Daniel O. Cervantes

Hematocrit measurement by dielectric spectroscopy

Based on permittivity changes, a new method to measure hematocrit (HCT) in extracorporeal blood systems is presented. Human blood samples were tested at different HCT levels pairing the values of permittivity change, obtained by means of a commercial impedance analyzer, with traditional centrifugation measurements. Data were correlated using both linear and nonlinear regression. When using the lineal model, the comparison yielded a high correlation coefficient (r=0.99). Theoretical simplifications suggest that the method is independent of changes in the conductivities of the intracellular and extracellular compartments. The influence of osmolarity and conductivity of the extracellular compartment was analyzed. It is shown that HCT can be predicted within an error lower than 5% when those parameters changed as much as 1 mS/cm and 50 mOsm/kg, respectively. Thus, the method appears as valid and viable showing good possibilities in applications such as renal dialysis.

Noninvasive electromechanical wave imaging and conduction-relevant velocity estimation in vivo

Electromechanical wave imaging is a novel technique for the noninvasive mapping of conduction waves in the left ventricle through the combination of ECG gating, high frame rate ultrasound imaging and radio-frequency (RF)-based displacement estimation techniques. In this paper, we describe this new technique and characterize the origin and velocity of the wave under distinct pacing schemes. First, in vivo imaging (30 MHz) was performed on anesthetized, wild-type mice (n=12) at high frame rates in order to take advantage of the transient electromechanical coupling occurring in the myocardium. The RF signal acquisition in a long-axis echocardiographic view was gated between consecutive R-wave peaks of the mouse electrocardiogram (ECG) and yielded an ultra-high RF frame rate of 8000 frames/s (fps). The ultrasound RF signals in each frame were digitized at 160 MHz. Axial, frame-to-frame displacements were estimated using 1D cross-correlation (window size of 240 microm, overlap of 90%). Three pacing protocols were sequentially applied in each mouse: (1) sinus rhythm (SR), (2) right-atrial (RA) pacing and (3) right-ventricular (RV) pacing. Pacing was performed using an eight-electrode catheter placed into the right side of the heart with the capability of pacing from any adjacent bipole. During a cardiac cycle, several waves were depicted on the electromechanical wave images that propagated transmurally and/or from base to apex, or apex to base, depending on the type of pacing and the cardiac phase. Through comparison between the ciné-loops and their corresponding ECG obtained at different pacing protocols, we were able to identify and separate the electrically induced, or contraction, waves from the hemodynamic (or, blood-wall coupling) waves. In all cases, the contraction wave was best observed along the posterior wall starting at the S-wave of the ECG, which occurs after Purkinje fiber, and during myocardial, activation. The contraction wave was identified based on the fact that it changed direction only when the pacing origin changed, i.e., it propagated from the apex to the base at SR and RA pacing and from base to apex at RV pacing. This reversal in the wave propagation direction was found to be consistent in all mice scanned and the wave velocity values fell within the previously reported conduction wave range with statistically significant differences between SR/RA pacing (0.85+/-0.22 m/s and 0.84+/-0.20 m/s, respectively) and RV pacing (-0.52+/-0.31 m/s; p<0.0001). This study thus shows that imaging the electromechanical function of the heart noninvasively is feasible. It may therefore constitute a unique noninvasive method for conduction wave mapping of the entire left ventricle. Such a technology can be extended to 3D mapping and/or used for early detection of dyssynchrony, arrhythmias, left-bundle branch block, or other conduction abnormalities as well as diagnosis and treatment thereof.

