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

The conductance catheter method has substantially enhanced the characteriza tion of in vivo cardiovascular function in mice. Absolute volume determinat ion requires assessment of parallel conductance (V-p) offset because of con ductivity of structures external to the blood pool. Although such a determi nation is achievable by hypertonic saline bolus injection, this method pose s potential risks to mice because of volume loading and/or contractility ch anges. We tested another method based on differences between blood and musc le conductances at various catheter excitation frequencies (20 vs. 2 kHz) i n 33 open-chest mice. The ratio of mean frequency-dependent signal differen ce 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 ap plied to a separate group of animals (n = 12), with a combined regression r elation 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, a nd mean difference = 0.6 +/- 1.4 mu l. Varying V-p(Sal) in a given animal r esulted 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 vent ricular wall itself, since surrounding the heart in the chest with physiolo gical saline or markedly varying right ventricular volumes had a minimal ef fect on the left ventricular volume signal. On the basis of V-p and flow pr obe-derived cardiac output, end-diastolic volume and ejection fraction in n ormal 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.