Name: cardiopulmonary bypass in a mouse model: a novel approach
Uploaded: 2017-09-22T14:00:00
Description: Watch this Scientific Journal Video about Cardiopulmonary Bypass in a Mouse Model: A Novel Approach at JoVE.com

The authors have no acknowledgements.

All animal experiments were performed in compliance with the German Animal Protection Law (TierSchG) and were approved by the local animal welfare committee (Lower Saxony State Office for Consumer Protection and Food Safety, Protocol TSA 14/1556). The minimal weight of mouse suitable for this model is 25 g.
1. Preoperative Preparations
NOTE: All procedures are carried out under clean, non-sterile conditions, with autoclaved instruments.
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We have developed a fully-functioning clinically-relevant model of CPB in a mouse. With more than thirty strains of mice having cardiovascular diseases, our model could be a starting point for development of new prospective protocols related to CPB. Moreover, due to the plethora of mouse-specific reagents and knockout-out mice, this model can not only replace the current rat model of CPB but will facilitate dissection of the molecular mechanisms involved in CPB-related organ damage. To date, CPB has not been applied in m...

Since the introduction of cardiopulmonary bypass (CPB) into the clinic, it has played an essential role in cardiac surgery1. In modern cardiac surgery, prolonged CPB time is essential to perform extensive aortic reconstructions and combined procedures. Although technological advances have been tremendous, the use of extracorporal circulation is associated with intra- and postoperative systemic and local organ damage2,3.
Large animal models have been developed to investigate the role of CPB on physiological processes4,5. Although these models have provided insight into some of the CPB associated complications, they are extremely costly and molecular tools (e.g., antibodies) are very limited. A more cost-efficient alternative has been developed in small animals. Since their development, multiple studies have been conducted to optimize a CPB model in rats and rabbits5,6,7,8,9. These models provide a good basis for measurements of pathophysiological disease processes; however, they are still insufficient to investigate cellular and humoral immunology due to the lack of relevant antibodies and reagents. This impairs their role in this field of research.
We have recently developed a mouse model of CPB. Due to a wide variety of mouse-specific reagents and genetically-modified mice, mouse models are in general the model of choice for physiological, molecular, and immunological research10,11. Therefore, our model will facilitate the study of CPB in relation to various comorbidities as there are many mice strains available with clinically-relevant diseases12,13. Accordingly, this paper describes, in detail, how to perform CPB in mice. Oxygen and hemodynamic parameters are closely monitored after deep respiratory and circulatory arrest.