Adrenergic regulation of a key cardiac potassium channel can contribute to atrial fibrillation: evidence from an IKs transgenic mouse

Inherited gain‐of‐function mutations of genes coding for subunits of the heart slow potassium (IKs) channel can cause familial atrial fibrillation (AF). Here we consider a potentially more prevalent mechanism and hypothesize that β‐adrenergic receptor (β‐AR)‐mediated regulation of the IKs channel, a natural gain‐of‐function pathway, can also lead to AF. Using a transgenic IKs channel mouse model, we studied the role of the channel and its regulation by β‐AR stimulation on atrial arrhythmias. In vivo administration of isoprenaline (isoproterenol) predisposes IKs channel transgenic mice but not wild‐type (WT) littermates that lack IKs to prolonged atrial arrhythmias. Patch‐clamp analysis demonstrated expression and isoprenaline‐mediated regulation of IKs in atrial myocytes from transgenic but not WT littermates. Furthermore, computational modelling revealed that β‐AR stimulation‐dependent accumulation of open IKs channels accounts for the pro‐arrhythmic substrate. Our results provide evidence that β‐AR‐regulated IKs channels can play a role in AF and imply that specific IKs deregulation, perhaps through disruption of the IKs macromolecular complex necessary for β‐AR‐mediated IKs channel regulation, may be a novel therapeutic strategy for treating this most common arrhythmia.

Model of Bipolar Electrogram Fractionation and Conduction Block Associated With Activation Wavefront Direction at Infarct Border Zone Lateral Isthmus Boundaries

Background—Improved understanding of the mechanisms underlying infarct border zone electrogram fractionation may be helpful to identify arrhythmogenic regions in the postinfarction heart. We describe the generation of electrogram fractionation from changes in activation wavefront curvature in experimental canine infarction. Methods and Results—A model was developed to estimate the extracellular signal shape that would be generated by wavefront propagation parallel to versus perpendicular to the lateral boundary (LB) of the reentrant ventricular tachycardia (VT) isthmus or diastolic pathway. LBs are defined as locations where functional block forms during VT, and elsewhere they have been shown to coincide with sharp thin-to-thick transitions in infarct border zone thickness. To test the model, bipolar electrograms were acquired from infarct border zone sites in 10 canine heart experiments 3 to 5 days after experimental infarction. Activation maps were constructed during sinus rhythm and during VT. The characteristics of model-generated versus actual electrograms were compared. Quantitatively expressed VT fractionation (7.6±1.2 deflections; 16.3±8.9-ms intervals) was similar to model-generated values with wavefront propagation perpendicular to the LB (9.4±2.4 deflections; 14.4±5.2-ms intervals). Fractionation during sinus rhythm (5.9±1.8 deflections; 9.2±4.4-ms intervals) was similar to model-generated fractionation with wavefront propagation parallel to the LB (6.7±3.1 deflections; 7.1±3.8-ms intervals). VT and sinus rhythm fractionation sites were adjacent to LBs ≈80% of the time. Conclusions—The results suggest that in a subacute canine infarct model, the LBs are a source of activation wavefront discontinuity and electrogram fractionation, with the degree of fractionation being dependent on activation rate and wavefront orientation with respect to the LB.

Comparative analysis of hematocrit measurements by dielectric and impedance techniques

In a previous paper, a new dielectric technique was used to estimate hematocrit (HTC) in extracorporeal blood circulation systems, independently of plasma conductivity or osmolarity. Although many impedance techniques have been formerly proposed in the literature, none has been evaluated against plasma conductivity and osmolarity. Herein, we estimate HTC based on permittivity changes and also with other four techniques found in the literature. Besides, the error incurred in each is also studied when plasma conductivity and osmolarity changed as much as 1 mS/cm and 50 mOsm/kg, respectively. The dielectric (permittivity) technique has an error close to 5.4%, while the others showed both tendencies, i.e., lower error (2.5%, two of them) and higher error (8.6% and 16.3%, the other two). The dielectric technique, even though did not produce the lowest error, provides a well-described physical model along with simple instrumentation.

