저자는이 프로젝트의 재정 지원을위한 생명 공학 교실, 인도의 정부를 인정합니다. Ajith 쿠마 GS는 과학 및 의학 연구, 인도 정부의 인도위원회에서 선임 연구 활동과 산업 연구, 인도 정부와 Binil 주권의 이사회에서 선임 연구 활동에 지원되었다.

동물 실험 기관 동물 윤리위원회의 승인을 얻은 후 시행 하였다. 위 스타 쥐 라이트 사이클 (CPCSEA 지침에 따라) 음식과 물을 임의로와 일정한 실내 온도 (24 ± 2 ° C)에 12 시간의 어두운에서 보관 하였다. 1) 수술 전 관리 및 마취 <ol><li> (: 물 500 ㎎ / L 용량) 경구 아목시실린을 투여하여 수술 전 항생제 우산 24 시간에서 쥐 (약 200 g 체중)을 유지합니다. </li><li> 15 분 동안 121 ° C에서 고압 증기 멸균에 의해 (가위, 집게, 클립 도포, 봉합 바늘, 바늘 홀더 등) 모든 수술 도구를 소독. </li><li> 심박수의 급격한 감소를 방지하기 위해 37 ° C의 주위 동물의 체온을 유지하기 위해 가열 패드를 사용한다. </li><li> 수술 전과 동안 동물의 탈수를 방지하기 위해주의하십시오. </li><li> 혼합 3 % 이소 플루 란으로 유도 챔버에서 래트를 마취0.5 ~ 1.0 L / 분 100 % 산소; 1.5 % 이소 플루 란으로 마취를 유지한다. </li><li> 성공적인 마취를 확인하기 위해 페달 반사를 확인합니다. </li></ol> 수술 부위의 2) 준비 <ol><li> 앙와위에서의 온도 제어 난방 패드의 상단에있는 쥐를 유지합니다. </li><li> 코 콘 마취를 유지하면서 위치에 동물을 유지하기 위해 쥐의 앞니에 고무 밴드를 배치합니다. </li><li> 목 둘레에서 모피를​​ 제거하고 (바람직하게는 전기 면도기를 사용) 쥐의 가슴 영역을 떠났다. </li><li> 다음 포비돈 - 요오드 용액과 70 % 에틸 알코올로 수술 부위를 소독. </li><li> 수술 절차 중에 만 수술 부위를 노출하는 멸균 드레이프를 사용합니다. 주 : 동물 보호를위한 추가 옵션으로 0.25 % Bupivicaine ID (2.5 ㎎ / ㎏)의 사전 국소 마취 / 무통 각 절개 사이트에서 절개에 통합 될 수있다. </li></ol> 쥐 3) 기관 흡인 삽관 <ol><li> 무균 수술 블레이드를 사용하여 기관에 피부 병렬에 작은 절개를 조심스럽게기도를 노출하기 위해 기본이되는 조직을 분리합니다. </li><li> 기관 아래 4-0 실크 봉합사 스레드의 넥타이를 적용하고 부드럽게 위쪽으로 넥타이를 올립니다. </li><li> 두 연골 고리 사이에 절반 방법의 절개를하고 쥐의 기관으로 기관 캐뉼라를 삽입합니다. </li><li> / 분, 1.70 ML의 호흡량과 (200g의 체중을 가진 쥐의 경우) 0.60 초 영감 시간 50 호흡의 호흡을 유지하기위한 설치류 인공 호흡기에 기관의 캐 뉼러를 연결합니다. </li></ol> 오름차순 대동맥 4) 수축 <ol><li> 손가락 리브의 위치를​​ 감지 한 후, 두 번째 및 세 번째 늑골 사이 왼쪽 가슴 벽에 약 2 ㎝의 피부 절개를 만든다. </li><li> 계층 늑간근 층을 분리하고 두 번째 및 세 번째 늑골 간 약 1.5 cm 긴 절개. (케어는 가지고 있어야한다갈비뼈 사이의 절개를하는 동안 폐에 부상을 방지하기 위해 N) </li><li> 갈비뼈를 철회하고 대동맥의 상승 부​​분을 찾습니다. </li><li> 원래 직경의 50 ~ 60 %에 대동맥을 죄기있다 주걱의 도움으로 상행 대동맥 주위에 작은 크기의 티타늄 클립을 놓습니다. </li><li> 대동맥 협착 다음, 중단 봉합 패턴에서 3.0 prolene을 가진 두 번째 및 세 번째 갈비뼈를 근사화. 동시에, 폐를 다시 팽창하기 위해 약 2-4 초 동안 인공 호흡기를 일시 중지합니다. </li><li> 3.0 prolene의 봉합 및 중단 봉합 패턴 4.0 실크 봉합사로 피부와 근육 층을 나란히 놓는다. 합성 비 흡수성 봉합사는 피부를 봉합 대신 실크 사용할 수 있습니다. </li><li> 한 번자가 호흡이 다시 설립 쥐에서 기관 캐뉼라를 제거합니다. </li><li> 3.0 prolene의 봉합 및 4.0 실크 봉합사로 피부 층을 가진 기관의 개방을 닫습니다. </li><li> 동물이 t에 복구 할 수그는 점차 마취 및 인공 호흡기의 도움 호흡을 낮추는 방법으로 패드를 가열. </li><li> 나이 일치 가짜 대조군에서 상행 대동맥의 수축없이 절개술 및 개흉술을 수행합니다. </li></ol> 5) 수술 후 관리 <ol><li> 포비돈 - 요오드 용액으로 수술 영역을 소독. </li><li> 수술 후 진통제로, 1 주 동안 (10 ㎎ / ㎏ 체중 / 일) 트라마돌의 복강 내 주입. </li><li> 탈수의 징후가 수술 (약 1 ㎖) 후 나타날 경우 멸균 생리 식염수를 복강 내 주입한다. </li><li> 칠일 (: 물 500 ㎎ / L 용량)의 경우, 혼합 된 식수, 경구 아목시실린을 관리 할 수​​ 있습니다. </li><li> 흡입 마취하에 수술 10 일 후 피부에 남아있는 실크 봉합사를 제거합니다. </li></ol> 오름차순 대동맥의 성공적인 수축의 6) 확인 <ol><li> INTEN을 결정하는 트랜스 흉부 두 차원 도플러 심 초음파 검사를 수행상행 대동맥의 수축에 의해 생성 된 압력 과부하 SITY. </li><li> 앞에서 설명한대로 쥐 1 주일 후 수술을 마취 (단계 1.5) </li><li> 상행 대동맥의 수축 부분에 걸쳐 압력 구배를 기록 위에 흉골 위치에 초음파 변환기를 놓습니다. 주 : 대동맥 수축 사이트에서 수은의 약 60 mm의 압력 구배와 쥐에 대한 8~10주 수술을 우편으로 심각한 심장 비대를 개발합니다. </li></ol>

