Parkinsonism following electrical injury to the hand.
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Adult↗
Biomedical subjects
D J Dick
Publications and source records attributed to D J Dick.
Mechanical modulation of stretch-induced premature ventricular beats: induction of mechanoelectric adaptation period.
OBJECTIVE: Mechanoelectric Feedback, a mechanical intervention inducing an electrical change, is gaining credence as a cause of cardiac arrhythmia in the clinical situation. However, the precise mechanism is unknown. To elucidate this we investigated mechanical and chemical modulation of stretch-induced premature ventricular beats. METHODS: We positioned a balloon in the left ventricle of an isolated heart (New Zealand White rabbit), perfused by the Langendorff technique. Balloon inflation regularly produces premature ventricular beats. Monophasic action potentials, ECG's and pressure recordings monitored changes, during mechanical intervention. The hearts were subjected to (i) variations in the degree of preload and duration of inflation, and (ii) cytoskeletal disrupters, colchicine and cytochalasin-B. RESULTS: Mechanical dilation of the left ventricle can not only induce premature ventricular beats, but also induce a period during which premature beats cannot be re-induced on a subsequent inflation, i.e. a mechanoelectric adaptation period. The trigger for the mechanoelectric adaptation period seems to occur immediately on balloon inflation and required up to 60 s to recover. This period started with an undershoot in the diastolic component of the monophasic action potential as well as in the peak systolic pressure, with return to control levels within the period. Deflation produced an overshoot (rather than undershoot) in the monophasic action potential duration, but this also returned to control levels within the period. Changes in preload, duration of inflation and disruption of the cytoskeleton failed to modulate the mechanically induced premature beats, or the mechanoelectric adaptation period. CONCLUSIONS: Transient ventricular stretch produces arrhythmia, followed by an antiarrhythmic adaptive period. Possible mechanisms are related to a mechanical influence on stretch-activated channels, changes in ionic concentration or diffusion, or second messenger systems, which influence membrane potential. The arrhythmic adaptation does not appear to be related to the mechanical properties of the cytoskeleton. Final elucidation of the mechanism of the mechanoelectric adaptation period demonstrated, may prove important in determining the mechanism of stretch-induced premature ventricular beats and consequently arrhythmia management.
Action Potentials↗
Multicore myopathy presenting in adulthood with respiratory failure.
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Adult↗
Regional workload induced changes in electrophysiology and immediate early gene expression in intact in situ porcine heart.
Cardiac remodelling and hypertrophy induced by chronic haemodynamic overload (stretch) eventually leads to a decrease in cardiac function, an increased incidence of ventricular arrhythmia and mortality. The mechanisms by which myocytes sense haemodynamic stress and activate growth signals are largely unknown. Nuclear immediate early genes may act as third messengers, converting the stretch stimulus into long-term changes of gene expression via cytoplasmic signal transduction. However, previous studies have used cell cultures and isolated hearts, neither of which are ideal models. We have developed a new in situ porcine heart model where local strain (stretch) can be applied, for several hours if required, thus allowing the comparison of changes in electrophysiology and gene expression with unstrained myocardium in the same preparation. A pneumatically controlled stretch-device was attached to a portion of the right ventricle of an anaesthetized animal using suction. Chronic stretch was applied for 30 min or 1 h. Regional loading produced (i) a transient decrease in monophasic action potential duration (3.5+/-0.8%; P<0.05), followed by (ii) an elongation by 15 min, despite maintained stretch (3.4+/-1.5%; P<0.05 compared to the pre-stretch situation). A control segment of the right ventricle did not show these changes. Northern blot analysis showed that both c-fos and c-myc were induced in the areas sampled, but they were 12-fold and three-fold higher, respectively, in stretched compared with control tissue after 30 min. Thus, prolonged regional stretch can produce complex changes in cardiac electrophysiology and increase expression of some immediate early genes. Our model may be useful for studying the cascade of events that lead to remodelling, hypertrophy, and arrhythmia.
