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Biomedical subjects

B Wohlfart

Publications and source records attributed to B Wohlfart.

At least 19 recordsLinked to original sources
PubMed2001

Arrhythmia as a result of poor intercellular coupling in the sinus node: a simulation study.

The effects of reduced intercellular coupling in the sinus node were investigated by means of simulations. Coupling was reduced both uniformly, and by introducing localized interaction blocks. In either case, model sinus node element networks typically splitted into frequency domains. These were defined as groups of neighbour elements which all attained the same mean firing frequency. In systems, simulating the vicinity of an impulse outlet to the atrium, the sinus node elements often splitted into two domains, one slowly firing just inside the outlet, and one normally firing large domain in the sinus node interior. This two-domain situation was analysed using a two-element system. Wenckebach conduction and advanced (m:1) exit blocks were seen, together with more odd block patterns and slow chaotic rhythms. The two-domain situation appeared also when two discrete outlets were considered. The slow domains around each outlet synchronized via the atrium. However, if there were some degree of exit block through one of the outlets only, brady-tachy like rhythms could be simulated due to a re-entrant circuit including both sinus node and atrial tissue. In conclusion, poor coupling in the sinus node seems to be sufficient to produce most arrhythmias in the sick sinus syndrome

Cell Communication↗
PubMed2001

Simulated sinoatrial exit blocks explained by circle map analysis.

In an accompanying study, it was seen that most cardiac arrhythmias that were simulated during poor intercellular coupling in the sinus node, were the same as those obtained in a two-element system in which one element suffered from a strong leakage current. This element corresponds to the sinus node periphery and is thus the one which feeds the atrium. In this paper, the interior element was replaced by a periodic stimulator. The dynamics of the peripheral element is then determined by its phase response curve. Phase response curves for sinus node elements subject to leakage were simulated for many different amplitudes of depolarizing stimuli. Simulations with circle maps based on these curves produced the same sequence of progressing levels of exit block as stimulus strength decreased, as did the two-element system when coupling strength was reduced. The bifurcations of the circle maps leading to the observed rhythms were identified. We found that the essential qualities of the phase response curves were determined by generally accepted properties of membrane currents. This suggests that the observed rhythms and bifurcations are generic.

Biological Clocks↗
PubMed2001

Day-to-day variation in oxygen consumption at submaximal loads during ergometer cycling by adolescents.

The day-to-day variation in oxygen consumption (VO2) during ergometer cycling by 20 healthy adolescents, 10 females and 10 males, was measured using indirect calorimetry. The two sets of measurements were performed on two consecutive days. Great care was taken to minimize possible disturbing factors. Cycling started at 50 and 100 W for female and male adolescents, respectively. The load was increased at a rate of 5 W 30 s(-1). In order to reach steady state, the load was kept constant for 3.5 min twice during the cycling session, at 100 and 130 W for the females and at 130 and 160 W for the males. Cycling continued until exhaustion. The maximal loads were 196 W (mean) and 271 W (mean) for females and males, respectively. At the maximal loads the day-to-day variation (+/-2 SD) in oxygen consumption (VO2) was +/-330 ml min(-1) for females and 390 ml min(-1) for males. At the submaximal loads the day-to-day variation in heart rate (HR) was 9.3 beats min(-1) (+/-2 SD) (coefficient of variation, CV=3.4% at 130 W) for both sexes. The day-to-day variation in oxygen consumption (VO2) was +/-199 ml min(-1) (+/-2 SD) at the different submaximal loads and did not differ between female and male adolescents (CV=5.7% at 130 W). This natural day-to-day variation must be taken into consideration when using a submaximal ergometer cycling test for the evaluation of physical capacity in the two sexes.

Adolescent↗
PubMed2001

High-frequency components in ECG analysed in guinea-pig Langendorf preparations.

