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B Wohlfart

Publications and source records attributed to B Wohlfart.

63 records · Page 4Linked to original sources

Analysis of mechanical alternans in rabbit papillary muscle.

Isometric force and action potentials were recorded in rabbit papillary muscles. It was found that the monophasic decline of the contractile potentiation that was recorded after an extrasystole (ES) was replaced by transient mechanical alternans (TMA) when temperature and calcium concentration of the perfusion medium had been lowered (from 37 degrees to 27 degrees C and from 2.0 to 0.5 mM, respectively). TMA in response to ES was also seen when the preparation was exposed to 2mM 4-aminopyridine. Furthermore, TMA could be induced by a shortening step during activity. Mechanical restitution curves were recorded by relating max. rate of force development of a test contraction to the duration of the preceding stimulus interval. It was found that the alternating contractions during TMA were associated with shifts of the mechanical restitution curve along the force axis. The duration of the action potential was inversely related to force development during TMA. It is proposed that TMA is due to a reduced damping of a regulatory feedback system between inotropic state and intake of activator calcium during the action potential. The following sequence of events are suggested: The abbreviated action potential accompanying a potentiated contraction is associated with reduced intake of activator calcium. This leads to depression of the subsequent contraction. The latter contraction is associated with increased calcium intake due to prolongation of the action potential. This will lead to potentiation of the next beat and the sequence is repeated. It is proposed that recirculation of calcium between heart beats will act as a damping factor of this system.

Action Potentials↗

Is action potential duration of the intact dog heart related to contractility or stimulus rate?

1. The contractility (maximum rate of rise of left ventricular pressure) and action potential duration were measured in intact closed-chest anaesthetized dogs with complete atrioventricular dissociation and beta-adrenergic blockade.2. Measurements were confined to test beats following a 1 sec interval. Prior to the test interval (priming period) a variety of potentiating stimulus trains were introduced.3. When the frequency of stimulation was increased in the priming period (frequency potentiation), there was an inverse relationship between action potential duration and contractility of the test beat.4. When the test beat was potentiated by a single beat terminating the priming period with one short interval (post-extrasystolic potentiation), there was no relationship between the action potential duration and contractility of the test beat.5. Paired pulse stimulation was used for any given frequency to vary contractility by short interval potentiation. For any given frequency of stimulation there was no relationship between action potential duration and contractility of the test beat. For any given value of contractility, action potential duration decreased with increased frequency of stimulation.6. The introduction of a high frequency train caused a step decrease in action potential duration on the first beat of the train. This was followed by a further slow decline in action potential duration with a time course of over 3 min. These two changes could be dissociated by the introduction during the train of one second interval test pulses, which only showed the slow shortening.7. The lack of a consistent relationship between action potential duration and contractility of the test beat disagrees with the hypothesis that repolarization is controlled by the activator calcium responsible for the contractility. The action potential shortening associated with increased frequency is related to the frequency change per se.8. The slow time course of change in action potential duration following an increase in stimulation frequency suggests that these changes are caused by the accumulation of an ion or metabolite, or possibly by changes of activity of the electrogenic Na(+)-K(+) pump.

Action Potentials↗

Effects of diethyl-stilboestrol on contractile response and action potential of rabbit papillary muscle.

The effects of diethyl-stilboestrol (DES) were studied on isolated papillary muscles from rabbits (37 degrees C). The preparation was paced at a frequency of 0.67 Hz and the muscle length was adjusted to 95% of the length of optimum force production. Membrane potentials and the isometric force production were recorded. DES (10 microM) reduced peak isometric force by 44.5% (mean of 6 preparations) and maximum rate of force development was reduced to approximately the same degree. The time to peak force, the time from peak force to half relaxation and the action potential duration were not significantly affected by DES. The results are consistent with the idea that DES reduces the calcium influx during the cardiac action potential without significantly influencing the calcium reuptake during relaxation. The data are compared to the effects of DES on uterine and skeletal muscles and the differences in metabolism of activator calcium in different kinds of muscles are discussed.

