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Abstract
Introduction
Protocol
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Discussion
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Entwicklungsbiologie

多変量慢性非麻酔下の録音のための短期的ヒツジ胎児の計測

Published: October 25, 2015
doi:
10.3791/52581
, , , , , , ,
1Département de sciences cliniques,CHUV, Université de Montréal, St-Hyacinthe, QC, 2Département d’obstetriques et de gynécologie,CHU Ste-Justine Research Centre, Université de Montréal, 3Département de neurosciences,CHU Ste-Justine Centre de recherche, Université de Montréal, 4Centre de recherche en reproduction animale (CRRA),Université de Montréal, St-Hyacinthe, QC

Summary

それは外科的配置およびカテーテルおよび電極、反復採血、物質の注入、生体電気活動の記録の維持、およびin vivoイメージングでを許可するため、慢性的に計装非麻酔下の胎児ヒツジモデルは、健康と病気におけるヒト胎児発達を研究するために使用されます。我々は、このモデルを確立するために必要な手順について説明します。

Abstract

The chronically instrumented pregnant sheep has been used as a model of human fetal development and responses to pathophysiologic stimuli such as endotoxins, bacteria, umbilical cord occlusions, hypoxia and various pharmacological treatments. The life-saving clinical practices of glucocorticoid treatment in fetuses at risk of premature birth and the therapeutic hypothermia have been developed in this model. This is due to the unique amenability of the non-anesthetized fetal sheep to the surgical placement and maintenance of catheters and electrodes, allowing repetitive blood sampling, substance injection, recording of bioelectrical activity, application of electric stimulation and in vivo organ imaging. Here we describe the surgical instrumentation procedure required to achieve a stable chronically instrumented non-anesthetized fetal sheep model including characterization of the post-operative recovery from blood gas, metabolic and inflammation standpoints.

Introduction

種々の動物モデルは、実験用げっ歯類、非ヒト霊長類、国内の反芻動物を含む正常と妥協妊娠、両方の研究のために存在する。1,2,3,4,5慢性的に計装妊娠羊のように50年のために広く使用されてきましたそのようなリポ多糖（LPS）などの病態生理学的刺激に対する人間の胎児の発育と応答のモデル。LPS暴露後6-10病変は、両種の同様の成熟プロフィールに起因するものである脳室周囲白質軟化症と早産児に見られる、まさに模倣します。 11、12

その他の妊娠合併症はまた、出産前グルココルチコイドは、肺の開発13-15と胎児16,17の子宮内発育制限（IUGR）の影響を理解を促進することが発見として非常に詳細に研究されています。

胎児ヒツジモデルの広範な使用は、uniqのが原因でありますカテーテルおよび電極の外科的配置およびメンテナンスに非麻酔下のヒツジ胎児のUE従順、反復採血、生体電気活動の記録、電気刺激の適用および in vivo脳イメージングにすることが可能となる。使用頻度の低いが、18テレメトリは、も可能ですまだ設定だけでなく、初期およびメンテナンスコストが高く洗練さに起因する。19

計測器の多くのバリエーションが関心のある施策に応じて可能であるためまた、胎児ヒツジモデルは、非常に汎用性があります。例えば、それは、数日から数週間にわたって記録することができるように胎児の呼吸の動き、電気的脳活動、心血管応答、心電図、臓器の範囲に局所血流に流量プローブまたはマイクロスフェアなどのおかげでの使用など、リアルタイムで多変量の信号この汎用性は、研究の広い範囲がカルディの開発などが行われていますovascularシステム20,21、視床下部-下垂体-副腎（HPA）軸22、特に24で脳の発達23とスリープ状態の開発、低酸素症の影響/仮死25、低体温療法26、炎症6-11、両方の27の組み合わせ、グルココルチコイド28,29、抗うつ30、気管支肺異形成症（BPD）31,32、前と分娩時の名前が、胎児プログラミング33,34,35,36,37,38,39又は新規胎児監視モダリティの開発調査のいくつかの領域。40,41,42,43

提示された方法の全体的な目標は、この汎用性の高いモデルの基本的な実装を示すことです。これは、急性および慢性実験統合的に胎児の生理学と病態生理学を研究プロトコル、臓器、細胞および分子レベルの多種多様を確立することができます。

Protocol

動物のケアは、動物実験と動物実験のモントリオール大学評議会（プロトコル＃10-RECH-1560）による承認のカナダ人評議会のガイドラインに従いました。使用される材料及び方法の詳細については、表1に提供されます。 1.麻酔頸静脈にシングルルーメンカテーテルを挿入します。 落ち着いた雌ヒツジ使用してアセプロマジン（Atravetを10mg / mL）を2 mgを静脈内…

Representative Results

38妊娠中の時間日付雌ヒツジは、（一般的な麻酔下で無菌技術を用いて、動脈、静脈および羊膜カテーテルおよび心電図（ECG）電極を用いて妊娠の128±2日（DGA、〜0.88妊娠、用語145 DGA）で雌羊と胎児の両方をインストルメントされました）。双子妊娠の場合には、より大きな胎児は触診と異時点間の直径の推定に基づいて選択されまし​​た。代わりに、インストルメントされる胎児の潜在?…

Discussion

慢性的に計装非麻酔下の胎児の羊：麻酔および手術の手順は、胎児の生理学と病態生理学を研究するための動物モデルを確立するために必要であることを提示しています。

プロトコル圏内の4つの重要なステップが強調されるべきです。まず、母体の脇腹を通ってカテーテルおよび電極を渡します。これは、任意の臓器損傷を避けるために、一度に行われることが重要で?…

Offenlegungen

The authors have nothing to disclose.

