Andrew Pollard - Academia.edu (original) (raw)

Papers by Andrew Pollard

AJP: Heart and Circulatory Physiology, 2004

This study was designed to test the hypothesis that analyses of central interstitial potential di... more This study was designed to test the hypothesis that analyses of central interstitial potential differences recorded during multisite stimulation with a set of interstitial electrodes provide sufficient data for accurate measurement of cardiac microimpedances. On theoretical grounds, interstitial current injected and removed using electrodes in close proximity does not cross the membrane, whereas equilibration of intracellular and interstitial potentials occurs distant from electrodes widely separated. Multisite interstitial stimulation should therefore give rise to interstitial potential differences recorded centrally that depend on intracellular and interstitial microimpedances, allowing independent measurement. Simulations of multisite stimulation with fine (25 μm) and wide (400 μm) spacing in one-dimensional models that included Luo-Rudy dynamic membrane equations were performed. Constant interstitial and intracellular microimpedances were prescribed for initial analyses. Discret...

AJP: Heart and Circulatory Physiology, 2006

We analyzed central interstitial potential differences during multisite stimulation to assess the... more We analyzed central interstitial potential differences during multisite stimulation to assess the feasibility of using those recordings to measure cardiac microimpedances in multidimensional preparations. Because interstitial current injected and removed using electrodes with different proximities allows modulation of the portion of current crossing the membrane, we hypothesized that multisite interstitial stimulation would give rise to central interstitial potential differences that depend on intracellular and interstitial microimpedances, allowing measurement of those microimpedances. Simulations of multisite stimulation with fine and wide spacing in two-dimensional models that included dynamic membrane equations for guinea pig ventricular myocytes were performed to generate test data (∂φo). Isotropic interstitial and intracellular microimpedances were prescribed for one set of simulations, and anisotropic microimpedances with unequal ratios (intracellular to interstitial) along a...

PLoS ONE, 2014

Background: Gap junctions (GJs) are the principal membrane structures that conduct electrical imp... more Background: Gap junctions (GJs) are the principal membrane structures that conduct electrical impulses between cardiac myocytes while interstitial collagen (IC) can physically separate adjacent myocytes and limit cell-cell communication. Emerging evidence suggests that both GJ and interstitial structural remodeling are linked to cardiac arrhythmia development. However, automated quantitative identification of GJ distribution and IC deposition from microscopic histological images has proven to be challenging. Such quantification is required to improve the understanding of functional consequences of GJ and structural remodeling in cardiac electrophysiology studies. Methods and Results: Separate approaches were employed for GJ and IC identification in images from histologically stained tissue sections obtained from rabbit and human atria. For GJ identification, we recognized N-Cadherin (N-Cad) as part of the gap junction connexin 43 (Cx43) molecular complex. Because N-Cad anchors Cx43 on intercalated discs (ID) to form functional GJ channels on cell membranes, we computationally dilated N-Cad pixels to create N-Cad units that covered all ID-associated Cx43 pixels on Cx43/N-Cad double immunostained confocal images. This approach allowed segmentation between ID-associated and non-ID-associated Cx43. Additionally, use of N-Cad as a unique internal reference with Z-stack layer-by-layer confocal images potentially limits sample processing related artifacts in Cx43 quantification. For IC quantification, color map thresholding of Masson's Trichrome blue stained sections allowed straightforward and automated segmentation of collagen from non-collagen pixels. Our results strongly demonstrate that the two novel image-processing approaches can minimize potential overestimation or underestimation of gap junction and structural remodeling in healthy and pathological hearts. The results of using the two novel methods will significantly improve our understanding of the molecular and structural remodeling associated functional changes in cardiac arrhythmia development in aged and diseased hearts.

... Shaw and J. Zhang 16 A Performance Model of True Fully Adaptive Routing in 87 Hypercubes A. K... more ... Shaw and J. Zhang 16 A Performance Model of True Fully Adaptive Routing in 87 Hypercubes A. Khonsari, H. Sarbazi-Azad and M ... D. Tavangarian 19 Use of Tabu Search in the logical topology design of wavelength 129 routed optical networks Kannan Achan, Yash Aneja and ...

