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Biomedical subjects

B Wohlfart

Publications and source records attributed to B Wohlfart.

At least 19 recordsLinked to original sources
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↗
PubMed1996

Clinical application of a microcomputer system for analysis of monophasic action potentials.

UNLABELLED: Computerized analysis of monophasic action potentials (MAPs) has rarely been reported in clinical setting. We developed a computer system featuring on-line acquisition and user-monitored automatic measurement of multichannel MAPs with the capability of manual corrections. This system has been used in 34 patients in whom two-channel MAPs and 1-lead ECG were digitized during sinus rhythm, pacing, and programmed stimulation (PS). In total, 41, 413 MAPs in 212 data files were measured. The correct determination rate was 100% for MAP onset and plateau, 99.78% (95.76% during PS) for MAP baseline, and 99.96% (54.29% during PS) for QRS onset. The comparison between the computerized and manual measurements in 292 MAPs showed that the former highly agreed with the latter, with the limits of agreement, defined as mean difference +/- 2 SD, being from -4.8-4.9 ms for activation time and from -4.1-6.0 ms for MAP duration measurements. Using this system, two-channel MAPs of more than 300 consecutive beats can be measured in a few minutes, which made it possible to determine the steady state of MAP duration individually, and evaluate the MAP changes during intervention in detail. The clinical routine procedure for testing the effective refractory period and several new MAP parameters were also evaluated using this system. CONCLUSION: The MAP measurement using this computer system is reliable, rapid and accurate; it can therefore replace the manual method and provide more useful information for clinical research.

Action Potentials↗
PubMed1995

The dispersion of repolarization in patients with ventricular tachycardia. A study using simultaneous monophasic action potential recordings from two sites in the right ventricle.

The role of increased dispersion of repolarization in the genesis of torsade de pointes and ventricular fibrillation has been well recognized generally, but not in the genesis of monomorphic ventricular tachycardia (VT). Monophasic action potentials (MAP) were therefore recorded simultaneously from the right ventricular (RV) apex (RVA) and outflow tract (RVOT) during sinus rhythm, RV pacing and programmed extra stimulation (PES) in 24 patients with VT. The activation time (AT), MAP duration at 90% repolarization (MAPd), and repolarization time (RT) were measured and their dispersions, defined as the differences in these parameters between RVA and RVOT, were calculated. During sinus rhythm and RV pacing, the dispersions of AT, MAPd and RT (dispersions) were significantly larger in the 17 patients with a VT induced than in those without. During PES, the dispersions were further augmented in the S2 beats in the seven patients with a sustained VT induced, the maximal dispersion of RT being 85 +/- 22 ms. Both the dispersion of AT and that of MAPd contributed to the dispersion of RT. In both of our two patients with a sustained VT induced during MAP recording, a marked increase in dispersions of RT (140 and 190 ms, respectively) was observed immediately before the initiation of the VT. A link between the dispersions and the inducibility of a monomorphic VT was found in our patients, which suggests that the increased dispersions play an important role in the genesis of a monomorphic VT.

Action Potentials↗
PubMed1995

A comparison between two exercise tests on cycle; a computerized test versus the Astrand test.

Two submaximal cycle ergometer test methods, the Astrand nomogram test and a computerized two-point extrapolation test (Cat Eye ergociser, commercially available), were compared in order to determine agreement and repeatability of estimates of maximum oxygen consumption (VO2max). Twenty healthy women, divided into two groups of ten according to their age (mean 35.3 and mean 46.9), performed test-retest with each method. In both methods the VO2max was estimated from workload and the corresponding heart rate. The correlation between the VO2max using the two methods was high (r = 0.85, P < 0.001). Some of the estimates derived from the computerized test had large errors, which reduced the agreement between the tests. The variation (2SD), expressed in per cent of mean VO2max was 19% for the Astrand test and 34% for the computerized test. Furthermore, the computerized test underestimated the VO2max with approximately 5 ml kg-1 min-1 compared with the Astrand test. Due to this underestimation and the greater variation of the VO2max in the computerized test, it is not recommended to use the two methods interchangeably in clinical practice.

Adult↗
PubMed1994

Effect of dofetilide on cardiac repolarization in patients with ventricular tachycardia. A study using simultaneous monophasic action potential recordings from two sites in the right ventricle.

