Long-term Blood Pressure Measurement in Freely Moving Mice Using Telemetry

Summary

The goal of this protocol is to assess systemic blood pressure in conscious freely moving mice using implantable radio-telemetry devices.

Abstract

During the development of new vasoactive agents, arterial blood pressure monitoring is crucial for evaluating the efficacy of the new proposed drugs. Indeed, research focusing on the discovery of new potential therapeutic targets using genetically altered mice requires a reliable, long-term assessment of the systemic arterial pressure variation. Currently, the gold standard for obtaining long-term measurements of blood pressure in ambulatory mice uses implantable radio-transmitters, which require artery cannulation. This technique eliminates the need for tethering, restraining, or anesthetizing the animals which introduce stress and artifacts during data sampling. However, arterial blood pressure monitoring in mice via catheterization can be rather challenging due to the small size of the arteries. Here we present a step-by-step guide to illustrate the crucial key passages for a successful subcutaneous implantation of radio-transmitters and carotid artery cannulation in mice. We also include examples of long-term blood pressure activity taken from freely moving mice after a period of post-surgery recovery. Following this procedure will allow reliable direct blood pressure recordings from multiple animals simultaneously.

Introduction

Hypertension is one of the major risk factors for cardiovascular diseases, arguably it is a major public health issue both in developed and developing countries¹. Several animal models of experimental hypertension have been developed to mimic hypertensive responses like those observed in humans². Among others, the ambulatory mouse represents an excellent model to study the genesis and the progression of hypertension allowing in vivo analysis of the consequences of chronic exposure to hypertension.

Blood pressure (BP) monitoring in mice has helped researchers to unravel several mechanisms involved in the p....

Protocol

Ethics statement: All animal procedures mentioned in this video-article were reviewed and approved by the Animal Care and Use Committee (IACUC) at the University of Tennessee Health Science Center.

Note: Use sterile microsurgery instruments throughout the surgical procedure. Surgical instruments may be sterilized utilizing an infrared sterilizer at an optimum sterilizing temperature of 1,500 °F (815.6 °C). Telemeters can be reused, however, before inserting it in the animal make sure to sterilize the entire transmitter according to the manufacturer instructions and that the tip of the catheter has been refilled with a special gel provided by the manufacturer.

Results

Data can be acquired remotely by a receiver; traces are visualized on a computer screen for quality control (Figure 1a). Details such as animal ID, diastolic blood pressure and systolic blood pressure are also shown (Figure 1b). Arterial BP can be recorded continuously (24/7), or for short programmed intervals (i.e., 60 sec acquisition every hour). Data can be automatically stored in a hard disk for later analysis. Averaged BP data from a 3-day c.......

Discussion

Implantable radio-telemetry has improved significantly over the last decade; smaller probe size makes the implant less traumatic for the animal, prolonged battery life helps to reduce the costs, and independent telemeter frequencies eliminate crosstalk between receivers. Telemetry is considered the state-of-the-art method for collecting a wide variety of physiological parameters from freely moving animals without the artifacts associated with the use of restraint, human interaction, or anesthesia that are required by oth.......

Materials

List of materials used in this article

Name	Company	Catalog Number	Comments
Small animal anesthesia system	Kent Scientific Corp, Torrington, Connecticut, USA		low-flow small animal anesthesia system
Pad warmer and mouse termometer	Kent Scientific Corp, Torrington, Connecticut, USA		allows monitoring body temperature, and homeothermic control in small animals
Binocular Microscope	Kent Scientific Corp, Torrington, Connecticut, USA	KSCXTS-1121	binocular body with boom stand pole and top LED
Hemostat Forceps	Kent Scientific Corp, Torrington, Connecticut, USA	INS750451	used to clamp blood vessels or tag sutures
Small metal Clips, 7 mm, Stainless Steel	Kent Scientific Corp, Torrington, Connecticut, USA	INS750344	used for skin closure
Betadine solution	Purdue Products L.P., Stamford, CT, USA	NDC-67618-150-01	10% povidone iodine topical solution
Normal saline solution	Abott Laboratories	04930-04-10	needed for preventing tissue from drying.
Nair (Hair remover lotion)			needed for fur removal from the site of incision/surgery
Braide silk suture	Teleflex Medical OEM, Coventry, Connecticut, USA		Size 5.0, 6.0, 7.0
Ethanol		2716	70% ethanol for disinfection
Spring scissors	Fine Science Tool	15000-10	for minor dissection
Scissors (angled to side)	Fine Science Tool	14063-011	No. 3 handle
Scalpel blade		2976-0	No. 10
Forceps (curved)	Fine Science Tool	11150-10	for holding tissue
Forceps (straight)	Fine Science Tool	11151-10	for holding tissue
Needle holder	Fine Science Tool	12002-12	for suturing
Fine needle nose Forceps	Fine Science Tool
Isoflurane	Henry Schein Animal Health, Melville, New York, USA		a general inhalation anesthetic agent
Sterilizer	Benchmark Scientific, 116 Corporate Blvd, South Plainfield, NJ, USA	B1000	sterilize surgical tools in 5-10 seconds using infrared heating
Gauze Pads	Johnson & Johnson, New Brunswick, NJ, USA	JJ8513	to use for wound cleaning, prepping, scrubbing or dressing
Telemetry Device	Data Sciences International, St. Paul, MN, USA	DSI-PA-C10	to record blood pressure in freely moving mice
Telemetry receiver system  coumpled with a PC	Data Sciences International, St. Paul, MN, USA
Tubing	Instech Laboratories, Plymouth Meeting, PA USA	BTPE-90
Vessel Cannulation Forceps, 13 cm, 0.5 mm OD	World Precision Instruments	503374	special vessel cannulation forceps
Tissue adhesive	3M Animal Care Products, St. Paul, MN, USA	NAC No.: 11380041	use to close minor wounds, often eliminating the need for sutures and/or bandages
Weighing scale		BB300	precision analytical laboratory balance