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Biomedical subjects

M J Lab

Publications and source records attributed to M J Lab.

At least 37 records · Page 2Linked to original sources
PubMed1997

Electrode for recording direction of activation, conduction velocity, and monophasic action potential of myocardium.

Conduction velocity and recovery of excitability are central facets of reentry arrhythmias, and yet there are no satisfactory techniques for the simultaneous measurement of both from the same area of myocardium. We have developed an electrode arrangement that allows the simultaneous recording of conduction velocity, repolarization of the myocardium together with an index of dispersion, and direction of activation of the myocardium. Three silver/silver chloride electrodes were arranged in an equilateral triangle with a reference electrode at the center. From this arrangement three monophasic action potentials were recorded. From the time of arrival of the wavefront of activation at each electrode the direction of activation and conduction velocity were calculated in real time by a computer. There was a good correlation for the in vivo signals from the circular electrode and the new electrode both for conduction velocity (r = 0.99, P < 0.001) and for direction of activation (r = 0.99, P < 0.001). This new mathematical method and electrode design allows the simultaneous measurement of conduction velocity and direction and monophasic action potential, and this can give a beat-by-beat indication of wavelength and dispersion of action potential duration.

Action Potentials↗
PubMed1996

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↗
PubMed1996

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↗
PubMed1996

Mechanoelectric feedback (transduction) in heart: concepts and implications.

It seems that one could regard mechanoelectric feedback in normal heart as an intrinsic regulatory process that modulates normal electromechanical interactions (Fig. 6, left loop). Any physiological mechano-electro-mechano perturbation is self-adjusting and homeostatic. This preserves the status quo, or the heart adapts to form a new electro-mechanoelectric situation. The position in cardiac pathology is different (Fig. 6, right loop), particularly if the disease process produces inhomogeneities. A premature ventricular contraction can be mechanically induced by several of the accepted electrophysiological arrhythmic mechanisms. Thereafter, instantaneous feedback develops within and between regional heterogeneous mechanical conditions. These non-linear recovery processes compound interacting non-linear time courses of recovery of restitution and excitability. Changes in initial loading or mechanical conditions could initiate arrhythmia. Both mechanical and electrical inhomogeneities (also diagrammed in Fig. 5) compound the situation in the intact ventricle. This would enable a milieu of altered excitability, arrhythmogenic current flow and re-entry, to sustain the arrhythmia.

Animals↗
PubMed1996

Calcium and mechanically induced potentials in fibroblasts of rat atrium.

OBJECTIVES: Electrically non-excitable cardiac fibroblasts in the sino-atrial node region are mechano-sensitive. Rhythmic contraction of adjacent myocardium, or artificial stretch of the tissue, produce a reversible change in the membrane potential: mechanically induced potentials (MIP). Stretch of normal cardiomyocytes can be associated with intracellular calcium changes. The purpose of this study is to use pharmacological interventions to investigate the possibility that stretch-induced Ca2+ entry through ion channels in the sarcolemma and Ca2+ release from internal stores play a role in MIP generation. METHODS: Isolated spontaneously contracting or artificially stretched preparations of right atrium of rat heart were superfused with physiological solutions. An intracellular floating microelectrode recorded fibroblast MIPs and was also used for injection of current. A dye, Lucifer yellow, applied through the micropipette, identified recording sites. We assessed the role of extracellular Ca2+ using EGTA in the bathing solution. For the role of intracellular Ca2+ in the generation of MIP, several substances that influence [Ca2+]i handling were applied intracellularly by diffusion from the recording microelectrode. These include: BAPTA (to chelate intracellular Ca2+); BHQ, thapsigargin and CPA (to deplete Ca2+ from intracellular stores by inhibition of the endoplasmic reticulum (ER) ATP Ca2+ pump), and caffeine and ryanodine (to induce ER Ca2+ release). RESULTS: All the pharmacological compounds which were introduced intracellulary, and EGTA applied extracellularly, decreased the amplitude of the MIP to variable degrees. Only thapsigargin induced a bi-phasic response with an initial increase in MIP amplitude, followed by a decrease. MIP duration was reduced by most interventions, exceptions being low extracellular Ca2+, BHQ and ryanodine. Short duration extracellular application of caffeine, which was added to the perfusate as a secondary contractile stimulus, partly restored the MIPs by activation of cardiac contraction. Intracellular current injection, before any intervention, linearly altered both membrane potential (Em) and MIP amplitude (Vm). Application of compounds listed above introduced non-linearity to the Em/Vm relationship. CONCLUSION: We suggest that mechanically induced Ca2+ influx, induced through stretch-activated channels in the plasma membrane, and release of Ca2+ from the endoplasmic reticulum, play key roles in the mechanism of MIP generation. Further, our results demonstrate the existence of functional ryanodine/caffeine-sensitive Ca2+ stores in cardiac fibroblasts.

