Name: the left pneumonectomy combined with monocrotaline or sugen as a model of pulmonary hypertension in rats
Uploaded: 2019-03-08T14:30:00
Description: Watch this Scientific Journal Video about The Left Pneumonectomy Combined with Monocrotaline or Sugen as a Model of Pulmonary Hypertension in Rats at JoVE.com

这份手稿得到了 nih 的支持 7r01 hl083078-10 赠款, 来自美国心脏协会 aha-17sdg33370112 和来自国家卫生研究院 nih k01 hl135474 至 y. s. 和从国家卫生研究院 r01 hl133554 至 l. h。

下面描述的程序已得到西奈山伊坎医学院动物护理和使用机构委员会 (iacuc) 的批准。所有老鼠都根据西奈山 "实验动物护理和使用指南" 得到人道照顾。
1. 手术准备
<ol><li>高压冷-梅奥弯曲剪刀 (大剪刀), 直虹膜剪刀 (小剪刀), 麦克弗森-万纳斯虹膜剪刀 (后剪刀), wwensteen 组织钳 (经耳组织钳), 杰拉尔德组织钳, 普通线镜片 (自我固定牵引器)、小血管尾草、纱布、双端探头、薄血?...

<ol>
	<li>Leopold, J., Maron, B. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Molecular+Mechanisms+of+Pulmonary+Vascular+Remodeling+in+Pulmonary+Arterial+Hypertension.">Molecular Mechanisms of Pulmonary Vascular Remodeling in Pulmonary Arterial Hypertension.</a> International Journal of Molecular Sciences. 17 (5), 761 (2016).</li><li>Gomez-Arroyo, J. G., 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=The+monocrotaline+model+of+pulmonary+hypertension+in+perspective.">The monocrotaline model of pulmonary hypertension in perspective.</a> American Journal of Physiology-Lung Cellular and Molecular Physiology. 302 (4), L363-L369 (2012).</li><li>van Albada, M. 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=The+role+of+increased+pulmonary+blood+flow+in+pulmonary+arterial+hypertension.">The role of increased pulmonary blood flow in pulmonary arterial hypertension.</a> European Respiratory Journal. 26 (3), 487-493 (2005).</li><li>Dickinson, M. G., Bartelds, B., Borgdorff, M. A. J., Berger, R. M. F. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+role+of+disturbed+blood+flow+in+the+development+of+pulmonary+arterial+hypertension:+lessons+from+preclinical+animal+models.">The role of disturbed blood flow in the development of pulmonary arterial hypertension: lessons from preclinical animal models.</a> American Journal of Physiology-Lung Cellular and Molecular Physiology. 305 (1), L1-L14 (2013).</li><li>Stenmark, K. R., Meyrick, B., Galie, N., Mooi, W. J., McMurtry, I. F. <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+pulmonary+arterial+hypertension:+the+hope+for+etiological+discovery+and+pharmacological+cure.">Animal models of pulmonary arterial hypertension: the hope for etiological discovery and pharmacological cure.</a> American Journal of Physiology-Lung Cellular and Molecular Physiology. 297 (6), L1013-L1032 (2009).</li><li>Cahill, 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=The+pathophysiological+basis+of+chronic+hypoxic+pulmonary+hypertension+in+the+mouse:+vasoconstrictor+and+structural+mechanisms+contribute+equally.">The pathophysiological basis of chronic hypoxic pulmonary hypertension in the mouse: vasoconstrictor and structural mechanisms contribute equally.</a> Experimental Physiology. 97 (6), 796-806 (2012).</li><li>Okada, K., 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=Pulmonary+hemodynamics+modify+the+rat+pulmonary+artery+response+to+injury.+A+neointimal+model+of+pulmonary+hypertension.">Pulmonary hemodynamics modify the rat pulmonary artery response to injury. A neointimal model of pulmonary hypertension.</a> American Journal of Pathology. 151 (4), 1019-1025 (1997).</li><li>Happ&#233;, C. M., 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=Pneumonectomy+combined+with+SU5416+induces+severe+pulmonary+hypertension+in+rats.">Pneumonectomy combined with SU5416 induces severe pulmonary hypertension in rats.</a> American Journal of Physiology-Lung Cellular and Molecular Physiology. 310 (11), L1088-L1097 (2016).</li><li>Tanaka, Y., Schuster, D. P., Davis, E. C., Patterson, G. A., Botney, M. D. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+role+of+vascular+injury+and+hemodynamics+in+rat+pulmonary+artery+remodeling.">The role of vascular injury and hemodynamics in rat pulmonary artery remodeling.</a> Journal of Clinical Investigation. 98 (2), 434-442 (1996).</li><li>Nishimura, T., Faul, J. L., Berry, G. J., Kao, P. N., Pearl, R. G. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Effect+of+a+surgical+aortocaval+fistula+on+monocrotaline-induced+pulmonary+hypertension.">Effect of a surgical aortocaval fistula on monocrotaline-induced pulmonary hypertension.</a> Critical Care Medicine. 31 (4), 1213-1218 (2003).</li><li>Linardi, D., 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=Ventricular+and+pulmonary+vascular+remodeling+induced+by+pulmonary+overflow+in+a+chronic+model+of+pretricuspid+shunt.">Ventricular and pulmonary vascular remodeling induced by pulmonary overflow in a chronic model of pretricuspid shunt.</a> Journal of Thoracic and Cardiovascular Surgery. 148 (6), 2609-2617 (2014).</li><li>White, R. J., 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=Plexiform-like+lesions+and+increased+tissue+factor+expression+in+a+rat+model+of+severe+pulmonary+arterial+hypertension.">Plexiform-like lesions and increased tissue factor expression in a rat model of severe pulmonary arterial hypertension.</a> American Journal of Physiology-Lung Cellular and Molecular Physiology. 293 (3), L583-L590 (2007).</li><li>Samson, N., Paulin, R. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Epigenetics,+inflammation+and+metabolism+in+right+heart+failure+associated+with+pulmonary+hypertension.">Epigenetics, inflammation and metabolism in right heart failure associated with pulmonary hypertension.</a> Pulmonary Circulation. 7 (3), 572-587 (2017).</li></ol>

