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C Krarup

Publications and source records attributed to C Krarup.

65 records · Page 4Linked to original sources

Enhancement and diminution of mechanical tension evoked by staircase and by tetanus in rat muscle.

1. Potentiation of the isometric twitch tension was compared during and after the staircase and after tetanic stimuli in the fast-twitch extensor digitorum longus muscle of adult Lewis rats at 37-38 degrees C.2. With up to 250 stimuli the potentiation rose with an increase in both the frequency and number of stimuli in the staircase (2-5/sec) and the tetanus (100-167/sec). After a tetanus of 375 stimuli (125/sec) the potentiation was smaller. The potentiation 2 sec after a tetanus of 250 stimuli (167/sec) was + 132 +/- 5% (n = 21, s.e. of mean) which was greater (P < 0.001) than at the 250th stimulus at 5/sec, +92+/-3% (n = 21, s.e. of mean).3. After the staircase the decay of potentiation was initially slow and later more rapid. This was taken to indicate both the recovery of a process that diminished twitch tension and the decay of a process causing potentiation. After 250 stimuli (5/sec) the rate of decay of the processes causing diminution and potentiation had time constants of 34.5 +/- 3.8 sec (n = 18, s.e. of mean) and 102.2 +/- 6.6 sec (n = 20, s.e. of mean) respectively. Compared with the potentiation, the process causing diminution became relatively more pronounced the greater the frequency of stimuli.4. The decay of post-tetanic potentiation showed an initial rapid and a later slower phase of decay. After a tetanus of 250 stimuli (167/sec) the rates of decay had time constants of 5.7 +/- 0.8 sec (n = 16, s.e. of mean) and 113.5 +/- 8.7 sec (n = 19, s.e. of mean) respectively.5. Compared with the unpotentiated response the time course of the twitch was shortened initially in the staircase and when the post-tetanic potentiation was low. The contraction time was then increasingly prolonged the greater the potentiation and the greater the number of stimuli in the staircase and in the tetanus. The half-relaxation time was the more prolonged the greater the number of stimuli.6. Potentiation can be described in terms of a two-compartment model of processes which show saturation. Both compartments were activated in a tetanus whereas only the compartment with a slow rate of decay was activated in the staircase. It is speculated that the two compartments are related to the excitation-contraction coupling. The process that caused diminution of twitch tension during the staircase may be due to fatigue. It is suggested that the energy consumption in 250 twitches is about 10 times greater than in a tetanus of 250 stimuli which may explain the presence of fatigue after the staircase whereas it was absent after the tetanus.

Action Potentials↗

Temperature dependence of enhancement and diminution of tension evoked by staircase and by tetanus in rat muscle.

1. The effect of temperature (20-37.5 degrees C) on the potentiation of twitch tension was examined during and after the staircase (250 stimuli, 5/sec) and after the tetanus (188 stimuli, 125/sec) in the extensor digitorum longus muscle of adult Lewis rats.2. During the staircase at 20 degrees C the twitch tension decreased (negative staircase) by 10-20%. At 25-30 degrees C the staircase was initially negative and later positive. At 37.5 degrees C the staircase was positive throughout the train. Both at the end of the staircase and 2 sec after the tetanus the potentiation increased linearly with increasing temperature.3. After the staircase and the tetanus at 20-30 degrees C the twitch tension increased initially rapidly and later after the staircase at a slower rate. Maximal potentiation at 20 degrees C was attained 3 min after the staircase (+ 30 +/- 3%, n = 10, s.e. of mean) and 1 min after the tetanus (+ 16 +/- 1%, n = 10, s.e. of mean). At 37.5 degrees C the potentiation decayed rapidly after the staircase and the tetanus.4. During the staircase the time course of the twitch was shortened twice as much at 20 as at 37.5 degrees C. At the end of the staircase and 2 sec after the tetanus the contraction time was the more prolonged the greater the potentiation. At maximal potentiation the contraction time was prolonged three times as much at 20 degrees C (+ 19 +/- 3%, n = 10, s.e. of mean) as at 37.5 degrees C (P < 0.005). The half-relaxation time at the end of the staircase was prolonged 10 times more at 20 than at 37.5 degrees C (P < 0.02).5. When extrapolated to time zero after the staircase and the tetanus the potentiation at 20 degrees C was still marked (20-50%). The rate of decay of potentiation (time constant, 20 degrees C, 561.2 +/- 37.4 sec, n = 20, s.e. of mean) increased with increasing temperature (Q(10) = 2.6). The event of potentiation with a fast rate of decay, present after the tetanus but not after the staircase at 37.5 degrees C, was abolished below 30 degrees C.6. The increase in twitch tension after the staircase and the tetanus at 20-30 degrees C was taken to indicate the recovery of events that diminished the twitch, occurring simultaneously with potentiation.7. (i) One process of diminution, present after the staircase but not after the tetanus, increased on cooling and was assumed to be due to fatigue. The rate of recovery of the process (time constant, 20 degrees C, 79.6 +/- 7.4 sec, n = 10, s.e. of mean) increased with increasing temperature (Q(10) = 1.9). The half-relaxation time of the last twitch in the staircase was the more prolonged the greater the process. (ii) Another process causing diminution was present after the staircase and the tetanus at 20-30 degrees C. It recovered at 20 degrees C with a time constant of 14.9 +/- 2.2 sec (n = 10, s.e. of mean). This process, possibly responsible for the initially negative staircase, was not thought to be due to fatigue. It may reflect a diminished depolarization of the transverse tubules by repetitive stimuli.

