Modification of a Transvalvular Microaxial Flow Pump for Instantaneous Determination of Native Cardiac Output and Volume.

BACKGROUND: The current Impella cardiopulmonary (CP) pump, used for mechanical circulatory support in patients with cardiogenic shock (CS), cannot assess native cardiac output (CO) and left ventricular (LV) volumes. These data are valuable in facilitating device management and weaning. Admittance technology allows for accurate assessment of cardiac chamber volumes. OBJECTIVES: This study tested the ability to engineer admittance electrodes onto an existing Impella CP pump to assess total and native CO as well as LV chamber volumes in an instantaneous manner. METHODS: Impella CP pumps were fitted with 4 admittance electrodes and were placed in the LVs of adult swine (n = 9) that were subjected to 3 different hemodynamic conditions, including Impella CP speed adjustments, administration of escalating doses of dobutamine and microsphere injections into the left main artery to result in cardiac injury. CO, according to admittance electrodes, was calculated from LV volumes and heart rate. In addition, CO was calculated in each instance via thermodilution, continuous CO measurement, the Fick principle, and aortic velocity-time integral by means of echocardiography. RESULTS: Modified Impella CP pumps were placed in swine LVs successfully. CO, as determined by admittance electrodes, was similar by trend to other methods of CO assessment. It was corrected for pump speed to calculate native CO, and calculated LV chamber volumes trended as expected in each experimental protocol. CONCLUSIONS: We report, for the first time, that an Impella CP pump can be fitted with admittance electrodes and used to determine total and native CO in various hemodynamic situations. CONDENSED ABSTRACT: Transvalvular mechanical circulatory support devices such as the Impella CP do not have the ability to provide real-time information on native cardiac output (CO) and left ventricular (LV) volumes. This information is critical in device management and in weaning in patients with cardiogenic shock. We demonstrate, for the first time, that Impella CP pumps coupled with admittance electrodes are able to determine native CO and LV chamber volumes in multiple hemodynamic situations such as Impella pump speed adjustments, escalating dobutamine administration and cardiac injury from microsphere injection.

Smart Drain for Post-Cardiac Surgery Left Ventricular Volumes Evaluated in Large Animal Models.

BACKGROUND: Open heart surgeries for coronary arterial bypass graft and valve replacements are performed on 400,000 Americans each year. Unexplained hypotension during recovery causes morbidity and mortality through cerebral, kidney, and coronary hypoperfusion. An early detection method that distinguishes between hypovolemia and decreased myocardial function before onset of hypotension is desirable. We hypothesized that admittance measured from a modified pericardial drain can detect changes in left ventricular end-systolic, end-diastolic, and stroke volumes. METHODS: Admittance was measured from 2 modified pericardial drains placed in 7 adult female dogs using an open chest preparation, each with 8 electrodes. The resistive and capacitive components of the measured admittance signal were used to distinguish blood and muscle components. Admittance measurements were taken from 12 electrode configurations in each experiment. Left ventricular preload was reduced by inferior vena cava occlusion. Physiologic response to vena cava occlusion was measured by aortic pressure, aortic flow, left ventricle diameter, left ventricular wall thickness, and electrocardiogram. RESULTS: Admittance successfully detected a drop in left ventricular end-diastolic volume (P < .001), end-systolic volume (P < .001), and stroke volume (P < .001). Measured left ventricular muscle resistance correlated with crystal-derived left ventricular wall thickness (R2 = 0.96), validating the method's ability to distinguish blood from muscle components. CONCLUSIONS: Admittance measured from chest tubes can detect changes in left ventricular end-systolic, end-diastolic, and stroke volumes and may therefore have diagnostic value for unexplained hypotension.

Why low-voltage shock impedance measurements fail to reliably detect insulation breaches in transvenous defibrillation leads.

BACKGROUND: Implantable cardioverter-defibrillators (ICDs) use low-voltage measures of shock impedance (LVSZ) to monitor integrity of leads. OBJECTIVE: To determine the separation distance between conductors required for LVSZ to detect insulation breaches that produce short circuits during shocks, causing failed defibrillation. METHODS: We simulated in-pocket insulation breaches between the ICD generator (CAN) and cables to the distal coil of 10 leads from 2 manufacturers. The ICD and lead were placed in an electrolyte bath. Polystyrene sheets were used to control the breach-CAN separation. We determined both the maximum lead-CAN separation for shorts during 800 V shocks and the shock strength at which shorts occurred for a fixed separation. We also calculated breach impedance and measured it using a low-voltage instrument. RESULTS: The maximum breach-CAN separation for shorting was 350-500 µm for all leads. The minimum shock strength to short varied from 650 to 771 V (24-32 J). LVSZ never triggered a warning, even with no separation between the cable's inner insulation and the CAN. Using low-voltage pulses, breach impedance was measured at approximately 500-1000 Ω. CONCLUSION: LVSZ is insensitive to insulation breaches that cause life-threatening, shorted shocks. The explanation likely relates to impedance differences between ionic conduction during LVSZ measurements and free-electron conduction in plasma discharges.