High-frequency components in ECG during global ischaemia were studied in isolated guinea-pig hearts perfused ad modum Langendorf. Electrocardiograph recordings were carried out from the epicardial surface both in normo- and low-flow perfusion. After bandpass filtering (5-500 Hz), signal-averaging, was undertaken. The high-frequency components either increased or decreased after low-flow perfusion was instituted. Root-mean-square voltage (RMS) of the depolarization signal correlated poorly with the signal amplitude, but highly with the first and second derivative, i.e. the velocity and the acceleration of the signal. It is concluded that high-frequency components are not pathological phenomena per se, but reflect the shape of the original electrocardiographic signal.

Animals↗
PubMed2001

Reference values for the physical work capacity on a bicycle ergometer for women between 20 and 80 years of age.

A sample of women (n=87) uniformly distributed in age (20-80 years) was randomly selected from the municipal population register and conventional clinical exercise tests were performed on a bicycle. The load started at 30 W and increased (5 W/30 s) until exhaustion. Care was taken to perform a maximum exercise test. The women were required to be cardiovascularly healthy and not on regular medication to be included in the study. The maximum work load was found to be dependent on age and height. The following equation described the maximum load. Max load (W)=(137.7 * Height (m) - 23.1)/(1 + exp (0.064 * (Age (years) - 75.9))). The upper and lower limits of the reference interval were 120 and 80% of the predicted load, respectively. The upper and lower limits for maximum heart rate were 110 and 90% of the maximum heart rate given by 190.2/(1 + exp (0.0453 * (Age - 107.5))). The reference value for maximum systolic blood pressure was taken as the interval between the two lines 153.3 + 0.281 * Age and 172.0 + 1.13 * Age. The reference values presented for work capacity are higher than those normally used in Sweden.

Adult↗
PubMed2001

Tolerability of concurrent use of nicotine gum and smoking in healthy volunteers.

Although nicotine replacement therapy (NRT) is mainly licensed as an aid for smoking cessation, many smokers alternate NRT with cigarettes. This study evaluated the cardiovascular tolerability of nicotine gum plus smoking. This open, three-way, randomized, multiple-dose, crossover study involved 19 healthy adult volunteer smokers. Three treatments (placebo gum+cigarette vs. nicotine 4-mg gum+unlit cigarette vs. nicotine 4-mg gum+cigarette) were each administered hourly seven times during one study day. Plasma nicotine, ECG variables (ST60 and ST(slope)), heart rate, and blood pressure were measured at rest and during/after 5 min exercise tests. Mean plasma nicotine levels were higher with gum plus smoking than with either gum or smoking alone. After the final administration, mean levels with gum plus smoking were 39.5 (range 27.6-54.4) ng/ml vs. 19.6 (11.8-30.1) ng/ml with gum and 22.6 (6.6-36.6) ng/ml with smoking alone. No signs of myocardial ischaemia were observed during concomitant use of gum plus smoking, despite high plasma nicotine levels. Decreases of ST60 and ST(slope) were observed in all treatment groups during exercise but were asymptomatic. Concomitant gum plus smoking did not increase the incidence of extrasystoles or arrhythmia. No serious adverse events occurred during the study. In conclusion, there were no signs of myocardial ischaemia during multiple submaximal exercise tests in healthy volunteers while smoking and using nicotine 4-mg gum.

Adult↗
PubMed2000

[Ca2+]i following extrasystoles in guinea-pig trabeculae microinjected with fluo-3 - a comparison with frog skeletal muscle fibres.