在受 pah 影响的肺中, 血管增生与新生内膜形成和肺动脉闭塞导致严重的血流动力学变化, 右心室衰竭和早期死亡7,8。血管壁的变化增加了对血液流动的抵抗力, 增加了动脉和右心室压力。在 pah 的早期, 通常在服用 mct 或苏根后 3周, 大鼠出现了非特异性的组织学改变, 如内侧肥大、外膜增厚以及小动脉和小动脉的肌肉化。这些更改可能是可逆的。在晚期, ?...

肺动脉高压 (pah) 是一种进行性和致命的疾病, 其特点是肺血流增加, 血管阻力增加, 炎症, 并重塑小肺血管 1.这种重塑通常会导致血管病变阻碍和闭塞小肺动脉, 导致血管收缩和增加右心室后负荷 2.pah 的药理治疗方法很少;因此, 与多环芳烃有关的死亡率仍然很高.近年来, 肺动脉高压病理生物学的研究重点已转向血管增殖的机制, 其中增加肺血流的作用被认为是肺血管发育的重要诱因重塑3,4。
肺动脉高压的动物模型提供了重要的见解, 有助于解释疾病的病理生理学, 并成为药物、细胞、基因和蛋白质传递的平台。传统上, 慢性低氧性肺动脉高压模型和 mct 肺损伤模型一直是研究 pah 病理生理学的主要模型5。然而, 与人类患者描述的改变相比, 它们不足以产生更多的肺血流和新内膜重塑模式。啮齿类动物的慢性缺氧模型导致血管壁增厚, 血管缺氧收缩, 无血管闭塞的小肺血管 6.此外, 缺氧条件是可逆的。因此, 缺氧模型也不足以产生严重的 pah。mct 肺损伤模型确实会引起一些内皮功能障碍, 但在严重原生 pah的人身上发现的复杂血管闭塞性病变在大鼠2中并不发生。此外, mct 治疗的大鼠往往死于 mct 引起的肺毒性、静脉闭塞性肝病和心肌炎, 而不是 pah2。最后, 仅有肺切除术还不足以在短时间内在小肺血管中产生新生内膜病变。肺切除术后, 肺动脉压7的升高最小。在人类中, 当对侧肺健康时, 肺切除术耐受性良好.
然而, 左肺切除术结合 mct 或苏根是有利的, 因为它模仿增加肺血流, 并导致肺血管重塑相当于严重的临床 pah。肺切除术是在左肺进行的, 左肺只有1个叶, 而不是右肺, 左肺有4个叶。如果右肺被摘除, 动物将无法补偿呼吸功能不全。在肺切除-mct 模型中, 90% 以上的手术动物进行了重塑, 形成了新的内膜模式.同样, 苏根和肺切除术的组合导致严重的 pah, 其特征是血管细胞迭代血管病变, 增殖, 凋亡, 和 rv 功能障碍8。左肺切除术与其他手术相比也是有利的, 以诱导 pah。在前描述的模型在大鼠增加肺血流量到肺包括主动脉腔分流或锁骨下肺动脉吻合术。这些模型是极其复杂的 7,9,10,11。要进行主动脉腔分流, 动物的腹部必须打开。分流被放置在腹主动脉, 这增加了流向所有腹部器官的血液, 而不仅仅是肺部, 因此, pah 需要更长的时间来发育。此外, 很难确定血液通过分流, 而与肺切除术的血液流量加倍剩余的肺。锁骨下肺动脉吻合术也有许多并发症。动脉血进入静脉可导致吻合血栓形成和出血。就像主动脉腔分流器一样, 很难确定通过吻合口的血液流动。此外, 这是一个昂贵和困难的技术, 需要血管外科技能。单侧左肺切除术使对侧肺的血流和剪切应力加倍, 并结合 mct 或苏根, 导致 pah 的典型血流动力学和组织病理学表现, 即内皮细胞损伤8,12岁
该手稿的新颖性是在非常详细和全面的大鼠左肺切除术手术方案和讨论这些模型的技术和生理挑战。由于目前还没有这种协议, 许多调查人员认为这种模式使用太困难。进行左肺切除术的调查人员面临着与不必要的动物损失有关的高死亡率和发病率, 这损害了科学评估。相反, 许多人将使用经典模型, 如 mct 注射, 慢性缺氧, 或只是肺切除术, 以创建 pah。然而, 这些模型的效果远远低于 mct 或苏根与左肺切除术的组合。本文的主要目的是为大鼠左单侧肺切除术提供第一个详细、可重复的手术方案, 并提供最佳的 pah 手术模式。将左单侧肺切除术与 mct 或 su5416 结合使用的这一方案将使研究人员能够创建一个更有效和临床相关的严重 pah 模型, 以研究这种致命疾病的发病机制。

