著者らは、この実験モデルの開発をサポートするために、それぞれのオペレーティング·助成金と設立資金のための医学研究のための健康の研究（MOP53116）とアルバータヘリテージ財団のカナダの協会に感謝したいと思います。

1。麻酔<ol><li> 2L/minで麻酔器の流量を設定する。真空吸引、排気を接続します。 </li><li> 5％（約3分）での麻酔ガス（イソフルラン）との電荷フェイスマスク。 </li><li>新生子豚は100％酸素の吸入イソフルラン5％（約3分）で誘導されます。 </li><li>イソフルランの2-3％で麻酔を維持している。必要に応じて、0.5％イソフルランの微調整は、しかし、それは0.5から子豚の状態に応じて5％までの範囲であってもよい。 </li><li>血管アクセスが確立された後、吸入麻酔はフェンタニル（5から50マイクログラム/キログラム/ h）とミダゾラム（200から500マイクログラム/ kg / h）で点滴を用いて静脈麻酔に切り替えることができます。パンクロニウム（50-100マイクログラム/ kg / h）で、動物の状態を観察する能力をしながら、手術の際に過度の筋肉の動きを制御するために必要になることがありますが、麻酔薬の調整のために保存されます。 </li><li>子豚は、パルスオキシメータ（経皮的酸素sによって監視されている95から100パーセントでaturation）と心電図（130から170拍/分時の心拍数）。 </li><li>子豚の直腸温度は、加熱毛布と暖かい晴れやかと38から40℃に維持されている。 </li><li>子豚の麻酔状態を定期的に行動（攪拌）、心血管（頻脈や高血圧）や呼吸器（頻呼吸）パラメータは、必要に応じて、神経（瞳孔の大きさ、引き裂き、体の動き）を使って実験期間を通じて評価されています。最小限の麻痺が与えられます。麻痺がある場合とない子豚の麻酔の経験が評価のために有用であろう。 </li><li>プロトコルは、静脈内ペントバルビタールの過剰投与（100 mg / kg）を用いた実験の終了時に動物の安楽死と非生存手順です。 </li></ol> 2。脚の付け根の血管カテーテルの外科的配置（図1） <ol><li>右脚の付け根の長い2〜3センチメートル切開を行います。 </li><li>右大腿静脈さ1cm righの1cmを解剖トン大腿動脈。各容器の周囲2 3から0までの文字列を入れてください。 </li><li>右大腿静脈カテーテル法：静脈の遠位をライゲーションする。 15センチメートルにアーガイルカテーテル（3.5または5フランス語、ダブルルーメン）（コヴィディエン、マンスフィールド、マサチューセッツ州）を挿入し、これは、右心房に配置されます。カテーテルを固定するために、両方の文字列を結ぶ。カテーテルは、維持液と薬の注入（セカンダリポート）と静脈/右心房圧測定（プライマリポート）は、中央に使用することができます。 </li><li>右大腿動脈カテーテル法：動脈の遠位をライゲーションする。血流を止めるために近位列を持ち上げます。 5cmにアーガイルカテーテル（3.5または5フランス語、シングルルーメン）を挿入します。これは、連続平均動脈圧測定と採血用のインフラ腎動脈に動脈カテーテルを配置します。カテーテルを固定するために、両方の文字列を結ぶ。 </li><li>皮膚を閉じます。 </li></ol> 3。機械換気（図2）を確立<ol><li>長い2〜3センチメートル水平を作る首の切開。 </li><li>解剖すると気管の1cm公開します。気管の周りに2 1から0の文字列を入れてください。 </li><li>気管に1センチメートルで気管内チューブ（3.0または3.5）を挿入します。人工呼吸器に接続して、機械的人工換気を開始。気管内チューブを固定します。 </li><li>総頸動脈を切開し、公開します。