<ol>
	<li>Patten, R. D., Hall-Porter, M. R. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Small+animal+models+of+heart+failure:+development+of+novel+therapies,+past+and+present.">Small animal models of heart failure: development of novel therapies, past and present.</a> Circ Heart Fail. 2, 138-144 (2009).</li><li>Weinberg, E. 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Effects on coronary resistance, contractility, and relaxation.</a> J Clin Invest. 86, 1913-1920 (1990).</li><li>Hasenfuss, G. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Animal+models+of+human+cardiovascular+disease,+heart+failure+and+hypertrophy.">Animal models of human cardiovascular disease, heart failure and hypertrophy.</a> Cardiovasc Res. 39, 60-76 (1998).</li><li>Litwin, S. E., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Serial+echocardiographic-Doppler+assessment+of+left+ventricular+geometry+and+function+in+rats+with+pressure-overload+hypertrophy.+Chronic+angiotensin-converting+enzyme+inhibition+attenuates+the+transition+to+heart+failure.">Serial echocardiographic-Doppler assessment of left ventricular geometry and function in rats with pressure-overload hypertrophy. Chronic angiotensin-converting enzyme inhibition attenuates the transition to heart failure.</a> Circulation. 91, 2642-2654 (1995).</li><li>Miyamoto, M. I., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Adenoviral+gene+transfer+of+SERCA2a+improves+left-ventricular+function+in+aortic-banded+rats+in+transition+to+heart+failure.">Adenoviral gene transfer of SERCA2a improves left-ventricular function in aortic-banded rats in transition to heart failure.</a> Proc Natl Acad Sci U S A. 97, 793-798 (2000).</li><li>Kagaya, Y., Hajjar, R. J., Gwathmey, J. K., Barry, W. H., Lorell, B. 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저자가 공개하는 게 없다.

압력 과부하 유도뿐만 아니라 심장 비대 및 심장 마비에 대한 몇 가지 수술 모델이 있습니다. 작은 동물에서 Lorell와 동료는 우리가 여기에서 기술 한 모델을 개발하고 그들이 보상 심장 비대 팔주 후 대동맥 밴딩 5의 발생을보고했다. 심장의 변화는 점차적으로 대상 부전 상태로 진행​​ 한 후 심장 마비의 원인. 이 모델의 가장 큰 장점은 좌심실 압력의 증가와 만성 고혈압의 임상 적 상?...