<table border="0" cellpadding="0" cellspacing="0" style="width:739px;" width="739">
	<tbody>
		<tr height="22">
			<td height="22" style="height:22px;width:223px;">Surgical Blade</td>
			<td style="width:111px;">Bard-Parker</td>
			<td style="width:153px;">371215</td>
			<td style="width:252px;">Incision</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:223px;">Forane (Isoflurane, USP)</td>
			<td style="width:111px;">Baxter</td>
			<td style="width:153px;">NDC 10019-360-40</td>
			<td>anesthesia</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:223px;">BD Angiocath 16 G</td>
			<td style="width:111px;">BD</td>
			<td style="width:153px;">381157</td>
			<td>intubation tube, chest tube</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:223px;">BD 1 mL Insulin Syringe</td>
			<td style="width:111px;">BD</td>
			<td style="width:153px;">329652</td>
			<td>administer buprinex post-operatively</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:223px;">Biogel Surgeons Surgical Gloves</td>
			<td style="width:111px;">Biogel</td>
			<td style="width:153px;">30460-01</td>
			<td>sterile surgical gloves</td>
		</tr>
		<tr height="42">
			<td height="42" style="height:42px;width:223px;">Wahl BravMini+ Trimmer</td>
			<td style="width:111px;">Braintree Scientific</td>
			<td style="width:153px;">CLP-41590 P</td>
			<td>shave surgical site</td>
		</tr>
		<tr height="42">
			<td height="42" style="height:42px;width:223px;">SU5416</td>
			<td style="width:111px;">Cayman Chemical</td>
			<td style="width:153px;">13342</td>
			<td>Sugen&#160;</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:223px;">Fiber Optic Illuminator</td>
			<td style="width:111px;">Cole-Parmer</td>
			<td style="width:153px;">EW-41723-02</td>
			<td>light for intubation</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:223px;">Surgipro II 4-0 Suture</td>
			<td style="width:111px;">Covidien</td>
			<td style="width:153px;">VP831X</td>
			<td>Closing intercostal muscles</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:223px;">Polysorb 5-0 Suture</td>
			<td style="width:111px;">Covidien</td>
			<td style="width:153px;">GL-885</td>
			<td>Closing skin</td>
		</tr>
		<tr height="42">
			<td height="42" style="height:42px;width:223px;">Medium Slide Top Induction Chamber</td>
			<td style="width:111px;">DRE Veterinary</td>
			<td style="width:153px;">12570</td>
			<td>oxygen &#38; isoflurane delivery</td>
		</tr>
		<tr height="42">
			<td height="42" style="height:42px;width:223px;">DRE Compact 150 Rodent Anesthesia Machine</td>
			<td style="width:111px;">DRE Veterinary</td>
			<td style="width:153px;">373</td>
			<td>oxygen &#38; isoflurane delivery</td>
		</tr>
		<tr height="42">
			<td height="42" style="height:42px;width:223px;">Small Vessel Cauterizer Kit</td>
			<td style="width:111px;">Fine Science Tools</td>
			<td style="width:153px;">18000-00</td>
			<td>cauterizer to minimize bleeding</td>
		</tr>
		<tr height="42">
			<td height="42" style="height:42px;width:223px;">VentElite Small Animal Ventilator</td>
			<td style="width:111px;">Harvard Apparatus</td>
			<td style="width:153px;">55-7040</td>
			<td>ventilator</td>
		</tr>
		<tr height="42">
			<td height="42" style="height:42px;width:223px;">MouseSTAT Jr</td>
			<td style="width:111px;">Kent Scientific</td>
			<td style="width:153px;">MSTAT-JR</td>
			<td style="width:252px;">pulse oximeter &#38; heart rate monitor</td>
		</tr>
		<tr height="42">
			<td height="42" style="height:42px;width:223px;">Mouse Paw Pulse Oximeter Sensor</td>
			<td style="width:111px;">Kent Scientific</td>
			<td style="width:153px;">SPO2-MSE</td>
			<td style="width:252px;">pulse oximeter &#38; heart rate paw sensor</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:223px;">PhysioSuite RightTemp</td>