Monophasic action potentials (MAP) were simultaneously recorded from the right ventricular (RV) apex (RVA) and the outflow tract (RVOT) before and after an infusion of dofetilide in 10 patients with documented ventricular tachycardia. After the drug infusion, the MAP duration (MAPd), repolarization time, and corrected QT interval were significantly prolonged during sinus rhythm, RV pacing, and RV extra stimulation. The prolongation of MAPd at 90% repolarization during RV pacing at a cycle length of 500 ms was 31 +/- 6 ms (13%) and 26 +/- 7 ms (11%) at RVA and RVOT, respectively. The ventricular effective refractory period was significantly prolonged by 33 +/- 9 ms (13%) and 22 +/- 7 ms (9%) at driving cycle lengths 600 and 500 ms, respectively. The MAPd shortening with decreasing diastolic time intervals was significantly diminished by dofetilide in early extra beats during RV extra stimulation, suggesting a relatively more pronounced effect of this drug at the early diastolic phase. The dispersion of repolarization, defined as the difference in MAPd between RVA and RVOT, and the activation time were not significantly changed. In conclusion, acute administration of dofetilide in patients with ventricular tachycardia significantly prolonged the time intervals of ventricular repolarization and refractoriness in a parallel fashion, without affecting intraventricular conduction. The effect of dofetilide on MAPd prolongation appeared not to be reverse use-dependent in this study in humans. These results verify the selective class III antiarrhythmic property of dofetilide and warrant further studies in patients.

Action Potentials↗
PubMed1994

Normal values for QT intervals in ECG during ramp exercise on bicycle.

The relation between QT interval and heart rate during ramp exercise tests on a bicycle was investigated in 37 healthy individuals (21 women) without regular medication and with a normal thallium-201 exercise scintigram (mean age 52.9 +/- 8.3, range 38-68). The test started at 20 W and the load increased by 10 W min-1. A 12-lead ECG was recorded twice every min and mean complexes (during a 15 s period) were calculated by computer. At rest the QT interval (in s) corrected for heart rate (QTc) for women and men was 0.408 +/- 0.004 and 0.399 +/- 0.005, respectively, P > 0.05). During exercise there was no difference in QT interval between women and men or between younger (< 50 years) and older (> 50 years) individuals. A straight line was used to describe the relation between QT interval and heart rate (beats min-1; QT = 0.459-12.3 x 10(-4)*HR). A 95% prediction interval around the regression line was determined using a non-parametric statistical method. When QTc was calculated using Bazett's formula with a cut-off value of QTc = 0.46, 19 individuals (11 women) had a prolonged QT interval during exercise. It is concluded that the relation between QT interval and heart rate can during exercise be described by a straight line for normal individuals. It is not valid to use Bazett's formula for correction of QT intervals during ramp exercise tests.

Adult↗
PubMed1994

Electrocardiographic changes in stroke patients without primary heart disease.

Consecutive electrocardiograms were recorded in 28 stroke patients without signs of primary heart disease. Individuals with subarachnoidal haemorrhage, or electrolyte disturbances were excluded. A computerized tomography of the brain was performed in each case and showed a cerebral haemorrhage (n = 4), cortical infarction (n = 6), subcortical infarction (n = 14) and normal finding (n = 4). One patient developed atrial fibrillation but no other case of serious disturbances in rate of rhythm occurred. None developed AV block, bundle branch blocks or significant changes in QRS complexes. The most common abnormalities in ECG were transient STT changes in lateral leads, which were seen in 13 cases. The typical findings were flat or slightly negative T waves, horizontal or down-sloping ST segments and sometimes a small ST depression. In no case did ECG show typical signs of acute myocardial infarction. A transient prolonged QT interval was seen in three patients and transient U waves in four. ECG did not correlate to the location of the vascular lesion seen on CT or the clinical outcome. It is concluded that STT changes of a small magnitude are seen in about half of the cases of stroke patients without primary heart disease and that they do not resemble the typical pattern of acute myocardial ischaemia.

Aged↗
PubMed1993

Mechanisms of excitation-contraction coupling studied using the principle of transient perturbation.