작은 동물 모델은 심장 비대 및 심장 마비로의 진행의 개발에 만성 변화의 연구에 대한 가장 선호하는 도구입니다. 이 동물이 열려 가슴 수술, 중환자 실의 심 초음파 검사 및 평가에 최적으로 수술 방법에 의한 심장 마비 모델은 원래 쥐에서 개발되었다. 또한 세포 조직 및 분자 수준의 연구 1 적절한 사후 샘플을 제공합니다. 대동맥의 수축 압력 과부하 심부전 2, 3을 생성하기위한 가장 일반적인 성공적인 수술 모델 중의 하나이다. 이 모델은 잘 비대에서 심장 마비 4로 전환하는 동안 세포 및 서브 셀룰러 리모델링 이벤트와 심장의 수축 특성을 연구하기에 적합합니다. 이 모델의 주요 이점은, 심장 05 압력 과부하 점진적 발병 &lt;/&gt; 6 한모금. 이 모델은 보상 때문에 심장 비대에서 대상성 상에 마지막으로 심장 마비 단계로의 느리지 만 꾸준한 진행의 임상 적으로 관련이 있습니다. 심장 마비와 관련된 생리적 변화에 심장 비대의 진행에 대한 지속 시간은 주로 ​​7을 생산 협착의 정도에 의해 영향을 받는다. 상행 대동맥 협착이 봉합사를 사용하거나 금속 클립 (8, 9)의인가에 의해 하나, 두 가지 방법으로 수행 될 수있다. 대동맥 수축을위한 금속 클립을 사용하는 주요 장점은 수술 절차가 덜 복잡하고 있다는 점이다. 이 방법에서는 하나는 위에 판막 상행 대동맥을 찾아 수축의 원하는 수준을 얻기 위해 대동맥 주위에 클립을 삽입 할 수 있습니다. 가슴 트랙터는이 절차에서 필요하지 않습니다. 봉합에 의한 대동맥 밴딩은 상행 대동맥 옆에 게이지 바늘을 배치하고 그 주위 봉합에 대한 더 많은 수술 조작을 필요로대동맥 협착의 원하는 수준을 생산하고 있습니다. 후자의 기술은 대동맥 수축을위한 금속 클립의 사용과 비교할 때 더 많은 시간이 소요되는 것이다. 이 비디오에서 설명하는 방법은 창조의 압력 과부하 좌심실 비대 모델을 할 수 있습니다 쥐의 대동맥 수축 상승에 대한 수술을 보여줍니다.

<table border="0" cellpadding="0" cellspacing="0" width="742">
	<tbody>
		<tr height="21">
			<td height="21" style="height:21px;width:255px;">Wistar rats</td>
			<td style="width:149px;"></td>
			<td style="width:119px;"></td>
			<td style="width:220px;">Maintained at ARF, RGCB</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:255px;">Inhalation anaesthesia systems&#160;</td>
			<td style="width:149px;">VetEquip</td>
			<td style="width:119px;">AB19276</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:255px;">Rodent ventilator</td>
			<td style="width:149px;">CWE Inc</td>
			<td style="width:119px;">SAR- 830/AP&#160;</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:255px;">Rat tracheal cannula</td>
			<td style="width:149px;">CWE Inc</td>
			<td style="width:119px;">13-21032</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:255px;">Ultrasound system</td>
			<td style="width:149px;">Philips</td>
			<td style="width:119px;">HD7</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:255px;">Ultrasound transducer</td>
			<td style="width:149px;">Philips</td>
			<td style="width:119px;">S 12</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:255px;">Titanium clip (small)</td>
			<td style="width:149px;">Horizon</td>
			<td style="width:119px;">1204</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:255px;">Clip applicator</td>
			<td style="width:149px;">Weck</td>
			<td style="width:119px;">137081</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:255px;">Electric shaver</td>
			<td style="width:149px;">Vinverth</td>
			<td style="width:119px;">VBT0817</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:255px;">BP blade (size:11)</td>
			<td style="width:149px;">Surgeon</td>
			<td style="width:119px;">REF10111</td>
			<td>Preparation of surgical site</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:255px;">Tramadol</td>
			<td style="width:149px;">Orchid health care</td>
			<td style="width:119px;">OCH043</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:255px;">Amoxycillin Hydrochloride</td>
			<td style="width:149px;">Ranbaxy</td>
			<td style="width:119px;"></td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:255px;">Isoflurane</td>
			<td style="width:149px;">Piramal health care</td>
			<td style="width:119px;">A23M10A</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:255px;">Syringes</td>
			<td style="width:149px;">BD</td>
			<td style="width:119px;">2015-09</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:255px;">4-0 braided silk</td>
			<td style="width:149px;">Diamond</td>
			<td style="width:119px;"></td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:255px;">3-0 prolene</td>
			<td style="width:149px;">Johnson&#38;Johnson</td>
			<td style="width:119px;">NW018</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:255px;">Surgical tape</td>
			<td style="width:149px;">Romsons</td>
			<td style="width:119px;">SH 6301</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:255px;">Povidone iodine</td>
			<td style="width:149px;">Win Medicare</td>
			<td style="width:119px;"></td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:255px;">Temp. controlled heating pad</td>
			<td style="width:149px;">Flamingo</td>
			<td style="width:119px;">HC1003</td>
			<td></td>
		</tr>
	</tbody>
</table>

