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Animal and Metabolic Core

picture of Ralph Shohet
Ralph Shohet, MD shohet@hawaii.edu 808-692-1469
picture of Olivier Le Saux
Olivier Le Saux, PhD lesaux@hawaii.edu 808-692-1504

In partnership with the University of Hawaii, including its Center for Cardiovascular Research and College of Natural Sciences, we provide a core for the use of investigators at the University, and by special arrangement, for investigators anywhere in Hawaii. We provide murine echocardiography, blood pressure determinations, surgical procedures and phlebotomy, real-time metabolic assessment, analyses of lipoprotein fractions and subfractions in fasting serum or plasma, animal CT scans and MRIs, as well as assistance with mouse husbandry and genotyping.

General Services

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Echocardiogram – An echocardiogram, often referred to in the medical community as a cardiac ECHO or simply an ECHO, is a sonogram of the heart. Also known as a cardiac ultrasound, it uses standard ultrasound techniques to image two-dimensional slices of the heart. In addition to creating two-dimensional pictures of the cardiovascular system, an echocardiogram can also produce accurate assessment of the velocity of blood and cardiac tissue at any arbitrary point using pulsed or continuous wave Doppler ultrasound. This allows assessment of cardiac valve areas and function, any abnormal communications between the left and right side of the heart, any leaking of blood through the valves (valvular regurgitation), and calculation of the cardiac output as well as the ejection fraction.

Blood Pressure Measurement – Blood pressure (BP) is the pressure (force per unit area) exerted by circulating blood on the walls of blood vessels, and constitutes one of the principal vital signs. The pressure of the circulating blood decreases as it moves away from the heart through arteries and capillaries, and toward the heart through veins. When unqualified, the term blood pressure usually refers to brachial arterial pressure: that is, in the major blood vessel of the upper left or right arm that takes blood away from the heart.

Complete in vivo Cardiovascular Studies – Long- or short-term studies that examine any aspect of cardiovascular disease for which a rodent model exists can be performed in our facility. Whether it involves long-term feeding (in the case of an atherosclerosis study) or a surgical procedure such as aortic banding or LAD ligation, complete studies from preparation of the mice and implementation of the procedure to harvesting of tissues and their preparation and analyses can be performed. Furthermore, combination of procedures to examine the effects of a therapeutic agent in any of the cardiovascular diseases can be carried out.

Animal MRI and CT Scans – Magnetic resonance imaging (MRI) is a medical imaging technique used in radiology to form pictures of the anatomy and the physiological processes of the body. MRI scanners use strong magnetic fields, magnetic field gradients, and radio waves to generate images of the organs in the body. MRI does not involve X-rays or the use of ionizing radiation, which distinguishes it from a CT scan. Computed tomography (CT) scans make use of computer-processed combinations of many X-ray measurements taken from different angles to produce cross-sectional (tomographic) images of specific areas of a scanned object, allowing the user to see inside the object without cutting.

Surgery Services

Aortic Banding – One of the most commonly used surgical intervention for pressure-overload induced hypertrophy is coarction of the ascending aorta i.e. aortic banding. This system has been very well characterized and proven to be highly reproducible with a low mortality rate of 10-20% or less in experienced hands. Aortic banding is an excellent model system to evaluate the process of development of left ventricular hypertrophy in response to hemodynamic stress. Furthermore, after several months, a subset of animals progresses into heart failure

Infarct – Two surgical methods of left ventricular infarction are commonly done in the Phenotyping Core; cryo-ablation and left anterior descending artery (LAD) ligation. Cryo-ablation is a procedure in which a portion of left ventricle is frozen with a liquid nitrogen cooled probe, resulting in tissue necrosis. See next topic for description of LAD ligation.

Histology of Cryo-injury Infarction – Panels A & B show H&E staining. Five days after infarction fiber loss and scar formation are evident around the injury. Panels C & D are darkfield images of TUNEL stained sections. At higher magnification in panel D one can appreciate the high frequency of TUNEL positive cells in the infarct zone, suggesting ongoing apoptosis, or necrosis, in this area.