Action Potentials↗
Contribution to heart rate variability by mechanoelectric feedback. Stretch of the sinoatrial node reduces heart rate variability.
BACKGROUND: Heart rate variability is an important prognostic indicator for sudden death. An increased risk of sudden death and arrhythmia is associated with reduced heart rate variability in heart failure. In heart failure, there is also dilatation of the atria, which raises the prospect that there could be some physiological basis to possibly link heart rate variability with atrial dilatation. We therefore investigated whether sustained atrial stretch could modulate heart rate variability directly. METHODS AND RESULTS: Pigs were anesthetized and their hearts exposed. A specially built device stretched the sinoatrial node before and after vagal section and then after administration of propranolol. Stretch of the sinoatrial node decreases heart rate variability in the following ways: The standard deviation of the beat-to-beat interval decreases (4.2 to 2.6 ms; P = .004), and the high-frequency components are reduced (control, 6.5 +/- 2.2 ms2, during stretch, 1.4 +/- 0.3 ms2, P = .003). After section of both vagi, the high-frequency components are reduced by stretch of the sinoatrial node (2.8 +/- 0.9 ms2 for control versus 1.2 +/- 0.3 ms2 during stretch; P = .05). Similarly, after both vagal section and beta-blockade, stretch of the sinoatrial node reduces the high-frequency components (10.6 +/- 3.5 ms2 for control verses 3.0 +/- 1.5 ms2 during stretch; P = .01). CONCLUSIONS: We conclude that stretch of the sinoatrial node reduces high-frequency heart rate variability. This may account in part for the reduced heart rate variability seen in clinical conditions in which the right atrium is dilated, such as congestive cardiac failure.
Adrenergic beta-Antagonists↗
Cycle length dependence of the electrophysiological effects of increased load on the myocardium.
BACKGROUND: Mechanoelectric feedback, the process by which changes in mechanical activity change the electrophysiology of the myocardium, has been linked to the genesis of arrhythmias. We investigated possible arrhythmogenic mechanisms by measuring changes in steady-state action potential duration and, more particularly, electrical restitution on a transiently applied load change, because action potential recovery may provide clues to arrhythmogenesis. METHODS AND RESULTS: Pigs were anesthetized and their hearts exposed. A snare was placed around the aorta, and the right atrium was paced. Ventricular pressure, monophasic action potential, and segment motion were recorded from the left ventricle. The action potential duration was measured before and during transient aortic occlusion. Electrical restitution curves were constructed from the records obtained during normal loading or during transient aortic occlusion. The degree of shortening of action potential duration on aortic occlusion decreased with decreases in the steady-state beat-to-beat interval (P = .0008). Control restitution curves had the typical configuration, with a rapid initial, usually monotonic, rise toward a plateau. Some curves showed a marginal "supernormal" section. Increased load reduced the action potential duration at the plateau of the restitution curve (9.4 ms, P < .0001) but increased the action potential duration at the start of the restitution curve (8.7 ms, P = .03). Increased loading increased the maximum slope of the electrical restitution curve by 32 ms/100 ms (P = .04). Increased load also increased the supernormal period of the electrical restitution curves. CONCLUSIONS: Mechanoelectric feedback produces changes in rate-dependent electrophysiology, which could favor a matrix conducive to arrhythmogenesis.
Action Potentials↗
Trifunctional enzyme deficiency: adult presentation of a usually fatal beta-oxidation defect.