ascending aortic constriction in rats for creation of pressure overload cardiac hypertrophy model

대동맥 협착을 상승하면 심장 비대 및 심장 마비를 유도 압력 과부하를 만들기위한 가장 일반적이고 성공적인 수술 모델입니다. 여기, 우리는 작은 금속 클립을 사용하여 상행 대동맥의 수축에 의해 쥐의 압력 과부하 및 심장 비대를 만들기위한 자세한 수술 절차를 설명합니다. 마취 후 기관은 기관의 두 연골 고리 사이에 절반 방법의 절개를 통해 정맥을 삽입하여 삽관된다. 이어서 피부 절개는 왼쪽 가슴 벽에 제 늑간의 레벨에서 이루어지고, 근육층은 대동맥의 상승 부​​분을 찾을 클리어된다. 상행 대동맥은 작은 크기의 티타늄 클립을 적용하여 원래의 직경이 50 ~ 60 %로 수축된다. 대동맥 협착 다음, 두 번째 및 세 번째 리브 prolene의 봉합으로 근사화된다. 기관 캐뉼라를 제거 한 번자가 호흡을 다시 설립되었다. 동물은 O를 복구하도록 허용점차적으로 마취를 낮추는 방법으로 가열 패드를 명. 대동맥의 수축에 의해 생성 된 압력 과부하의 강도는 트랜스 흉부 이차원 도플러 초음파 검사를 사용하여 압력 구배를 기록함으로써 결정된다. 전반적으로이 프로토콜은 심장 마비 단계에 보상 심장 비대의 점진적 발병과 진행하는 동안 리모델링 이벤트와 심장의 수축 특성을 연구하는 데 유용합니다.

우리의 실험에서 우리는 80 % 이상 생존율을 달성 할 수 있습니다. 대동맥 수축의 효과는 도플러 심 초음파 검사를 수행하여 확인 하였다. 쥐 (N = 6) 대동맥 수축 사이트에서 수은의 약 60 mm의 압력 구배와 8 주 동안 관찰과 심장 비대의 개발 (그림 1)에 대한 분석을 희생했다. 팔주 후 수술 후 심 초음파 평가는 가짜 운영에 비해, 같은 대동맥 협착을받은 동물의 간 심실 중격 두께, 좌심실...

Watch this Scientific Journal Video about Ascending Aortic Constriction in Rats for Creation of Pressure Overload Cardiac Hypertrophy Model at JoVE.com

Ascending Aortic Constriction in Rats for Creation of Pressure Overload Cardiac Hypertrophy Model

우리는 작은 금속 클립을 사용하여 상행 대동맥의 수축에 의해 위 스타 쥐의 압력 과부하 및 좌심실 비대를 만들기위한 단계별 절차를 설명합니다. 이 모델은 광범위하게 심장 비대 동안 리모델링 변경을 공부하고 이러한 변화의 회귀를위한 전략을 파악하고 평가하기 위해 사용된다.

압력 과부하 심장 비대 모델의 창조를위한 쥐의 대동맥 수축 오름차순

Ascending aortic constriction is the most common and successful surgical model for creating pressure overload induced cardiac hypertrophy and heart ...

ascending-aortic-constriction-rats-for-creation-pressure-overload

Research

JoVE Journal

Medicine

17.0K 조회수.  Rajiv Gandhi Centre for Biotechnology.  우리는 작은 금속 클립을 사용하여 상행 대동맥의 수축에 의해 위 스타 쥐의 압력 과부하 및 좌심실 비대를 만들기위한 단계별 절차를 설명합니다. 이 모델은 광범위하게 심장 비대 동안 리모델링 변경을 공부하고 이러한 변화의 회귀를위한 전략을 파악하고 평가하기 위해 사용된다. 

