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.

Data automated bag breathing unit for COVID-19 ventilator shortages.

BACKGROUND: The COVID-19 pandemic has caused a global mechanical ventilator shortage for treatment of severe acute respiratory failure. Development of novel breathing devices has been proposed as a low cost, rapid solution when full-featured ventilators are unavailable. Here we report the design, bench testing and preclinical results for an 'Automated Bag Breathing Unit' (ABBU). Output parameters were validated with mechanical test lungs followed by animal model testing. RESULTS: The ABBU design uses a programmable motor-driven wheel assembled for adult resuscitation bag-valve compression. ABBU can control tidal volume (200-800 ml), respiratory rate (10-40 bpm), inspiratory time (0.5-1.5 s), assist pressure sensing (- 1 to - 20 cm H2O), manual PEEP valve (0-20 cm H2O). All set values are displayed on an LCD screen. Bench testing with lung simulators (Michigan 1600, SmartLung 2000) yielded consistent tidal volume delivery at compliances of 20, 40 and 70 (mL/cm H2O). The delivered fraction of inspired oxygen (FiO2) decreased with increasing minute ventilation (VE), from 98 to 47% when VE was increased from 4 to 16 L/min using a fixed oxygen flow source of 5 L/min. ABBU was tested in Berkshire pigs (n = 6, weight of 50.8 ± 2.6 kg) utilizing normal lung model and saline lavage induced lung injury. Arterial blood gases were measured following changes in tidal volume (200-800 ml), respiratory rate (10-40 bpm), and PEEP (5-20 cm H2O) at baseline and after lung lavage. Physiological levels of PaCO2 (≤ 40 mm Hg [5.3 kPa]) were achieved in all animals at baseline and following lavage injury. PaO2 increased in lavage injured lungs in response to incremental PEEP (5-20 cm H2O) (p < 0.01). At fixed low oxygen flow rates (5 L/min), delivered FiO2 decreased with increased VE. CONCLUSIONS: ABBU provides oxygenation and ventilation across a range of parameter settings that may potentially provide a low-cost solution to ventilator shortages. A clinical trial is necessary to establish safety and efficacy in adult patients with diverse etiologies of respiratory failure.

Admittance to detect alterations in left ventricular stroke volume.

BACKGROUND: Implantable cardioverter-defibrillators monitor intracardiac electrograms (EGMs) to discriminate between ventricular and supraventricular tachycardias. The incidence of inappropriate shocks remains high because of misclassification of the tachycardia in an otherwise hemodynamically stable individual. Coupling EGMs with an assessment of left ventricular (LV) stroke volume (SV) could help in gauging hemodynamics during an arrhythmia and reducing inappropriate shocks. OBJECTIVE: The purpose of this study was to use the admittance method to accurately derive LV SV. METHODS: Ultrasonic flow probe and LV endocardial crystals were used in canines (n = 12) as the standard for LV SV. Biventricular pacing leads were inserted to obtain admittance measurements. A tetrapolar, complex impedance measurement was made between the Bi-V leads. The real and imaginary components of impedance were used to discard the myocardial component from the blood component to derive instantaneous blood conductance (Gb). Alterations in SV were measured during right ventricular pacing, dopamine infusion, and inferior vena cava occlusion. RESULTS: Gb tracks steady-state changes in SV more accurately than traditional magnitude (ie, |Y|, without removal of the muscle signal) during right ventricular pacing and dopamine infusion (P = .004). Instantaneous LV volume also was tracked more accurately by Gb than ∣Y∣ in the subset of subjects that underwent inferior vena cava occlusions (n = 5, P = .025). Finite element modeling demonstrates that admittance shifts more sensitivity of the measurement to the LV blood chamber as the mechanism for improvement (see Online Appendix). CONCLUSION: Monitoring LV SV is possible using the admittance method with biventricular pacing leads. The technique could be piggybacked to complement EGMs to determine if arrhythmias are hemodynamically unstable.

Effect of formalin fixation on thermal conductivity of the biological tissue.

Effect of formalin fixation on thermal conductivity of the biological tissues is presented. A self-heated thermistor probe was used to measure the tissue thermal conductivity. The thermal conductivity of muscle and fatty tissue samples was measured before the formalin fixation and then 27 hours after formalin fixation. The results indicate that the formalin fixation does not cause a significant change in the tissue thermal conductivity of muscle and fatty tissues. In the clinical setting, tissues removed surgically are often fixed in formalin for subsequent pathological analysis. These results suggest that, in terms of thermal properties, it is equally appropriate to perform in vitro studies in either fresh tissue or formalin-fixed tissue.