Action Potentials↗

Effects of 4-aminopyridine on contractile response and action potential of rabbit papillary muscle.

The effects of 4-aminopyridine (4-AP) were studied on isolated papillary muscles from the heart of reserpinized rabbits (at 37 degrees C). The preparations were paced to contract at 0.67 Hz under isometric conditions and the muscle length was adjusted to 95% of the length for optimum force production. Simultaneous recordings of isometric force and membrane potentials were performed. 4-AP (50 microM) increased peak force by approximately 20% of the control and prolonged the action potential by 20%. Higher concentrations of 4-AP (800 microM) resulted in further increments of force and action potential duration (60 and 70% of controls, respectively). Prolongation of the action potential and potentiation of the isometric force was still present one hour after withdrawal of the drug from the perfusate. The results are consistent with the view that 4-AP prolongs the action potential by inhibiting the late repolarizing potassium current. It is suggested that the calcium uptake by the ventricular cell during the prolonged action potential is increased and that this leads to the positive inotropic effect.

4-Aminopyridine↗

The action-potential duration and contractile response of the intact heart related to the preceding interval and the preceding beat in the dog and cat.

1. Simultaneous measurements were made in anaesthetized dogs of monophasic action potentials from the right ventricle and of the maximum rate of rise of left ventricular pressure (dP(lv)/dt(max)). Atrio-ventricular dissociation was induced and the heart paced via right ventricular electrodes.2. A control period of steady pacing was followed by a test stimulus after a variable interval called the ;test-pulse interval'. The duration of the action potential of the test beat (measured at 70% repolarization) increased with test-pulse interval and reached an approximately steady value at intervals of 1.0-1.5 sec. This constitutes the ;electrical restitution curve'.3. An increase in the frequency of stimulation prior to the introduction of the test pulses caused a downward displacement of the electrical restitution curve.4. Stimulation at 2 Hz and paired pulse stimulation at 1 Hz (same number of stimuli per min) were introduced prior to the test pulses and produced very similar electrical restitution curves.5. For a constant frequency of stimulation in the control period, adrenaline produced downward displacement of the restitution curve.6. It is concluded that there is no obvious relationship between the restitution of the action potential duration and of the contractile response. We suggest therefore that electrical and mechanical restitution occur through separate processes, the former through time-dependent recovery in membrane conductances and the latter through time-dependent increase in availability of intracellular calcium for release.7. Contractions were introduced with a test-pulse interval shorter than the optimum, and were followed by a second test pulse fixed at the optimum interval of 0.8-1.0 sec. The second test beats were potentiated (post-extrasystolic potentiation). In isolated ejecting cat hearts, there was an optimum interval for the first test pulse to produce the greatest potentiation of the second test beat. This interval was 0.2-0.3 sec, and was shortened by an increase in frequency of stimulation prior to the first test beat.8. The interval preceding the first test pulse was then varied within a range (0.8-2.0 sec) which did not produce potentiation. These first test pulses were sometimes preceded by one extrasystole. The timing of this extrasystole was altered to vary the post-extrastolic potentiation of the first test pulse.9. Multiple regression analysis, carried out between dP(lv)/dt(max) of the second test pulse (DP(2), the dependent variable) and the action potential duration (AP(1)) and dP(lv)/dt(max) (DP(1)) of the first test pulse (independent variables) yielded correlation coefficients between 0.88 and 0.99. Each determination of the coefficient included data from beats with and without post-extrasystolic potentiation.10. It is postulated that the coefficient relating DP(2) to DP(1) in the multiple regression analysis (mean value 0.75) is an index of the proportion of calcium stored during relaxation which is released again on the next beat.11. When the decay of post-extrasystolic potentiation was examined in consecutive beats at the optimum interval, the action potential durations of these beats were found to be nearly constant. A plot of dP(lv)/dt(max) of each beat against dP(lv)/dt(max) of the previous beat yielded a curvilinear relationship which was less steep than that relating DP(2) to DP(1) in the two test pulse analysis; this was attributed to inconstancy of calcium ion entry during the action potential.