Force production of cardiac muscle is highly dependent on the interval between the excitations. The aim was to investigate relations between intracellular calcium ([Ca2+]i) and force when a stimulus protocol, with three extrasystoles (ESs) at various intervals, was used. The relation between [Ca2+]i and force was compared with that in frog skeletal muscle fibre. Fluo-3 was microinjected into thin cardiac trabeculae to monitor [Ca2+]i. During steady-state [Ca2+]i consisted of a rapid rise (phase 1) that lasted until peak dF/dt (rate of force development) and was followed by a slower rise (phase 2) that coincided with the action potential and had a peak after peak force. The decline in [Ca2+]i outlasted the duration of the contraction. As the ES intervals were prolonged, there was a gradual restitution of force and of the amplitude and rate of rise of phase 1 [Ca2+]i. Peak dF/dt was linearly related to the amplitude of phase 1 [Ca2+]i during restitution and potentiation of force. Skeletal muscle fibres were loaded with fluo-3-AM. From [Ca2+]i the amount of calcium bound to troponin ([Ca-T]) as a function of time was estimated. Force production of the skeletal muscle fibre could be predicted from [Ca-T] when the signal was delayed (time constant 36 ms). This finding indicates that the recorded [Ca2+]i in skeletal muscle represents activator calcium. In cardiac muscle probably only phase 1 [Ca2+]i represents activator calcium. Phase 2 [Ca2+]i probably represents calcium entry during the action potential and does not activate the contractile system to any significant extent.

Action Potentials↗
PubMed2000

Vectorcardiographic loop alignment and the measurement of morphologic beat-to-beat variability in noisy signals.

The measurement of subtle morphologic beat-to-beat variability in the electrocardiogram (ECG)/vectorcardiogram (VCG) is complicated by the presence of noise which is caused by, e.g., respiration and muscular activity. A method was recently presented which reduces the influence of such noise by performing spatial and temporal alignment of VCG loops. The alignment is performed in terms of scaling, rotation and time synchronization of the loops. Using an ECG simulation model based on propagation of action potentials in cardiac tissue, the ability of the method to separate morphologic variability of physiological origin from respiratory activity was studied. Morphologic variability was created by introducing a random variation in action potential propagation between different compartments. The results indicate that the separation of these two activities can be done accurately at low to moderate noise levels (less than 10 microV). At high noise levels, the estimation of the rotation angles was found to break down in an abrupt manner. It was also shown that the breakdown noise level is strongly dependent on loop morphology; a planar loop corresponds to a lower breakdown noise level than does a nonplanar loop.

Action Potentials↗
PubMed1999

Dissociation between force and [Ca2+]i during extra systoles in guinea-pig ventricular muscle microinjected with fura-2.

Thin trabeculae were dissected from the right ventricle of guinea-pig heart and stimulated to contract isometrically at 0.5 Hz (26 degrees C). Rapid and transient changes of force were obtained by inducing three extra systoles (ES1-3) at 450-ms intervals. The two regular contractions (P1-2) following (ES1-3) were potentiated. Fura-2 salt was microinjected into the preparation to monitor intracellular calcium ([Ca2+]i). Three distinct phases of [Ca2+]i were seen: (1) a rapid rising phase to about 200 nmol L(-1), (2) a slower rising phase to a peak at 400 nmol L(-1), and (3) a slow decline to about 50 nmol L(-1). During ES1, there was a discrepancy between force, which decreased, and peak [Ca2+]i, which increased to 600 nmol L(-1). It is likely that the increased [Ca2+]i during the extra systoles reflects increased sarcolemmal calcium inflow, causing post-extra-systolic potentiation. Ryanodine (1-2 microM) was added to inhibit the intracellular calcium release and thus reduce the intracellular [Ca2+]i gradients following excitation. Ryanodine inhibited phase 1 of [Ca2+]i and abolished post-extra-systolic potentiation. There was a close relationship between dF/dt and [Ca2+]i with ryanodine during control and ES1-3. It is likely that fura-2 reports a spatially averaged [Ca2+]i and that phase 1 of the signal therefore apparently underestimates activator calcium in the close vicinity of the contractile elements.

Animals↗
PubMed1999

Effects of [Na+]o, [Ca2+]o and cyclopiazonic acid on decline of post-extrasystolic potentiation and twitch kinetics in guinea-pig and human myocardial preparations.

