysm for an easy stentgraft introduction, and with adequate proximal and distal neck to prevent endoleaks. Lots of failure can result to stentgraft introduction which sometimes lead to aorta tear with pain and troubles to stitch it, and endothelial damage with post op aorta thrombosis. Giving aspirin to rats before stentgraft implantation decreases failure rate without major hemorrhage. Clamping time activates neutrophils, endothelium and platelets, and may interfere with biological analysis.

Histological and biochemical modifications after aneurysm endograft exclusion are still unclear. We describe a new model of endograft implantation on a murine aneurysm. Through thrombus analysis with and without persistant circulating blood stream interface, and new endovascular biomaterials evaluation, this model will help to better understand endovascular aneurysm exclusion pathobiology.

혈관 동맥류 수리의 새로운 쥐과 모델

Endovascular aneurysm exclusion is a validated technique to prevent aneurysm rupture. Long-term results highlight technique limitations and new aspects of ...

Reproducable Paraplegia by Thoracic Aortic Occlusion in a Murine Model of Spinal Cord Ischemia-reperfusion

Background 
Lower extremity paralysis continues to complicate aortic interventions. The lack of understanding of the underlying pathology has hindered advancements to decrease the occurrence this injury.&#160;The current model demonstrates reproducible lower&#160;extremity paralysis following thoracic aortic occlusion.
Methods 
Adult male C57BL6 mice were anesthetized with isoflurane. Through a cervicosternal incision the aorta was exposed. The descending thoracic aorta and left subclavian arteries were identified without entrance into pleural space. Skeletonization of these arteries was followed by immediate closure (Sham) or occlusion for 4 min (moderate ischemia) or 8 min (prolonged ischemia). The sternotomy and skin were closed and the mouse was transferred to warming bed for recovery.&#160; Following recovery, functional analysis was obtained at 12 hr intervals until 48 hr.
Results 
Mice that underwent sham surgery showed no observable hind&#160;limb deficit. Mice subjected to moderate ischemia for 4 min had minimal functional deficit at 12 hr followed by progression to complete paralysis at 48 hr. Mice subjected to prolonged ischemia had an immediate paralysis with no observable hind-limb movement at any point in the postoperative period. There was no observed intraoperative or post&#160;operative mortality.
Conclusion 
Reproducible lower extremity paralysis whether immediate or delayed can be achieved in a murine model. Additionally, by using a median sternotomy and careful dissection, high survival rates, and reproducibility can be achieved.

The lack of mechanistic understanding of spinal cord ischemia-reperfusion injury has hindered further adjuncts to prevent paraplegia following high risk aortic operations. Thus, the development of animal models is imperative. This manuscript demonstrates reproducible lower extremity paralysis following thoracic aortic occlusion in a murine model.

척수 허혈 - 재관류의 생쥐 모델에서 흉부 대동맥 폐색에 의해 재생산 할 하반신 마비

Background
Lower extremity paralysis continues to complicate aortic interventions. The lack of understanding of the underlying pathology has hindered ...

Creation of a Rodent Model of Abdominal Aortic Aneurysm by Blocking Adventitial Vasa Vasorum Perfusion

The adventitial vasa vasorum (VV) provides oxygen and nourishment to the aortic wall. Hypoxia in the aortic wall can cause enlarged abdominal aortic aneurysms (AAAs). This article introduces and describes a standard protocol used to induce AAAs through adventitial VV hypoperfusion created with a combination of polyurethane catheter insertion into the aortic lumen and suture ligation of the infrarenal abdominal aorta.
The protocol involves the use of male rats weighing 300-400 g, which are provided food and water ad libitum. After laparotomy with a ventral midline abdominal incision, exfoliation of the aorta is performed, which blocks blood flow from the perivascular tissue. Aortotomy involving a small incision adjacent to the renal artery branches is performed, and a polyurethane catheter is inserted using an 18-gauge indwelling needle. After repairing the incision, tight ligation of the aorta over the catheter blocks VV blood flow from the proximal direction through the aortic wall without disturbing the aortic blood flow. This technique can induce an AAA with progressive aortic dilatation.
The greatest benefit of this model is that VV hypoperfusion causes tissue hypoxia and the development of an infrarenal AAA, which has morphological and pathological characteristics similar to those of a human AAA.

Polyurethane catheter insertion into the aortic lumen and suture ligation of the aorta induce chronic hypoxia due to hypoperfusion of the adventitial vasa vasorum. This article describes a novel animal model of abdominal aortic aneurysm (AAA) with characteristics similar to those of AAA in humans.

Adventitial 바사 Vasorum 관류를 차단 하 여 복 부 대동맥 동맥 류의 설치류 모델의 생성

The adventitial vasa vasorum (VV) provides oxygen and nourishment to the aortic wall. Hypoxia in the aortic wall can cause enlarged abdominal aortic ...

