Estimation of parallel conductance by dual-frequency conductance catheter in mice

The conductance catheter method has substantially enhanced the characterization of in vivo cardiovascular function in mice. Absolute volume determination requires assessment of parallel conductance (V-p) 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 V-p derived by hypertonic saline injection was consistent [0.095 +/- 0.01 (SD), n = 11], and both methods were strongly correlated (r(2) = 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 V-p(DF) = 1.1 * V-p(Sal) - 2.5 [where V-p(DF) is V-p derived by the dual-frequency method and V-p(Sal) is V-p derived by hypertonic saline bolus injection], r(2) = 0.95, standard error of the estimate = 1.1 mu l, and mean difference = 0.6 +/- 1.4 mu l. Varying V-p(Sal) in a given animal resulted in parallel changes in V-p(DF) (multiple regression r(2) = 0.92, P< 0.00001). The dominant source of V-p 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 V-p and flow probe-derived cardiac output, end-diastolic volume and ejection fraction in normal mice were 28 +/- 3 mu l 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.