Cardiac electrical activity is significantly affected by variations in the conductance of gap jun... more Cardiac electrical activity is significantly affected by variations in the conductance of gap junctions that connect myocytes to one another. To better understand how intrinsic (single cell) electrical activity is modulated by junctional conductance, we used a two-myocyte coupling system in which physically separate cells were electrically coupled via a variable resistance set by the investigator. This brief review summarizes our findings regarding: (1) the effect of the early phase of action potential repolarization (phase 1) and transient outward current (I(to)) on action potential conduction, and (2) the effect of coupling on the action potential plateau (late repolarization). We found that inhibition of I(to) markedly increased the ability of action potentials to propagate from cell-to-cell when junctional conductance was low. Electrically coupling two myocytes together also suppressed their beat-to-beat variability in action potential duration and contraction. Similarly, early afterdepolarizations (EADS) were readily suppressed by connecting a normal myocyte to one generating EADs. This high sensitivity of the plateau to variations in junctional interactions arises from the large increase in membrane resistance that occurs during this phase of the action potential.

... Res., vol. 50, pp. 192-200, 1982. [2] MS Spach, JM Kootsey, JM and JDSloan, "Active mod ... more ... Res., vol. 50, pp. 192-200, 1982. [2] MS Spach, JM Kootsey, JM and JDSloan, "Active mod ulation of electrical coupling between cardiac cells of the dog," Cire. Res., vol. 51, pp. 347-62, 1982. [3] AE Pollard and RC Barr, "Computer simulations of activa tion in an anatomically ...

AJP: Heart and Circulatory Physiology, 2010

Alterations to cell-to-cell electrical conductance and to the structural arrangement of the colla... more Alterations to cell-to-cell electrical conductance and to the structural arrangement of the collagen network in cardiac tissue are recognized contributors to arrhythmia development, yet no present method allows direct in vivo measurements of these conductances at their true microscopic scale. The present report documents such a plan, which involves interstitial multisite stimulation at a subcellular to cellular size scale, and verifies the performance of the method through biophysical modeling. Although elements of the plan have been analyzed previously, their performance as a whole is considered here in a comprehensive way. Our analyses take advantage of a three-dimensional structural framework in which interstitial, intracellular, and membrane components are coupled to one another on the fine size scale, and electrodes are separated from one another as in arrays we fabricate routinely. With this arrangement, determination of passive tissue resistances can be made from measurements...

Journal of Cardiovascular Electrophysiology, 2006

Objectives: Interactions between paced wavefronts and monomorphic ventricular tachycardia (VT) di... more Objectives: Interactions between paced wavefronts and monomorphic ventricular tachycardia (VT) dictate antitachycardia pacing outcomes. We used optical mapping to assess those interactions during single and dual site pacing of rabbit ventricular epicardium.Methods and Results: Monomorphic VTs were initiated in six isolated rabbit hearts that were endocardially cryoablated to limit viable tissue to visible epicardium and establish apical tissue as the anatomic anchor. Preparations were optically mapped during single (n = 39) and dual (n = 43) site pacing at 50%–90% of VT cycle length (CL) with eight pulses per trial. Overall, we found six pulses that abruptly terminated VT. This occurred because the VT wavefront collided with the antidromic portion of the paced wavefront and the orthodromic portion of paced wavefront blocked in the VT's refractory region. When effective, dual site pacing that captured tissue at both leads simultaneously terminated the VT immediately, while single site pacing or dual site pacing that captured tissue at only one lead terminated the VT after resetting advanced the orthodromic wavefront. We found 12 pulses that induced polymorphic VT, with 11 of those pulses occurring during capture at only one lead. Expansion of the combined antidromic-VT wavefront around one or both ends of the arc of conduction block formed by the interaction of the orthodromic wavefront with the VT's refractory region initiated functional reentry. Six of these polymorphic VTs were nonsustained because the underlying wavefronts self-terminated. The wavefronts did persist for 4.2 ± 3.5 cycles before self-terminating in these trials, and the post-pacing cycles presented a 146% increase in CL variability, compared with the variability prior to pacing. These temporal characteristics are similar to those of delayed termination in patients with ICDs.Conclusions: The main difference between pulses that terminated abruptly and pulses that induced polymorphic VT was the effective separation of the antidromic and orthodromic portions of the paced wavefront from one another.