			<td style="width:111px;">Kent Scientific</td>
			<td style="width:153px;">PS-02</td>
			<td>temperature pad</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:223px;">PVP Prep Solution</td>
			<td style="width:111px;">Medline</td>
			<td style="width:153px;">MDS093944</td>
			<td>Cleaning surgical site</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:223px;">Poly-lined Drape</td>
			<td style="width:111px;">Medline</td>
			<td style="width:153px;">NON21002Z</td>
			<td>cover animal</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:223px;">3 mL syringe</td>
			<td style="width:111px;">Medline</td>
			<td style="width:153px;">SYR103010</td>
			<td>administer fluids post-operatively</td>
		</tr>
		<tr height="83">
			<td height="83" style="height:83px;width:223px;">Microsurgical Kits, Integra&#160;</td>
			<td style="width:111px;">Miltex</td>
			<td style="width:153px;">95042-540</td>
			<td style="width:252px;">surgical tools: plain wire speculum, double-ended probe, McPherson-Vannas Iris scissors straight, straight iris scissors</td>
		</tr>
		<tr height="42">
			<td height="42" style="height:42px;width:223px;">Hemostatic forceps - Micro-Jacobson-Mosquito</td>
			<td style="width:111px;">Miltex</td>
			<td style="width:153px;">17-2602</td>
			<td>mosquito</td>
		</tr>
		<tr height="42">
			<td height="42" style="height:42px;width:223px;">Buprenorphrine HCl 0.3 mg/mL</td>
			<td style="width:111px;">Par Pharmaceutical</td>
			<td style="width:153px;">NDC 42023-179-01</td>
			<td>Pain relief</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:223px;">Cooley-Mayo curved scissors</td>
			<td style="width:111px;">Pilling</td>
			<td style="width:153px;">352090</td>
			<td>Large scissors</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:223px;">Gerald Tissue forceps</td>
			<td style="width:111px;">Pilling</td>
			<td style="width:153px;">351900</td>
			<td>forceps</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:223px;">Wangesnsteen Tissue Forceps</td>
			<td style="width:111px;">Pilling</td>
			<td style="width:153px;">342929</td>
			<td>atraumatic forceps</td>
		</tr>
		<tr height="42">
			<td height="42" style="height:42px;width:223px;">Pilling Thin Vascular Needle Holder</td>
			<td style="width:111px;">Pilling</td>
			<td style="width:153px;">354962DG</td>
			<td>needle holder</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:223px;">Crotaline</td>
			<td style="width:111px;">Sigma-Aldrich</td>
			<td style="width:153px;">C2401-1G</td>
			<td>MCT</td>
		</tr>
		<tr height="42">
			<td height="42" style="height:42px;width:223px;">Surflash 20 G IV Catheter</td>
			<td style="width:111px;">Terumo</td>
			<td style="width:153px;">SR*FF2051</td>
			<td style="width:252px;">For pressure reading during organ harvest</td>
		</tr>
		<tr height="42">
			<td height="42" style="height:42px;width:223px;">ADVantage PV System with 1.2 Fr Catheter</td>
			<td style="width:111px;">Transonic Inc</td>
			<td style="width:153px;">ADV500</td>
			<td style="width:252px;">Record pulmonary artery and right ventricle pressure</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:223px;">Medium Hemoclip</td>
			<td style="width:111px;">Weck</td>
			<td style="width:153px;">523700</td>
			<td>ligate vessels</td>
		</tr>
		<tr height="42">
			<td height="42" style="height:42px;width:223px;">Open Ligating Clip Applicator; Medium, curved</td>
			<td style="width:111px;">Weck Horizon</td>
			<td style="width:153px;">237081</td>
			<td>hemoclip applicator</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:223px;">Surgical Microscope</td>
			<td style="width:111px;">Zeiss OPMI MD</td>
			<td style="width:153px;">1808</td>
			<td>magnification</td>
		</tr>
	</tbody>
</table>

