Techniques and Support Services

The methods listed in the table below are currently available in the Phenotyping Core Facility. Click the links below to see individual protocols. In addition to offering these methodologies, the core lab has assisted investigators in designing new technologies for evaluating cardiovascular, cardiopulmonary, and metabolic function in genetically altered murine models.

1. Cardiac Catheterization and Telemetric Monitoring Techniques

Methodology

a. Arterial and venous cannulation (ascending aorta via carotid artery, superior vena cava or right atrium via jugular vein). Both acute and chronic studies (performed without need for anesthesia or restraint).

Measurements Possible

Heart rate, blood pressure, central venous pressure
Arteriovenous blood sampling for metabolic studies (e.g. oxygen, lactate)

b. Fluorescent-labeled microspheres (injected into ascending aorta or left ventricle via carotid cannulation).Can be performed at rest or during exercise.

Cardiac output
Organ blood flow (kidney, brain, liver, etc.)
Redistribution of regional blood flow during exercise

c. Doppler flowprobe (intravascular flowprobe directly in ascending aorta or cuff flowprobe around ascending aorta).

Cardiac output
Stroke volume
Aortic blood flow velocity

d. Telemetric ECG/blood pressure/core temperature (implanted abdominally). Chronic studies performed without anesthesia or restraint.

Chronic, continuous measurement of HR, BP, ECG (for arrhythmia evaluation), core temperature.

e. Heart rate variability studies

Assessment of autonomic tone.

f. High frequency transducer-tipped catheterization (ascending aorta or left ventricle via carotid artery). Requires anesthesia.

Left and right ventricular +dP/dt, -dP/dt
High-fidelity recordings of systolic and diastolic blood pressures

g. Electrophysiologic studies (octopolar recording/ pacing catheter in right ventricle. Requires light anesthesia.

Cardiac electrophysiology
Arrhythmogenicity evaluation

h. Conductance catheter studies(pressure volume loops)

Inotropy: End-systolic elastance (EES), time-varying elastance (E(T)), preload-recruitable stoke work (PRSW), arterial elastance (EA), maximum dP/dt-EDV relationship. Lusitropy: dP/dtmin, Tau.

Methodology

a. M-mode echocardiography (usually requires light anesthesia).

Measurements Possible

Cardiac chamber dimensions (LVEDD, LVESD)
Cardiac mass
Systolic cardiac function (%FS, EF, VCF, CO)

b. Doppler echocardiography (usually requires light anesthesia).

Systolic and diastolic cardiac function
Aortic and peripheral arterial blood flow velocity
Cardiac Output
Pressure gradients across aortic and pulmonary artery bands
Assessment of valvar insufficiency

c. Tissue Doppler and Strain Rate Imaging

Myocardial peak wall velocities: Sm (ventricular systole), Em (early relaxation), Am (atrial systole) and the Em/Am ratio. Strain rate. Indices of ventricular dyssynchrony.

3. Treadmill exercise studies

Methodology

a. Treadmill exercise testing (graded and constant).

Measurements Possible

VO2, VO2peak, VCO2, RER
Anaerobic threshold, oxygen pulse, total exercise capacity, lactate production

4. Isolated ex vivo preparations

Methodology

a. Isolated cardiac muscle strips

Measurements Possible

Cardiac contractility

b. Isolated vascular bed resistance studies

Peripheral vascular resistance

c. Isolated arterial rings

Endothelium-dependent and independent reactivity

d. Isolation of neonatal and adult cardiomyocytes

All cardiac cell culture studies

e. Langendorf (isolated heart) preparations

Contractile function, ischemia-reperfusion studies

5. Calcium Transients and Contractility of Isolated Myocytes

Methodology

a. Calcium measurements (Fura-2)

Measurements Possible

Resting and peak [Ca2+]i, maximum rate of rise and decline, and the time to peak and decline, SR Ca2+ load

b. Sarcomere contractility studies

Peak shortening, rise time (50% to peak), time-to-peak, decay time (50% to baseline), time-to-relengthening, and maximal velocities of shortening (+dL/dt) and relengthening (-dL/dt)

c. Intracellular pH

Intracellular pH measurements

6. Models of Cardiovascular Disease Currently Available

Methodology

a. Transverse aortic constriction

Measurements Possible

LV hypertrophy and failure
b. Pulmonary artery banding
RV hypertrophy and failure
c. Coronary artery ligation
Ischemia and heart failure
d. Head-down tilt
Microgravity simulation
e. Doxorubicin cardiotoxicity
Toxic cardiomyopathy
f. Genetic cardiomyopathy
Various genetically altered models of dilated and hypertrophic cardiomyopathy