継続的に血流を測定するために通過時間の超音波流量プローブ（2SBまたは2RB、トランソニックシステムズ、Ithica、NY）を容器を取り囲んでいます。 </li></ol> 4。上腸間膜における流量プローブの配置（図3）と左腎（図4）動脈<ol><li>余分なフェンタニルの用量（5-10マイクログラム/ kg）およびアセプロマジンは（0.01から0.02 mg / kg）の前に皮膚切開する必要があります。 </li><li>長い肋骨下、側腹切開を行い、慎重に筋層を切開。 </li><li>腹部大動脈を公開します。 </li><li>血管処理（攣縮）やリンパの傷害を最小限に抑えることができます。 </li><li> 0.5〜1センチメートル上腸間膜動脈を切開し、その周り遷音速流プローブ（3SB）をつけて下さい。 </li><li> 0.5〜1センチメートル左腎動脈を切開し、その周り遷音速流プローブ（2SB）をつけて下さい。 </li><li>皮膚を閉じ、流量プローブを固定します。 </li></ol> 5。肺動脈カテーテルの配置（図5）とフロープローブ（図6） <ol><li>余分なフェンタニルの用量（5-10マイクログラム/ kg）およびアセプロマジンは（0.01から0.02 mg / kg）の前に皮膚切開する必要があります。 </li><li>右側臥位で動物が眠っているのです。 </li><li>左第4肋間で開胸術。 </li><li>必要に応じて内胸動脈と静脈に気をつけろ、結紮する。 </li><li>左肺を下に押して、必要に応じて酸素を増加させる歯科綿棒を使用しています。 </li><li>心膜を開きます。 </li><li>大動脈肺動脈から実行動脈管を識別します。 </li><li>動脈管は、クリップを配置することによって、またはその原点に厚い &quot;3-O絹&quot;タイで連結することができる。 </li><li>主肺動脈、無料でAVを渡す厚い &quot;0&quot;タイを使用してascularスリング。 </li><li>肺動脈カテーテルを配置するための基地で巾着（5-0プロレン）縫合を行います。 </li><li> 1cmの最大巾着を通して20G Angiocathを（カテーテルの先端から1cm未満で3側孔付き）を挿入します。 </li><li>静脈血の自由な流れを確認してください。 </li><li>圧力変換器に接続し、肺動脈圧と波形を確認してください。 </li><li>巾着を締め、肺カテーテルを固定します。 </li><li>主肺動脈の周り遷音速流プローブ（6SB）を置きます。 </li><li>最適な信号伝達を可能にするためにフロープローブと動脈の間に超音波ゲルを置きます。 </li><li>湿った生理食塩水ガーゼで傷口をカバーしています。 </li></ol> 6。低酸素および再酸素化プロトコル<ol><li>低酸素血症を誘発するために吸入窒素ガスの濃度を増加させることにより10％に吸入酸素濃度を下げます。 </li><li>吸入酸素を調整します2時間30から40パーセントの20〜40 mmHgまたはSAO 2のPAO 2を取得するために10％と15％の間の濃度。 </li><li>パコ2を評価し、それに応じて人工呼吸器の速度を調整するために動脈血分析を実行します。 </li><li>低酸素血症の誘導と、最初の一時間は着実に頻脈（および心拍出量）応答を誘導するに捧げられています。 </li><li>総頸動脈、上腸間膜と左腎動脈の血流の変化を継続的に監視します。 </li><li>低酸素症の二時間の間に、低酸素ストレスがベースラインの30〜40％まで徐々に低い心拍出量を増加させ、30から35 mmHgのと動脈血pH 6.95から7.05への平均動脈圧。 </li><li>低酸素ストレスが途中で終了したり、必要に応じて15分延長することができる。 </li><li>純酸素を継続しながら、突然100％には、窒素ガスを中止することによって突然引き起こされた酸素濃度を増加させます。 </li><li>動脈圧および他の血行動態パラを意味し、心拍出量を監視急速な回復のためのメートル。 </li><li> 100％酸素と蘇生は0.5時間継続することができる。この期間の後、21％に素早く吸入酸素濃度を低下させる。 </li><li>実験の残りの期間の21％の酸素と酸素化を続行します。必要に応じて吸入酸素濃度は25％まで滴定することができる。 </li><li> 10ミリリットル/ kgの乳酸リンゲル液の流体ボーラスは実験期間の間に、必要に応じて必要となる場合があります。その使用はprotocolizedする必要があります。 </li></ol> 7。代表的な結果： 低酸素症の最初の一時間以上新生豚における低酸素血症の誘導は120％-130％のベースライン（ 図7A）と心拍数（ 図7B）に心拍出量（肺動脈の血流）を増加させる必要があります。典型的には、心拍出量は、低酸素の最初の0.5時間と1時間の間にそのピーク補償に達する必要があります。また、血液の流れが私を減少、結果として中央集中型になるべきsentericおよび腎灌流が、保持または増加頚動脈フロー（ 図8）。低酸素症の二時間の間に、心拍出量の着実な減少が低血圧の開発（ 図9A）、があり、不整脈の有無にかかわらず、心拍数減少が発生しました。低酸素症は時々心拍出量が減少すると低酸素の最後の30分で下げる可能性が増加した肺動脈圧（ 図9B）と肺高血圧症を誘発する必要があります。 蘇生時には、すべての血行動態パラメータはすぐに徐々に再酸素化の第一時間以上かけて回復し、腎血流量を除いて、正常酸素ベースラインに回復します。しかし、特に心拍出量および平均動脈圧血行動態パラメータは、徐々にそれぞれ、正常酸素ベースラインと35から45 mmHgの70から75％程度に再酸素化の最初の2時間以上悪くなります。この心臓血管dysfunctiには、このような血管作用と強心薬などの心筋素晴らしいとワラント心臓血管の支持療法のために、少なくとも部分的にである。 <img alt="図1" src="/files/ftp_upload/3166/3166fig1.jpg" /> 図1：大腿動脈および静脈カテーテルの配置と脚の付け根の切開<img alt="図2" src="/files/ftp_upload/3166/3166fig2.jpg" /> 図2：総頸動脈の周りに気管内チューブの配置と流れのプローブを使って首の切開<img alt="図3" src="/files/ftp_upload/3166/3166fig3.jpg" /> 図3：上腸間膜動脈の分離と側腹切開<img alt="図4" src="/files/ftp_upload/3166/3166fig4.jpg" /> 図4：左腎動脈の分離と側腹切開<img alt="図5" srcは= &quot;/ files/ftp_upload/3166/3166fig5.jpg&quot; /&gt; 図5：肺動脈カテーテルの配置と開胸<img alt="図6" src="/files/ftp_upload/3166/3166fig6.jpg" /> 図6：主肺動脈の周りの遷音速流れのプローブの配置と開胸<img alt="図7" src="/files/ftp_upload/3166/3166fig7.jpg" /> 図7（A）、心拍出量（肺動脈流）と（B）の心拍数と低酸素再酸素化時の経時変化<img alt="図8" src="/files/ftp_upload/3166/3166fig8.jpg" /> 図8（A）総頸動脈の血流の経時変化、低酸素および再酸素化時に（B）の上腸間膜および（C）の左腎動脈<img alt="図9" src="/files/ftp_upload/3166/3166fig9.jpg" /> 図9：時（A）の平均動脈圧と低酸素および再酸素化時に（B）の肺動脈圧の変化