Reproducible Motor Deficit Following Aortic Occlusion in a Rat Model Of Spinal Cord Ischemia

Spinal cord ischemia is a fatal complication following thoracoabdominal aortic aneurysm surgery. Researchers can investigate the strategies for preventing and treating this complication using experimental models of spinal cord ischemia. The model described here demonstrates varying degrees of paraplegia that relate to the length of occlusion following thoracic aortic occlusion in a rat spinal cord ischemia model.
A 2-Fr. balloon-tipped catheter was advanced through the femoral artery into the descending thoracic aorta until the catheter tip was placed at the left subclavian artery in anesthetized male Sprague-Dawley rats. Spinal cord ischemia was induced by inflating the catheter balloon. After a set period of occlusion (9, 10, or 11 min), the balloon was deflated. Neurologic assessment was performed using the motor deficit index at 24 h after surgery, and the spinal cord was harvested for histopathological examination.
Rats that underwent 9 min of aortic occlusion showed mild and reversible motor impairment in the hind limb. Rats subjected to 10 min of aortic occlusion presented with moderate but reversible motor impairment. Rats subjected to 11 min of aortic occlusion displayed complete and persistent paralysis. The motor neurons in the spinal cord sections were more preserved in rats subjected to shorter duration of aortic occlusion.
Researchers can achieve a reproducible hind limb motor deficit following thoracic aortic occlusion using this spinal cord ischemia model.

This study demonstrates the technique to make a minimally invasive and easily reproducible model of spinal cord ischemia in rats. Various degrees of hind limb motor deficit can be produced by controlling the aortic occlusion time.

척수 쇄 허혈 모델에서 대동맥 폐쇄 후 재현성 운동 부족

Spinal cord ischemia is a fatal complication following thoracoabdominal aortic aneurysm surgery. Researchers can investigate the strategies for preventing ...

Balloon-based Injury to Induce Myointimal Hyperplasia in the Mouse Abdominal Aorta

The use of animal models is essential for a better understanding of MH, one major cause for arterial stenosis.In this article, we demonstrate a murine balloon denudation model, which is comparable with established vessel injury models in large animals. The aorta denudation model with balloon catheters mimics the clinical setting and leads to comparable pathobiological and physiological changes. Briefly, after performing a horizontal incision in the aorta abdominalis, a balloon catheter will be inserted into the vessel, inflated, and introduced retrogradely. Inflation of the balloon will lead to intima injury and overdistension of the vessel. After removing the catheter, the aortic incision will be closed with single stiches. The model shown in this article is reproducible, easy to perform, and can be established quickly and reliably. It is especially suitable for evaluating expensive experimental therapeutic agents, which can be applied in an economical fashion. By using different knockout-mouse strains, the impact of different genes on MH development can be assessed.

This article demonstrates a murine model to study the development of myointimal hyperplasia (MH) after aortic balloon injury.

풍선-기반 부상 마우스 복 부 대동맥에서 Myointimal 증식을 유도 하

The use of animal models is essential for a better understanding of MH, one major cause for arterial stenosis.In this article, we demonstrate a murine ...

Quantitative Micro-CT Analysis of Aortopathy in a Mouse Model of &#946;-aminopropionitrile-induced Aortic Aneurysm and Dissection

Aortic aneurysm and dissection is associated with significant morbidity and mortality in the population and can be highly lethal. While animal models of aortic disease exist, in vivo imaging of the vasculature has been limited. In recent years, micro-computerized tomography (micro-CT) has emerged as a preferred modality for imaging both large and small vessels both in vivo and ex vivo. In conjunction with a method of vascular casting, we have successfully used micro-CT to characterize the frequency and distribution of aortic pathology in &#946;-aminopropionitrile-treated C57/Bl6 mice. Technical limitations of this method include variations in the quality of the perfusion introduced by poor animal preparation, the application of proper methodologies for vessel size quantification, and the non-survivability of this procedure. This article details a methodology for the intravascular perfusion of a lead-based radiopaque silicone rubber for the quantitative characterization of aortopathy in a mouse model of aneurysm and dissection. In addition to visualizing aortic pathology, this method may be used for examining other vascular beds in vivo or vascular beds removed post-mortem.

This article describes a detailed methodology of using a radiopaque lead-based silicone rubber to perfuse the murine vasculature for aortic diameter quantification in a mouse model of aortic aneurysm and dissection.

Β-aminopropionitrile-유도 대동맥 동맥 및 해 부의 마우스 모델에서 Aortopathy의 양적 마이크로 CT 분석

Aortic aneurysm and dissection is associated with significant morbidity and mortality in the population and can be highly lethal. While animal models of ...

Murine Cervical Aortic Transplantation Model using a Modified Non-Suture Cuff Technique

With the introduction of powerful immunosuppressive protocols, distinct advances are possible in the prevention and therapy of acute rejection episodes. However, only minor improvement in the long-term results of transplanted solid organs could be observed over the past decades. In this context, chronic allograft vasculopathy (CAV) still represents the leading cause of late organ failure in cardiac, renal and pulmonary transplantation.
Thus far, the underlying pathogenesis of CAV development remains unclear, explaining why effective treatment strategies are presently missing and emphasizing a need for relevant experimental models in order to study the underlying pathophysiology leading to CAV formation. The following protocol describes a murine heterotopic cervical aortic transplantation model using a modified non-suture cuff technique. In this technique, a segment of the thoracic aorta is interpositioned in the right common carotid artery. With the use of the non-suture cuff technique, an easy to learn and reproducible model can be established, minimizing the possible heterogeneity of sutured vascular micro anastomoses.