the left pneumonectomy combined with monocrotaline or sugen as a model of pulmonary hypertension in rats

在该协议中, 我们详细介绍了正确的程序步骤和必要的预防措施, 以成功地进行左肺切除术和诱导 pah 的大鼠与补充单氯胺 (mct) 或 su5416 (苏根) 的额外给药。我们还将这两个模型与研究中常用的其他 pah 模型进行了比较。在过去的几年里, 动物 pah 模型的重点已经转向研究神经丛病变的血管增生机制, 其中增加肺血流的作用被认为是严重肺发育的重要触发因素血管重塑。增加肺流量的啮齿类动物模型之一是单侧左肺切除术, 再加上 mct 或苏根的 "第二次命中"。左肺的切除导致肺血流和血管重塑的增加和动荡。目前, 还没有详细的大鼠肺切除术程序。本文详细介绍了男性 sprague-dawley 大鼠肺切除术和术后护理的分步方案。简单地说, 动物被麻醉, 胸部被打开。一旦左肺动脉, 肺静脉和支气管被可视化, 他们结扎, 左肺被切除。随后, 胸部关闭, 动物恢复。血液只在右肺循环。这种增加的血管压力导致一个渐进的重塑和闭塞的小肺动脉。第二次击中 mct 或苏根是使用一周后的治疗诱导内皮功能障碍。增加血液流动的结合在肺和内皮功能障碍产生严重的 pah。这个程序的主要限制是, 它需要一般的外科技能。

根据公认的分类制度, 肺动脉高压的特点是平均肺动脉压 (mpap) 超过正常肺动脉压的上限 (即25毫米汞)。在肺切除术 + mPAP 组, 严重的 pah 在第21天发展, mpap 增加 (图 1)。mpap 是通过以下公式计算的:
<img alt="Equation" src="/files/ftp_upload/59050/59050eq1.jpg">
用连接到 advantage...

Watch this Scientific Journal Video about The Left Pneumonectomy Combined with Monocrotaline or Sugen as a Model of Pulmonary Hypertension in Rats at JoVE.com

The Left Pneumonectomy Combined with Monocrotaline or Sugen as a Model of Pulmonary Hypertension in Rats

左肺切除术联合单氯联氨酸或苏根为大鼠肺动脉高压的模型

啮齿类动物左肺切除术是肺动脉高压研究中的一项有价值的技术。在这里, 我们提出了一个协议来描述大鼠肺切除术程序和术后护理, 以确保最低的发病率和死亡率。

In this protocol, we detail the correct procedural steps and necessary precautions to successfully perform a left pneumonectomy and induce PAH in rats ...