We have studied the responses to a brief interruption of a train of steady state beats, namely: (1) a single prolonged depolarisation within the train; (2) a single short interval within the train; (3) a single long interval within the train. These responses are predicted by a two compartment model of intracellular calcium handling. They are characterised by the following phenomena. (1) Prolongation of one depolarisation/action potential in the steady state train causes potentiation of the following beat. We postulate on the basis of the published evidence that this may be due to "reversed" sodium/calcium exchange during late systole leading to extra calcium entry during the prolonged depolarisation. (2) Postextrasystole potentiation is postulated to share this mechanism when a depolarisation (extrasystole) is introduced immediately after one of the steady state depolarisations (single short interval). The postextrasystolic beat is then potentiated. (3) A single short interval during the steady state train also leads to attenuation of contractile force on the beat immediately after the short interval, that is, the extrasystole. Mechanical restitution is the term applied to the recovery of this force with increasing interval. This consists of two phases. The initial rapid phase is ryanodine and caffeine insensitive, indicating possible independence of sarcoplasmic reticular function. We postulate that a "membrane compartment" of internal calcium may be responsible. The second, slower, phase of mechanical restitution is ryanodine and caffeine sensitive, indicating that it is likely to be a property of the sarcoplasmic reticulum.(ABSTRACT TRUNCATED AT 250 WORDS)

Action Potentials↗
PubMed1993

Simulation of the electrogram from ion currents.

The electrogram can be constructed as the difference between two action potentials starting with a slight time difference. In the present study, the action potentials were simulated from ion currents showing time- and voltage-dependent activation and inactivation. Simple mathematics like straight lines and single exponential functions were used. The aim was not to give a precise description of the action potential but to obtain a model with electronic interaction between action potentials. Four currents were incorporated. The upstroke of the action potential was due to the inflow of sodium ions. The plateau was maintained by a calcium current and repolarization followed from a slowly activated and outwardly directed potassium current. There was also a time-independent background current of potassium showing inward rectification. Basically the same equations were used for calculation of the four current voltage relations. Also, currents during a depolarizing voltage step could be reproduced by the model. Two action potentials were coupled to each other by means of a resistor to simulate the behaviour of gap junctions. A flat T-wave in the electrogram occurred when the action potentials had the same characteristics because of the electrotonic interaction. When the first action potential was longer than the second in a pair positive T-waves were seen. A negative T-wave occurred when the second action potential of the pair was made longer. The model forms a base for further simulations of ECG.

Action Potentials↗
PubMed1993

Simulation of ECG from two pairs of action potentials.

A simple model for simulation of ECG is presented with the purpose to mimic some common ECG configurations and to generate a hypothesis regarding their electrophysiological background. Action potentials (AP) were simulated on a personal computer from ion currents as described previously (Wohlfart & Arlock, 1993). The difference between two APs of a pair was used to create an electrogram (EG). The subendocardial AP of the pair was triggered by means of a simulated current injection and the subepicardial Ap was triggered from the first AP due to electric coupling within the pair. The subendocardial APs were of longer duration than the epicardial AP because of differences in background currents. A second pair of APs representing another ventricular site was simulated in an analogous way and this pair was activated somewhat later in time. ECG was calculated as the difference between the two EGs. Right-bundle branch block could be imitated by reducing the coupling between the APs representing the right ventricle. Left-bundle branch block was generated in an analogous way. ECG in acute myocardial infarction was created after making one of the epicardial APs ischaemic in appearance (reduced amplitude, short duration). Status-post infarction ECG (Q-wave and negative T) was produced by reducing the influence from the EG of the infarcted area. Negative T and increased R-wave as in hypertrophy could also be reproduced. Down sloping ST-segment and negative T as in subendocardial ischaemia was also possible to imitate. The simulations showed that biphasic T-waves or T and U-waves follows when the two EGs are separated properly in time.

Action Potentials↗
PubMed1992

Myocardial force interval relationships: influence of external sodium and calcium, muscle length, muscle diameter and stimulation frequency.