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特別な利害関係は宣言されません。

現在の実験プロトコルは、低酸素および再酸素化プロセスの間に新生児の被験者の全身および地域の血行動態の変化を検討するという利点があります。また、リカバリ時に心血管機能を改善するために用いた介入のそれぞれの効果を調べることができます。私たちと他の人が心血管1、肺2、神経3、胃腸4、肝5、6腎、副腎7および血液8シ...

a swine model of neonatal asphyxia

仮死に関連するものとして、毎年100万人以上の新生児は、世界中で死ぬ。窒息した新生児は、一般的に低血圧、血流障害、低酸素性虚血性脳症、肺高血圧症、vasculopathic腸炎、腎不全、血栓塞栓性合併症を含む多臓器不全を持っている。動物モデルは、私たちは新生児仮死の病態生理学や薬理学の理解を助けるために開発されています。げっ歯類と新生児の子羊と比較して、生まれたばかりの子豚は、貴重なモデルであることが証明されています。生まれたばかりの子豚は、36から38週と同様の開発を含め、いくつかの利点があり、動物の計測とモニタリングを可能との交絡変数を制御匹敵するボディシステム、大規模なボディサイズ（出生時〜1.5〜2キロ）を持つヒトの胎児低酸素症および血行動態撹乱。 我々はここで新生児仮死をシミュレートする実験プロトコルを説明し、私たちはの体系を調べることができますマイクや地域の血行動態の変化窒息及び再酸素化プロセスの間だけでなく、介入のそれぞれの効果。さらに、このモデルは多臓器不全または機能不全同時に、様々な身体のシステムとの相互作用を研究することの利点を持っています。実験モデルは、機械換気、血管（動脈、中心静脈）アクセスの設立を可能にするために生まれたばかりの子豚の外科手術用器具類（1-3、日齢および1.5〜2.5キロの重量混合された品種）を含む非生存の手順ですと主肺、総頸動脈、上腸間膜と左腎動脈を含む様々な動脈にわたる血管内の圧力と血流の連続モニタリング用カテーテルとフロープローブ（トランソニック株式会社）の配置。血行動態パラメータと正常な血液ガスのZ &lt;10％の変動によって定義されるように30〜60分間安定した後、これらの外科的にインストルメントされた豚を使用して、我々は実験プロトコルを開始normocapnic肺胞低酸素症を介して誘導され、重篤な低酸素血症の。子豚は30〜40％の動脈血酸素飽和度を目指して、2時間窒素ガスの吸入濃度を増加させることにより10〜15％酸素で換気される。低酸素血症の程度は、この重要な臓器への血流低下と重篤な代謝性アシドーシスの臨床仮死、全身性低血圧および心原性ショックを生成します。低酸素症は0.5時間、100％酸素とその後3.5時間で21％の酸素と酸素化が続いている。薬理学的介入は、追って紹介し、その効果は盲検、無作為化されたブロックの方法で調べることができます。

Watch this Scientific Journal Video about A Swine Model of Neonatal Asphyxia at JoVE.com

A Swine Model of Neonatal Asphyxia

大型動物モデルは、新生児仮死の生理学や薬理学の試験で良い並進値を持っています。生まれたばかりの子豚を使用して、我々は全身の血行動態および地域的、生化学的および病理学的経路と相関を持つ酸素の輸送を研究の利点を持っている新生児仮死をシミュレートするための実験プロトコルを開発しています。

新生児仮死の新型モデル

Annually more than 1 million neonates die worldwide as related to asphyxia. Asphyxiated neonates commonly have multi-organ failure including hypotension, ...

Research

JoVE Journal

Medicine

14.2K ビュー.  University of Alberta. 大型動物モデルは、新生児仮死の生理学や薬理学の試験で良い並進値を持っています。生まれたばかりの子豚を使用して、我々は全身の血行動態および地域的、生化学的および病理学的経路と相関を持つ酸素の輸送を研究の利点を持っている新生児仮死をシミュレートするための実験プロトコルを開発しています。

ビデオ: A Swine Model of Neonatal Asphyxia

A Piglet Model of Neonatal Hypoxic-Ischemic Encephalopathy

Birth asphyxia, which causes hypoxic-ischemic encephalopathy (HIE), accounts for 0.66 million deaths worldwide each year, about a quarter of the world&#8217;s 2.9 million neonatal deaths. Animal models of HIE have contributed to the understanding of the pathophysiology in HIE, and have highlighted the dynamic process that occur in brain injury due to perinatal asphyxia. Thus, animal studies have suggested a time-window for post-insult treatment strategies. Hypothermia has been tested as a treatment for HIE in pdiglet models and subsequently proven effective in clinical trials. Variations of the model have been applied in the study of adjunctive neuroprotective methods and piglet studies of xenon and melatonin have led to clinical phase I and II trials1,2. The piglet HIE model is further used for neonatal resuscitation- and hemodynamic studies as well as in investigations of cerebral hypoxia on a cellular level. However, it is a technically challenging model and variations in the protocol may result in either too mild or too severe brain injury. In this article, we demonstrate the technical procedures necessary for establishing a stable piglet model of neonatal HIE. First, the newborn piglet (&#60; 24 hr old, median weight 1500 g) is anesthetized, intubated, and monitored in a setup comparable to that found in a neonatal intensive care unit. Global hypoxia-ischemia is induced by lowering the inspiratory oxygen fraction to achieve global hypoxia, ischemia through hypotension and a flat trace amplitude integrated EEG (aEEG) indicative of cerebral hypoxia. Survival is promoted by adjusting oxygenation according to the aEEG response and blood pressure. Brain injury is quantified by histopathology and magnetic resonance imaging after 72 hr.