The decline of post-extrasystolic potentiation was investigated in atrial and ventricular muscle of guinea-pigs and in human atrial muscle. This decline is described in terms of the recirculation fraction (RF) for calcium in myocardial cells. Under control conditions, the mean values for RF were as follows: 0.61 +/- 0.03 in the guinea-pig atrium, 0.32 +/- 0.05 in the guinea-pig ventricle and 0.51 +/- 0.10 in the human atrium. Upon increasing calcium concentrations within the range of 0.5-10 mM or decreasing the sodium to 70%, the steady-state force and recirculation fraction increased concomitantly in all three types of muscles. Cyclopiazonic acid (CPA), in a 5-20 microM concentration, decreased force in the guinea-pig preparations and decreased RF. The effects of CPA were great in atrial muscle, 20 microM CPA decreasing RF from 0.61 to 0. 39. In ventricular muscle, this effect was small and not statistically significant. When changing calcium or sodium concentrations, increased force was accompanied by slower relaxation in atrial muscle, but an unchanged or slightly faster relaxation in ventricular muscle. In guinea-pig myocardium, CPA (5-20 microM) prolonged the time to peak force (TPF), but it slowed relaxation only in the ventricle. Reducing the calcium outflow by Na/Ca exchange increased RF as expected, and reducing the SR calcium re-uptake decreased RF. These interventions were also expected to reduce the rate of decline of intracellular calcium, but relaxation was not consistently prolonged. This indicates that factors other than the SR calcium pump and sarcolemmal Na/Ca exchange determine, or at least influence, the rate of relaxation.

Action Potentials↗
PubMed1999

Properties of spiral waves in a piece of isotropic myocardium.

Tachyarrhythmias of the heart can be due to the presence of one or more spiral waves of electrical activity. Spiral waves were simulated using a previously described ionic model of cardiac action potentials in a 75 x 75 network of compartments. The compartments were connected by means of resistors and made isotropic in order to catch basic properties of spiral waves. The cross-field stimulation technique was used to generate single or double spiral waves. The analysis showed that a spiral wave was created when the second excitation front became critically curved, in the wake of the preceding wave, so that decremental propagation occurred. A spiral wave could also be generated from a wave circulating around an obstacle when the obstacle size was suddenly reduced. The spiral waves steadily circled around an area with excitable but unexcited cells. An undisturbed spiral wave in the isotropic medium circled around in a stable pathway, but drifted along the borders of cells made non-excitable. An excitation within an existing spiral wave could generate new spiral waves that interacted with each other and formed complex excitation patterns. A sudden prolongation of the refractory period reduced the central area with unexcited cells in the spiral pathway but only slightly prolonged the revolution time. A further prolongation of the refractory period extinguished the spiral wave when the tip of the spiral wave invaded refractory areas. The described ionic compartment model could accurately produce spiral waves with properties in line with experimental results reported by others.

Action Potentials↗
PubMed1999

Day-to-day variation in oxygen consumption and energy expenditure during submaximal treadmill walking in female adolescents.

The day-to-day variation in oxygen consumption (VO2) and energy expenditure (EE) during horizontal treadmill walking was measured using indirect calorimetry in 20 female adolescents (mean age 17.3 years). Two different walking speeds were used: 5 km h-1 and an individually convenient speed of 3.0 km h-1 (mean). The two sets of measurements were performed on 2 consecutive days, and great care was taken to minimize possible disturbing factors. The mean VO2 was 919 ml min-1 at 5 km h-1 and 622 ml min-1 at the individual speed, and the mean values of EE were 4.5 kcal min-1 and 3.1 kcal min-1 respectively. The individual day-to-day variation in VO2 (at 5 km h-1) was between -11.7% and +12.6% of the mean VO2. The coefficient of variation (CV) was 6.4% when values were calculated in ml min-1 kg-1. The energy expenditure varied somewhat less between the 2 days (CV = 5.7%). The corresponding value for EE when walking at the individual speed was 7.2%, and the mean day-to-day variation in VO2 was 7.5% (CV). The rate of perceived exertion according to Borg's scale was lower on day 2 (11.9) compared with day 1 (13.0) when walking at 5 km h-1. There was no difference in heart rate between the 2 days. It is concluded that EE varies somewhat less than VO2 on successive days, probably because of an interchangeable relationship between breathing gases, depending on which substrate is used for combustion. When using VO2 and EE for evaluation of physical capacity, the day-to-day variation in the measurements must be taken into consideration.