该协议是重要的，因为它产生肺动脉高血压的最佳模型。没有其他模型产生在人类PAH患者中发现的胸膜病变。主要优点是，我们双倍的血液流在右肺和肺动脉，造成内皮损伤，迫使肺工作两倍的辛勤工作。我们组已开发出一种高效的肺动脉高血压模型，以开发治疗方案。除了肺动脉高血压，这种方法可能有助于再生医学，并可以见解其他疾病与增加的肺流量，如先天性心脏缺陷或肺切除术后患者。对于从未执行过这种技术的人，我的建议是完全遵循协议，并确保外科医生能够确切地看到他们在做什么。用4%等值的异丙醇麻醉大鼠后，用光纤鹅灯对大鼠进行插管，以照亮气管。将 16 量的导管插入喉部，并使用冷镜观察导管呼出的呼吸中湿度的凝结，以确认插管。将大鼠连接到呼吸机，将大鼠置于显微镜下，在 37 摄氏度加热垫上的右侧下落位置。用胶带固定前肢，并使用剪子将左胸从前腿后面剃到肋骨的端。使用三种连续的 10% povidone 碘溶液和 70% 乙醇湿巾清洁暴露的皮肤，并在大鼠的脚上放置脉搏血氧计，以在整个手术过程中监测心率和氧饱和度。现在，调整显微镜，使手术视图成为焦点。然后，在大鼠的身体和仪器托盘上放置一个无菌窗帘，以创建一个无菌环境。最后，将无菌仪器放在无菌仪器托盘上。要进行左肺切除术，请使用 Cooley-Mayo 剪刀和杰拉尔德组织钳在手术窗帘上切割一个两到三厘米的孔，并使用手术刀片在左胸做两厘米长的横向切口。使用 Cooley-Mayo 剪刀切割每层组织，直到肋骨和骨骼间肌肉暴露。用蚊子在第三个间空间的肌肉中打个洞。使用双端探针，移动肺动脉以可视化肺动脉，并使用麦克弗森-范纳斯虹膜剪刀将骨质间肌肉打开至大约一到两厘米的宽度。将一个小的自固定缩回器放入左胸膜，使肋骨和肌肉保持开放，并在腹部将左肺下部移动，以便进入肺动脉和支气管。对于左主支气管和肺动脉的结扎，首先，将一个中等血夹加载到连接夹施用器中，并使用旺森特创伤钳小心地抬起左肺上部以暴露肺动脉。关闭动脉周围的夹子和施用器，注意不要关闭或破裂左酶静脉。并打开切口进一步使用扁桃体分离肌肉纤维。将另一个中等血球加载到连接夹施用器后，使用创伤钳和标准组织钳将肺的下部从切口中抬出，直到左主支气管和左肺静脉被可视化。小心地将左主支气管和肺静脉与第二个血球一起夹住，并使用剪刀取出肺，而不会切割或撕裂夹子。然后，使用一小块无菌纱布来吸收任何血液并止血。使用针架和4-0的针线缝合关闭肋骨和间关节肌肉。在关闭腹间肌肉之前，将一个 16 量的导管插入胸腔，远离手术切口，插入第七个腹腔空间，并立即取出针头，将导管留在位。将 5-0 缝合线放入皮肤和胸管周围，以便取出胸管时，将孔系上，并系上缝合线以关闭肋骨。用运行 5-0 缝合关闭皮肤和皮下空间，并使用三毫升注射器通过导管从胸腔中排空，以恢复胸部的正常负压。使用针架立即夹紧导管，以防止空气回到胸腔。拆下导管并系上缝合线以关闭孔。在肺切除术和单胸科组，严重的肺高血压在第21天发展，与控制未经治疗的假动物相比，平均肺动脉压力增加就证明了这一点。在肺切除术加苏根组，平均肺动脉压力是对照组的三倍。与对照组相比，单轴线和苏根治疗的动物的右心室收缩压也高得多。在血氧素和 eosin 染色的正常大鼠肺组织部分，肺活体和肺骨结构之间的空间是明显的，并且容器是清晰和正常的厚度。在肺动脉高血压肺，有证据表明重塑，血管壁变厚，血管严重收缩，炎症和焦点肺动脉炎。动物必须补偿失去肺，所以在恢复期间保持耐心是重要的。监测生命体征，并提供必要的氧气或肺体积。Sugen产生内皮凋亡，这是肺动脉高血压的临床相关迹象。啮齿动物的左肺切除术模型为科学家研究水流异常和开发治疗肺动脉高血压的新疗法铺平了道路。由于在此型号中使用异氟兰、苏根和/或 MCT，必须时刻佩戴个人防护设备。