AJP: Heart and Circulatory Physiology, 2004

This study was designed to test the hypothesis that analyses of central interstitial potential di... more This study was designed to test the hypothesis that analyses of central interstitial potential differences recorded during multisite stimulation with a set of interstitial electrodes provide sufficient data for accurate measurement of cardiac microimpedances. On theoretical grounds, interstitial current injected and removed using electrodes in close proximity does not cross the membrane, whereas equilibration of intracellular and interstitial potentials occurs distant from electrodes widely separated. Multisite interstitial stimulation should therefore give rise to interstitial potential differences recorded centrally that depend on intracellular and interstitial microimpedances, allowing independent measurement. Simulations of multisite stimulation with fine (25 μm) and wide (400 μm) spacing in one-dimensional models that included Luo-Rudy dynamic membrane equations were performed. Constant interstitial and intracellular microimpedances were prescribed for initial analyses. Discret...

AJP: Heart and Circulatory Physiology, 2006

We analyzed central interstitial potential differences during multisite stimulation to assess the... more We analyzed central interstitial potential differences during multisite stimulation to assess the feasibility of using those recordings to measure cardiac microimpedances in multidimensional preparations. Because interstitial current injected and removed using electrodes with different proximities allows modulation of the portion of current crossing the membrane, we hypothesized that multisite interstitial stimulation would give rise to central interstitial potential differences that depend on intracellular and interstitial microimpedances, allowing measurement of those microimpedances. Simulations of multisite stimulation with fine and wide spacing in two-dimensional models that included dynamic membrane equations for guinea pig ventricular myocytes were performed to generate test data (∂φo). Isotropic interstitial and intracellular microimpedances were prescribed for one set of simulations, and anisotropic microimpedances with unequal ratios (intracellular to interstitial) along a...

PLoS ONE, 2014

Background: Gap junctions (GJs) are the principal membrane structures that conduct electrical imp... more Background: Gap junctions (GJs) are the principal membrane structures that conduct electrical impulses between cardiac myocytes while interstitial collagen (IC) can physically separate adjacent myocytes and limit cell-cell communication. Emerging evidence suggests that both GJ and interstitial structural remodeling are linked to cardiac arrhythmia development. However, automated quantitative identification of GJ distribution and IC deposition from microscopic histological images has proven to be challenging. Such quantification is required to improve the understanding of functional consequences of GJ and structural remodeling in cardiac electrophysiology studies. Methods and Results: Separate approaches were employed for GJ and IC identification in images from histologically stained tissue sections obtained from rabbit and human atria. For GJ identification, we recognized N-Cadherin (N-Cad) as part of the gap junction connexin 43 (Cx43) molecular complex. Because N-Cad anchors Cx43 on intercalated discs (ID) to form functional GJ channels on cell membranes, we computationally dilated N-Cad pixels to create N-Cad units that covered all ID-associated Cx43 pixels on Cx43/N-Cad double immunostained confocal images. This approach allowed segmentation between ID-associated and non-ID-associated Cx43. Additionally, use of N-Cad as a unique internal reference with Z-stack layer-by-layer confocal images potentially limits sample processing related artifacts in Cx43 quantification. For IC quantification, color map thresholding of Masson's Trichrome blue stained sections allowed straightforward and automated segmentation of collagen from non-collagen pixels. Our results strongly demonstrate that the two novel image-processing approaches can minimize potential overestimation or underestimation of gap junction and structural remodeling in healthy and pathological hearts. The results of using the two novel methods will significantly improve our understanding of the molecular and structural remodeling associated functional changes in cardiac arrhythmia development in aged and diseased hearts.

... Shaw and J. Zhang 16 A Performance Model of True Fully Adaptive Routing in 87 Hypercubes A. K... more ... Shaw and J. Zhang 16 A Performance Model of True Fully Adaptive Routing in 87 Hypercubes A. Khonsari, H. Sarbazi-Azad and M ... D. Tavangarian 19 Use of Tabu Search in the logical topology design of wavelength 129 routed optical networks Kannan Achan, Yash Aneja and ...

