Name: an in vivo mouse model of total intravenous anesthesia during cancer resection surgery
Uploaded: 2021-06-08T14:30:00
Description: Watch this Scientific Journal Video about An In Vivo Mouse Model of Total Intravenous Anesthesia During Cancer Resection Surgery at JoVE.com

The authors wish to thank members of the Cancer Neural-Immune Laboratory and Dr. Cameron Nowell at Monash Institute of Pharmaceutical Sciences, Monash University, Parkville. This work was supported by grants from National Health and Medical Research Council 1147498, the National Breast Cancer Foundation IIRS-20-025, the Australian and New Zealand College of Anaesthetists (ANZCA), Perpetual and CTC for Cancer Therapeutics.

All animal studies were undertaken under the approval of the Institutional Animal Care and Use Committee at Monash University. In this study, female Balb/c mice aged 6-8 weeks were used.
1. Prepare cancer cells
<ol>
	<li>Culture tumor cells in medium. Culture 66cl4 murine mammary cancer cells in alpha-MEM containing 10% FBS and 200 mM glutamine. Cells should text negative for mycoplasma. OPTIONAL:&#160;Use cells that are stably transduced to express firefly luciferase for bioluminescence ima...

<ol>
	<li>Sullivan, R., 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=Global+cancer+surgery:+delivering+safe,+affordable,+and+timely+cancer+surgery.">Global cancer surgery: delivering safe, affordable, and timely cancer surgery.</a> Lancet Oncology. 16 (11), 1193-1224 (2015).</li><li>Lim, J. A., 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+effect+of+propofol+and+sevoflurane+on+cancer+cell,+natural+killer+cell,+and+cytotoxic+T+lymphocyte+function+in+patients+undergoing+breast+cancer+surgery:+an+in+vitro+analysis.">The effect of propofol and sevoflurane on cancer cell, natural killer cell, and cytotoxic T lymphocyte function in patients undergoing breast cancer surgery: an in vitro analysis.</a> BMC Cancer. 18 (1), 159 (2018).</li><li>Pandit, J. 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=5th+National+Audit+Project+(NAP5)+on+accidental+awareness+during+general+anesthesia:+protocol,+methods,+and+analysis+of+data.">5th National Audit Project (NAP5) on accidental awareness during general anesthesia: protocol, methods, and analysis of data.</a> British Journal of Anaesthesia. 113 (4), 540-548 (2014).</li><li>Yap, A., Lopez-Olivo, M. A., Dubowitz, J., Hiller, J., Riedel, B. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Anesthetic+technique+and+cancer+outcomes:+a+meta-analysis+of+total+intravenous+versus+volatile+anesthesia.">Anesthetic technique and cancer outcomes: a meta-analysis of total intravenous versus volatile anesthesia.</a> Canadian Journal of Anesthesia. 66 (5), 546-561 (2019).</li><li>Makito, K., Matsui, H., Fushimi, K., Yasunaga, H. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Volatile+versus+total+intravenous+anesthesia+for+cancer+prognosis+in+patients+having+digestive+cancer+surgery.">Volatile versus total intravenous anesthesia for cancer prognosis in patients having digestive cancer surgery.</a> Anesthesiology. 133 (4), 764-773 (2020).</li><li>Oh, T. K., Kim, H. H., Jeon, Y. T. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Retrospective+analysis+of+1-year+mortality+after+gastric+cancer+surgery:+Total+intravenous+anesthesia+versus+volatile+anesthesia.">Retrospective analysis of 1-year mortality after gastric cancer surgery: Total intravenous anesthesia versus volatile anesthesia.</a> Acta Anaesthesiologica Scandinavica. 63 (9), 1169-1177 (2019).</li><li>Lai, H. C., 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=Propofol-based+total+intravenous+anesthesia+is+associated+with+better+survival+than+desflurane+anesthesia+in+hepatectomy+for+hepatocellular+carcinoma:+a+retrospective+cohort+study.">Propofol-based total intravenous anesthesia is associated with better survival than desflurane anesthesia in hepatectomy for hepatocellular carcinoma: a retrospective cohort study.</a> British Journal of Anaesthesia. 123 (2), 151-160 (2019).</li><li>Hong, B., 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=Anesthetics+and+long-term+survival+after+cancer+surgery-total+intravenous+versus+volatile+anesthesia:+a+retrospective+study.">Anesthetics and long-term survival after cancer surgery-total intravenous versus volatile anesthesia: a retrospective study.</a> BMC Anesthesiology. 19 (1), 233 (2019).</li><li>Flecknell, P. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Special+Techniques.">Special Techniques.</a> Laboratory Animal Anaesthesia. Fourth edition. , (2015).</li><li>Cicero, L., Fazzotta, S., Palumbo, V. D., Cassata, G., Lo Monte, A. I. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Anesthesia+protocols+in+laboratory+animals+used+for+scientific+purposes.">Anesthesia protocols in laboratory animals used for scientific purposes.</a> Acta Biomedica. 89 (3), 337-342 (2018).</li><li>Sloan, E. 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=The+sympathetic+nervous+system+induces+a+metastatic+switch+in+primary+breast+cancer.">The sympathetic nervous system induces a metastatic switch in primary breast cancer.</a> Cancer Research. 70 (18), 7042-7052 (2010).</li><li>Al-Hashimi, M., Scott, S. W. M., Thompson, J. P., Lambert, D. G. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Opioids+and+immune+modulation:+more+questions+than+answers.">Opioids and immune modulation: more questions than answers.</a> British Journal of Anaesthesia. 111 (1), 80-88 (2013).</li><li>DeMarco, G. J., Nunamaker, E. A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+Review+of+the+effects+of+pain+and+analgesia+on+immune+system+function+and+inflammation:+relevance+for+preclinical+studies.">A Review of the effects of pain and analgesia on immune system function and inflammation: relevance for preclinical studies.</a> Comparative Medicine. 69 (6), 520-534 (2019).</li><li>Hiller, J. G., Perry, N. J., Poulogiannis, G., Riedel, B., Sloan, E. K. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Perioperative+events+influence+cancer+recurrence+risk+after+surgery.">Perioperative events influence cancer recurrence risk after surgery.</a> Nature Reviews Clinical Oncology. 15 (4), 205-218 (2018).</li></ol>