Here, we present a protocol of heterotopic aortic transplantation in mice using the non-suture cuff technique in a cervical murine model. This model can be used to study the underlying pathology of chronic allograft vasculopathy (CAV) and can help evaluate new therapeutic agents in order to prevent its formation.

수정된 비봉합사 커프 기술을 사용한 뮤린 자궁 경부 대동맥 이식 모델

With the introduction of powerful immunosuppressive protocols, distinct advances are possible in the prevention and therapy of acute rejection episodes. ...

Murine Surgical Model of Topical Elastase Induced Descending Thoracic Aortic Aneurysm

According to the Center for Disease Control, aortic aneurysms (AAs) were considered a leading cause of death in all races and both sexes from 1999-2016. An aneurysm forms as a result of progressive weakening and eventual dilation of the aorta, which can rupture or tear once it reaches a critical diameter. Aneurysms of the descending aorta in the chest, called descending thoracic aortic aneurysms (dTAA), make up a large proportion of aneurysm cases in the United States. Uncontained dTAA rupture is almost universally lethal, and elective repair has a high rate of morbidity and mortality. The purpose of our model is to study dTAA specifically, to elucidate the pathophysiology of dTAA and to search for molecular targets to halt the growth or reduce the size of dTAA. By having a murine model to study thoracic pathology precisely, targeted therapies can be developed to specifically test dTAA. The method is based on the placement of porcine pancreatic elastase (PPE) directly on the outer murine aortic wall after surgical exposure. This creates a destructive and inflammatory reaction, which weakens the aortic wall and allows for aneurysm formation over weeks to months. Though murine models possess limitations, our dTAA model produces robust aneurysms of predictable size. Furthermore, this model can be used to test genetic and pharmaceutical targets which may arrest dTAA growth or prevent rupture. In human patients, interventions such as these could help avoid aneurysm rupture, and difficult surgical intervention.

We describe a surgical protocol to consistently induce robust descending thoracic aortic aneurysms in mice. The procedure involves left thoracotomy, thoracic aorta exposure, and placement of a sponge soaked in porcine pancreatic elastase on the aortic wall.

국소 엘라스타아제의 뮤린 외과 모델은 내림차순 흉부 대동맥류를 유도

According to the Center for Disease Control, aortic aneurysms (AAs) were considered a leading cause of death in all races and both sexes from 1999-2016. ...

Porcine Model of Infrarenal Abdominal Aortic Aneurysm

Large animal models to study abdominal aortic aneurysms are sparse. The purpose of this model is to create reproducible, clinically significant infrarenal abdominal aortic aneurysms (AAA) in swine. To achieve this, we use a combination of balloon angioplasty, elastase and collagenase, and a lysyl oxidase inhibitor, called &#946;-aminopropionitrile (BAPN), to create clinically significant infrarenal aortic aneurysms, analogous to human disease.
Noncastrated male swine are fed BAPN for 7 days prior to surgery to achieve a steady state in the blood. A midline laparotomy is performed and the infrarenal aorta is circumferentially dissected. An initial measurement is recorded prior to aneurysm induction with a combination of balloon angioplasty, elastase (500 units)/collagenase (8000 units) perfusion, and topical elastase application. Swine are fed BAPN daily until terminal procedure on either postoperative day 7, 14, or 28, at which time the aneurysm is measured, and tissue procured. BAPN + surgery pigs are compared to pigs that underwent surgery alone.
Swine treated with BAPN and surgery had a mean aortic dilation of 89.9% &#177; 47.4% at day 7, 105.4% &#177; 58.1% at day 14, and 113.5% &#177; 30.2% at day 28. Pigs treated with surgery alone had significantly smaller aneurysms compared to BAPN + surgery animals at day 28 (p &#60; 0.0003). The BAPN + surgery group had macroscopic and immunohistochemical evidence of end stage aneurysmal disease.
Clinically significant infrarenal AAA can be induced using balloon angioplasty, elastase/collagenase perfusion and topical application, supplemented with oral BAPN. This model creates large, clinically significant AAA with hallmarks of human disease. This has important implications for the elucidation of AAA pathogenesis and testing of novel therapies and devices for the treatment of AAA. Limitations of the model include variation in BAPN ingested by swine, quality of elastase perfusion, and cost of BAPN.&#160;

This novel model creates robust infrarenal abdominal aortic aneurysms in swine using a combination of balloon angioplasty, elastase/collagenase perfusion, topical elastase application, and oral compound &#946;-aminopropionitrile administration, which interferes with collagen cross-linking.

돼지 모델 의 관막 복 대동맥류

Large animal models to study abdominal aortic aneurysms are sparse. The purpose of this model is to create reproducible, clinically significant infrarenal ...