Murine Cardiovascular Phenotyping Core

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.

Methodology Measurements Possible
1. Cardiac Catheterization and Telemetric Monitoring Techniques
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). 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.

2. Echocardiographic Studies (Videos)

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

a. Treadmill exercise testing (graded and constant). VO2, VO2peak, VCO2, RER
Anaerobic threshold, oxygen pulse, total exercise capacity, lactate production

4. Isolated ex vivo preparations

a. Isolated cardiac muscle strips 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

a. Calcium measurements (Fura-2) 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

a. Transverse aortic constriction 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

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