This study reports on a protocol for administering total intravenous anesthesia (TIVA) with propofol in a mouse model of breast cancer that replicates key aspects of clinical practice for TIVA in patients requiring cancer surgery. The protocol allows investigation of both short-term and long-term clinically relevant outcomes after cancer surgery in a mouse model of cancer progression, including measurement of cytokine levels and cancer recurrence (Figure 2, and Figure 3<...

More than 60% of patients with cancer receive anesthesia for surgical resection1. Currently, there are no specific clinical guidelines that determine the choice of anesthesia used in cancer patients. Surveys of anesthesiologists indicate a preference for volatile-based anesthesia, including during cancer surgery2,3. However, there is a growing body of evidence that the use of propofol-based total intravenous anesthesia (TIVA) during cancer surgery may associate with improved postoperative outcomes (progression-free survival, overall survival) when compared to volatile anesthesia4. Subsequent clinical studies continue to report contradicting results5,6,7,8. These findings support the need for preclinical studies to better understand the mechanistic effects of different anesthetic agents on cancer-related outcomes.
However, in in vivo studies that model cancer surgery, anesthesia is frequently an incidental part of the procedure. The rationale for the choice of anesthesia is&#160;often not the focus of the experimental design, and its impact on cancer-related endpoints may not be evaluated. For example, in vivo studies that require maintenance of anesthesia for cancer surgery most commonly use inhaled volatile anesthesia9. Where propofol has been used in in vivo studies, it has been delivered by single bolus dosing with intraperitoneal delivery, which does not replicate clinical onco-anesthetic protocols10. That approach of propofol administration induces light anesthesia that is suitable for rapid procedures. However, it does not allow maintenance of anesthesia that is required for cancer resection surgery which may be protracted. Furthermore, the absorption kinetics of intraperitoneal delivery is distinct to clinical methods of administration.
A model of propofol-based TIVA for cancer resection surgery was developed to address this need. A protocol for sustained maintenance of anesthesia with titration of the anesthetic agent to allow response to the surgical stimulus was developed to replicate key aspects of anesthetic delivery to patients having cancer surgery. The resulting protocol is used with a mouse model of cancer to provide TIVA during cancer resection surgery. The effect on short-term and long-term cancer-related outcomes is evaluated.