Several inotropic interventions were studied in thin papillary muscles under dynamic conditions. The effects on mechanical restitution and postextrasystolic potentiation were analysed. The decay of postextrasystolic potentiation was taken as a measure of recirculation fraction of activator calcium. The mechanical restitution curve had a plateau phase on its rising phase which was abolished in low extracellular sodium but pronounced in increased extracellular calcium. The recirculation fraction (RF) in control was 0.35 +/- 0.03; lowering the extracellular sodium by 20% increased the RF to 0.46 +/- 0.04 (n = 10). A reduction of sodium by 40% increased the RF to 0.57 +/- 0.04, whereas increasing extracellular calcium to 4 mM gave an RF of 0.48 +/- 0.05 (n = 10 in all cases). There was no significant effect on RF of changing basic stimulation frequency or muscle preparation length. These findings support RF as a good index of myocardial contractility. Furthermore, at muscle diameters above 0.65 mm the RF was found to be reduced, suggesting this diameter as critical for muscle function. Also, postextrasystolic potentiation in relation to preceding steady state contraction was markedly increased at these diameters. In conclusion, this study shows that RF is independent of stimulation frequency and muscle length, and that it is increased when calcium extrusion by the sodium/calcium exchange is reduced. Furthermore, RF is critically dependent upon the diameter of the preparation and mechanical restitution is changed by altered extracellular sodium concentration.

Animals↗
PubMed1992

Force production in voltage-clamped human atrial muscle.

Human atrial muscle preparations obtained during open heart surgery were mounted in a sucrose gap. Force and membrane currents were recorded during voltage clamp. After a 20-s rest, 10 clamps from a holding potential of -40 to 0 mV at 1.0 Hz were given. This was followed by a test clamp (called 1) of a varied duration and amplitude and two more test clamps (called 2 and 3) as during the priming period. Peak force of contraction 1 (F1) was independent of clamp duration from 2s to about 100 ms but declined at shorter durations. Peak force of contraction 2 (F2) and 3 (F3) increased with the duration and became potentiated. Increasing the clamp amplitude raised F1 to an optimum value at about +10 mV and there was a decline at higher voltages. Both F2 and F3 increased at higher amplitudes. A conventional bell-shaped current-voltage relation for the second inward current was obtained during clamp 1 with maximum inward current around -10 mV. In control experiments on isolated human myocytes peak current was recorded at somewhat more positive potentials. The relation between F3 and F2 was linear both when duration and amplitude of clamp 1 was varied. The slope of the line, interpreted as a measure of recirculation of activator calcium, was 0.4. It is concluded that force during voltage clamp in human atrial muscle is similarly related to membrane voltage as previously reported for guinea pig and ferret preparations.

Atrial Function↗
PubMed1992

Integrity of the alveolar-capillary barrier and alveolar surfactant system in smokers.

BACKGROUND: The permeability of the alveolar-capillary barrier to technetium-99m labelled diethylenetriamine pentaacetate (99mTc DTPA) is known to be greatly increased in smokers, but the underlying mechanism is poorly understood. Abnormal permeability of the alveolar epithelium as well as impaired surfactant function has been suggested. The purpose of this study was to examine transudation of urea and albumin into the alveoli and alveolar surfactant function in smokers and non-smokers and to relate these variables to the rate of alveolar-capillary transfer of 99mTc DTPA. METHODS: Standardised bronchoalveolar lavage was performed and the yield of urea and albumin measured in the lavage fluid. The integrity of the alveolar surfactant system was assessed by measurement of the surface activity and of the yield of phospholipids in alveolar lavage fluid. RESULTS: The mean decay constant for the pulmonary clearance of 99mTc DTPA was 0.028/min in the smokers and 0.009/min in the non-smokers. The recovery of albumin and urea in alveolar lavage fluid was very similar in the two groups. The surface activity of alveolar lavage fluid was lower in smokers than in non-smokers (minimum surface tension 37.9 versus 28.6 mN/m) and the yield of phospholipids was reduced (2.08 versus 3.86 mg). The rate constant for the pulmonary clearance of 99mTc DTPA correlated with the yield of phospholipids at bronchoalveolar lavage. CONCLUSIONS: The study shows that increased alveolar-capillary transfer of 99mTc DTPA in smokers is not accompanied by increased transudation of small or large molecules into the alveoli. The findings support the hypothesis that increased clearance of 99mTc DTPA in smokers is related to surfactant dysfunction.

Adult↗
PubMed1991

Temperature effects on the Na and Ca currents in rat and hedgehog ventricular muscle.