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			<td height="23" style="height:23px;width:297px;">Sterofundin</td>
			<td style="width:279px;">B.Braun Petzold GmbH</td>
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			<td height="21" style="height:21px;width:297px;">Tetraspan 6% HES Solution</td>
			<td style="width:279px;">B. Braun Melsungen AG</td>
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			<td>priming volume, 1:1 with Sterofundin</td>
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			<td height="21" style="height:21px;width:297px;">Heparin Natrium 25.000</td>
			<td style="width:279px;">Ratiopharm GmbH</td>
			<td style="width:181px;">PZN: 3029843</td>
			<td>2.5 IU per ml of priming solution</td>
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			<td height="21" style="height:21px;width:297px;">NaHCO3 8,4% Solution</td>
			<td style="width:279px;">B. Braun Melsungen AG</td>
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			<td>3% in priming solution</td>
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			<td height="21" style="height:21px;width:297px;">KCL 7,45 % Solution</td>
			<td style="width:279px;">B. Braun Melsungen AG</td>
			<td style="width:181px;">PZN: 2418577</td>
			<td>0.1 ml for cardioplegia</td>
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			<td height="21" style="height:21px;width:297px;">Carprofen</td>
			<td style="width:279px;">Zoetis Inc., USA</td>
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			<td>5 mg/kg/BW</td>
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			<td style="width:279px;">Instechlabs INC., USA</td>
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			<td>carotid artery</td>
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			<td height="21" style="height:21px;">Vasofix Safety catheter 20G</td>
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			<td>orotracheal intubation</td>
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			<td height="21" style="height:21px;width:297px;">8-0 Silk suture braided</td>
			<td>Ashaway Line &#38; Twine Mfg. Co., USA</td>
			<td style="width:181px;">75290</td>
			<td>ligature</td>
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			<td height="21" style="height:21px;width:297px;">Isoflurane</td>
			<td style="width:279px;">Piramal Critical Care Deutschland GmbH</td>
			<td style="width:181px;">PZN:9714675</td>
			<td>narcosis</td>
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			<td height="21" style="height:21px;">CLINITUBES blood capillaries</td>
			<td style="width:279px;">Radiomed GmbH</td>
			<td style="width:181px;">51750132</td>
			<td>blood sampling 60 - 95 microliter</td>
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			<td height="21" style="height:21px;">Spring Scissors - 6mm Blades</td>
			<td>Fine Science Tools GmbH</td>
			<td style="width:181px;">15020-15</td>
			<td>instruments</td>
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			<td height="21" style="height:21px;">Spring Scissors - 2mm Blades</td>
			<td>Fine Science Tools GmbH</td>
			<td style="width:181px;">15000-03</td>
			<td>instruments</td>
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			<td height="21" style="height:21px;">Halsted-Mosquito Hemostat</td>
			<td>Fine Science Tools GmbH</td>
			<td style="width:181px;">13009-12</td>
			<td>instruments</td>
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			<td height="21" style="height:21px;">Dumont #55 Forceps</td>
			<td>Fine Science Tools GmbH</td>
			<td style="width:181px;">11295-51</td>
			<td>instruments</td>
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			<td height="21" style="height:21px;">Castroviejo Micro Needle Holder - 9cm</td>
			<td>Fine Science Tools GmbH</td>
			<td style="width:181px;">12060-02</td>
			<td>instruments</td>
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			<td height="21" style="height:21px;">Micro Serrefines</td>
			<td>Fine Science Tools GmbH</td>
			<td>18555-01</td>
			<td>instruments</td>
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			<td height="21" style="height:21px;">Bulldog Serrefine</td>
			<td>Fine Science Tools GmbH</td>
			<td style="width:181px;">18050-28</td>
			<td>instruments</td>
		</tr>
		<tr height="23">
			<td height="23" style="height:23px;width:297px;">MiniVent Ventilator for Mice (Model 845)</td>
			<td style="width:279px;">Harvard Apparatus</td>
			<td style="width:181px;">73-0044</td>
			<td>mechanical ventilation</td>
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			<td height="21" style="height:21px;width:297px;">Isoflurane Vaporizer Drager 19.1</td>
			<td style="width:279px;">Dr&#228;gerwerk AG &#38; Co. KGaA</td>
			<td style="width:181px;"></td>
			<td>anesthesia 1.3 -2.5%</td>
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			<td height="21" style="height:21px;">PowerLab data acquisition device 4/35</td>
			<td>ADInstruments Ltd, New Zealand</td>
			<td style="width:181px;">PL3504</td>
			<td>invasive pressure, ECG, temperature</td>
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			<td height="21" style="height:21px;">ABL 800 Flex</td>
			<td>Radiometer GmbH</td>
			<td style="width:181px;"></td>
			<td>blood gas analysis</td>
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			<td height="21" style="height:21px;width:297px;">NMRI mice</td>
			<td style="width:279px;">Charles River Laboratories</td>
			<td style="width:181px;">Crl:NMRI(Han)</td>
			<td>male, 30-35 g, 12 weeks old, housed at least 1 week before the experiment</td>
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cardiopulmonary bypass in a mouse model: a novel approach

As prolonged cardiopulmonary bypass becomes more essential during cardiac interventions, an increasing clinical demand arises for procedure optimization and for minimizing organ damage resulting from prolonged extracorporal circulation. The goal of this paper was to demonstrate a fully functional and clinically relevant model of cardiopulmonary bypass in a mouse. We report on the device design, perfusion circuit optimization, and microsurgical techniques. This model is an acute model, which is not compatible with survival due to the need for multiple blood drawings. Because of the range of tools available for mice (e.g., markers, knockouts, etc.), this model will facilitate investigation into the molecular mechanisms of organ damage and the effect of cardiopulmonary bypass in relation to other comorbidities.

This protocol describes the perfusion circuit, surgical procedures, and monitoring of physiological parameters during CPB of a mouse. When performed by an adequately skilled microsurgeon, the results are consistently and reproducibly obtained.
To maintain adequate tissue perfusion, the mean arterial pressure is always kept between 40 and 60 mmHg by adjusting the CPB blood flow and adding of extra volume. Depending on the weight ...

Watch this Scientific Journal Video about Cardiopulmonary Bypass in a Mouse Model: A Novel Approach at JoVE.com

Cardiopulmonary Bypass in a Mouse Model: A Novel Approach

This paper describes how to perform cardiopulmonary bypass in mice. This novel model will facilitate the investigation of the molecular mechanisms involved in organ damage.

As prolonged cardiopulmonary bypass becomes more essential during cardiac interventions, an increasing clinical demand arises for procedure optimization ...

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