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Division of Cardiology, Department of Medicine and Department of Biomedical Engineering, The Johns Hopkins Medical Institutions, Baltimore, Maryland 21287
The conductance catheter method has
substantially enhanced the characterization of in vivo cardiovascular
function in mice. Absolute volume determination requires assessment of
parallel conductance (Vp) offset because of
conductivity of structures external to the blood pool. Although such a
determination is achievable by hypertonic saline bolus injection, this
method poses potential risks to mice because of volume loading and/or
contractility changes. We tested another method based on differences
between blood and muscle conductances at various catheter excitation
frequencies (20 vs. 2 kHz) in 33 open-chest mice. The ratio of mean
frequency-dependent signal difference to Vp
derived by hypertonic saline injection was consistent [0.095 ± 0.01 (SD), n = 11], and both methods were strongly
correlated (r2 = 0.97, P < 0.0001). This correlation persisted when the ratio was prospectively
applied to a separate group of animals (n = 12), with a
combined regression relation of Vp(DF) = 1.1 * Vp(Sal) 
2.5 [where
Vp(DF) is Vp derived by
the dual-frequency method and Vp(Sal) is
Vp derived by hypertonic saline bolus
injection], r2 = 0.95, standard error of
the estimate = 1.1 µl, and mean difference = 0.6 ± 1.4 µl. Varying Vp(Sal) in a given animal
resulted in parallel changes in Vp(DF) (multiple
regression r2 = 0.92, P < 0.00001). The dominant source of Vp in mice was
found to be the left ventricular wall itself, since surrounding the heart in the chest with physiological saline or markedly varying right
ventricular volumes had a minimal effect on the left ventricular volume
signal. On the basis of Vp and flow
probe-derived cardiac output, end-diastolic volume and ejection
fraction in normal mice were 28 ± 3 µl and 81 ± 6%,
respectively, at a heart rate of 622 ± 28 min
1.
Thus the dual-frequency method and independent flow signal can be used
to provide absolute volumes in mice.
mouse; hemodynamics; ventricular function; methods
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