Adolescent↗
PubMed1998

Beat-to-beat QRS variability in the 12-lead ECG and the detection of coronary artery disease.

The aim of this article was to study beat-to-beat QRS variability in patients with ischemia and old myocardial infarction using the 12-lead resting electrocardiogram (ECG). The variability analysis was based on beats that have been synchronized in time with an iterative alignment technique. The QRS variability was measured in patients submitted for myocardial scintigraphy. Those with a normal myocardial scintigraphy (called NO, n = 34, mean age 57 years, 23 women) were compared with a group with both myocardial infarction and exercise-induced ischemia (called ISCINF, n = 27, mean age 57 years, 5 women). The mean QRS variability was somewhat smaller in lead I in ISCINF than in NO, and there was no statistically significant difference in QRS variability among the groups in leads II, III, and V1-V6. Using a multivariate approach, the joint variability in leads I, II, II, and V1-V6 was used for calculating receiver operating characteristics based on a leave-one-out procedure. The sensitivity for detecting coronary artery disease was 75% at a specificity of 50%. It is concluded that beat-to-beat QRS variability in the 12-lead ECG does not discriminate between the presence and absence of coronary artery disease sufficiently well for clinical purposes.

Coronary Disease↗
PubMed1998

Potentiation of the contraction following a prolonged depolarization in isolated ferret myocardium.

The contractile force was studied in ferret papillary muscles during voltage clamp depolarizations, using the single sucrose gap method. Prolongation of a test depolarization within a train produced potentiation of the following contraction. The effects of varied duration and membrane potential of the test depolarization upon the potentiated force of the following beat were studied. We assumed that force of a beat was an index of calcium entry on the previous depolarization. The relationship between the peak contractile force of the following potentiated beat and the systolic membrane potential of the test depolarization revealed an equilibrium around -18 mV. This was manifest after 100 ms of no effect. Positive potentials caused potentiation of force of the following beat; negative potentials caused suppression of force of the following beat. Calcium entry, if carried by an electrogenic exchange mechanism, would be revealed as a membrane current developing after 100 ms. Membrane current at these times was always outward. When the duration of the test depolarization was prolonged, outward current prior to repolarisation progressively increased. When the duration of the test depolarization was held constant, outward current was varied by variation in membrane potential. Force of the following beat was proportional to the test clamp membrane potential. The potentiation of the contraction following a prolonged depolarization was abolished by substituting 75% of the sodium in the perfusion medium with lithium. These results are compatible with the hypothesis that potentiation of force following a prolonged depolarization is derived from calcium entry into myocardial cells by reversed sodium-calcium exchange.

Animals↗
PubMed1997

Signed value of monophasic action potential duration difference. A useful measure in evaluation of dispersion of repolarization in patients with ventricular arrhythmias.