Action Potentials↗

The effect of dantrolene on the enhancement and diminution of tension evoked by staircase and by tetanus in rat muscle.

1. The effect of Dantrolene on the potentiation of isometric twitch tension was examined during and after the staircase (5/sec, 250 stimuli) and after the tetanus (167/sec, 250 stimuli) in the extensor digitorum longus muscle of adult Lewis rats at 37-38 degrees C.2. The study confirmed that Dantrolene decreased the twitch tension much more than the tetanic tension. The drug shortened the contraction time of the twitch. The rate of force development of the twitch was diminished by only half that of the twitch tension. The findings may suggest that the drug both shortened and diminished the activation of the muscle during the twitch.3. Dantrolene decreased the potentiation produced by a given number of stimuli early in the staircase. At the 250th stimulus the staircase was about 25% larger after than before application of the drug. Dantrolene increased the potentiation 2 sec after the tetanus by about 60%.4. After application of Dantrolene, the decay of potentiation after the staircase indicated that the process that diminished the twitch during the staircase, present before application of the drug, was absent. The size of the process causing potentiation was the same with and without the drug. Both events of potentiation after the tetanus were increased by Dantrolene. Both after the staircase and after the tetanus, Dantrolene increased the slow phase of decay by 60-70%. The fast rate of decay after the tetanus was unchanged by the drug.5. The contraction time was prolonged less in the potentiated twitch after than before application of Dantrolene. This was presumably due to a greater relative increase in activation rather than to a prolongation of the time during which the muscle was activated.6. A model is proposed where the delay in potentiation during the staircase and the increase in potentiation after the tetanus are due to the proportion of sites in the excitation-contraction coupling occupied by Dantrolene being reduced by repetitive depolarizations of the transverse tubules during trains of repetitive stimuli.

Action Potentials↗

Immunological studies in thymectomized and non-thymectomized patients with myasthenia gravis.

Eleven thymectomized and ten non-thymectomized patients with myasthenia gravis, matched with respect to sex, age, duration and severity of the disease were investigated with respect to routine clinical features, electrophysiological examination, HLA-typing, auto-antibodies, lymphocyte subpopulations in peripheral blood, Concanavalin A-induced release of leucocyte migration inhibitory factor (LIF), in vitro lymphocyte activation by mitogens and antigens and response to primary immunization with dinitrochlorobenzene measured in vivo and in vitro. The following conclusions could be drawn. The immune response to external antigens seems to be normal in myasthenia gravis and thymectomy is not followed by general defects in immune competence; at least as investigated by current techniques. The only reduction of responsiveness demonstrable in the thymectomized group was a decreased release of LIF by Concanavalin A-stimulated lymphocytes. Primary immune responses appear to be increased after adult thymectomy, which may be due to a decrease in suppressor T-lymphocyte activity. A hypothesis is formulated that Concanavalin A-induced release of LIF may reflect the competence of suppressor T-lymphocytes in man.

Adolescent↗

Electrical and mechanical responses in the platysma and in the adductor pollicis muscle: in normal subjects.

In the platysma of 34 normal subjects the amplitude of the action potential and twitch tension and tetanic tension were lower, the contraction time of the isometric twitch was 1.4 times shorter, and the potentiation of twitch tension in a staircase and after tetanus was two to four times greater than in m. adductor pollicis. Differences in twitch kinetics and potentiation were related to the four times higher incidence of fast fibres in the platysma than in the adductor pollicis muscle, as determined by histochemistry. Ninety-five per cent confidence limits were established for comparison with patients with myasthenia gravis.

Adult↗

Electrical and mechanical responses in the platysma and in the adductor pollicis muscle: in patients with myasthenia gravis.

Electrical and mechanical muscular responses to single and repetitive stimuli were recorded in 24 patients with myasthenia gravis. Findings in the platysma were compared with those in m. adductor pollicis (ADP). In the platysma, but not in the ADP, electrical and mechanical responses to single stimuli were often lower than normal, and could be normalised after tetanus and by endrophonium. The decrement of electrical and mechanical responses to repetitive stimuli was two to three times greater in the platysma than in the ADP; post-tetanic facilitation of the action potential was four times greater. The staircase phenomenon was abnormal in the platysma in patients with moderate and severe myasthenia, and also in the ADP in some patients without decrement in the action potential. Edrophonium was more effective in alleviating decrement in the platysma than in the ADP. In the platysma, block of neuromuscular transmission could account for most abnormalities. The finding in some patients of an abnormal staircase after correction for block of fibres indicates a lesion in excitation-contraction coupling. In six patients only the platysma showed abnormalities, in 10 patients abnormalities were more pronounced in the platysma than in the ADP, and in three patients more pronounced in the ADP than in the platysma; in five patients the platysma and the ADP were equally affected.

