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S Dokos

Publications and source records attributed to S Dokos.

10 recordsLinked to original sources
PubMed2001

Regional heterogeneity of function in nonischemic dilated cardiomyopathy.

OBJECTIVE: To quantify regional three-dimensional (3D) motion and myocardial strain using magnetic resonance (MR) tissue tagging in patients with non-ischemic dilated cardiomyopathy (DCM). METHODS: MR grid tagged images were obtained in multiple short- and long-axis planes in thirteen DCM patients. Regional 3D displacements and strains were calculated with the aid of a finite element model. Five of the patients were also imaged after LV volume reduction by partial left ventriculectomy (PLV), combined with mitral and tricuspid valve repair. RESULTS: DCM patients showed consistent, marked regional heterogeneity. Systolic lengthening occurred in the septum in both circumferential (%S(C) -5+/-7%) and longitudinal (%S(L) -2+/-5%) shortening components (negative values indicating lengthening). In contrast, the lateral wall showed relatively normal systolic shortening (%S(C) 12+/-6% and %S(L) 6+/-5%, P<0.001 lateral vs. septal walls). A geometric estimate of regional stress was correlated with shortening on a regional basis, but could not account for the differences in shortening between regions. In the five patients imaged post-PLV, septal function recovered (%S(C) 9+/-5%,%S(L) 6+/-5%, P<0.02 pre vs. post) with normalization of wall stress, whereas lateral wall shortening was reduced (%S(C) 7+/-6%,%S(L) 3+/-3%, P<0.02 pre vs. post) around the site of surgical resection. CONCLUSIONS: A consistent pattern of regional heterogeneity of myocardial strain was seen in all patients. Reduced function may be related to increased wall stress, since recovery of septal function is possible after PLV. However, simple geometric stress determinants are not sufficient to explain the functional heterogeneity observed.

Adult↗
PubMed2001

Vagal entrainment of heart rate is simulated by an integrator with feedback.

Paradoxical stable entrainment of heart rate to inhibitory vagal impulses can be simulated with two distinct mathematical models; a complex ionic current model of sinoatrial node pacemaker activity, as well as a simple integrator with non-linear feedback. We show that both models exhibit similar entrainment characteristics to repetitive vagal stimuli. By applying a sharp disturbance to each model whilst entrained, the subsequent path of cycle length recovery can be described by dynamic phase response curves and phase-phase plots, the properties of which dictate whether stable entrainment is possible.

Feedback↗
PubMed2001

Inhomogeneity of action potential waveshape assists frequency entrainment of cardiac pacemaker cells.

In this paper, we have employed ionic models of sinoatrial node cells to investigate the synchronization of a pair of coupled cardiac pacemaker cells from central and peripheral regions of the sinoatrial node. The free-running cycle length of the cell models was perturbed using two independent techniques and the minimum coupling conductance required to achieve frequency entrainment was used to assess the relative ease with which various cell pairs achieve entrainment. The factors effecting entrainment were further investigated using single-cell models paced with an artificial biphasic coupling current. Our simulation results suggest that dissimilar cell types, those with largely different upstroke velocities entrain more easily, that is, they require less coupling conductance to achieve 1:1 frequency entrainment. We, therefore, propose that regional variation in action-potential waveshape within the sinoatrial node assists frequency synchronization in vivo.

Action Potentials↗
PubMed2000

A triaxial-measurement shear-test device for soft biological tissues.

A novel shear-test device for soft biological tissue, capable of applying simple shear deformations simultaneously in two orthogonal directions while measuring the resulting forces generated in three axes, is described. We validated the device using a synthetic gel, the properties of which were ascertained from independent tensile and rotational shear tests. Material parameters for the gel were fitted using neo-Hookean analytical solutions to the independent test data, and these matched the results from the device. Preliminary results obtained with rat septal myocardium are also presented to demonstrate the feasibility of the apparatus in determining the shear characteristics of living tissue.

Animals↗
PubMed1998

Review of ionic models of vagal-cardiac pacemaker control.