<table border="1" fo:keep-together.within-page="1" fo:keep-with-next.within-page="always">
	<tbody>
		<tr>
			<td>0.9% saline</td>
			<td>Fresnius Kabi</td>
			<td>AUST R 197198</td>
			<td></td>
		</tr>
		<tr>
			<td>Artery forceps</td>
			<td>Proscitech</td>
			<td>TS1322-140</td>
			<td></td>
		</tr>
		<tr>
			<td>Buprenorphine</td>
			<td>Temgesic</td>
			<td>TEMG I</td>
			<td></td>
		</tr>
		<tr>
			<td>Heated surgical mat</td>
			<td>Custom</td>
			<td>-</td>
			<td></td>
		</tr>
		<tr>
			<td>Hypodermic needle (30 G, 1 mL insulin syringe)</td>
			<td>Terumo</td>
			<td>NN3013R</td>
			<td></td>
		</tr>
		<tr>
			<td>IVIS Lumina</td>
			<td>PerkinElmer</td>
			<td>126274</td>
			<td></td>
		</tr>
		<tr>
			<td>Luciferin</td>
			<td>Promega</td>
			<td>P1041/2/3</td>
			<td></td>
		</tr>
		<tr>
			<td>Polyurethane catheter</td>
			<td>Intramedic</td>
			<td>427401</td>
			<td></td>
		</tr>
		<tr>
			<td>Povidone Iodine</td>
			<td>Betadine</td>
			<td>AUST R 29562</td>
			<td></td>
		</tr>
		<tr>
			<td>Propofol Lipuro, 2%</td>
			<td>Braun</td>
			<td>3521490</td>
			<td></td>
		</tr>
		<tr>
			<td>Sevoflurane</td>
			<td>Baxter</td>
			<td>ANZ2L9117</td>
			<td></td>
		</tr>
		<tr>
			<td>Sevoflurane vaporiser</td>
			<td>Vetquip</td>
			<td>VQ1334</td>
			<td></td>
		</tr>
		<tr>
			<td>Sterile gauze</td>
			<td>Multigate Medical Products</td>
			<td>11-600A</td>
			<td></td>
		</tr>
		<tr>
			<td>Surgical scissors</td>
			<td>Proscitech</td>
			<td>TS1044</td>
			<td></td>
		</tr>
		<tr>
			<td>Sutures, 5-0 nylon</td>
			<td>Dynek</td>
			<td>V504</td>
			<td></td>
		</tr>
		<tr>
			<td>Syringe pump</td>
			<td>Harvard Apparatus</td>
			<td>70-4500</td>
			<td></td>
		</tr>
		<tr>
			<td>Syringes (1 mL)</td>
			<td>Terumo</td>
			<td>SS+01T</td>
			<td></td>
		</tr>
	</tbody>
</table>

an in vivo mouse model of total intravenous anesthesia during cancer resection surgery

Anesthesia is a routine component of cancer care that is used for diagnostic and therapeutic procedures. The anesthetic technique has recently been implicated in impacting long-term cancer outcomes, possibly through modulation of adrenergic-inflammatory responses that impact cancer cell behavior and immune cell function. Emerging evidence suggests that propofol-based total intravenous anesthesia (TIVA) may be beneficial for long-term cancer outcomes when compared to inhaled volatile anesthesia. However, the available clinical findings are inconsistent. Preclinical studies that identify the underlying mechanisms involved are critically needed to guide the design of clinical studies that will expedite insight. Most preclinical models of anesthesia have been extrapolated from the use of anesthesia in in vivo research and are not optimally designed to study the impact of anesthesia itself as the primary endpoint. This paper describes a method for delivering propofol-TIVA anesthesia in a mouse model of breast cancer resection that replicates key aspects of clinical delivery in cancer patients. The model can be used to study mechanisms of action of anesthesia on cancer outcomes in diverse cancer types and can be extrapolated to other non-cancer areas of preclinical anesthesia research.