Validation of a defibrillation lead ventricular volume measurement compared to three-dimensional echocardiography.

BACKGROUND: There is increasing evidence that using frequent invasive measures of pressure in patients with heart failure results in improved outcomes compared to traditional measures. Admittance, a measure of volume derived from preexisting defibrillation leads, is proposed as a new technique to monitor cardiac hemodynamics in patients with an implantable defibrillator. OBJECTIVE: The purpose of this study was to evaluate the accuracy of a new ventricular volume sensor (VVS, CardioVol) compared with 3-dimenssional echocardiography (echo) in patients with an implantable defibrillator. METHODS: Twenty-two patients referred for generator replacement had their defibrillation lead attached to VVS to determine the level of agreement to a volume measurement standard (echo). Two opposite hemodynamic challenges were sequentially applied to the heart (overdrive pacing and dobutamine administration) to determine whether real changes in hemodynamics could be reliably and repeatedly assessed with VVS. Equivalence of end-diastolic volume (EDV) and stroke volume (SV) determined by both methods was also assessed. RESULTS: EDV and SV were compared using VVS and echo. VVS tracked expected physiologic trends. EDV was modulated -10% by overdrive pacing (14 mL). SV was modulated -13.7% during overdrive pacing (-6 mL) and increased over baseline +14.6% (+8 mL) with dobutamine. VVS and echo mean EDVs were found statistically equivalent, with margin of equivalence 13.8 mL (P <.05). Likewise, mean SVs were found statistically equivalent with margin of equivalence 15.8 mL (P <.05). CONCLUSION: VVS provides an accurate method for ventricular volume assessment using chronically implanted defibrillator leads and is statistically equivalent to echo determination of mean EDV and SV.

Murine heart volume: numerical comparison and calibration of conductance catheter models.

A full set of finite-element method (FEM) studies of the catheter within a cylindrical cuvette and within an elliptical cuvette are presented along with novel insight on the fundamental electromagnetic properties of the catheter. An in vitro experiment with modified small mouse pressure-volume catheters was conducted and the results are presented as a validation of the FEM models. In addition, sensitivity analysis on the electrode size and position is conducted and the results allow for a novel calibration factor based on catheter geometry to be presented. This calibration factor is used in conjunction with Wei's conductance volume equations to reduce the average measured error in cuvette volume measurements from 26.5% to 5%.

Validation of admittance computed left ventricular volumes against real-time three-dimensional echocardiography in the porcine heart.

The admittance and Wei's equation is a new technique for ventricular volumetry to determine pressure-volume relations that addresses traditional conductance-related issues of parallel conductance and field correction factor. These issues with conductance have prevented researchers from obtaining real-time absolute ventricular volumes. Moreover, the time-consuming steps involved in processing conductance catheter data warrant the need for a better catheter-based technique for ventricular volumetry. We aimed to compare the accuracy of left ventricular (LV) volumetry between the new admittance catheterization technique and transoesophageal real-time three-dimensional echocardiography (RT3DE) in a large-animal model. Eight anaesthetized pigs were used. A 7 French admittance catheter was positioned in the LV via the right carotid artery. The catheter was connected to an admittance control unit (ADVantage; Transonic Scisense Inc.), and data were recorded on a four-channel acquisition system (FA404; iWorx Systems). Admittance catheterization data and transoesophageal RT3DE (X7-2; Philips) data were simultaneously obtained with the animal ventilated, under neuromuscular blockade and monitored in baseline conditions and during dobutamine infusion. Left ventricular volumes measured from admittance catheterization (Labscribe; iWorx Systems) and RT3DE (Qlab; Philips) were compared. In a subset of four animals, admittance volumes were compared with those obtained from traditional conductance catheterization (MPVS Ultra; Millar Instruments). Of 37 sets of measurements compared, admittance- and RT3DE-derived LV volumes and ejection fractions at baseline and in the presence of dobutamine exhibited general agreement, with mean percentage intermethod differences of 10% for end-diastolic volumes, 14% for end-systolic volumes and 9% for ejection fraction; the respective intermethod differences between admittance and conductance in eight data sets compared were 11, 11 and 12%. Admittance volumes were generally higher than those obtained by RT3DE, especially among the larger ventricles. It is concluded that it is feasible to derive pressure-volume relations using admittance catheterization in large animals. This study demonstrated agreements between admittance and RT3DE to within 10-14% mean intermethod difference in the estimation of LV volumes. Further investigation will be required to examine the accuracy of volumes in largest ventricles, where intermethod divergence is greatest.