Analysis of the spatial sensitivity of conductance/admittance catheter ventricular volume estimation.

Conductance catheters are known to have a nonuniform spatial sensitivity due to the distribution of the electric field. The Geselowitz relation is applied to murine and multisegment conductance catheters using finite element models to determine the spatial sensitivity in a uniform medium and simplified left ventricle models. A new formulation is proposed that allows determination of the spatial sensitivity to admittance. Analysis of FEM numerical modeling results using the Geselowitz relation provides a true measure of parallel conductance in simplified left ventricle models for assessment of the admittance method and hypertonic saline techniques. The spatial sensitivity of blood conductance (Gb) is determined throughout the cardiac cycle. Gb is converted to volume using Wei's equation to determine if the presence of myocardium alters the nonlinear relationship through changes to the electric field. Results show that muscle conductance (Gm) from the admittance method matches results from the Geselowitz relation and that the relationship between Gb and volume is accurately fit using Wei's equation. Single-segment admittance measurements in large animals result in a more evenly distributed sensitivity to the LV blood pool. The hypertonic saline method overestimates parallel conductance throughout the cardiac cycle in both murine and multisegment conductance catheters.

A bio-telemetric device for measurement of left ventricular pressure-volume loops using the admittance technique in conscious, ambulatory rats.

This paper presents the design, construction and testing of a device to measure pressure-volume loops in the left ventricle of conscious, ambulatory rats. Pressure is measured with a standard sensor, but volume is derived from data collected from a tetrapolar electrode catheter using a novel admittance technique. There are two main advantages of the admittance technique to measure volume. First, the contribution from the adjacent muscle can be instantaneously removed. Second, the admittance technique incorporates the nonlinear relationship between the electric field generated by the catheter and the blood volume. A low power instrument weighing 27 g was designed, which takes pressure-volume loops every 2 min and runs for 24 h. Pressure-volume data are transmitted wirelessly to a base station. The device was first validated on 13 rats with an acute preparation with 2D echocardiography used to measure true volume. From an accuracy standpoint, the admittance technique is superior to both the conductance technique calibrated with hypertonic saline injections, and calibrated with cuvettes. The device was then tested on six rats with 24 h chronic preparation. Stability of animal preparation and careful calibration are important factors affecting the success of the device.

Left ventricular epicardial admittance measurement for detection of acute LV dilation.

There are two implanted heart failure warning systems incorporated into biventricular pacemakers/automatic implantable cardiac defibrillators and tested in clinical trials: right heart pressures, and lung conductance measurements. However, both warning systems postdate measures of the earliest indicator of impending heart failure: left ventricular (LV) volume. There are currently no proposed implanted technologies that can perform LV blood volume measurements in humans. We propose to solve this problem by incorporating an admittance measurement system onto currently deployed biventricular and automatic implantable cardiac defibrillator leads. This study will demonstrate that an admittance measurement system can detect LV blood conductance from the epicardial position, despite the current generating and sensing electrodes being in constant motion with the heart, and with dynamic removal of the myocardial component of the returning voltage signal. Specifically, in 11 pigs, it will be demonstrated that 1) a physiological LV blood conductance signal can be derived; 2) LV dilation in response to dose-response intravenous neosynephrine can be detected by blood conductance in a similar fashion to the standard of endocardial crystals when admittance is used, but not when only traditional conductance is used; 3) the physiological impact of acute left anterior descending coronary artery occlusion and resultant LV dilation can be detected by blood conductance, before the anticipated secondary rise in right ventricular systolic pressure; and 4) a pleural effusion simulated by placing saline outside the pericardium does not serve as a source of artifact for blood conductance measurements.

Accuracy considerations in catheter based estimation of left ventricular volume.

Cardiac volume estimation in the Left Ventricle from impedance or admittance measurement is subject to two major sources of error: parallel current pathways in surrounding tissues and a non uniform current density field. The accuracy of volume estimation can be enhanced by incorporating the complex electrical properties of myocardium to identify the muscle component in the measurement and by including the transient nature of the field non uniformity. Cardiac muscle is unique in that the permittivity is high enough at audio frequencies to make the muscle component of the signal identifiable in the imaginary part of an admittance measurement. The muscle contribution can thus be uniquely identified and removed from the combined muscle - blood measurement. In general, both error sources are transient and are best removed in real time as data are collected. This paper reviews error correction methods and establishes that the relative magnitudes of the error concerns are different in small and large hearts.

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).

Effect of formalin fixation on thermal conductivity of the biological tissue.

