Medicine Amp Science in Sports Amp Exercise, Nov 1, 1995
Sixteen young, healthy males each performed five to seven randomly assigned, exhaustive exercise ... more Sixteen young, healthy males each performed five to seven randomly assigned, exhaustive exercise bouts on a cycle ergometer, with each bout on a separate day and at a different power, to compare estimates of critical power (PC) and anaerobic work capacity (W') among five different models: t = W'/(Pmax-PC) (two-parameter nonlinear); t = (W'/P-PC))-(W'/(Pmax-PC)) (three-parameter nonlinear); P.t = W' + (PC.t) (linear (P.t)); P = (W'/t) + PC (linear (P)); P = PC + (Pmax-PC)exp(-t/tau) (exponential). The data fit each of the models well (mean R2 = 0.96 through 1.00 for each model). However, significant differences among models were observed for both PC (mean +/- standard deviation (SD) for each model was 195 +/- 29 W through 242 +/- 21 W) and W' (18 +/- 5 kJ through 58 +/- 19 kJ). PC estimates among models were significantly correlated (r = 0.78 through 0.99). For W', between-model correlations ranged from 0.25 to 0.95. For a group of six subjects, the ventilatory threshold for long-term exercise (LTE Tvent; 189 +/- 34 W) was significantly lower than PC for all models except the three-parameter nonlinear (PC = 197 +/- 30 W); PC for each model was, however, positively correlated with LTE Tvent (r = 0.69 through 0.91).(ABSTRACT TRUNCATED AT 250 WORDS)
American Journal of Physiology Heart and Circulatory Physiology, Feb 1, 2001
Generation of wave break is a characteristic feature of cardiac fibrillation. In this study, we i... more Generation of wave break is a characteristic feature of cardiac fibrillation. In this study, we investigated how dynamic factors and fixed electrophysiological heterogeneity interact to promote wave break in simulated two-dimensional cardiac tissue, by using the Luo-Rudy (LR1) ventricular action potential model. The degree of dynamic instability of the action potential model was controlled by varying the maximal amplitude of the slow inward Ca(2+) current to produce spiral waves in homogeneous tissue that were either nearly stable, meandering, hypermeandering, or in breakup regimes. Fixed electrophysiological heterogeneity was modeled by randomly varying action potential duration over different spatial scales to create dispersion of refractoriness. We found that the degree of dispersion of refractoriness required to induce wave break decreased markedly as dynamic instability of the cardiac model increased. These findings suggest that reducing the dynamic instability of cardiac cells by interventions, such as decreasing the steepness of action potential duration restitution, may still have merit as an antifibrillatory strategy.
Physical Review E Statistical Nonlinear and Soft Matter Physics, 2003
We studied spiral wave dynamics in an oscillatory reaction diffusion system. We find a new phenom... more We studied spiral wave dynamics in an oscillatory reaction diffusion system. We find a new phenomenon: without the appearance of any global modulation mode, stable spiral waves break up directly. By investigating the one-dimensional version of the system and the isolated local dynamics, we find that the unstable focus in the local dynamics plays an important role. For different boundary conditions (BCs), we find a transition between spiral waves and traveling waves for periodic BCs and drifting spiral wave for no-flux BC.
Heart failure is a leading cause of death, yet its underlying electrophysiological (EP) mechanism... more Heart failure is a leading cause of death, yet its underlying electrophysiological (EP) mechanisms are not well understood. In this study, we use a multiscale approach to analyze a model of heart failure and connect its results to features of the electrocardiogram (ECG). The heart failure model is derived by modifying a previously validated electrophysiology model for a healthy rabbit heart. Specifically, in accordance with the heart failure literature, we modified the cell EP by changing both membrane currents and calcium handling. At the tissue level, we modeled the increased gap junction lateralization and lower conduction velocity due to downregulation of Connexin 43. At the biventricular level, we reduced the apex-to-base and transmural gradients of action potential duration (APD). The failing cell model was first validated by reproducing the longer action potential, slower and lower calcium transient, and earlier alternans characteristic of heart failure EP. Subsequently, we c...