Novel approach to admittance to volume conversion for ventricular volume measurement.

The conductance catheter is a widely used tool to determine ventricular volumes in animal models. A tetra-polar catheter is inserted into the ventricle to measure instantaneous conductance, which is a combination of ventricular blood and surrounding myocardium. Various techniques have been used to separate the blood conductance signal from the combined measured signal [1], [2]. The blood conductance is then converted to volume using a linear relationship proposed by Baan [1] or an improved non linear relationship proposed by Wei [3]. We propose a novel approach that uses the combined blood-muscle signal to calculate volume, thereby eliminating the need to subtract out the muscle. In vivo experiments were performed in mice to validate this new approach and the results were compared with volumes obtained using ultrasound imaging.

Dynamic correction for parallel conductance, GP, and gain factor, alpha, in invasive murine left ventricular volume measurements.

The conductance catheter technique could be improved by determining instantaneous parallel conductance (G(P)), which is known to be time varying, and by including a time-varying calibration factor in Baan's equation [alpha(t)]. We have recently proposed solutions to the problems of both time-varying G(P) and time-varying alpha, which we term "admittance" and "Wei's equation," respectively. We validate both our solutions in mice, compared with the currently accepted methods of hypertonic saline (HS) to determine G(P) and Baan's equation calibrated with both stroke volume (SV) and cuvette. We performed simultaneous echocardiography in closed-chest mice (n = 8) as a reference for left ventricular (LV) volume and demonstrate that an off-center position for the miniaturized pressure-volume (PV) catheter in the LV generates end-systolic and diastolic volumes calculated by admittance with less error (P < 0.03) (-2.49 +/- 15.33 microl error) compared with those same parameters calculated by SV calibrated conductance (35.89 +/- 73.22 microl error) and by cuvette calibrated conductance (-7.53 +/- 16.23 microl ES and -29.10 +/- 31.53 microl ED error). To utilize the admittance approach, myocardial permittivity (epsilon(m)) and conductivity (sigma(m)) were calculated in additional mice (n = 7), and those results are used in this calculation. In aortic banded mice (n = 6), increased myocardial permittivity was measured (11,844 +/- 2,700 control, 21,267 +/- 8,005 banded, P < 0.05), demonstrating that muscle properties vary with disease state. Volume error calculated with respect to echo did not significantly change in aortic banded mice (6.74 +/- 13.06 microl, P = not significant). Increased inotropy in response to intravenous dobutamine was detected with greater sensitivity with the admittance technique compared with traditional conductance [4.9 +/- 1.4 to 12.5 +/- 6.6 mmHg/microl Wei's equation (P < 0.05), 3.3 +/- 1.2 to 8.8 +/- 5.1 mmHg/microl using Baan's equation (P = not significant)]. New theory and method for instantaneous G(P) removal, as well as application of Wei's equation, are presented and validated in vivo in mice. We conclude that, for closed-chest mice, admittance (dynamic G(P)) and Wei's equation (dynamic alpha) provide more accurate volumes than traditional conductance, are more sensitive to inotropic changes, eliminate the need for hypertonic saline, and can be accurately extended to aortic banded mice.

Electrical conductivity and permittivity of murine myocardium.

A classic problem in traditional conductance measurement of left ventricular (LV) volume is the separation of the contributions of myocardium from blood. Measurement of both the magnitude and the phase of admittance allow estimation of the time-varying myocardial contribution, which provides a substantial improvement by eliminating the need for hypertonic saline injection. We present in vivo epicardial surface probe measurements of electrical properties in murine myocardium using two different techniques (a digital and an analog approach). These methods exploit the capacitive properties of the myocardium, and both methods yield similar results. The relative permittivity varies from approximately 100,000 at 2 kHz to approximately 5000 at 50 kHz. The electrical conductivity is approximately constant at 0.16 S/m over the same frequency range. These values can be used to estimate and eliminate the time-varying myocardial contribution from the combined signal obtained in LV conductance catheter measurements, thus yielding the blood contribution alone. To study the effects of albumin on the blood conductivity, we also present electrical conductivity estimates of murine blood with and without typical administrations of albumin during the experiment. The blood conductivity is significantly altered (p < 0.0001) by administering albumin (0.941 S/m with albumin, 0.478 S/m without albumin).