Hypoxic-ischemic encephalopathy following perinatal asphyxia can be studied using animal models. We demonstrate the procedures necessary for establishing a piglet model of neonatal hypoxic-ischemic encephalopathy.

新生児低酸素性虚血性脳症の子豚モデル

Birth asphyxia, which causes hypoxic-ischemic encephalopathy (HIE), accounts for 0.66 million deaths worldwide each year, about a quarter of the ...

医学

A Neonatal Mouse Spinal Cord Compression Injury Model

Spinal cord injury (SCI) typically causes devastating neurological deficits, particularly through damage to fibers descending from the brain to the spinal cord. A major current area of research is focused on the mechanisms of adaptive plasticity that underlie spontaneous or induced functional recovery following SCI. Spontaneous functional recovery is reported to be greater early in life, raising interesting questions about how adaptive plasticity changes as the spinal cord develops. To facilitate investigation of this dynamic, we have developed a SCI model in the neonatal mouse. The model has relevance for pediatric SCI, which is too little studied. Because neural plasticity in the adult involves some of the same mechanisms as neural plasticity in early life1, this model may potentially have some relevance also for adult SCI. Here we describe the entire procedure for generating a reproducible spinal cord compression (SCC) injury in the neonatal mouse as early as postnatal (P) day 1. SCC is achieved by performing a laminectomy at a given spinal level (here described at thoracic levels 9-11) and then using a modified Yasargil aneurysm mini-clip to rapidly compress and decompress the spinal cord. As previously described, the injured neonatal mice can be tested for behavioral deficits or sacrificed for ex vivo physiological analysis of synaptic connectivity using electrophysiological and high-throughput optical recording techniques1. Earlier and ongoing studies using behavioral and physiological assessment have demonstrated a dramatic, acute impairment of hindlimb motility followed by a complete functional recovery within 2 weeks, and the first evidence of changes in functional circuitry at the level of identified descending synaptic connections1.

This article describes a method for generating a reproducible spinal cord compression injury (SCI) in the neonatal mouse. The model provides an advantageous platform for studying mechanisms of adaptive plasticity that underlie spontaneous functional recovery.

新生児マウス脊髄圧縮損傷モデル

Spinal cord injury (SCI) typically causes devastating neurological deficits, particularly through damage to fibers descending from the brain to the spinal ...

Myocardial Infarction in Neonatal Mice, A Model of Cardiac Regeneration

Myocardial infarction induced by coronary artery ligation has been used in many animal models as a tool to study the mechanisms of cardiac repair and regeneration, and to define new targets for therapeutics. For decades, models of complete heart regeneration existed in amphibians and fish, but a mammalian counterpart was not available. The recent discovery of a postnatal window during which mice possess regenerative capabilities has led to the establishment of a mammalian model of cardiac regeneration. A surgical model of mammalian cardiac regeneration in the neonatal mouse is presented herein. Briefly, postnatal day 1 (P1) mice are anesthetized by isoflurane and placed on an ice pad to induce hypothermia. After the chest is opened, and the left anterior descending coronary artery (LAD) is visualized, a suture is placed around the LAD to inflict myocardial ischemia in the left ventricle. The surgical procedure takes 10-15 min. Visualizing the coronary artery is crucial for accurate suture placement and reproducibility. Myocardial infarction and cardiac dysfunction are confirmed by triphenyl-tetrazolium chloride (TTC) staining and echocardiography, respectively. Complete regeneration 21 days post myocardial infarction is verified by histology. This protocol can be used to as a tool to elucidate mechanisms of mammalian cardiac regeneration after myocardial infarction.

This protocol describes a highly reproducible model of cardiac regeneration by surgical induction of myocardial infarction in the left ventricle of postnatal day 1 mice. The method involves induction of hypothermic anesthesia and ligation of the left anterior descending coronary artery.