This method describes a model of total intravenous anesthesia (TIVA) with propofol during cancer resection surgery in mice. Propofol is delivered in this mouse model through an intravenous catheter using a syringe pump (Figure 1A,B) to replicate delivery of TIVA in the clinical setting of anesthesia for cancer surgery. Use of the syringe pump minimizes exposure to volatile anesthesia by allowing rapid conversion from initial induction by inhalational anesthesia to intravenou...

Watch this Scientific Journal Video about An In Vivo Mouse Model of Total Intravenous Anesthesia During Cancer Resection Surgery at JoVE.com

An In Vivo Mouse Model of Total Intravenous Anesthesia During Cancer Resection Surgery

This paper describes a method for modeling total intravenous anesthesia (TIVA) during cancer resection surgery in mice. The goal is to replicate key features of anesthesia delivery to patients with cancer. The method allows investigation of how anesthetic technique affects cancer recurrence after resection surgery.

An In Vivo Mouse Model of Total Intravenous Anesthesia During Cancer Resection Surgery

Anesthesia is a routine component of cancer care that is used for diagnostic and therapeutic procedures. The anesthetic technique has recently been ...

Research

JoVE Journal

Medicine

Quantitative Analysis of Cancer Metastasis using an Avian Embryo Model

During metastasis cancer cells disseminate from the primary tumor, invade into surrounding tissues, and spread to distant organs. Metastasis is a complex ...

Multi-photon Imaging of Tumor Cell Invasion in an Orthotopic Mouse Model of Oral Squamous Cell Carcinoma

Loco-regional invasion of head and neck cancer is linked to metastatic risk and presents a difficult challenge in designing and implementing patient ...

Combination Radiotherapy in an Orthotopic Mouse Brain Tumor Model

Glioblastoma multiforme (GBM) are the most common and aggressive adult primary brain tumors1. In recent years there has been substantial progress in the ...

An Ex vivo Model to Study Hormone Action in the Human Breast

An Ex vivo Model to Study Hormone Action in the Human Breast

The study of hormone action in the human breast has been hampered by lack of adequate model systems. Upon in vitro culture, primary mammary epithelial ...

An Orthotopic Mouse Model of Spontaneous Breast Cancer Metastasis

Metastasis is the primary cause of mortality of breast cancer patients. The mechanism underlying cancer cell metastasis, including breast cancer ...

Depletion of Mouse Cells from Human Tumor Xenografts Significantly Improves Downstream Analysis of Target Cells

The use of in vitro cell line models for cancer research has been a useful tool. However, it has been shown that these models fail to reliably mimic ...

An Anesthesia, Surgery, and Harvest Method for the Evaluation of Transpedicular Screws Using an In Vivo Porcine Lumbar Spine Model

An Anesthesia, Surgery, and Harvest Method for the Evaluation of Transpedicular Screws Using an In Vivo Porcine Lumbar Spine Model

Pedicle screw fixation is the gold standard for the treatment of spinal diseases. However, many studies have reported the issue of loosening pedicle ...

In Vivo Evaluation of Fracture Callus Development During Bone Healing in Mice Using an MRI-compatible Osteosynthesis Device for the Mouse Femur

In Vivo Evaluation of Fracture Callus Development During Bone Healing in Mice Using an MRI-compatible Osteosynthesis Device for the Mouse Femur

Endochondral fracture healing is a complex process involving the development of fibrous, cartilaginous, and osseous tissue in the fracture callus. The ...

Noninvasive Determination of Vortex Formation Time Using Transesophageal Echocardiography During Cardiac Surgery

Trans-mitral blood flow produces a three-dimensional rotational body of fluid, known as a vortex ring, that enhances the efficiency of left ventricular ...

A Pre-Clinical Porcine Model of Orthotopic Heart Transplantation

Fifty-years following the first successful report, cardiac transplantation remains the gold-standard treatment for eligible patients with advanced heart ...