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Abstract

Introduction

Protocol

Representative Results

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Neuroscience

Mouse Cardiac Arrest Model for Brain Imaging and Brain Physiology Monitoring During Ischemia and Resuscitation

Published: April 14th, 2023

DOI:

10.3791/65340

1Multidisciplinary Brain Protection Program, Department of Anesthesiology, Duke University Medical Center, 2Department of Biomedical Engineering, Duke University, 3Department of Anesthesiology and Pain Management, UT Southwestern University Medical Center

This protocol demonstrates a unique mouse model of asphyxia cardiac arrest that does not require chest compression for resuscitation. This model is useful for monitoring and imaging the dynamics of brain physiology during cardiac arrest and resuscitation.

Most cardiac arrest (CA) survivors experience varying degrees of neurologic deficits. To understand the mechanisms that underpin CA-induced brain injury and, subsequently, develop effective treatments, experimental CA research is essential. To this end, a few mouse CA models have been established. In most of these models, the mice are placed in the supine position in order to perform chest compression for cardiopulmonary resuscitation (CPR). However, this resuscitation procedure makes the real-time imaging/monitoring of brain physiology during CA and resuscitation challenging. To obtain such critical knowledge, the present protocol presents a mouse asphyxia CA model that does not require the chest compression CPR step. This model allows for the study of dynamic changes in blood flow, vascular structure, electrical potentials, and brain tissue oxygen from the pre-CA baseline to early post-CA reperfusion. Importantly, this model applies to aged mice. Thus, this mouse CA model is expected to be a critical tool for deciphering the impact of CA on brain physiology.

Cardiac arrest (CA) remains a global public health crisis1. More than 356,000 out-of-hospital and 290,000 in-hospital CA cases are reported annually in the US alone, and most CA victims are over 60 years old. Notably, post-CA neurologic impairments are common among survivors, and these represent a major challenge for CA management2,3,4,5. To understand post-CA brain pathologic changes and their effects on neurologic outcomes, various neurophysiologic monitoring and brain tissue monitoring techniq....

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All the procedures described here were conducted in accordance with the National Institutes of Health (NIH) guidelines for the care and use of animals in research, and the protocol was approved by the Duke Institute of Animal Care and Use Committee (IACUC). C57BL/6 male and female mice aged 8-10 weeks old were used for the present study.

1. Surgical preparation

  1. Weigh a mouse on a digital scale, and place it into a 4 in x 4 in x 7 in plexiglass anesthesia induc.......

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To induce CA, the mouse was anesthetized with 1.5% isoflurane and ventilated with 100% nitrogen. This condition led to severe bradycardia in 45 s (Figure 1). Following 2 min of anoxia, the heart rate dramatically reduced (Figure 2), the blood pressure decreased below 20 mmHg, and the cerebral blood flow ceased completely (Figure 1). As the isoflurane was turned off, the body temperature was no longer managed and slowly dropped .......

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In experimental CA studies, asphyxia, potassium chloride injections, or electrical current-derived ventricular fibrillation have been used to induce CA16,17,18,19,20,21,22,23. Normally, CPR is required for resuscitation in these CA models, especially in mic.......

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The authors thank Kathy Gage for her editorial support. This study was supported by funds from the Department of Anesthesiology (Duke University Medical Center), American Heart Association grant (18CSA34080277), and National Institutes of Health (NIH) grants (NS099590, HL157354, NS117973, and NS127163).

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Name Company Catalog Number Comments
Adrenalin Par Pharmaceutical NDC 42023-159-01
Alcohol swabs BD 326895
Animal Bio Amp ADInstruments FE232
BP transducer ADInstruments MLT0699
Bridge Amp ADInstruments FE117
Heparin sodium injection, USP Fresenius Kabi NDC 63323-540-05
Isoflurane Covetrus NDC 11695-6777-2
Laser Doppler perfusion monitor Moor Instruments moorVMS-LDF1
Laser speckle imaging system RWD RFLSI III
Lubricant eye ointment Bausch + Lomb 339081
Micro clip Roboz RS-5431
Mouse rectal probe Physitemp RET-3
Needle electrode ADInstruments MLA1213 29 Ga, 1.5 mm socket
Nitrogen Airgas UN1066
Optic plastic fibre Moor Instruments POF500
Otoscope Welchallyn 728 2.5 mm Speculum
Oxygen Airgas UN1072
PE-10 tubing BD 427401 Polyethylene tubing
Povidone-iodine CVS 955338
PowerLab 8/35 ADInstruments
Rimadyl (carprofen) Zoetis 6100701 Injectable 50 mg/ml
Small animal ventilator Kent Scientific RoVent Jr.
Temperature controller Physitemp TCAT-2DF
Triple antibioric & pain relief CVS NDC 59770-823-56
Vaporizer RWD R583S
0.25% bupivacaine Hospira NDC 0409-1159-18
0.9% sodium chroride ICU Medical NDC 0990-7983-03
1 mL plastic syringe BD 309659
4-0 silk suture Look SP116 Black braided silk
6-0 nylon suture Ethilon 1698G
8.4% sodium bicarbonate Inj., USP Hospira NDC 0409-6625-02
20 G IV catheter BD 381534 20GA 1.6 IN
30 G PrecisionGlide needle BD 305106 30 G X 1/2

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