LAD Ligation – (LAD) ligation is a procedure to ligate the left anterior descending artery to induce an infarction. In addition, a LAD ligation can be performed as a component of ischemia-reperfusion studies, where the liagture is removed after a set period of time.

Specialized Procedure – If you have a procedure in mind that is not listed here, please do not hesitate to let us know. We are well versed in many procedures that are not necessarily listed here.

Tail Vein Injection – We use a catheter-based system for tail vein injections allowing for continual infusions (when used in conjunction with a pump). We also perform traditional direct syringe/needle tail vein injections used for single bolus delivery.

Osmotic Pump Implantation – a pump based on a piston powered by osmotic pressure which pumps drug/s into the body over an extended period. The unit is implanted under the skin and has no external or protruding parts.

Other Services

Training – Training and advice for general mouse surgery techniques.

Physical Activity – The effect of exercise on any aspect of cardiovascular function can be measured in our facility. Mice can be individually housed in cages equipped with running wheels, and wheel-running activity can be monitored continuously with a Dataquest Acquisition & Analysis System (Data Sciences International). Activity can be quantified by counting wheel revolutions, tabulated as number of revolutions per 5 minutes, and printed as a tracing.

Atherosclerosis – Using one of several available mouse strains that are susceptible to atherosclerosis such as apolipoprotein E-null or low density lipoprotein receptor-null mice, studies involving the feeding of high fat and high cholesterol diet can be performed to induce atherosclerosis in mice. The appropriate tissues can be harvested at the end of the study and the extent of atherosclerosis can be quantitatively measured.

Hypoxia – The principal purpose of the cardiovascular system is the delivery of oxygen to other organs of the body. A convenient and noninvasive way to perturb this function is to expose mice to a hypoxic environment. We offer chronic exposure to hypoxia in the MPC as it can also serve as a valuable stress to reveal subtle phenotypes of cardiovascular limitation in any mouse model. We can combine the wheel running capability described above with the hypoxia chamber to evaluate limitations on exercise capacity.

Equipment

The Animal and Metabolic Core is predominantly located at the Kakaako campus of the University of Hawaii and has a number of pieces of equipment:

  • Visual Sonics Vevo 2100 High Resolution Imaging System for echocardiography
  • Two Ventilators
  • ECG equipment (AD instruments)
  • Olympus dissection/surgery microscope with camera and monitor
  • VisualSonics Imaging Station with ECG/HR
  • Millar catheters for blood pressure measurement
  • Kent Scientific Mouse Tail cuff blood pressure instrumentation
  • GENIE infusion pump
  • Sterilizing equipment
  • AD instruments Working Heart
  • angendorff apparatus
  • Leica S6 Microscope with Leica L2 light source
  • Isoflurane vaporizer/with O2 flowmeter
  • Harvard Apparatus Inspira Advanced Safety Ventilator
  • Temperature controlled surgical table and instruments. Warming pad and oxygen chamber for surgery recovery
  • Exercise equipment and hypoxic chambers with treadmills
  • Lipoprint

How to Request Services

The following information is required to request services:

General Information
Date of Request:
Principal Investigator:
IACUC Approved Animal Protocol Number:
Contact Researcher:
Contact Researcher Phone:
Contact Researcher email:

Services Requested
State research aims briefly

Study Design:

  1. Mouse groups and number (including species/strain/gender/age (DOB)/BW)
  2. Animal services, including pre- and post-operation
  3. Timetable, including operation date and sacrifice date

Special surgical procedure (please state aims and requirement(s))

TERMS AND CONDITIONS

  1. Prior animal protocol by IACUC must be obtained by the Principal Investigator
  2. The Principal Investigator is responsible for transferring animals to the Core’s in/out Processing Rooms (#147), post-operation animal care, and for collecting tissue samples at the end of the study
  3. The Principal Investigator is responsible for housing cost and service charges

Faculty Co-Directors

picture of Olivier Le Saux
 
 
 
 
Olivier Le Saux, PhD | lesaux@hawaii.edu | 808-692-1504

picture of Ralph Shohet
 
 
 
 
Ralph Shohet, MD | shohet@hawaii.edu | 808-692-1469

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