비디오: Ascending Aortic Constriction in Rats for Creation of Pressure Overload Cardiac Hypertrophy Model

Ultrasound Based Assessment of Coronary Artery Flow and Coronary Flow Reserve Using the Pressure Overload Model in Mice

Transthoracic Doppler echocardiography (TTDE) is a clinically useful, noninvasive tool for studying coronary artery flow velocity and coronary flow reserve (CFR) in humans. Reduced CFR is accompanied by marked intramyocardial and pericoronary fibrosis and is used as an indication of the severity of dysfunction. This study explores, step-by-step, the real-time changes measured in the coronary flow velocity, CFR and systolic to diastolic peak velocity (S/D) ratio in the setting of an aortic banding model in mice. By using a Doppler transthoracic imaging technique that yields reproducible and reliable data, the method assesses changes in flow in the septal coronary artery (SCA), for a period of over two weeks in mice, that previously either underwent aortic banding or thoracotomy. 
During imaging, hyperemia in all mice was induced by isoflurane, an anesthetic that increased coronary flow velocity when compared with resting flow. All images were acquired by a single imager. Two ratios, (1) CFR, the ratio between hyperemic and baseline flow velocities, and (2) systolic (S) to diastolic (D) flow were determined, using a proprietary software and by two independent observers. Importantly, the observed changes in coronary flow preceded LV dysfunction as evidenced by normal LV mass and fractional shortening (FS). 
The method was benchmarked against the current gold standard of coronary assessment, histopathology. The latter technique showed clear pathologic changes in the coronary artery in the form of peri-coronary fibrosis that correlated to the flow changes as assessed by echocardiography. 
The study underscores the value of using a non-invasive technique to monitor coronary circulation in mouse hearts. The method minimizes redundant use of research animals and demonstrates that advanced ultrasound-based indices, such as CFR and S/D ratios, can serve as viable diagnostic tools in a variety of investigational protocols including drug studies and the study of genetically modified strains.

Coronary flow reserve (CFR) is useful for assessment of myocardial oxygen demand and evaluation of cardiovascular risk. This study establishes a step-by-step transthoracic Doppler echocardiographic (TTDE) method for longitudinal monitoring of the changes in CFR, as measured from coronary artery in mice, under the experimental pressure overload of aortic banding.

마우스의 압력 과부하 모델을 사용하여 관상 동맥 흐름 및 관상 동맥 흐름 준비 제도 이사회의 초음파를 바탕으로 평가

Transthoracic Doppler echocardiography (TTDE) is a clinically useful, noninvasive tool for studying coronary artery flow velocity and coronary flow ...

연구

의학

Assessment of Cardiac Morphological and Functional Changes in Mouse Model of Transverse Aortic Constriction by Echocardiographic Imaging

Transverse aortic constriction (TAC) in mice has been used as a valuable model to study mechanisms of cardiac hypertrophy and heart failure1. A reliable noninvasive method is essential to assess real-time cardiac morphological and functional changes in animal models of heart disease. Transthoracic echocardiography represents an important tool for noninvasive assessment of cardiac structure and function2. Here we used a high-resolution ultrasound imaging system to monitor myocardial remodeling and heart failure progression over time in a mouse model of TAC. B-mode, M-mode, and Doppler imaging were used to precisely assess cardiac hypertrophy, ventricular dilatation, and functional deterioration in mice following TAC. Color and pulse wave (PW) Doppler imaging was used to noninvasively measure pressure gradient across the aortic constriction created by TAC and to assess transmitral blood flow in mice. Thus transthoracic echocardiographic imaging provides comprehensive noninvasive measurements of cardiac dimensions and function in mouse models of heart disease.

The goal of this protocol is to noninvasively assess cardiac structural and functional changes in a mouse model of heart disease created by transverse aortic constriction, using B- and M-mode echocardiography and color/pulse wave Doppler imaging.

심 초음파 이미징에 의해 가로 대동맥 수축의 마우스 모델에서 심장 형태 학적 평가 및 기능 변경

Transverse aortic constriction (TAC) in mice has been used as a valuable model to study mechanisms of cardiac hypertrophy and heart failure1. A reliable ...