Disorders of mitochondrial fatty acid oxidation are a common cause of exercise-induced rhabdomyolysis and myoglobinuria. We report three adult patients from a family with symptoms of recurrent exercise-induced rhabdomyolysis. This presentation closely resembles adult-type carnitine palmitoyltransferase II deficiency except that these patients had an associated peripheral neuropathy. Investigation of fatty acid oxidation in the patients revealed a deficiency of the mitochondrial trifunctional enzyme of beta-oxidation, a newly described fatty acid oxidation disorder with multiorgan involvement and a usually fatal outcome in early childhood. Our cases therefore represent a new phenotype of the disease, which is characterized by recurrent rhabdomyolysis and peripheral neuropathy, but without involvement of other organs, and which is associated with prolonged survival beyond the fourth decade. A low-fat/high-carbohydrate diet proved beneficial in one of the patients, drastically reducing the frequency of rhabdomyolytic episodes. Our findings suggest that mitochondrial trifunctional enzyme deficiency should be considered in patients with recurrent episodes of myoglobinuria and peripheral neuropathy presenting in later life.
Adult↗
Electrical alternans and the onset of rate-induced pulsus alternans during acute regional ischaemia in the anaesthetised pig heart.
OBJECTIVES: Electrical alternans and mechanical alternans are both associated with cardiac ischaemia and in the case of electrical alternans there is a strong link with serious ventricular arrhythmia. We elected to investigate the relationship between electrical and mechanical alternans in control and acutely ischaemic myocardium in the intact porcine heart to determine the nature of their interaction and in particular to determine if abnormal mechanical events play a role in arhythmogenesis as has been suggested in non-ischaemic preparations. METHODS: We used rapid atrial pacing to induce regional mechanical alternans and pulsus alternans before and then at 5-min intervals after the onset of acute ischaemia induced by a 30-min ligation of a diagonal branch of the left anterior descending artery. Regional mechanical activity is measured with epicardial tripodal strain gauges and regional electrical activity is measured using suction-based monophasic action potential electrodes. To test whether alternate stretching of ischaemic segments during pulsus alternans contributed to electrical alternans we simulated pulsus alternans by clamping the proximal aorta on alternate beats. RESULTS: In control areas there was a constant discordant relationship between peak systolic pressure during alternans and action potential duration. In contrast, the ischaemic areas showed electromechanical alternans that was most frequently concordant. Clamping the proximal aorta on alternate beats produced an electrical alternans in control areas but not in the ischaemic area. CONCLUSIONS: Pulsus alternans during acute ischaemia is associated with electrical alternans that can be out of phase in control and ischaemic areas. This could increase electrical dispersion which may be pro-arrhythmic.
Action Potentials↗
Sympathomimetic modulation of load-dependent changes in the action potential duration in the in situ porcine heart.
AIMS: Increased sympathetic stimulation is known to be arrhythmogenic. Likewise increased loading of the myocardium can directly generate arrhythmias. The interaction between the two on the electrophysiology of the myocardium has not been investigated before. We investigated the effect of dobutamine infusion on the shortening of the monophasic action potential duration secondary to increased loading. This was investigated during steady-state pacing and during an alteration in beat-to-beat interval in the form of a restitution curve. METHODS: Pigs were anaesthetised and their hearts exposed. Monophasic action potentials and segment lengths were recorded from the anterior surface of the left ventricle. The loading of the ventricle was increased by transiently occluding the aorta. Steady-state pacing and a restitution curve were performed. Recordings were taken before and during dobutamine infusion. RESULTS: At steady state, increased loading of the heart shortened the monophasic action potential duration by a mean (+/- s.e.m.) of 4.0 (+/- 0.5) ms (P < 0.001). During dobutamine infusion this shortening of the monophasic action potential increased. Shortening of the action potential duration increased with the dose of dobutamine up to 10 micrograms/kg/min after which a plateau was reached. By comparison to control, dobutamine depressed the electrical restitution curve at short test pulse intervals did not significantly alter the plateau. Increased loading elevated the initial section of the electrical restitution curve at short test pulse intervals and depressed the plateau in both the control recordings and those taken during dobutamine infusion. Increased loading increased the amplitude of the supernormal phase of the electrical restitution curve in control recordings and those taken during dobutamine infusion. Sympathetic stimulation by dobutamine during the steady state potentiates the effect of mechanoelectric feedback on the myocardium. The effect on the restitution curve varies with test pulse interval. At short test pulse intervals the effect of sympathetic stimulation dominates with only minor antagonistic modification by increased loading. However, at longer test pulse intervals the effect of mechanoelectric feedback is equal to that of sympathetic stimulation and is synergistic with it. CONCLUSIONS: The mechanically induced changes we describe in the normal pig heart in situ are relatively small. However, they are in the right direction to possibly contribute to arrhythmia under pathological conditions where mechanical as well as electrophysiological inhomogeneity is prominent.