Action Potentials↗

Cellular calcium as a determinant of action potential duration in rabbit myocardium.

It has been suggested that the amount of calcium in the myocardial cell determines force production as well as the duration of the action potential. We have examined two factors proposed to determine the action potential duration: (1) the inotropic state of the muscle and (2) the preceding stimulation interval. The experiments were performed on isolated papillary muscles from rabbits. The preparations were stimulated to contrast isometrically at a temperature of 37 degrees C and intracellular recordings of action potentials were made. An increased inotropic state produced either by raised external calcium concentration or by increased stimulation frequency was associated with shortened action potentials, confirming factor (1) above. The dependence of the action potential duration on the preceding stimulation interval (factor (2) above) disappeared over a wide range of intervals when the preparation was exposed to 4 microM D600. The action potential duration was, however, still dependent on the preceding stimulation interval when the extracellular calcium concentration had been lowered from 2.0 mM to 1.0 and 0.5 mM respectively. The results are discussed in terms of a model which postulates an inverse relationship between the amount of calcium in a membrane compartment and the action potential duration.

Action Potentials↗

Relationships between peak force, action potential duration and stimulus interval in rabbit myocardium.

Isometric force and membrane action potential were recorded simultaneously in rabbit papillary muscles (36.5 degrees--37.5 degrees C). One to three test stimuli were given at various intervals (0.20--10.0 s) after a series of control contractions at constant stimulation intervals (1.0--1.5 s). Optimum peak force always occurred when the preceding test interval was 0.80 s. When this interval was greater than 0.80 s, time to peak force was a linear function of the action potential duration. Furthermore, under these conditions the action potential duration (AP1) and peak force (F1) of the test contraction could be used to predict peak force (F2) of the subsequent contraction elicited after a fixed interval (0.80--1.50 s) according to the equation (regression plane): F2 = BAPAP1 + BFF1 + A. Constants BAP and BF are interpreted to provide information about calcium influx during the action potential and of the recirculation of calcium between contractions, respectively. F2 deviated towards higher values than predicted from the equation when the preceding test contraction was triggered to occur at an interval less than 0.80 s. This may be due to an intensified calcium transport into the cell during the action potential after these short intervals. The action potential duration was inversely related to both the inotropic state of the muscle (representing a feed-back mechanism) and the preceding stimulation interval.

Action Potentials↗

Relationship between sarcomere length and active force in rabbit papillary muscle.

Isometric peak twitch force (stimulation frequency 0.5/s; 29.5-30.5 degrees C) was correlated with sarcomere length in isolated papillary muscles of the rabbit. Sarcomere length was measured from photographic recordings (1.5 ms exposure time) performed at rest between contractions and at the time of isometric peak twitch force. The sarcomere length at rest was found to be relatively uniform throughout the preparation and to be linearly related to the overall muscle length within the range Lmax-0.85Lmax. The distribution of sarcomere lengths increased considerably as the muscle went from rest to activity. Studies of surface markers showed different degrees of shortening (or elongation) of individual segments along the length of the preparation. The mean resting sarcomere length at Lmax (the optimum muscle length for force production) was 2.44 +/- 0.01 micron (grand mean +/- S.E., 7 muscles). The means active sarcomere length at Lmax was 2.29 +/- 0.04 micron. Active force declined steeply as the muscle length was reduced below Lmax. At a resting sarcomere length of 2.0 micron, active force was approximately 1/3 of the maximum. The observed differences between the length-tension relat-onships in myocardium (twitch responses) and skeletal muscle (tetanic contractions) are discussed on the basis of a length dependency of the activation process in cardiac muscle.

Animals↗