Mathematical models of ion currents in pacemaker cells of the heart and their associated modulation by vagal stimulation have provided numerous insights into the ionic mechanisms underlying parasympathetic control of heart rate. In this article, ionic models described in the literature are reviewed and compared, with a view to examining their effectiveness in reproducing known chronotropic responses to vagal stimulation.

Computer Simulation↗
PubMed1996

Vagal control of sinoatrial rhythm: a mathematical model.

The ionic mechanisms underlying vagal control of the cardiac pacemaker were investigated using a new single cell mathematical model of sinoatrial node electrical activity. The model was formulated from a wide range of electrophysiological data available in the literature, with particular reference to whole cell recordings from enzymatically isolated sinoatrial node cells. Development of the model was prompted by the lack of an existing physiologically accurate formulation of sinoatrial node activity that could reproduce the known complex chronotropic response of the pacemaker to brief-burst vagal stimulation, as observed in whole animal and isolated sinus node preparations. Features of the model include the dynamic modulation of the hyperpolarisation-activated current (i(f)) and the L-type calcium current (iCa,L) by acetylcholine, the improved characterisation of the muscarinic potassium current (iK,ACh), assigning the entire background potassium current (ib,K) to spontaneous openings of its channels, and the utilisation of second order kinetics for acetylcholine within the neuroeffector junction. Simulations performed using brief vagal stimuli elicited a strong hyperpolarisation of the membrane which prolonged the cycle in which it was delivered in a phase-dependent manner. This phase-dependency was presented in the form of a standard phase response curve which was characterised by a positive linear slope region, a breakpoint characteristic and a "no effect" zone in which the vagal pulse could no longer prolong the cycle. The breakpoint was manifested as a discontinuity in the curve which was examined by bracketing this point at the limit of the double precision arithmetic employed. At these boundary points on either side of the breakpoint, the vagal stimulus was able to activate outward iK,ACh in such a manner as to finely balance the increasing inward iCa,L trying to generate phase 0 upstroke. On decay of iK,ACh, the membrane either subsequently repolarised or fired to produce an action potential depending on the precise phase of the stimulus. The positive linear slope portion of the PRC was characterised by a strong resetting type behaviour in which the membrane hyperpolarised to approximately the same value, irrespective of the phase of stimulus delivery. For vagal stimulus bursts applied throughout the "no effect" zone, outward iK,ACh was not sufficiently activated in order to overcome the strong inward drive of iCa,L and could not prevent upstroke occurring. For these vagal stimuli, the subsequent cycle was hyperpolarised and prolonged. The size of the "no effect" zone was directly related to the inherent latency incorporated in the activation characteristic of iK,ACh. In contrast to previous models of vagal pacemaker control, our new model was able to reproduce the classical triphasic chronotropic response to brief vagal stimulation characterised by a primary inhibition response, a postinhibitory rebound and a secondary inhibition response. In particular, the postinhibitory rebound was due to activation of the inward hyperpolarisation-activated current by the vagally-induced membrane hyperpolarisation, whilst the secondary inhibition phase resulted from the inhibition of the hyperpolarisation-activated current by acetylcholine. The model suggests that the complex chronotropic responses of the cardiac pacemaker to brief vagal stimulation arises from inherent ionic mechanisms operating within the sinoatrial node.

Acetylcholine↗
PubMed1996

Ion currents underlying sinoatrial node pacemaker activity: a new single cell mathematical model.