Acknowledgements

authors gratefully acknowledge funding support from the Molly Towell Perinatal Research Foundation, Canadian Institutes of Health Research (CIHR), and Fonds de Recherche du Québec – Santé (FRQS) (to MGF) and CIHR-Quebec Training Network in Perinatal Research (QTNPR) (to LDD).

The authors wish to thank Esther Simard, Marco Bosa, Carl Bernard and Carmen Movila for technical assistance.

Materials

ACE Light source Schott-Fostec A20500
Dissecting scissors Fine Science Tools 14060 – 11
Angled dissecting scissors Fine Science Tools 15006 – 09
Scalpel handle Fine Science Tools 10003 – 12 alternating dissecting tool
Curved scalpel blades #12 Fine Science Tools 10012 – 00 alternating dissecting tool
Bone scissors Fine Science Tools 16044 – 10
S & T suture tying forceps Fine Science Tools 00272 – 13
Dumont SS forceps – angled Fine Science Tools 11203 – 25 
Braided silk suture size 6-0 Teleflex Medical 07 – 30  – 10
Medical Tape transpore 3M
Ketamine hydrochloride 100 mg/ml Hospira NDC 0409 – 2051 – 05 Final Does is 80 mg/kg
Tranqui Ved Injection (xylazine 100 mg/ml) Vecdo NDC 50989 – 234 – 11 Final Does is 10 mg/kg
Reactive orange 14 Sigma – Aldrich R – 8254
Ringers Solution Components Solution is gas equilibrated with 95% O2 and 5% Co2, final pH 7.4
Sodium chloride Sigma – Aldrich S7653 Final Concentration: 118 mM
Potassium chloride Fisher Scientific P217 – 3 Final Concentration: 4.7 mM
Calcium chloride dihydrate Fisher Scientific C79 – 500 Final Concentration: 2.5 mM
Potassium phosphate monobasic Fisher Scientific P -285 Final Concentration: 1.2 mM
Magnesium sulfate J.T. Baker Jan-00 Final Concentration: 0.57 mM
4-(2-Hydroxyethyl)piperazine-1-ethanesulfonic acid (HEPES) Fisher Scientific BP 310 – 500 Final Concentration: 5.95 g/L
Glucose Sigma – Aldrich G8270 Final Concentration: 5.5 mM
LifeWindow Digicare Biomedical Technology
CED bioamplifier and ADC units Cambridge Electronic Design Limited,
Unit 4, Science Park,
Milton Road,
Cambridge CB4 0FE
ENGLAND.		 Bioamp: 1902; ADC: micro1401; Data acquisition software: Spike 2, V7.13
Neurolog analog signal bioamplifier Digitimer Ltd
37 Hydeway
Welwyn Garden City
Hertfordshire, AL7 3BE, England		 NL108A
ABL800Flex Radiometer Canada; 200 Aberdeen Dr, London, ON N5V 4N2
Eppendorf 5804R Eppendorf Canada; 2810 Argentia Road, #2
Mississauga, Ontario, L5N 8L2
Arrow Jugular Catheterization Set Arrow International, Inc., 2400 Bernville Road, Reading, PA 19605 USA
Atravet 10 mg/mL
Diazepam 5mg/mL
Ketamine Ketalar 100 mg/mL
Propofol 10 mg/mL
SurgiVeT Endotracheal Tubes; Smiths Medical ASD, Inc. St. Paul, MN 55112, USA
Cook Airway Exchange Catheter with RAPI-FIT Adapters Cook Critical Care 750, Bloomington IN 47402-0489 USA
Dispomed Ventilator Dispomed Ltd., 745 Nazaire-Laurin, Joliette, Quebec J6E 0L6
BD Insyte-W Becton Dickinson, Infusion Therapy Systems Inc., 9450 S State St, Sandy Utah 84070 USA 22 to 20 G; 1 in [0.9 x 25 mm] to 1.16 in [1.1 x 30 mm]
Edwards Lifesciences Ref: PX272 Pressure monitoring kit with TruWave Disposable Pressure
LifeWindow LW6000 Digicare Biomedical Technology 107 Commerce Road, Boynton Beach, FL 33426-9365 USA
Gaymar
Babcock
Polyvinyl catheters SCI (Scientific Commodities Inc.) 2 meters
2-0 Vicryl
Castroviejo scissors
electrocardiogram (ECG) LIFYY, Metrofunk Kabel-Union, Berlin, Germany four copper electrodes in single sheath, 2 meters
2-O Vicryl
3-0 Vicryl
PDS II USP
Trimethoprim sulfadoxine
Ampicillin
Stopcock Argon Medical, Cat 041220001A Double 4-way Stopcock with male luer lock
Needles Tyco Healthcare 8881202389 Monoject aluminum hub blunt needles, 22Gx, 0.7mmx 38.1mm: for fetal arterial and venous catheters
Needles Tyco Healthcare 8881202322 Monoject aluminum hub blunt needles, 16Gx, 1.6mmx38.1mm: for amniotic catheters
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Referenzen

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Tags

Keywords: Fetal SheepChronic InstrumentationMultivariate RecordingsNon-anesthetizedFetal DevelopmentPathophysiologic StimuliGlucocorticoid TreatmentTherapeutic HypothermiaCatheter PlacementBioelectrical ActivityIn Vivo Organ Imaging
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Burns, P., Liu, H. L., Kuthiala, S., Fecteau, G., Desrochers, A., Durosier, L. D., Cao, M., Frasch, M. G. Instrumentation of Near-term Fetal Sheep for Multivariate Chronic Non-anesthetized Recordings. J. Vis. Exp. (104), e52581, doi:10.3791/52581 (2015).
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