新生児マウスの心筋梗塞、心臓再生のモデル

Myocardial infarction induced by coronary artery ligation has been used in many animal models as a tool to study the mechanisms of cardiac repair and ...

A Chronic Cardiac Ischemia Model in Swine Using an Ameroid Constrictor

Cardiovascular disease remains the number one cause of mortality in the United States. There are numerous approaches to treating these diseases, but regardless of the approach, an in vivo model is needed to test each treatment. The pig is one of the most used large animal models for cardiovascular disease. Its heart is very similar in anatomy and function to that of a human. The ameroid placement technique creates an ischemic area of the heart, which has many useful applications in studying myocardial infarction. This model has been used for surgical research, pharmaceutical studies, imaging techniques, and cell therapies.
There are several ways of inducing an ischemic area in the heart. Each has its advantages and disadvantages, but the placement of an ameroid constrictor remains the most widely used technique. The main advantages to using the ameroid are its prevalence in existing research, its availability in various sizes to accommodate the anatomy and size of the vessel to be constricted, the surgery is a relatively simple procedure, and the post-operative monitoring is minimal, since there are no external devices to maintain. This paper provides a detailed overview of the proper technique for the placement of the ameroid constrictor.

The purpose of this protocol is to demonstrate the placement of a delayed constricting device (an ameroid constrictor) around a coronary artery in a swine model. This device creates an ischemic area of the heart that is useful for studying new diagnostic imaging techniques and new methods of treatment.

アメロイド収縮を使用して豚の慢性心筋虚血モデル

Cardiovascular disease remains the number one cause of mortality in the United States. There are numerous approaches to treating these diseases, but ...

Tachycardia-Induced Cardiomyopathy As a Chronic Heart Failure Model in Swine

A stable and reliable model of chronic heart failure is required for many experiments to understand hemodynamics or to test effects of new treatment methods. Here, we present such a model by tachycardia-induced cardiomyopathy, which can be produced by rapid cardiac pacing in swine.
A single pacing lead is introduced transvenously into fully anaesthetized healthy swine, to the apex of the right ventricle, and fixated. Its other end is then tunneled dorsally to the paravertebral region. There, it is connected to an in-house modified heart pacemaker unit that is then implanted in a subcutaneous pocket. 
After 4 - 8 weeks of rapid ventricular pacing at rates of 200 - 240 beats/min, physical examination revealed signs of severe heart failure - tachypnea, spontaneous sinus tachycardia, and fatigue. Echocardiography and X-ray showed dilation of all heart chambers, effusions, and severe systolic dysfunction. These findings correspond well to decompensated dilated cardiomyopathy and are also preserved after the cessation of pacing.
This model of tachycardia-induced cardiomyopathy can be used for studying the pathophysiology of progressive chronic heart failure, especially hemodynamic changes caused by new treatment modalities like mechanical circulatory supports. This methodology is easy to perform and the results are robust and reproducible.

Here, we present a protocol to produce tachycardia-induced cardiomyopathy in swine. This model represents a potent way to study the hemodynamics of progressive chronic heart failure and the effects of applied treatment.

豚の慢性心不全モデルとして頻拍誘発性心筋

A stable and reliable model of chronic heart failure is required for many experiments to understand hemodynamics or to test effects of new treatment ...

Severe Burn Injury in a Swine Model for Clinical Dressing Assessment

Wound healing is a dynamic repair process and is the most complex biological process in human life. In response to burn injury, alterations in biological pathways impair the inflammation response, resulting in delayed wound healing. Impaired wound healing frequently occurs in patients with diabetes leading to unfavorable outcomes such as amputation. Hence, dressings having beneficial effect in promoting burn wound repair are needed. However, studies on burn wound treatment are limited due to lack of proper animal models. Our previous study demonstrated wound-healing performance in rat and swine models using a minimally invasive surgical technique. This study aimed to demonstrate a swine model of severe burn injury that eliminates wound contraction and more closely approximates the human processes of re-epithelialization and new tissue formation. This protocol provides a detailed procedure for creating consistent burn wounds and examining the wound-healing performance under the treatment of an experimental dressing in a swine model. Six burn wounds were created symmetrically on the dorsum, which were covered with a clinical dressing composed of four layers: an inner contact layer of experimental materials, an inner intermediate layer of waterproof film, an outer intermediate layer of gauze, and an outer layer of adhesive plaster. Upon the completion of experiments, wound closure, wound area, and Vancouver Scar Scale score were examined. The samples of skin resected from each animal post-sacrifice were histologically prepared and stained using hematoxylin and eosin staining. Antibacterial activity of each dressing in the context of wound healing was also examined. The application of the clinical dressing to the wounds in swine model mimics the biological processes of human wound healing with respect to the processes of epithelialization, cellular proliferation, and angiogenesis. Therefore, this swine model provides an easy-to-learn, cost-effective, and robust method to assess the effect of clinical dressings in severe burn injury.