Effect of formalin fixation on thermal conductivity of the biological tissues is presented. A self-heated thermistor probe was used to measure the tissue thermal conductivity. The thermal conductivity of porcine aorta, fat, heart, and liver was measured before the formalin fixation and then 1 day, 4 days, and 11 days after formalin fixation. The results indicate that the formalin fixation does not cause a significant change in the tissue thermal conductivity of the tissues studied. In the clinical setting, tissues removed surgically are often fixed in formalin for subsequent pathological analysis. These results suggest that, in terms of thermal properties, it is equally appropriate to perform in vitro studies in either fresh tissue or formalin-fixed tissue.

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.

Volume catheter parallel conductance varies between end-systole and end-diastole.

In order for the conductance catheter system to accurately measure instantaneous cardiac blood volume, it is necessary to determine and remove the contribution from parallel myocardial tissue. In previous studies, the myocardium has been treated as either purely resistive or purely capacitive when developing methods to estimate the myocardial contribution. We propose that both the capacitive and the resistive properties of the myocardium are substantial, and neither should be ignored. Hence, the measured result should be labeled admittance rather than conductance. We have measured the admittance (magnitude and phase angle) of the left ventricle in the mouse, and have shown that it is measurable and increases with frequency. Further, this more accurate technique suggests that the myocardial contribution to measured admittance varies between end-systole and end-diastole, contrary to previous literature. We have tested these hypotheses both with numerical finite-element models for a mouse left ventricle constructed from magnetic resonance imaging images, and with in vivo admittance measurements in the murine left ventricle. Finally, we propose a new method to determine the instantaneous myocardial contribution to the measured left ventricular admittance that does not require saline injection or other intervention to calibrate.

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.

Finite element analysis and experimental verification of multilayered tissue characterization using the thermal technique.

The objective of this research is to develop noninvasive techniques to determine thermal properties of layered biologic structures based on measurements from the surface. The self-heated thermistor technique is evaluated both numerically and experimentally. The finite element analyses, which confirm the experimental results, are used to study the temperature profiles occurring in the thermistor-tissue system. An in vitro tissue model was constructed by placing Teflon of varying thickness between the biologic tissue and the self-heated thermistor. The experiments were performed using two different-sized thermistors on six tissue samples. A self-heated thermistor was used to determine the thermal conductivity of tissue covered by a thin layer Teflon. The results from experimental data clearly indicate that this technique can penetrate below the thin layers of Teflon and thus is sensitive to the thermal properties of the underlying tissue. The factors which may introduce error in the experimental data are (i) poor thermal/physical contact between the thermistor probe and tissue sample, and (ii) water loss from tissue during the course of experimentation. The finite element analysis was used to simulate the experimental conditions and to calculate transient temperature profile generated by the thermistor bead. The results of finite element analysis are in accordance with the experimental data.

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.

Effects of the time response of the temperature sensor on thermodilution measurements.

Thermodilution is widely used to measure cardiac output, ejection fraction and end diastolic volume. Even though the method is based on dynamic temperature measurements, little attention has been paid to the characterization of the dynamic behavior of the temperature sensor and to its influence on the accuracy of the method. This paper presents several theoretical and empirical results related to the thermodilution method. The results show that, at flow velocities above 0.2 m s(-1), the response of temperature sensors embedded in Swan-Ganz catheters can be accurately described by a convolution operation between the true temperature of the blood and the impulse response of the sensor. The model developed is used to assess the influence of the probe response on the measurement of cardiac output, and this study leads us to the conclusion that the probe response can cause errors in the cardiac output measurement, but this error is usually small (2% in cases with a high degree of arrhythmia). The results show that these small errors appear during arrhythmias that affect the R-R interval and when the real temperature distribution at the pulmonary artery does not possess a shape with perfect temperature plateaux.

Nonlinear conductance-volume relationship for murine conductance catheter measurement system.

The conductance catheter system is a tool to determine instantaneous left ventricular volume in vivo by converting measured conductance to volume. The currently adopted conductance-to-volume conversion equation was proposed by Baan, and the accuracy of this equation is limited by the assumption of a linear conductance-volume relationship. The electric field generated by a conductance catheter is nonuniform, which results in a nonlinear relationship between conductance and volume. This paper investigates this nonlinear relationship and proposes a new nonlinear conductance-to-volume conversion equation. The proposed nonlinear equation uses a single empirically determined calibration coefficient, derived from independently measured stroke volume. In vitro experiments and numerical model simulations were performed to verify and validate the proposed equation.