Daniel Escobedo

Detection of vulnerable plaque in a murine model of atherosclerosis with optical coherence tomography

The aim of this study was to evaluate the feasibility of optical coherence tomography (OCT) to identify the components of vulnerable plaques in a well‐established murine model of human atherosclerosis.

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).

Enhancement of Contractility With Sustained Afterload in the Intact Murine Heart Blunting of Length-Dependent Activation

Background 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. Methods and Results 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/μl; P<0.001) resulted in an increase in end‐diastolic volume (31±8 to 35±9 μL; 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 μL; P<0.001). No additional augmentation of systolic function was found at 7 minutes. Conclusions 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. (Circulation. 2003;107: 2962‐2968.)

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.

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.

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.

Enhanced left ventricular systolic function early in type 2 diabetic mice: clinical implications

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.

Embedded Medical Devices: Pressure Volume Loops in Rodents

Man has been instrumenting the human body with electrical devices since the early 1800s. McWilliam built an electrical stimulator of the heart in 1889. In the 1930s, Hyman built and patented multiple versions of an artificial pacemaker. The first one was operated by a hand crank and spring motor to generate and supply the electricity. Around 1960, battery powered pacemakers arrived on the scene. There are five companies that currently provide pacemakers: Biotronik, Boston Scientific, Medtronic, St. Jude Medical, and Sorin. Hearing aids, glucose monitors, artificial joints and limbs, and biopotentials monitors are additional devices that can be implanted.

Imaging flow dynamics in Murine coronary arteries with spectral domain optical Doppler tomography

Blood flow in murine epicardial and intra-myocardial coronary arteries was measured in vivo with spectral domain optical Doppler tomography (SD-ODT). Videos at frame rates up to 180 fps were collected and processed to extract phase shifts associated with moving erythrocytes in the coronary arteries. Radial averaging centered on the vessel lumen provided spatial smoothing of phase noise in a single cross-sectional frame for instantaneous peak velocity measurement without distortion of the flow profile. Temporal averaging synchronized to the cardiac cycle (i.e., gating) was also performed to reduce phase noise, although resulting in lower flow profiles. The vessel angle with respect to incident imaging beam was measured with three-dimensional raster scans collected from the same region as the high speed cross-sectional scans. The variability in peak phase measurement was 10-15% from cycle to cycle on a single animal but larger for measurements among animals. The inter-subject variability is attributed to factors related to real physiological and anatomical differences, instrumentation variables, and measurement error. The measured peak instantaneous flow velocity in a ~40-µm diameter vessel was 23.5 mm/s (28 kHz Doppler phase shift). In addition to measurement of the flow velocity, we observed several dynamic features of the vessel and surrounding myocardium in the intensity and phase sequences, including asymmetric vessel deformation and rapid flow reversal immediately following maximum flow, in confirmation of known coronary artery flow dynamics. SD-ODT is an optical imaging tool that can provide in vivo measures of structural and functional information on cardiac function in small animals.

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.