To closely mimic the mode of burn injuries requires the interplay between clinical observation and studies in animal models. In this study, a swine model of severe burn injury was established to assess an experimental dressing in physiological and pathophysiological settings.

豚モデルでドレッシングの臨床評価のための重症熱傷

Wound healing is a dynamic repair process and is the most complex biological process in human life. In response to burn injury, alterations in biological ...

Isometric Contractility Measurement of the Mouse Mesenteric Artery Using Wire Myography

The wire myograph technique is used to assess the contractility of vascular smooth muscles in response to depolarization, GPCR agonists/inhibitors and drugs. It is widely used in many studies on the physiological functions of vascular smooth muscle, the pathogenesis of vascular diseases such as hypertension, and the development of smooth muscle relaxant drugs. The mouse is a widely used model animal with a large pool of disease models and genetically modified strains. We introduced this method to measure the isometric contraction of mouse mesenteric artery in detail. A 1.4-mm segment of mouse mesenteric resistance artery was isolated and mounted on a myograph chamber by passing two steel wires through its lumen. After equilibration and normalization steps, the vessel segment was potentiated by a high-K+ solution twice prior to the contraction assay. As an example of the application of this method in drug development, we measured the relaxant effect of a novel natural substance, neoliensinine, isolated from a Chinese herb, embryos of the lotus seed (Nelumbo nucifera Gaertn.) on mouse mesenteric arteries. The vessel segments mounted on the myograph chamber were stimulated with a high-K+ solution. When the force tension reached a stable sustained phase, cumulative doses of neoliensinine were added to the chamber. We found that neoliensinine had a dose-dependent relaxant effect on smooth muscle contraction, thus suggesting that it bears potential activity against hypertension. In addition, as the vessel segment can survive at least 4 hours after mounting and maintain contractility induced by the high-K+ solution for many times, we suggest that the wire myograph system may be used for the time-consuming process of drug screening.

The wire myograph technique is used to investigate vascular smooth muscle functions and screen new drugs. We report a detailed protocol for measuring the isometric contractility of the mouse mesenteric artery and for screening new relaxants of vascular smooth muscle.

ワイヤー図法を使用してマウスの腸間膜動脈の等尺性収縮力測定

The wire myograph technique is used to assess the contractility of vascular smooth muscles in response to depolarization, GPCR agonists/inhibitors and ...

Establishing a Swine Model of Post-myocardial Infarction Heart Failure for Stem Cell Treatment

Although advances have been achieved in the treatment of heart failure (HF) following myocardial infarction (MI), HF following MI remains one of the major causes of mortality and morbidity around the world. Cell-based therapies for cardiac repair and improvement of left ventricular function after MI have attracted considerable attention. Accordingly, the safety and efficacy of these cell transplantations should be tested in a preclinical large animal model of HF prior to clinical use. Pigs are widely used for cardiovascular disease research due to their similarity to humans in terms of heart size and coronary anatomy. Therefore, we sought to present an effective protocol for the establishment of a porcine chronic HF model using closed-chest coronary balloon occlusion of the left circumflex artery (LCX), followed by rapid ventricular pacing induced with pacemaker implantation. Eight weeks later, the stem cells were administered by intramyocardial injection in the peri-infarct area. Then the infarct size, cell survival, and left ventricular function (including echocardiography, hemodynamic parameters, and electrophysiology) were evaluated. This study helps establish a stable preclinical large animal HF model for stem cell treatment.