Action Potentials↗
Cerebellar ataxia in coeliac disease--no evidence of a humoral aetiology.
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Aged↗
Testosterone deficiency myopathy.
Testosterone is recognized to have a positive effect on nitrogen balance and muscle development in hypogonadal men, but significantly myopathy secondary to testosterone deficiency has been reported only rarely. We describe a patient who presented with a myopathy associated with testosterone deficiency, and who demonstrated a significant functional and myometric response to treatment.
Aged↗
Regional alternans in relaxation and the onset of pulsus alternans in the heart of the anaesthetized pig.
1. The factors leading to the alternation in myocardial contractility believed primarily responsible for pulsus alternans are not known. We examine regional and global contraction patterns in the in situ heart at stimulation rates just below the threshold for pulsus alternans to determine if events occurring in the transition to alternans can give clues to cellular mechanisms. 2. Twelve pigs were anaesthetized, the chest wall removed and regional contraction measured in three areas of the left ventricle using tripodal strain gauges. We analysed regional and global dynamics during right atrial pacing at cycle lengths 50-150 ms greater than the threshold for pulsus alternans. 3. At pacing cycle lengths 50 ms greater than that required to produce pulsus alternans seven of twelve pigs showed alternans in the maximum rate of ventricular pressure decay but none showed alternans in the maximum rate of pressure rise. Pigs showing alternans in global relaxation were more likely to show alternans in regional contracility (P < 0.05). 4. Twenty-six of the thirty-six areas sampled showed alternans in end-diastolic length at pacing rates below the threshold for pulsus alternans. In fifteen of these areas alternation in end-diastolic length occurred in the absence of alternans in measures of contractility. 5. Alternans in global measures of relaxation may simply be a manifestation of regional alternans in contractility. It is therefore not appropriate, from global haemodynamic data, to suppose that alternans in relaxation is the primary abnormality in the generation of pulsus alternans.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Mechanically induced changes in action potential duration and left ventricular segment length in acute regional ischaemia in the in situ porcine heart.
OBJECTIVE: The electrophysiological events accompanying early ischaemia are important. The aim of this study was to investigate mechano-electric feedback in acute regional myocardial ischaemia in the intact heart in situ by measuring the change in action potential duration in response to increased ventricular loading imposed by transient aortic occlusion. METHODS: 11 landrace pigs were anaesthetised and their hearts exposed. A pneumatically operated blood pressure clamp was placed around the aorta. Monophasic action potentials and an index of segment motion were recorded from the epicardium in and around the ischaemic area produced by a snare placed around a coronary artery. Ventricular and systemic arterial pressures were measured. An initial aortic clamp was performed during which control recordings were taken. The coronary artery was then tied and the aorta clamped for 5-10 s every 5 min for the duration of the 30 min tie. Recordings were taken from the ischaemic area and non-ischaemic areas. RESULTS: Aortic clamp before ischaemia increased intraventricular diastolic and systolic pressure and reduced action potential duration in all the areas studied (p < 0.001). During acute regional myocardial ischaemia aortic clamping resulted in significantly more shortening of the action potential in the ischaemic area after 10 min of ischaemia than in the control area (5 ms v 10 ms, p = 0.008). Over the following 20 min the degree of shortening decreased. The greater shortening at 10 min could not be attributed to changes in the end diastolic segment length or peak ventricular pressure and could thus represent a change in the expression of mechano-electric feedback by ischaemic myocardium rather than a change in loading conditions. CONCLUSIONS: During the first 30 min following a coronary artery occlusion mechano-electric feedback in the ischaemic myocardium varies with time.