A Model of Cardiac Remodeling Through Constriction of the Abdominal Aorta in Rats

Heart failure is one of the leading causes of death worldwide. It is a complex clinical syndromethat includes fatigue, dyspnea, exercise intolerance, and fluid retention. Changes in myocardial structure, electrical conduction, and energy metabolism develop with heart failure, leading to contractile dysfunction, increased risk of arrhythmias, and sudden death. Hypertensive heart disease is one of the key contributing factors of cardiac remodeling associated with heart failure. The most commonly-used animal model mimicking hypertensive heart disease is created via surgical interventions, such as by narrowing the aorta. Abdominal aortic constriction is a useful experimental technique to induce a pressure overload, which leads to heart failure. The surgery can be easily performed, without the need for chest opening or mechanical ventilation. Abdominal aortic constriction-induced cardiac pathology progresses gradually, making this model relevant to clinical hypertensive heart failure. Cardiac injury and remodeling can be observed 10 weeks after the surgery. The method described here provides a simple and effective approach to produce a hypertensive heart disease animal model that is suitable for studying disease mechanisms and for testing novel therapeutics.

A rat model of abdominal aortic constriction that induces cardiac hypertrophy and remodeling is described. An efficient, highly-reproducible, and minimally-invasive method is used to provide a simple yet useful platform for research in myocardial hypertrophy and dysfunction.

쥐의 복부 대동맥의 수축을 통해 심장 리모델링의 모델

Heart failure is one of the leading causes of death worldwide. It is a complex clinical syndromethat includes fatigue, dyspnea, exercise intolerance, and ...

Minimally Invasive Transverse Aortic Constriction in Mice

Minimally invasive transverse aortic constriction (MTAC) is a more desirable method for the constriction of the transverse aorta in mice than standard open-chest transverse aortic constriction (TAC). Although transverse aortic constriction is a highly functional method for the induction of high pressure in the left ventricle, it is a more difficult and lengthy procedure due to its use of artificial ventilation with tracheal intubation. TAC is oftentimes also less survivable, as the newer method, MTAC, neither requires the cutting of the ribs and intercostal muscles nor tracheal intubation with a ventilation setup. In MTAC, as opposed to a thoracotomy to access to the chest cavity, the aortic arch is reached through a midline incision in the anterior neck. The thyroid is pulled back to reveal the sternal notch. The sternum is subsequently cut down to the second rib level, and the aortic arch is reached simply by separating the connective tissues and thymus. From there, a suture can be wrapped around the arch and tied with a spacer, and then the sternal cut and skin can be closed. MTAC is a much faster and less invasive way to induce left ventricular hypertension and enables the possibility for high-throughput studies. The success of the constriction can be verified using high-frequency trans-thoracic echocardiography, particularly color Doppler and pulsed-wave Doppler, to determine the flow velocities of the aortic arch and left and right carotid arteries, the dimension of the blood vessels, and the left ventricular function and morphology. A successful constriction will also trigger significant histopathological changes, such as cardiac muscle cell hypertrophy with interstitial and perivascular fibrosis. Here, the procedure of MTAC is described, demonstrating how the resulting flow changes in the carotid arteries can be examined with echocardiography, gross morphology, and histopathological changes in the heart.

Minimally invasive transverse aortic constriction (MTAC) conserves the essentials of regular transverse aortic constriction (TAC) while eliminating the use of a ventilator with tracheal intubation. It proves to be a highly desirable method for high-throughput studies on left ventricular overload, particularly in translational studies.

마우스의 최소 침습 가로 대동맥 수축

Minimally invasive transverse aortic constriction (MTAC) is a more desirable method for the constriction of the transverse aorta in mice than standard ...

Technique of Minimally Invasive Transverse Aortic Constriction in Mice for Induction of Left Ventricular Hypertrophy

Transverse aortic constriction (TAC) in mice is one of the most commonly used surgical techniques for experimental investigation of pressure overload-induced left ventricular hypertrophy (LVH) and its progression to heart failure. In the majority of the reported investigations, this procedure is performed with intubation and ventilation of the animal which renders it demanding and time-consuming and adds to the surgical burden to the animal. The aim of this protocol is to describe a simplified technique of minimally invasive TAC without intubation and ventilation of mice. Critical steps of the technique are emphasized in order to achieve low mortality and high efficiency in inducing LVH.
Male C57BL/6 mice (10-week-old, 25-30 g, n=60) were anesthetized with a single intraperitoneal injection of a mixture of ketamine and xylazine. In a spontaneously breathing animal following a 3-4 mm upper partial sternotomy, a segment of 6/0 silk suture threaded through the eye of a ligation aid was passed under the aortic arch and tied over a blunted 27-gauge needle. Sham-operated animals underwent the same surgical preparation but without aortic constriction. The efficacy of the procedure in inducing LVH is attested by a significant increase in the heart/body weight ratio. This ratio is obtained at days 3, 7, 14 and 28 after surgery (n = 6 - 10 in each group and each time point). Using our technique, LVH is observed in TAC compared to sham animals from day 7 through day 28. Operative and late (over 28 days) mortalities are both very low at 1.7%.
In conclusion, our cost-effective technique of minimally invasive TAC in mice carries very low operative and post-operative mortalities and is highly efficient in inducing LVH. It simplifies the operative procedure and reduces the strain put on the animal. It can be easily performed by following the critical steps described in this protocol.