We studied the stability of linear vortex filaments in 3-dimensional (3D) excitable media, using ... more We studied the stability of linear vortex filaments in 3-dimensional (3D) excitable media, using both analytical and numerical methods. We found an intrinsic 3D instability of vortex filaments that is diffusion-induced, and is due to the slower diffusion of the inhibitor. This instability can result either in a single helical filament or in chaotic scroll breakup, depending on the specific kinetic model. When the 2-dimensional dynamics were in the chaotic regime, filament instability occurred via on-off intermittency, a failure of chaos synchronization in the third dimension.
Physical Review E Statistical Physics Plasmas Fluids and Related Interdisciplinary Topics, Nov 1, 1998
We studied the dynamics of a wave propagating around a circular obstacle in a two-dimensional car... more We studied the dynamics of a wave propagating around a circular obstacle in a two-dimensional cardiac tissue model. By starting with a large obstacle and decreasing its radius, a continuous transition was created between the two major types of reentrant cardiac arrhythmias: anatomical reentry (essentially one-dimensional) and functional reentry. As the radius of the obstacle decreases, a sequence of transitions occurs, from periodic motion to a modulated period-2 rhythm, and then to spiral wave breakup. These results may provide a useful basis for refining cardiac ablation techniques currently in use.
American Journal of Physiology Heart and Circulatory Physiology, May 1, 2002
The focal source hypothesis of ventricular fibrillation (VF) posits that rapid activation from a ... more The focal source hypothesis of ventricular fibrillation (VF) posits that rapid activation from a focal source, rather than action potential duration (APD) restitution properties, is responsible for the maintenance of VF. We injected aconitine (100 microg) into normal isolated perfused swine right ventricles (RVs) stained with 4-[beta-[2-(di-n-butylamino)-6-naphthyl]vinyl]pyridinium (di-4-ANEPPS) for optical mapping studies. Within 97 +/- 163 s, aconitine induced ventricular tachycardia (VT) with a mean cycle length 268 +/- 37 ms, which accelerated before converting to VF. Drugs that flatten the APD restitution slope, including diacetyl monoxime (10-20 mM, n = 6), bretylium (10-20 microg/ml, n = 3), and verapamil (2-4 microg/ml, n = 3), reversibly converted VF to VT in all cases. In two RVs, VF persisted despite of the excision of the aconitine site. Simulations in two-dimensional cardiac tissue showed that once VF was initiated, it remained sustained even after the "aconitine" site was eliminated. In this model of focal source VF, the VT-to-VF transition occurred due to a wave break outside the aconitine site, and drugs that flattened the APD restitution slope converted VF to VT despite continuous activation from aconitine site.
The collective behaviors of coupled, stochastically excitable elements subjected to global period... more The collective behaviors of coupled, stochastically excitable elements subjected to global periodic forcing are investigated numerically and analytically. We show that the whole system undergoes a period-doubling bifurcation as the driving period decreases, while the individual elements still exhibit random excitations. Using a mean-field representation, we show that this macroscopic bifurcation behavior is caused by interactions between the random excitation, the refractory period, and recruitment (spatial cooperativity) of the excitable elements.
Regional hyperkalemia during acute myocardial ischemia is a major factor promoting electrophysiol... more Regional hyperkalemia during acute myocardial ischemia is a major factor promoting electrophysiological abnormalities leading to ventricular fibrillation (VF). However, steep action potential duration restitution, recently proposed to be a major determinant of VF, is typically decreased rather than increased by hyperkalemia and acute ischemia. To investigate this apparent contradiction, we simulated the effects of regional hyperkalemia and other ischemic components (anoxia and acidosis) on the stability of spiral wave reentry in simulated two-dimensional cardiac tissue by use of the Luo-Rudy ventricular action potential model. We found that the hyperkalemic "ischemic" area promotes wavebreak in the surrounding normal tissue by accelerating the rate of spiral wave reentry, even after the depolarized ischemic area itself has become unexcitable. Furthermore, wavebreak and fibrillation can be prevented if the dynamical instability of the normal tissue is reduced significantly by targeting electrical restitution properties, suggesting a novel therapeutic approach.