Reprint of 'Model of unidirectional block formation leading to reentrant ventricular tachycardia in the infarct border zone of postinfarction canine hearts'

Background When the infarct border zone is stimulated prematurely, a unidirectional block line (UBL) can form and lead to double-loop (figure-of-eight) reentrant ventricular tachycardia (VT) with a central isthmus. The isthmus is composed of an entrance, center, and exit. It was hypothesized that for certain stimulus site locations and coupling intervals, the UBL would coincide with the isthmus entrance boundary, where infarct border zone thickness changes from thin-to-thick in the travel direction of the premature stimulus wavefront. Method A quantitative model was developed to describe how thin-to-thick changes in the border zone result in critically convex wavefront curvature leading to conduction block, which is dependent upon coupling interval. The model was tested in 12 retrospectively analyzed postinfarction canine experiments. Electrical activation was mapped for premature stimulation and for the first reentrant VT cycle. The relationship of functional conduction block forming during premature stimulation to functional block during reentrant VT was quantified. Results For an appropriately placed stimulus, in accord with model predictions: (1) The UBL and reentrant VT isthmus lateral boundaries overlapped (error: 4.8±5.7 mm). (2) The UBL leading edge coincided with the distal isthmus where the center-entrance boundary would be expected to occur. (3) The mean coupling interval was 164.6±11.0 ms during premature stimulation and 190.7±20.4 ms during the first reentrant VT cycle, in accord with model calculations, which resulted in critically convex wavefront curvature with functional conduction block, respectively, at the location of the isthmus entrance boundary and at the lateral isthmus edges. Discussion Reentrant VT onset following premature stimulation can be explained by the presence of critically convex wavefront curvature and unidirectional block at the isthmus entrance boundary when the premature stimulation interval is sufficiently short. The double-loop reentrant circuit pattern is a consequence of wavefront bifurcation around this UBL followed by coalescence, and then impulse propagation through the isthmus. The wavefront is blocked from propagating laterally away from the isthmus by sharp increases in border zone thickness, which results in critically convex wavefront curvature at VT cycle lengths.

2I-6 Imaging the Electromechanical Wave Activation of the Left Ventricle in Vivo

The heart is a mechanical pump that is electrically driven. We have previously shown that the contractility of the cardiac muscle can reliably be used in order to assess the extent of ischemia. In this paper, in vivo imaging (35 MHz) was performed on anesthetized mice before and after left anterior descending (LAD) coronary artery ligation at high frame rates (Vevo 770, Visualsonics, Inc.) in order to better explore the electromechanical coupling within the heart muscle. The acquisition was triggered on the mouse electrocardiogram (ECG) and yielded a high frame rate of 8 kHz. RF signals from long-axis views were digitized and stored in real-time at a similar sampling rate for off-line processing. Axial displacements were estimated using 1D cross-correlation (window size of 60 microns, overlapping at 90%) and displayed at 8 kHz. The mice were initially imaged during sinus rhythm (i.e., at the natural pacing of the heart (100 ms period)), right-atrial pacing (at 100 ms) and right-ventricular pacing (at 100 ms). Pacing was achieved using catheterization through the right side of the heart, where the catheter carried nine electrodes that could be separately activated for varying the pacing location. In some of the scans, the catheter was within the imaging field-of-view and allowed for imaging of the pacing wave during ventricular pacing. The most pronounced wave propagating during sinus rhythm and atrial pacing was the contraction wave, or wave originating at the isovolumic contraction phase, that propagated along the longitudinal direction of the myocardium initiating radial thickening in its path. The contraction wave started at the apex, right at the QRS peak, and then propagated along the septum first and then the posterior wall. So, the direction of propagation was counterclockwise in a long-axis view. A relaxation wave was also detected propagating across the septum, i.e., from the endo- to the epicardial level. Right-atrial pacing, i.e., similar to sinus rhythm, induced the same counter-clockwise pattern as in the sinus rhythm during contraction. Right-ventricular pacing induced a reverse direction on the contraction wave that started from the tip of the catheter (close to the base) with two waves propagating from base to apex, one along the septum and one along the posterior wall. In summary, strong contraction waves were imaged at 8 kHz frame rate in the septum (from base to apex) and the posterior wall (from apex to base) that changed direction or speed according to the pacing scheme induced. These preliminary results indicate that through electromechanical coupling, motion estimation at high frame rates may yield a novel non-invasive method for conduction mapping of the live myocardium and diagnosis of related diseases