The ionic currents underlying autorhythmicity of the mammalian sinoatrial node and their wider contribution to each phase of the action potential have been investigated in this study using a new single cell mathematical model. The new model provides a review and update of existing formulations of sinoatrial node membrane currents, derived from a wide range of electrophysiological data available in the literature. Simulations of spontaneous activity suggest that the dominant mechanism underlying pacemaker depolarisation is the inward background Na+ current, ib,Na. In contrast to previous models, the decay of the delayed rectifying K+ current, iK, was insignificant during this phase. Despite the presence of a pseudo-outward background current throughout the pacemaker range of potentials (Na-K pump+leak currents), the hyperpolarisation-activated current i(f) was not essential to pacemaker activity. A closer inspection of the current-voltage characteristics of the model revealed that the "instantaneous" time-independent current was inward for holding potentials in the pacemaker range, which rapidly became outward within 2 ms due to the inactivation of the L-type Ca2+ current, iCa,L. This suggests that reports in the literature in which the net background current is outward throughout the pacemaker range of potentials may be exaggerated. The magnitudes of the action potential overshoot and the maximum diastolic potential were determined largely by the reversal potentials of iCa,L and iK respectively. The action potential was sustained by the incomplete deactivation of iCa,L and the Na-Ca exchanger, iNaCa. Despite the incorporation of "square-root" activation by [K]o of all K+ currents, the model was unable to correctly simulate the response to elevated [K]o.

Action Potentials↗
PubMedDate not supplied

Modification of DiFrancesco-Noble equations to simulate the effects of vagal stimulation on in vivo mammalian sinoatrial node electrical activity.

We present a new mathematical model for vagal control of rabbit sinoatrial (SA) node electrical activity based on the DiFrancesco-Noble equations. The original equations were found to be unstable, resulting in progressive cycle by cycle depletion or accumulation of ions in intra- and extracellular compartments. This problem was overcome by modifying the maximum Na-K pump current and the time constant for uptake of intracellular calcium. We also included a formulation for the acetylcholine (ACh)-activated potassium current which was consistent with experimental data. This formulation was based on kinetics first proposed by Osterrieder and later modified by Yanagihara. The resulting model exhibits cycle-cycle ionic stability, and includes an ACh-activated potassium current which accurately reproduces experimentally observed effects of vagal stimulation on both the membrane potential and its time-derivative. Simulations were performed for both brief-burst and prolonged vagal stimulation using simplified square wave profiles for the concentration of ACh in the synaptic cleft space. This protocol permits the isolation of cardiac period dynamics caused by changes in membrane potential and intra- and extracellular ionic concentrations from those caused by other mechanisms including the dynamics of ACh release, diffusion, hydrolysis and washout. Simulation results for the effects of brief-burst single cycle stimulation on the cardiac period agree closely with experimental data reported in the literature, accurately reproducing changes in membrane potential and the phasic dependency of the response to the position of vagal stimulus bursts within the cycle. Simulation of the effects of prolonged vagal stimulation accurately reproduced the steady-state characteristics of heart period response, but did not yield the complex multimodal dynamics of the recovery phase, or the pronounced post vagal tachycardia observed experimentally at the termination of the stimulus. Our results show that the major chronotropic effects of vagal stimulation on the SA cell membrane can be explained in terms of the ACh-activated potassium current. The effects of this membrane current however are generally fast acting and cannot contribute to any long lasting dynamics of the cardiac period response. The modified DiFrancesco-Noble model presented in this article provides a valuable theoretical tool for further analysis of the dynamics of vagal control of the cardiac pacemaker.

Acetylcholine↗
PubMedDate not supplied

Simulations of postvagal tachycardia at the single cell pacemaker level: a new hypothesis.

Simulations performed on a single cell model of rabbit sinoatrial node activity after prolonged vagal stimulation have been able to reproduce the known characteristics of cycle length recovery, including the presence of rapid and slow recovery phases and the transient undershoot phenomenon known as postvagal tachycardia (PVT). In the model, the PVT component has been hypothesized to result from the recovery of background levels of the muscarinic K+ current iK,ACh from desensitization due to prolonged exposure to acetylcholine (ACh) neurotransmitter. Other components of the recovery were found to be due to the inactivation of iK,ACh after the hydrolysis of ACh (rapid phase) and the recovery of the hyperpolarizing-activated current i(f) from its ACh-induced inhibition (slow phase). The magnitudes of both the rapid component and the PVT were found to increase linearly with preceding vagally mediated increase in cycle length, whereas the gain of the slow component was found to saturate, reflecting the limited contribution of i(f) inhibition to cycle prolongation.

Acetylcholine↗