Cardiac transmembrane potentials and Na and Ca currents were recorded at different temperatures in rat and hedgehog ventricular muscle. At 35 degrees C in both species resting potential was about -80 mV and upstroke velocity (Vmax) of the action potential above 100 V/s. The shape of the action potential in hedgehog ventricular cells at 35 degrees C was similar to that in the rat showing a fast repolarization phase. When temperature was decreased, the membrane resting potential depolarized and action potential amplitude and Vmax declined. In rat ventricular cells at 10 degrees C, the resting potential was about -40 to -50 mV and Vmax was reduced to about 5 V/s. In hedgehog ventricular cells, however, the transmembrane potentials and Vmax were better maintained at low temperature. Phase 3 of the action potential was markedly prolonged below 20 degrees C in hedgehog but not in rat ventricular cells. When temperature was decreased to 10 degrees C the availability curve of the Na current shifted toward more negative potentials and ICa.peak declined in rat ventricular cells. In hedgehog cardiac preparations, the Na current was less influenced by the cooling and ICa.peak did not change very much at low temperatures. A transient inward current usually considered to induce cardiac arrhythmias could be recorded in rat ventricular cells below 20 degrees C but not in hedgehog preparations. These features of hedgehog cardiac membranes may contribute to the cold tolerance and the resistance to ventricular fibrillation during the hypothermia in mammalian hibernators.

Action Potentials↗
PubMed1991

Cardiac cell membrane repolarization is required for onset of mechanical restitution in papillary muscle.

In 10 voltage clamped ferret papillary muscles at 37 degrees C (single sucrose gap), the duration of resting (diastolic, holding) potential was varied in order to define the mechanical restitution process. Following a period of steady state voltage clamp depolarizations to +20 mV, a single test depolarization clamp of 200 or 500 ms duration was introduced. Then, the following period at resting (holding) potential was varied. All the mechanical restitution curves for the 500 ms clamps were delayed by 300 ms compared with the 200 ms clamps. When mechanical restitution was plotted as the relationship between contractile force and test electrical diastolic interval, all processes started from zero interval (i.e. the time of repolarization). Variation of diastolic holding potential between -70 mV and -40 mV did not affect the starting time, but the final force values at full restitution were approached faster and were higher for -70 mV than for -40 mV. There was an inverse relationship between force and second inward current during mechanical restitution after an initial phase of restitution of current. Mechanical restitution is postulated to be due to passage of contractile calcium with time from an uptake to a release compartment within the sarcoplasmic reticulum. Thus the rise of contractile force with increasing test cycle duration should have been independent of whether a 200 or 500 ms depolarization was used. In order to accommodate the discrepancy, we postulate either that (1) sarcoplasmic reticulum calcium release channels require sarcolemmal repolarization to begin to be reactivated or (2) that trigger calcium (calcium induced calcium release from the sarcoplasmic reticulum) is derived from the sarcolemma.

Animals↗
PubMed1991

The action of 2,3-butane-dionemonoxime on the inotropic state in guinea-pig myocardium.

Isolated papillary muscles from guinea-pig right ventricles were used (temperature 33 degrees C, stimulation frequency 0.5 Hz). Isometric twitch and action potentials were recorded. Upon addition of 2,3-butane-dionemonoxime (BDM) (2 mM) the peak twitch force was reduced from 4.17 +/- 0.4 mN/mm2 to 1.68 +/- 0.3 mN/mm2 (n = 9, P less than 0.001). The time course of the isometric twitch was slightly altered. Time to peak tension (TPT) was reduced by 12.0 +/- 3% (n = 9, P less than 0.001) whereas time to half relaxation (THR) was left unaffected. The rate of rise of force was reduced by 35 +/- 3.2 mN/mm2s i.e. 46 +/- 3%. The action potential duration and amplitude was not significantly changed by the drug. The shape of the curve relating peak twitch force of an extra beat to the preceding test interval, i.e. mechanical restitution, was affected by 2 mM 2,3-butane-dionemonoxime. The curve reached its maximum faster after addition of the drug. Maximum postextrasystolic potentiation (force in response to the prepreceding test interval) was 3.2 +/- 0.4 mN/mm2 in 2 mM 2,3-butane-dionemonoxine and 7.6 +/- 0.7 mN/mm2 in control (n = 6). However the percentage potentiation was very similar in control (82%) and in presence of 2,3-butane-dionemonoxime (91%). Peak twitch force in relation to peak force of the preceding potentiated contraction during decay of postextrasystolic potentiation was analysed. There was a linear relation between the variables, the slope being 0.34 +/- 0.04 in control and 0.30 +/- 0.02 in 2,3-butane-dionemonoxime. This suggests that the drug is without an action on the fraction of calcium recirculating within the cell.(ABSTRACT TRUNCATED AT 250 WORDS)

Action Potentials↗