We sought to establish a swine model of heart failure induced by left circumflex artery blockage and rapid pacing to test the effect and safety of intramyocardial administration of stem cells for cell-based therapies.

幹細胞治療のための心筋梗塞後心不全の豚モデルの確立

Although advances have been achieved in the treatment of heart failure (HF) following myocardial infarction (MI), HF following MI remains one of the major ...

Myocardial Infarction by Percutaneous Embolization Coil Deployment in a Swine Model

Myocardial infarction (MI) is the leading cause of mortality worldwide. Despite the use of evidence-based treatments, including coronary revascularization and cardiovascular drugs, a significant proportion of patients develop pathological left-ventricular remodeling and progressive heart failure following MI. Therefore, new therapeutic options, such as cellular and gene therapies, among others, have been developed to repair and regenerate injured myocardium. In this context, animal models of MI are crucial in exploring the safety and efficacy of these experimental therapies before clinical translation. Large animal models such as swine are preferred over smaller ones due to the high similarity of swine and human hearts in terms of coronary artery anatomy, cardiac kinetics, and the post-MI healing process. Here, we aimed to describe an MI model in pig by permanent coil deployment. Briefly, it comprises a percutaneous selective coronary artery cannulation through retrograde femoral access. Following coronary angiography, the coil is deployed at the target branch under fluoroscopic guidance. Finally, complete occlusion is confirmed by repeated coronary angiography. This approach is feasible, highly reproducible, and emulates the pathogenesis of human non-revascularized MI, avoiding the traditional open-chest surgery and the subsequent postoperative inflammation. Depending on the time of follow-up, the technique is suitable for acute, sub-acute, or chronic MI models.

Myocardial infarction (MI) animal models that emulate the natural process of the disease in humans are crucial to understanding pathophysiological mechanisms and testing the safety and efficacy of new emergent therapies. Here, we describe an MI swine model created by deploying a percutaneous embolization coil.

豚モデルにおける経皮塞栓コイル展開による心筋梗塞

Myocardial infarction (MI) is the leading cause of mortality worldwide. Despite the use of evidence-based treatments, including coronary revascularization ...

A Neonatal BALB/c Mouse Model of Necrotizing Enterocolitis

Necrotizing enterocolitis (NEC) is the most severe gastrointestinal (GI) disease that often occurs in premature infants, especially very low birth weight infants, with high mortality and unclear pathogenesis. The cause of NEC may be related to inflammatory immune regulatory system abnormalities. An NEC animal model is an indispensable tool for NEC disease immune research. NEC animal models usually use C57BL/6J neonatal mice; BALB/c neonatal mice are rarely used. Related studies have shown that when mice are infected, Th2 cell differentiation is predominant in BALB/c mice compared to C57BL/6J mice. Studies have suggested that the occurrence and development of NEC are associated with an increase in T helper type 2 (Th2) cells and are generally accompanied by infection. Therefore, this study used neonatal BALB/c mice to induce an NEC model with similar clinical characteristics and intestinal pathological changes as those observed in children with NEC. Further study is warranted to determine whether this animal model could be used to study Th2 cell responses in NEC.

Necrotizing enterocolitis (NEC) is the most severe gastrointestinal (GI) disease that often occurs in premature infants, especially very low birth weight infants, with high mortality and unclear pathogenesis. The cause of NEC may be related to inflammatory immune regulatory system abnormalities. An NEC animal model is an indispensable tool for NEC disease immune research. NEC animal models usually use C57BL/6J neonatal mice; BALB/c neonatal mice are rarely used. Related studies have shown that when mice are infected, Th2 cell differentiation is predominant in BALB/c mice compared to C57BL/6J mice. Studies have suggested that the occurrence and development of NEC are associated with an increase in T helper type 2 (Th2) cells and are generally accompanied by infection. Therefore, this study used neonatal BALB/c mice to induce an NEC model with similar clinical characteristics and intestinal pathological changes as those observed in children with NEC. Further study is warranted to determine whether this animal model could be used to study Th2 cell responses in NEC.

壊死性腸炎の新生児BALB/cマウスモデル

Necrotizing enterocolitis (NEC) is the most severe gastrointestinal (GI) disease that often occurs in premature infants, especially very low birth weight ...