AIMS: To evaluate the usefulness of the signed value of monophasic action potential duration difference in analysing the cause of dispersion of ventricular repolarization. METHODS AND RESULTS: Monophasic action potentials were simultaneously recorded from the right ventricular apex and outflow tract during programmed stimulation in 36 patients with ventricular arrhythmias. The time difference between the ends of repolarization on the two monophasic action potentials was used as a measure of the dispersion of ventricular repolarization, and the signed value of the monophasic action potential duration difference was used to specify the contributions of the activation time difference and the monophasic action potential duration difference to the dispersion of ventricular repolarization. During right ventricular pacing, single and double programmed stimulation and at the induction of ventricular arrhythmias, the dispersion of ventricular repolarization and the signed value of monophasic action potential duration difference were markedly greater in the 11 patients with polymorphic ventricular tachycardia/ventricular fibrillation induced than in the 13 patients with monomorphic ventricular tachycardia induced, and in the 10 patients with clinical polymorphic ventricular tachycardia/ventricular fibrillation/cardiac arrest than in the 12 patients with sustained monomorphic ventricular tachycardia. This disclosed that the increased dispersion of ventricular repolarization was caused by increases in both the activation time difference and the monophasic action potential duration difference in the former, but mainly by an increased activation time difference in the latter groups. CONCLUSION: The signed value of monophasic action potential duration difference can specify whether an increased dispersion of ventricular repolarization is caused by inhomogeneous repolarization, inhomogeneous conduction or both, and thereby it is useful in study of the mechanism of ventricular arrhythmias.

Action Potentials↗
PubMed1996

Dispersion of repolarization following double and triple programmed stimulation. A clinical study using the monophasic action potential recording technique.

To study the dispersion of ventricular repolarization following double and triple programmed stimulation and its correlation with the inducibility of ventricular arrhythmias, monophasic action potentials were simultaneously recorded from the right ventricular apex and outflow tract during programmed stimulation in 12 patients with ventricular arrhythmias and a normal QT interval. The time difference between the ends of the two monophasic action potentials were used as a measure of the dispersion of ventricular repolarization, which consists of the activation time difference and the monophasic action potential duration difference. During double and triple programmed stimulation, the dispersion of ventricular repolarization increased significantly with the shortening of the coupling interval but decreased slightly with the shortening of the preceding interval. The induction of the ventricular arrhythmias in these patients was invariably associated with a marked increase in the dispersion of ventricular repolarization. The maximal dispersion of ventricular repolarization was significantly larger in the seven patients with polymorphic ventricular tachycardia and/or ventricular flutter/fibrillation induced than in the four patients with monomorphic ventricular tachycardia induced. Analysis of the two components of the dispersion of ventricular repolarization revealed that the increased dispersion of ventricular repolarization was mainly caused by an increase in the activation time difference in the monomorphic ventricular tachycardia subgroup, and by increases in both the activation time difference and monophasic action potential duration difference in the polymorphic ventricular tachycardia/fibrillation subgroup. These findings suggest that increased dispersion of ventricular repolarization is one of the underlying mechanisms accounting for the myocardial vulnerability to ventricular arrhythmias and that repolarization disturbance is important for the genesis of polymorphic ventricular tachycardia/fibrillation.

Action Potentials↗
PubMed1996

Simulation of re-entry in a piece of myocardial tissue: strong sensitivity to spatial and temporal conditions.

A simple model for the simulation of re-entrant excitation was created. The model consists of a matrix of 15x15 compartments, where each compartment has its own action potential that depends dynamically on four ion currents (INa, ICa, Ik and Ib) having time and voltage-dependent activation and inactivation kinetics. The compartments were combined with resistors to simulate electrotonic interaction. At short excitation intervals the action potential was shortened in duration, and at even shorter coupling intervals decremental propagation occurred. Re-entry around an obstacle could be elicited in response to a properly timed extra stimulus. A time dependent unidirectional block was made by making some of the action potentials longer in duration. An obstacle was not a necessary substrate for re-entry, but the timing of the extra stimulus was critical. In the presence of an obstacle, the induction of re-entry was critically dependent on the shape of the obstacle. The most important result of the simulations is that the system is highly sensitive to the initial spatial and temporal conditions. These sensitivities are generic features of dynamic systems that are described by non-linear differential equations and are typical for chaotic systems. The system studied shows features associated with deterministic chaos.

Action Potentials↗