The aim of this protocol is to describe step-by-step the technique of minimally invasive transverse aortic constriction (TAC) in mice. By elimination of intubation and ventilation which are mandatory for the commonly used standard procedure, minimally invasive TAC simplifies the operative procedure and reduces the strain put on the animal.

왼쪽된 심 실 비 대의 유도 대 한 생쥐에서 최소 침 습 가로 대동맥 수축의 기술

Transverse aortic constriction (TAC) in mice is one of the most commonly used surgical techniques for experimental investigation of pressure ...

A Closed-chest Model to Induce Transverse Aortic Constriction in Mice

Research on cardiac hypertrophy and heart failure is frequently based on pressure overload mouse models induced by TAC. The standard procedure is to perform a partial thoracotomy to visualize the transverse aortic arch. However, the surgical trauma caused by the thoracotomy in open-chest models changes the respiratory physiology as the ribs are dissected and left unattached after chest closure. To prevent this, we established a minimally invasive, closed chest approach via lateral thoracotomy. Herein we approach the aortic arch via the 2nd intercostal space without entering the chest cavities, leaving the mouse with a less traumatic injury to recover from. We perform this operation using standard laboratory settings for open chest TAC procedures with equal survival rates. Apart from maintaining physiological breathing patterns due to the closed chest approach, the mice seem to benefit by showing rapid recovery, as the less invasive technique appears to facilitate a fast healing process and to reduce immune response after trauma.

Here, we present a protocol of Transverse Aortic constriction (TAC) via a lateral thoracotomy. This technique is a minimally invasive, closed chest surgical procedure aiming to simulate pressure overload and heart failure in mice utilizing standard TAC laboratory settings.

마우스에 가로 대동맥 수축 유도를 폐쇄 가슴 모델

Research on cardiac hypertrophy and heart failure is frequently based on pressure overload mouse models induced by TAC. The standard procedure is to ...

A Pulmonary Trunk Banding Model of Pressure Overload Induced Right Ventricular Hypertrophy and Failure

Right ventricular (RV) failure induced by sustained pressure overload is a major contributor to morbidity and mortality in several cardiopulmonary disorders. Reliable and reproducible animal models of RV failure are therefore warranted in order to investigate disease mechanisms and effects of potential therapeutic strategies. Banding of the pulmonary trunk is a common method to induce isolated RV hypertrophy but in general, previously described models have not succeeded in creating a stable model of RV hypertrophy and failure.
We present a rat model of pressure overload induced RV hypertrophy caused by pulmonary trunk banding (PTB) that enables different phenotypes of RV hypertrophy with and without RV failure. We use a modified ligating clip applier to compress a titanium clip around the pulmonary trunk to a pre-set inner diameter. We use different clip diameters to induce different stages of disease progression from mild RV hypertrophy to decompensated RV failure.
RV hypertrophy develops consistently in rats subjected to the PTB procedure and depending on the diameter of the applied banding clip, we can accurately reproduce different disease severities ranging from compensated hypertrophy to severe decompensated RV failure with extra-cardiac manifestations.
The presented PTB model is a valid and robust model of pressure overload induced RV hypertrophy and failure that has several advantages to other banding models including high reproducibility and the possibility of inducing severe and decompensated RV failure.

We present a surgical method to induce right ventricular hypertrophy and failure in rats.

압력 과부하의 모델 밴딩 폐 트렁크 유도 오른쪽 심 실 비 대 및 실패

Right ventricular (RV) failure induced by sustained pressure overload is a major contributor to morbidity and mortality in several cardiopulmonary ...

Operating Transverse Aortic Constriction with Absorbable Suture to Obtain Transient Myocardial Hypertrophy

Based on twice transverse aortic constrictions (TACs) in mice, it is proved that myocardial hypertrophic preconditioning (MHP) could attenuate cardiomyocyte hypertrophy and slow down progression to heart failure. For novices, however, the MHP model is usually quite difficult to establish because of the technical obstacles in ventilator operation, opening the chest repeatedly, and bleeding caused by debanding. To facilitate this model, to increase the surgical success rate and to reduce the incidence of bleeding, we switched to absorbable sutures for the first TAC combing with a ventilator-free technique. Using a 2-week absorbable suture, we demonstrated that this procedure could cause significant myocardial hypertrophy in 2 weeks; and 4 weeks after surgery, myocardial hypertrophy was almost completely regressed to the baseline. Using this protocol, the operators could master the MHP model easily with a lower operation mortality.