Cardiac electrical activity is significantly affected by variations in the conductance of gap jun... more Cardiac electrical activity is significantly affected by variations in the conductance of gap junctions that connect myocytes to one another. To better understand how intrinsic (single cell) electrical activity is modulated by junctional conductance, we used a two-myocyte coupling system in which physically separate cells were electrically coupled via a variable resistance set by the investigator. This brief review summarizes our findings regarding: (1) the effect of the early phase of action potential repolarization (phase 1) and transient outward current (I(to)) on action potential conduction, and (2) the effect of coupling on the action potential plateau (late repolarization). We found that inhibition of I(to) markedly increased the ability of action potentials to propagate from cell-to-cell when junctional conductance was low. Electrically coupling two myocytes together also suppressed their beat-to-beat variability in action potential duration and contraction. Similarly, early afterdepolarizations (EADS) were readily suppressed by connecting a normal myocyte to one generating EADs. This high sensitivity of the plateau to variations in junctional interactions arises from the large increase in membrane resistance that occurs during this phase of the action potential.

... Res., vol. 50, pp. 192-200, 1982. [2] MS Spach, JM Kootsey, JM and JDSloan, "Active mod ... more ... Res., vol. 50, pp. 192-200, 1982. [2] MS Spach, JM Kootsey, JM and JDSloan, "Active mod ulation of electrical coupling between cardiac cells of the dog," Cire. Res., vol. 51, pp. 347-62, 1982. [3] AE Pollard and RC Barr, "Computer simulations of activa tion in an anatomically ...

AJP: Heart and Circulatory Physiology, 2010

Alterations to cell-to-cell electrical conductance and to the structural arrangement of the colla... more Alterations to cell-to-cell electrical conductance and to the structural arrangement of the collagen network in cardiac tissue are recognized contributors to arrhythmia development, yet no present method allows direct in vivo measurements of these conductances at their true microscopic scale. The present report documents such a plan, which involves interstitial multisite stimulation at a subcellular to cellular size scale, and verifies the performance of the method through biophysical modeling. Although elements of the plan have been analyzed previously, their performance as a whole is considered here in a comprehensive way. Our analyses take advantage of a three-dimensional structural framework in which interstitial, intracellular, and membrane components are coupled to one another on the fine size scale, and electrodes are separated from one another as in arrays we fabricate routinely. With this arrangement, determination of passive tissue resistances can be made from measurements...

Journal of Cardiovascular Electrophysiology, 2006

Objectives: Interactions between paced wavefronts and monomorphic ventricular tachycardia (VT) di... more Objectives: Interactions between paced wavefronts and monomorphic ventricular tachycardia (VT) dictate antitachycardia pacing outcomes. We used optical mapping to assess those interactions during single and dual site pacing of rabbit ventricular epicardium.Methods and Results: Monomorphic VTs were initiated in six isolated rabbit hearts that were endocardially cryoablated to limit viable tissue to visible epicardium and establish apical tissue as the anatomic anchor. Preparations were optically mapped during single (n = 39) and dual (n = 43) site pacing at 50%–90% of VT cycle length (CL) with eight pulses per trial. Overall, we found six pulses that abruptly terminated VT. This occurred because the VT wavefront collided with the antidromic portion of the paced wavefront and the orthodromic portion of paced wavefront blocked in the VT's refractory region. When effective, dual site pacing that captured tissue at both leads simultaneously terminated the VT immediately, while single site pacing or dual site pacing that captured tissue at only one lead terminated the VT after resetting advanced the orthodromic wavefront. We found 12 pulses that induced polymorphic VT, with 11 of those pulses occurring during capture at only one lead. Expansion of the combined antidromic-VT wavefront around one or both ends of the arc of conduction block formed by the interaction of the orthodromic wavefront with the VT's refractory region initiated functional reentry. Six of these polymorphic VTs were nonsustained because the underlying wavefronts self-terminated. The wavefronts did persist for 4.2 ± 3.5 cycles before self-terminating in these trials, and the post-pacing cycles presented a 146% increase in CL variability, compared with the variability prior to pacing. These temporal characteristics are similar to those of delayed termination in patients with ICDs.Conclusions: The main difference between pulses that terminated abruptly and pulses that induced polymorphic VT was the effective separation of the antidromic and orthodromic portions of the paced wavefront from one another.