Medicine Amp Science in Sports Amp Exercise, Nov 1, 1995
Sixteen young, healthy males each performed five to seven randomly assigned, exhaustive exercise ... more Sixteen young, healthy males each performed five to seven randomly assigned, exhaustive exercise bouts on a cycle ergometer, with each bout on a separate day and at a different power, to compare estimates of critical power (PC) and anaerobic work capacity (W') among five different models: t = W'/(Pmax-PC) (two-parameter nonlinear); t = (W'/P-PC))-(W'/(Pmax-PC)) (three-parameter nonlinear); P.t = W' + (PC.t) (linear (P.t)); P = (W'/t) + PC (linear (P)); P = PC + (Pmax-PC)exp(-t/tau) (exponential). The data fit each of the models well (mean R2 = 0.96 through 1.00 for each model). However, significant differences among models were observed for both PC (mean +/- standard deviation (SD) for each model was 195 +/- 29 W through 242 +/- 21 W) and W' (18 +/- 5 kJ through 58 +/- 19 kJ). PC estimates among models were significantly correlated (r = 0.78 through 0.99). For W', between-model correlations ranged from 0.25 to 0.95. For a group of six subjects, the ventilatory threshold for long-term exercise (LTE Tvent; 189 +/- 34 W) was significantly lower than PC for all models except the three-parameter nonlinear (PC = 197 +/- 30 W); PC for each model was, however, positively correlated with LTE Tvent (r = 0.69 through 0.91).(ABSTRACT TRUNCATED AT 250 WORDS)
American Journal of Physiology Heart and Circulatory Physiology, Feb 1, 2001
Generation of wave break is a characteristic feature of cardiac fibrillation. In this study, we i... more Generation of wave break is a characteristic feature of cardiac fibrillation. In this study, we investigated how dynamic factors and fixed electrophysiological heterogeneity interact to promote wave break in simulated two-dimensional cardiac tissue, by using the Luo-Rudy (LR1) ventricular action potential model. The degree of dynamic instability of the action potential model was controlled by varying the maximal amplitude of the slow inward Ca(2+) current to produce spiral waves in homogeneous tissue that were either nearly stable, meandering, hypermeandering, or in breakup regimes. Fixed electrophysiological heterogeneity was modeled by randomly varying action potential duration over different spatial scales to create dispersion of refractoriness. We found that the degree of dispersion of refractoriness required to induce wave break decreased markedly as dynamic instability of the cardiac model increased. These findings suggest that reducing the dynamic instability of cardiac cells by interventions, such as decreasing the steepness of action potential duration restitution, may still have merit as an antifibrillatory strategy.
Physical Review E Statistical Nonlinear and Soft Matter Physics, 2003
We studied spiral wave dynamics in an oscillatory reaction diffusion system. We find a new phenom... more We studied spiral wave dynamics in an oscillatory reaction diffusion system. We find a new phenomenon: without the appearance of any global modulation mode, stable spiral waves break up directly. By investigating the one-dimensional version of the system and the isolated local dynamics, we find that the unstable focus in the local dynamics plays an important role. For different boundary conditions (BCs), we find a transition between spiral waves and traveling waves for periodic BCs and drifting spiral wave for no-flux BC.
Heart failure is a leading cause of death, yet its underlying electrophysiological (EP) mechanism... more Heart failure is a leading cause of death, yet its underlying electrophysiological (EP) mechanisms are not well understood. In this study, we use a multiscale approach to analyze a model of heart failure and connect its results to features of the electrocardiogram (ECG). The heart failure model is derived by modifying a previously validated electrophysiology model for a healthy rabbit heart. Specifically, in accordance with the heart failure literature, we modified the cell EP by changing both membrane currents and calcium handling. At the tissue level, we modeled the increased gap junction lateralization and lower conduction velocity due to downregulation of Connexin 43. At the biventricular level, we reduced the apex-to-base and transmural gradients of action potential duration (APD). The failing cell model was first validated by reproducing the longer action potential, slower and lower calcium transient, and earlier alternans characteristic of heart failure EP. Subsequently, we c...