Adult↗

Post-tetanic mechanical tension and evoked action potentials in McArdle's disease.

The tension produced by the cramp evoked in the adductor pollicis muscle by repetitive stimuli to the nerve (20/s for 50 s) and by full voluntary effort in the brachial biceps was measured in a patient with McArdle's disease. The contracture was 17% of the peaktetanic tension, and was not associated with action potentials. Twitches superimposed on the contracture were at most diminished to half, as were their action potentials. Both slow and fast muscle fibres participated in the contracture. The contraction time of the twitches elicited after the tetanus was prolonged more in the patient than in a normal subject of the same age. There was evidence of delayed firing, first observed 90 seconds after the peak of the contracture. The patient had electromyographic and histological signs of myopathy.

Action Potentials↗

Experimental autoimmune myasthenia gravis in the rat: a preliminary report.

In chronic experimental myasthenia gravis (EAMG) in rat, the decrement of electrical and mechanical responses evoked by maximal repetitive (3-167/sec) stimuli to the nerve was greater in the slow-twitch soleus (SOL) than in the fast-twitch extensor digitorum longus (EDL) muscle. Excitation-contraction coupling was impaired in moderate to severe EAMG, as evidenced by a diminished staircase phenomenon and by diminished posttetanic potentiation (PTP) of twitch tension in two EDLs. The only morphologic abnormality observed was an increase in length of the endplates in the EDLs of those animals that had had an acute phase of EAMG. The latter had more than a 90% reduction in the amplitude of the action potential and in the twitch tension of the EDL when stimuli were applied to the nerve. Stimuli applied directly to the muscle evoked a tetanic tension that was one-third of normal. The staircase and PTP were normal. Necrosis occurred in the endplate and in the adjacent segment of muscle fiber; outside the endplate region, the muscle fiber was normal.

Animals↗

Evoked responses of the elbow flexors in control subjects and in myopathy patients.

Electrical and mechanical responses were evoked in the elbow flexors (EFs) of normal subjects and myopathy patients by maximal stimulation of the musculocutaneous nerve by a wire electrode in the axilla. In normals, the decrement in the mechanical responses during short trains of twitches was small (10%). The potentiation during a staircase decreased with increasing frequency of stimuli, but the potentiation 30 sec after the 100-sec staircase was the same at all frequencies. Posttetanic potentiation was twice as large as the maximal potentiation attained during the staircase. The staircase phenomenon probably results from two opposing events, diminution and potentiation. Findings in 11 patients with myopathy varied according to the severity of involvement. Slight weakness of the EFs was associated with an increased twitch:tetanus ratio, decreased tetanic tension, and decrease in the staircase and posttetanic potentiation. Additionally, severe weakness of the EFs was associated with a diminution in twitch tension.

Adolescent↗

A new regional curare test of the elbow flexors in myasthenia gravis.

Electrical and mechanical responses of the elbow flexors (EFs) and the adductor pollicis muscle (ADP) were evoked in 31 patients with myasthenia gravis (MG). Thirteen patients with moderate or severe involvement showed a decrement during trains of repetitive stimuli in both muscle types, greater in the proximal ones than in the distal one. Seven of 18 patients with mild generalized or ocular MG showed abnormalities in the EFs, and 4 patients showed abnormalities in the ADP. A regional curare test was performed in the EFs of 11 patients with borderline or no abnormalities in the EFs and the ADP. All patients were more sensitive to curare than were control subjects; in 2, a decrement outside the range of controls could only be provoked in the partly curarized muscle during posttetanic exhaustion. Excitation-contraction coupling, as evidenced by the staircase phenomenon and after correction for blackade of fibers, was abnormal in 5 of 31 patients in the EFs, and in 11 patients in the ADP. In both muscles, the action potential was a more sensitive criterion of abnormality than the mechanical response. The decrement in the action potentials during 3/sec stimuli gave the largest diagnostic yield.

Action Potentials↗

Conduction studies in peripheral nerve.

Conventional nerve conduction studies assess only a small proportion of the fiber population in peripheral nerve. Nerve conduction velocity is a measure of the very fast conducting fibers and varies with temperature and age. The amplitude of the compound nerve action potential is determined by fibers 9-14 microns in diameter and is dependent on the number of active fibers. The amplitude of the normal sural nerve action potential varies by a factor of 3-4 due to the large variation in the number of large myelinated fibers (1700-3300 per nerve, 7-14 microns). Nerve conduction studies performed under adequate conditions are of value in ascertaining whether there is involvement of peripheral nerve. Due to the large variation in normal nerve these studies are, however, not well suited as screening procedures in individuals exposed to toxic substances.

Adolescent↗