Measuring left ventricular function in the normal, infarcted and CORM-3-preconditioned mouse heart using complex admittance-derived pressure volume loops.

INTRODUCTION: Miniaturized conductance catheters have been successfully applied to measure left ventricular (LV) function in the mouse to assess cardiac or pharmacological interventions. Complex admittance, in contrast to existing methods using conductance catheters, produces an estimate of the parallel admittance of cardiac muscle that can be used to correct the measurement in real-time. The aim of this study was to validate the use of complex admittance to assess LV function in normal and infarcted hearts. METHODS: Using a single conductance catheter, we directly compared measures of LV function using a specially developed admittance system (ADVantage system) and a traditional conductance-derived pressure-volume (PV) system. We subjected mice to focal myocardial ischaemia-reperfusion injury while measuring cardiac function to determine the ability of the new system to distinguish between normal, and dysfunctional LV, contractile performance. RESULTS: LV pressure-volume loops from complex admittance is a reproducible and reliable method of determining LV function, producing data similar to that of the conductance catheter. Our data suggest that the ADVantage system records larger systolic LV cavity volumes when compared to the traditional conductance system in the same animal. In addition, we demonstrate marked LV dysfunction following coronary artery occlusion and reperfusion which is ameliorated using CORM-3, a cardioprotective agent that liberates carbon monoxide (CO). CONCLUSION: The ADVantage system is both effective and reproducible in measuring LV function and dysfunction in the mouse, without the need for complicated interventions to calibrate the measurements. This may mark the way toward an accurate assessment of murine cardiac function.

Design of a wireless telemetric backpack device for real-time in vivo measurement of pressure-volume loops in conscious ambulatory rats.

Pressure - Volume (PV) analysis is the de facto standard for assessing myocardial function. Conductance based methods have been used for the past 27 years to generate instantaneous left ventricular (LV) volume signal. Our research group has developed the instrumentation and the algorithm for obtaining PV loops based on the measurement of real - time admittance magnitude and phase from the LV of anaesthetized mice and rats. In this study, the instrumentation will be integrated into an ASIC (Application Specific Integrated Circuit) and a backpack device will be designed along with this ASIC. This will enable measurement of real-time in vivo P-V loops from conscious and ambulatory rats, useful for both acute and chronic studies.

Impact of physiological variables and genetic background on myocardial frequency-resistivity relations in the intact beating murine heart.

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.

Real time pressure-volume loops in mice using complex admittance: measurement and implications.

Real time left ventricular (LV) pressure-volume (P-V) loops have provided a framework for understanding cardiac mechanics in experimental animals and humans. Conductance measurements have been used for the past 25 years to generate an instantaneous left ventricular (LV) volume signal. The standard conductance method yields a combination of blood and ventricular muscle conductance; however, only the blood signal is used to estimate LV volume. The state of the art techniques like hypertonic saline injection and IVC occlusion, determine only a single steady-state value of the parallel conductance of the cardiac muscle. This is inaccurate, since the cardiac muscle component should vary instantaneously throughout the cardiac cycle as the LV contracts and fills, because the distance from the catheter to the muscle changes. The capacitive nature of cardiac muscle can be used to identify its contribution to the combined conductance signal. This method, in contrast to existing techniques, yields an instantaneous estimate of the parallel admittance of cardiac muscle that can be used to correct the measurement in real time. The corrected signal consists of blood conductance alone. We present the results of real time in vivo measurements of pressure-admittance and pressure-phase loops inside the murine left ventricle. We then use the magnitude and phase angle of the measured admittance to determine pressure volume loops inside the LV on a beat by beat basis. These results may be used to achieve a substantial improvement in the state of the art in this measurement method by eliminating the need for hypertonic saline injection.

Electric field penetration depth of myocardial surface catheters and the measurement of myocardial resistivity.

The in vivo measurement of cardiac conductance in mice offers a method to generate an instantaneous left ventricular volume signal. In order to translate the measured conductance to volume, it is necessary to determine the resistivity of the myocardial tissue. This is done using tetrapolar surface conductance catheters, placed on the surface of the left ventricle. It is important to determine the depth of penetration of the electric field of this surface catheter to ensure that the electric field is confined within the myocardium and does not extend into the left ventricle blood volume. The depth of penetration is experimentally determined by a technique described by Foster et al. [2].

Design of instrumentation and data-acquisition system for complex admittance measurement.

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.

Evidence of time-varying myocardial contribution by in vivo magnitude and phase measurement in mice.

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.