Action Potentials↗
Regional electromechanical alternans in anesthetized pig hearts: modulation by mechanoelectric feedback.
Electrical and mechanical alternans have often been found to coexist. However, the factors controlling their interdependence are not known. In this study we measure regional electrical and mechanical activity during mechanical alternans to investigate this relationship. Mechanical alternans was induced by rapid atrial pacing in 18 anesthetized, open-chest pigs. Regional segmental contraction and monophasic action potential were measured in three areas of left ventricle using epicardial tripodal strain gauges and suction electrodes. Electrical alternans always accompanied pulsus alternans. The phase of electrical alternans was not related to any measure of regional mechanical activity but did show a constant discordant relation to peak ventricular pressure. This suggested that mechanically dependent changes in action potential duration (mechanoelectric feedback) may be important in modulation electrical alternans. In support of this, pulsus alternans simulated by clamping the proximal aorta on alternate beats was associated with electrical alternans comparable to that produced with rapid atrial pacing. Mechanoelectric feedback modulates regional electrophysiology in the intact heart and may be important in the generation of electrical alternans.
Anesthesia, General↗
Characterisation of regional myocardial dynamics during mechanical alternans in heart of anaesthetised pig.
OBJECTIVE: The aim was to investigate the behaviour of regional myocardium during mechanical alternans in a multidirectional manner. METHODS: Mechanical alternans was induced in 12 anaesthetised open chested pigs by rapid atrial pacing. In contrast to previous studies, regional mechanical activity was simultaneously assessed at up to three different sites on the left ventricle using epicardial measuring devices able to provide multidirectional information on segment motion. Pressure-length loops were plotted to assess different patterns of segmental motion. The integral of pressure and length was calculated to obtain a regional work index for each beat. RESULTS: Pressure-length loops revealed profound abnormalities in segment motion and work index during regional mechanical alternans. Myocardial segments either performed alternate amounts of positive work on each beat or alternate amounts of positive and negative work on each beat. Alternating segments contracted out of phase with each other and were occasionally stretched during systole. CONCLUSIONS: The spatio-temporal heterogeneity of regional mechanical behaviour is greatly increased during mechanical alternans.
Anesthesia, General↗
Acute dystonia due to amitriptyline.
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Adult↗
Visuospatial working memory in Parkinson's disease.
Visuospatial impairment is frequently reported in Parkinson's disease but the psychological mechanisms which subserve the impaired abilities and the way in which breakdown of the mechanisms leads to performance deficits have not been precisely delineated. This paper reports experimental investigations designed to test the hypothesis that the locus of the impairment is the visuospatial subsystem of working memory. Subjects were a group of sixteen patients with Parkinson's disease of mild to moderate severity and a matched control group. They performed complex visuospatial and verbal memory tasks. The Parkinsonian group were significantly slower than the control group when performing the visuospatial task. They were not significantly slower and made no more errors than the control group on the verbal task. The findings are compatible with the hypothesis that the visuospatial subsystem of working memory is impaired in Parkinson's disease. It is demonstrated that the impairment is not the result of a reduction in the capacity of this subsystem but is due to difficulty in utilising information stored in the subsystem to perform complex visuospatial tasks.
Aged↗
Neuronal anti-nuclear antibody in paraneoplastic sensory neuronopathy.
Sera from 3 patients with a paraneoplastic sensory neuronopathy and small cell carcinoma of the lung were found to contain an IgG directed against neuronal nuclei and the nuclei of cells in adrenal medulla. Plasma from one of these patients was injected into laboratory mice for 100 days but passive transfer of the syndrome could not be effected. Plasma did not affect the viability of the dorsal root ganglia cells in tissue culture but did appear to bind to their nuclei. The role of this antibody remains uncertain.
Aged↗