Research

JoVE Journal

Medicine

5/6th Nephrectomy in Combination with High Salt Diet and Nitric Oxide Synthase Inhibition to Induce Chronic Kidney Disease in the Lewis Rat

5/6th联合切除术，高盐饮食和一氧化氮合酶抑制剂诱导Lewis大鼠慢性肾脏病

Chronic kidney disease (CKD) is a global problem. Slowing CKD progression is a major health priority. Since CKD is characterized by complex derangements ...

科研

医学

Increasing Pulmonary Artery Pulsatile Flow Improves Hypoxic Pulmonary Hypertension in Piglets

增加肺动脉脉动流改善缺氧性肺动脉高压的仔猪

Pulmonary arterial hypertension (PAH) is a disease affecting distal pulmonary arteries (PA). These arteries are deformed, leading to right ventricular ...

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

心脏重构通过大鼠腹主动脉缩窄的模型

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

Shunt Surgery, Right Heart Catheterization, and Vascular Morphometry in a Rat Model for Flow-induced Pulmonary Arterial Hypertension

分流手术，右心导管，血管形态计量学在大鼠模型中的流量引起的肺动脉高压

In this protocol, PAH is induced by combining a 60 mg/kg monocrotalin (MCT) injection with increased pulmonary blood flow through an aorto-caval shunt ...

Murine Echocardiography of Left Atrium, Aorta, and Pulmonary Artery

左心房，主动脉和肺动脉的超声心动图小鼠

The present methodology teaches the investigator how to measure and use the LAV as a surrogate of chronic elevations in Left Ventricular diastolic ...

Direct Re-implantation of Left Coronary Artery into the Aorta in Adults with Anomalous Origin of Left Coronary Artery from the Pulmonary Artery (ALCAPA)

Direct Re-implantation of Left Coronary Artery into the Aorta in Adults with Anomalous Origin of Left Coronary Artery from the Pulmonary Artery ALCAPA

左冠状动脉直接再注入与从肺动脉左冠状动脉起源异常成人主动脉（ALCAPA）

Anomalous origin of the left coronary artery from the pulmonary artery (ALCAPA) is a rare congenital anomaly which is one of leading causes of myocardial ...

Left Atrial Stenosis Induced Pulmonary Venous Arterialization and Group 2 Pulmonary Hypertension in Rat

左心房狭窄致大鼠肺静脉动脉化及第2组肺动脉高压

The mechanism of mitral stenosis-induced pulmonary venous arterialization and group 2 pulmonary hypertension (PH) is unclear. There is no rodent model of ...

Induction and Characterization of Pulmonary Hypertension in Mice using the Hypoxia/SU5416 Model

使用缺氧/SU5416模型对小鼠的肺高血压进行诱导和特征

Pulmonary Hypertension (PH) is a pathophysiological condition, defined by a mean pulmonary arterial pressure exceeding 25 mm Hg at rest, as assessed by ...

A Model of Reverse Vascular Remodeling in Pulmonary Hypertension Due to Left Heart Disease by Aortic Debanding in Rats

大鼠主动脉切除术治疗左心病肺动脉高压反向血管重塑模型

Pulmonary hypertension due to left heart disease (PH-LHD) is the most common form of PH, yet its pathophysiology is poorly characterized than pulmonary ...

Multiple Intravenous Bolus Dosing and Invasive Hemodynamic Assessment in a Hypoxia-Induced Mouse Pulmonary Artery Hypertension Model

Pulmonary arterial hypertension (PAH) is a progressive life-threatening disease, primarily affecting small pulmonary arterioles of the lung. Currently, ...