We studied the stability of linear vortex filaments in 3-dimensional (3D) excitable media, using ... more We studied the stability of linear vortex filaments in 3-dimensional (3D) excitable media, using both analytical and numerical methods. We found an intrinsic 3D instability of vortex filaments that is diffusion-induced, and is due to the slower diffusion of the inhibitor. This instability can result either in a single helical filament or in chaotic scroll breakup, depending on the specific kinetic model. When the 2-dimensional dynamics were in the chaotic regime, filament instability occurred via on-off intermittency, a failure of chaos synchronization in the third dimension.
Physical Review E Statistical Physics Plasmas Fluids and Related Interdisciplinary Topics, Nov 1, 1998
We studied the dynamics of a wave propagating around a circular obstacle in a two-dimensional car... more We studied the dynamics of a wave propagating around a circular obstacle in a two-dimensional cardiac tissue model. By starting with a large obstacle and decreasing its radius, a continuous transition was created between the two major types of reentrant cardiac arrhythmias: anatomical reentry (essentially one-dimensional) and functional reentry. As the radius of the obstacle decreases, a sequence of transitions occurs, from periodic motion to a modulated period-2 rhythm, and then to spiral wave breakup. These results may provide a useful basis for refining cardiac ablation techniques currently in use.
American Journal of Physiology Heart and Circulatory Physiology, May 1, 2002
The focal source hypothesis of ventricular fibrillation (VF) posits that rapid activation from a ... more The focal source hypothesis of ventricular fibrillation (VF) posits that rapid activation from a focal source, rather than action potential duration (APD) restitution properties, is responsible for the maintenance of VF. We injected aconitine (100 microg) into normal isolated perfused swine right ventricles (RVs) stained with 4-[beta-[2-(di-n-butylamino)-6-naphthyl]vinyl]pyridinium (di-4-ANEPPS) for optical mapping studies. Within 97 +/- 163 s, aconitine induced ventricular tachycardia (VT) with a mean cycle length 268 +/- 37 ms, which accelerated before converting to VF. Drugs that flatten the APD restitution slope, including diacetyl monoxime (10-20 mM, n = 6), bretylium (10-20 microg/ml, n = 3), and verapamil (2-4 microg/ml, n = 3), reversibly converted VF to VT in all cases. In two RVs, VF persisted despite of the excision of the aconitine site. Simulations in two-dimensional cardiac tissue showed that once VF was initiated, it remained sustained even after the "aconitine" site was eliminated. In this model of focal source VF, the VT-to-VF transition occurred due to a wave break outside the aconitine site, and drugs that flattened the APD restitution slope converted VF to VT despite continuous activation from aconitine site.
The collective behaviors of coupled, stochastically excitable elements subjected to global period... more The collective behaviors of coupled, stochastically excitable elements subjected to global periodic forcing are investigated numerically and analytically. We show that the whole system undergoes a period-doubling bifurcation as the driving period decreases, while the individual elements still exhibit random excitations. Using a mean-field representation, we show that this macroscopic bifurcation behavior is caused by interactions between the random excitation, the refractory period, and recruitment (spatial cooperativity) of the excitable elements.
Regional hyperkalemia during acute myocardial ischemia is a major factor promoting electrophysiol... more Regional hyperkalemia during acute myocardial ischemia is a major factor promoting electrophysiological abnormalities leading to ventricular fibrillation (VF). However, steep action potential duration restitution, recently proposed to be a major determinant of VF, is typically decreased rather than increased by hyperkalemia and acute ischemia. To investigate this apparent contradiction, we simulated the effects of regional hyperkalemia and other ischemic components (anoxia and acidosis) on the stability of spiral wave reentry in simulated two-dimensional cardiac tissue by use of the Luo-Rudy ventricular action potential model. We found that the hyperkalemic "ischemic" area promotes wavebreak in the surrounding normal tissue by accelerating the rate of spiral wave reentry, even after the depolarized ischemic area itself has become unexcitable. Furthermore, wavebreak and fibrillation can be prevented if the dynamical instability of the normal tissue is reduced significantly by targeting electrical restitution properties, suggesting a novel therapeutic approach.
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Papers by alan garfinkel