Experimental Options
Ultrasound echocardiography provides a non-invasive measure of ventricular dimensions and function in the heart. Mice or rats are imaged and the electrocardiogram (ECG) recorded with either a Visual Sonics 3100 instrument with a 30 MHz probe or an Acuson Sequoia C256 instrument with a 15 MHz probe. Long axis, short axis and apical views provide two-dimensional, M-mode and spectral Doppler images at physiological heart rates. Following analysis, we can provide you with LV chamber dimensions (EDD & ESD), septal and posterior wall thicknesses (VST & PWT), ejection times, heart rates, LV masses, indices of valve function (E/A ratios) and indices of chamber function like fractional shortening, velocity of circumferential fiber shortening (Vcf), stroke volume, cardiac output and ejection fraction. Echocardiographic analyses provide a means to non-invasively assess changes in the degree of ventricular hypertrophy and dysfunction over time or after other interventions such as trans-aortic constriction (see surgical section) or drug infusions.
Blood pressure and the ECG are fundamental parameters in the assessment of an animal's phenotype and physiological status. We can obtain blood pressures and electrocardiogram (ECG) for you from mice and rats using a variety of invasive or non-invasive methods.
- The tail cuff method can provide a screening for systolic and mean arterial pressure in awake, but restrained animals.
- Arterial catheterizations provide a more comprehensive and accurate measure of pressures from anesthetized animals. Along with the ECG, Millar catheters and Doppler flow probes, we can provide you with continuous arterial, venous, ventricular pressures, heart rates, ECG analysis, stroke volumes, cardiac outputs, and indices of contractility (dP/dT) from your animals. Furthermore, we can infuse drugs or blockers of your choosing during the study to alter the conditions. For example, the infusion of inotropic agents such as dobutamine and isoproterenol will transiently increase pressures and stress the system.
- Implantable radio telemetry devices provide the highest quality continuous measurement of arterial pressure along with heart rate and cage activity in awake, free-roaming animals for weeks at a time. See the telemetric section below for more details.
The mouse physiology laboratory is a world leader in the application of telemetric recording from mice and rats. Telemetry is the "gold standard" for the continuous validation of blood pressure, the electrocardiogram (ECG), electroencephalogram (EEG), body temperature, and cage activity in awake, free-roaming animals. From these waveforms, arterial pressures, heart rates, heart rate variability, arrhythmia detection, brain activity, cage activity and diurnal rhythms can be evaluated to assess the physiological status of the animal. These values can be measured 24 hours a day over extended periods of time to monitor the same animal for months at a time.
The mouse physiology lab will implant the transmitter, record all the data and work with you on the analysis. Many of the parameters can be measured at once depending on the exact study protocol. See our publications for examples of telemetric studies in a variety of rodent models.
The autonomic nervous system (ANS) is the key regulator of blood pressure, heart rate, heart rate variability (HRV), respiratory rate and many other aspects of normal physiological function. The mouse physiology laboratory can evaluate several aspects of autonomic function in your animal models via hemodynamic and telemetric measurements.
The sensitivity of the baroreceptors for pressure and heart rate regulation can be evaluated in catheterized or telemetry implanted animals by serial injections of angiotensin II, phenylephrine and sodium nitroprusside. We can perform analysis of heart rate variability in the both time and frequency domains to reveal any ANS dysfunction in telemetry implanted animals. We can also monitor pressure during periods of exercise, induced stress or postural changes.
The mouse physiology laboratory can perform exercise and endurance testing on mice. Using a RotaRod treadmill, mice can be run to reveal their level of fitness or to stress their cardiovascular system. Intolerance to running is often a sign of dysfunction in one or more organ systems. Long-term running programs can also be used to induce a physiological conditioning or hypertrophy to the heart. When combined with telemetry, mouse blood pressures, heart rates and body temperatures can be simultaneously recorded.
We can also perform simple metabolic tests to assess for any disorders. We can perform glucose tolerance testing (GTT), insulin tolerance testing (ITT) and oxygen saturation (SaO2) monitoring in awake animals to reveal a wide range metabolic disorders.
Following any non-survival procedure, the mouse physiology laboratory will do a postmortem examination of animal. We will measure the mass of all the individual organs of interest along with the animal mass and tibia length for normalization. We can also fix the tissue for you using standard procedures from simple formalin fixation to pressure fixation of the heart or the entire animal with paraformaldehyde or OCT. We can also freeze tissues for biochemical, molecular or microscopic assays in liquid nitrogen with or without isopentane.
The mouse physiology laboratory can perform a wide variety of surgical procedures on your mice or rats. Non-survival procedures include, but are not limited to, carotid and femoral vessel catheterizations for hemodynamics and drug infusions along with the isolation of the aorta for Doppler flow measurements. See the hemodynamics and autonomic testing sections for more details.
The mouse physiology laboratory specializes in a wide variety of survival surgical procedures. These include, but are not limited to, trans-aortic constriction (TAC) to increase hemodynamic load, coronary artery ligation to infarct the heart, regenerative (stem) cell infusion therapy, osmotic pump implantation, vessel injury, and telemetric transmitter implantation (see telemetric recording section). We will work with you to custom design any surgical procedure for your studies.
The mouse physiology laboratory will work with you to custom design the best possible experiments to reveal the phenotype of your animal model. We will consult on such custom designs even if we do not ultimately do the study in our lab. Finally, we will help you with grant proposals, animal protocols and manuscript writing in conjunction with any study.