[Show abstract][Hide abstract] ABSTRACT: Conductance measurements for generation of an instantaneous left ventricular (LV) volume signal in the mouse are limited, because the volume signal is a combination of blood and LV muscle, and only the blood signal is desired. We have developed a conductance system that operates at two simultaneous frequencies to identify and remove the myocardial contribution to the instantaneous volume signal. This system is based on the observation that myocardial resistivity varies with frequency, whereas blood resistivity does not. For calculation of LV blood volume with the dual-frequency conductance system in mice, in vivo murine myocardial resistivity was measured and combined with an analytic approach. The goals of the present study were to identify and minimize the sources of error in the measurement of myocardial resistivity to enhance the accuracy of the dual-frequency conductance system. We extended these findings to a gene-altered mouse model to determine the impact of measured myocardial resistivity on the calculation of LV pressure-volume relations. We examined the impact of temperature, timing of the measurement during the cardiac cycle, breeding strain, anisotropy, and intrameasurement and interanimal variability on the measurement of intact murine myocardial resistivity. Applying this knowledge to diabetic and nondiabetic 11- and 20- to 24-wk-old mice, we demonstrated differences in myocardial resistivity at low frequencies, enhancement of LV systolic function at 11 wk and LV dilation at 20-24 wk, and histological and electron-microscopic studies demonstrating greater glycogen deposition in the diabetic mice. This study demonstrated the accurate technique of measuring myocardial resistivity and its impact on the determination of LV pressure-volume relations in gene-altered mice.
[Show abstract][Hide abstract] ABSTRACT: It is unclear whether the increase in availability of substrates for energy production in diabetes can lead to enhanced systolic function early in the disease, before the onset of structural changes to the myocardium. To examine this issue, BKS.Cg-m +/+ Lepr db (db/db) mice with type 2 diabetes and wild type controls had left ventricular pressure-volume relationships determined in situ. We demonstrated that the db/db mice, when compared to their wild type controls, generated greater left ventricular pressure and an enhancement of left ventricular systolic function based on enhanced power/EDV, positive dP/dt, preload recruitable stroke work, dP/dt--EDV relationship, and curvilinear end-systolic elastance. This enhancement in systolic function occurred despite the db/db mice having greater body weight, but similar preload (end-diastolic volume) and afterload (effective arterial elastance). We postulate that the previously described enhancement in renal glomerular filtration rate seen early in type 2 diabetes may be in part due to enhanced left ventricular systolic function early in this disease.
[Show abstract][Hide abstract] ABSTRACT: Cardiac volume can be estimated by a conductance catheter system. Both blood and myocardium are conductive, but only the blood conductance is desired. Therefore, the parallel myocardium contribution should be removed from the total measured conductance. Several methods have been developed to estimate the contribution from myocardium, and they only determine a single steady state value for the parallel contribution. Besides, myocardium was treated as purely resistive or mainly capacitive when estimating the myocardial contribution. We question these assumptions and propose that the myocardium is both resistive and capacitive, and its contribution changes during a single cardiac cycle. In vivo magnitude and phase experiments were performed in mice to confirm this hypothesis.
Conference proceedings: ... Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Conference 02/2004; 5:3674-7. DOI:10.1109/IEMBS.2004.1404032
[Show abstract][Hide abstract] ABSTRACT: Instantaneous left ventricular volume measurements have been made for many years using a tetrapolar conductance catheter. The main objective is to determine the efficiency of the beating heart, using a tetrapolar catheter inserted in the left ventricle of transgenic mice. The effect of the parallel myocardium contribution must be removed from the total measurement. A dual-frequency technique involving 1 kHz and 100 kHz was chosen because it has been established that the imaginary part (the capacitive reactance) of the complex admittance of the cardiac muscle is much smaller in the lower frequency than at the higher frequency. The design involves generation of an accurate frequency source for both the frequencies careful selection of operational amplifiers for the current conversion stage so that the current is not too large to kill the mouse and that it is capable of performing at high frequencies. The band pass filter stage involved careful design with minimal overlap of the pass bands of both the channels. The overall circuit was designed so that there is minimal shift in the phase due to the circuit elements alone. Work also involved design of GPIB--based data acquisition system using LabVIEW and a digital oscilloscope for effective data acquisition even at high frequencies, which are normally limited by the sampling frequency. This data acquisition system is currently being used in laboratory studies in vivo.
[Show abstract][Hide abstract] ABSTRACT: It has been hypothesized that because of its rapid heart rate, the intact murine heart functions near maximal contractility in the basal state. If this hypothesis is correct, then the fast and slow components of myocardial length-dependent activation should be blunted compared with larger mammals.
Mice (n=24) were anesthetized, and via an open chest, LV pressure-volume relationships were determined by a dual-frequency conductance catheter system. Baseline pressure-volume relationships were determined during transient occlusion of the inferior vena cava, and repeat measurements were made after 1 (n=10) and 7 (n=21) minutes of sustained aortic occlusion. Control experiments were performed in a subset of mice (n=3). For baseline to 1 minute, an increase in afterload (maximal pressure 95+/-9 to 126+/-7 mm Hg; P<0.001) and effective arterial elastance (5.9+/-3.1 to 9.2+/-3.9 mm Hg/microl; P<0.001) resulted in an increase in end-diastolic volume (31+/-8 to 35+/-9 microL; P<0.001). The result was maintenance of stroke volume (17+/-6 to 15+/-6; P=NS) owing to an increase in contractility (leftward shift in V100 [the volume of end-systolic elastance at 100 mm Hg], 24+/-9 to 16+/-5 microL; P<0.001). No additional augmentation of systolic function was found at 7 minutes.
This study demonstrates that the fast phase of length-dependent activation is intact but not the slow phase, consistent with murine myocardium functioning near maximal contractility in the basal state.