This protocol presents an improved method to obtain transient myocardial hypertrophy with absorbable suture, simulating left ventricular hypertrophy decrease after removing pressure overload. It could be valuable for the studies on myocardial hypertrophic preconditioning.

과도 심근 비대증을 얻기 위해 흡수 가능한 봉합사와 횡단 대동맥 수축 을 작동

Based on twice transverse aortic constrictions (TACs) in mice, it is proved that myocardial hypertrophic preconditioning (MHP) could attenuate ...

O-Ring Aortic Banding Versus Traditional Transverse Aortic Constriction for Modeling Pressure Overload-Induced Cardiac Hypertrophy

Aortic banding in mice is one of the most commonly used experimental models for cardiac pressure overload-induced cardiac hypertrophy and the induction of heart failure. The previously used technique is based on a threaded suture around the aortic arch tied over a blunted 27 G needle to create stenosis. This method depends on the surgeon manually tightening the thread and, thus, leads to high variance in the diameter size. A newly refined method described by Melleby et al. promises less variance and more reproducibility after surgery. The new technique, o-ring- aortic banding (ORAB), uses a non-slip rubber ring instead of a suture with a thread, resulting in reduced variation in pressure overload and reproducible phenotypes of cardiac hypertrophy. During surgery, the o-ring is placed between the brachiocephalic and left carotid arteries. Successful constriction is confirmed by echocardiography. After 1 day, correct placement of the ring results in an increased flow velocity in the transverse aorta over the o-ring-induced stenosis. After 2 weeks, impaired cardiac function is proven by decreased ejection fraction and increased wall thickness. Importantly, besides less variance in the diameter size, ORAB is associated with lower intra- and post-operative mortality rates compared with transverse aortic constriction (TAC). Thus, ORAB represents a superior method to the commonly used TAC surgery, resulting in more reproducible results and a possible reduction in the number of animals needed.

The present protocol describes a new technique of aortic banding in mice to induce pressure overload cardiac hypertrophy. For banding, a rubber ring with a fixed inner diameter is used. This new technique promises less variance and more reproducible data for future experiments.

O-링 대동맥 밴딩 대 압력 과부하로 인한 심장 비대 모델링을 위한 기존의 횡대동맥 수축

Aortic banding in mice is one of the most commonly used experimental models for cardiac pressure overload-induced cardiac hypertrophy and the induction of ...

Modified Heterotopic Abdominal Heart Transplantation and a Novel Aortic Regurgitation Model in Rats

Over the past 50 years, many researchers have reported heterotopic abdominal heart transplantation in mice and rats, with some variations in the surgical technique. Modifying the transplantation procedure to strengthen the myocardial protection could prolong the ischemia time while preserving the donor&#39;s cardiac function. This technique&#39;s key points are as follows: transecting the donor&#39;s abdominal aorta before harvesting to unload the donor&#39;s heart; perfusing the donor&#39;s coronary arteries with a cold cardioplegic solution; and topical cooling of the donor&#39;s heart during the anastomosis procedure. Consequently, since this procedure prolongs the acceptable ischemia time, beginners can easily perform it and achieve a high success rate.
Moreover, a new aortic regurgitation (AR) model was established in this work using a technique different from the existing one,&#160;which is created by inserting a catheter from the right carotid artery and puncturing the native aortic valve under continuous echocardiographic guidance. A heterotopic abdominal heart transplantation was performed using the novel AR model. In the protocol, after the donor&#39;s heart is harvested, a stiff guidewire is inserted into the donor&#39;s brachiocephalic artery and advanced toward the aortic root. The aortic valve is punctured by pushing the guidewire further even after the resistance is felt, thus inducing AR. It is easier to damage the aortic valve using this method than with the procedure described in the conventional AR model. Additionally, this novel AR model does not contribute to the recipient&#39;s circulation; therefore, this method is expected to produce a more severe AR model than the conventional procedure.

This study demonstrates a reproducible heterotopic abdominal heart transplantation technique in rats that beginners can learn and perform. Additionally, a novel aortic regurgitation model in rats is generated by performing heterotopic abdominal heart transplantation and damaging the donor's aortic valve using a guidewire after harvesting.

쥐의 수정된 이종 복부 심장 이식 및 새로운 대동맥 역류 모델

Over the past 50 years, many researchers have reported heterotopic abdominal heart transplantation in mice and rats, with some variations in the surgical ...