Action Potentials↗
PubMed1996

Mechanoelectric feedback in the atrium of the isolated guinea-pig heart.

OBJECTIVES: Atrial arrhythmias are prevalent during clinically abnormal myocardial loading, e.g. when the atrium is dilated or stretched. The initiating cause of the first premature beat that leads to this arrhythmia is unclear, as are the reasons for sustaining it. One possibility is that abnormal mechanical factors induce electrophysiological changes conductive to arrhythmia via 'mechanoelectric feedback'. The aim of this study is to investigate the concept that atrial stretch modulates the electrophysiological properties of the atrium via mechanoelectric feedback, and that mechanoelectric feedback can produce atrial arrhythmias. METHODS: Guinea-pigs were humanely killed by cervical dislocation and the hearts removed and perfused with oxygenated Krebs-Henseleit solution by the Langendorff method. The heart was paced at an atrial site near the sinus node. Monophasic action potentials and electrocardiograms were recorded form the left atrium and left ventricle with suction electrodes. Transient stretch was induced by inflating a fluid-filled intra-atrial latex balloon catheter. RESULTS: Increase in atrial volume produced several significant changes in the epicardial monophasic action potentials. It produced (i) decreases in the amplitude; (ii) a decrease in duration from 62.55 to 51.95 ms measured at 50% repolarisation (10.6 +/- 3.6 ms, P < 0.05, n = 6); (iii) an increase in duration from 122.45 to 140 ms measured at 90% repolarisation (17.55 +/- 4.5 ms, P < 0.05, n = 6) --due to the presence of early afterdepolarisations. (iv) These load-induced electrophysiological changes coincided with the occurrence of arrhythmia or premature atrial beats. CONCLUSIONS: Load changes in the atrium can produce electrophysiological changes of a kind that may be relevant to clinical atrial arrhythmia.

Action Potentials↗
PubMed1996

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↗
PubMed1996

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↗
PubMed1995

Integrative models and responses in cardiac ischemia.

This chapter considers the study of electrophysiological changes during ischemia and incorporates mechanoelectric feedback, i.e., mechanical changes affecting electrophysiology. It considers these interactions in the cell, through multicell systems, the intact heart and the intact organism.

Animals↗
PubMed1994

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↗
PubMed1994

Dynamical model of signal propagation in the heart.

We present a simple model, describing the propagation of a travelling signal in a media that is intended to model phenomena in cardiac tissue. The model is a caricature designed to examine some characteristics of a propagating medium that can support spontaneous and non-stimulated fibrillation behaviour. The model consists of a large number of weakly interacting components, each of which operates according to a simplified set of rules. Specifically it is a form of cellular automaton, with the introduction of probabilistic nature in terms of a random refractory period.

Computer Simulation↗
PubMed1994

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↗
PubMed1994

Effects of gadolinium on length-dependent force in guinea-pig papillary muscle.

The degree to which stretch-activated channels operate during physiological length changes in multicellular heart preparations, or how much the channels could contribute to length-dependent activation, is not known. We studied the relationship between muscle length and contractile force in guinea-pig papillary muscles superfused with gadolinium chloride (10 microM), a stretch-activated channel blocker, and compared the effects to those with nifedipine (0.25 microM), a calcium channel blocker. Gadolinium reduced contractile force statistically significantly more at the longer muscle lengths than at the short muscle lengths. This did not apply with nifedipine, although a marginally greater effect at longer lengths was perceptible. The results can only partly be explained by gadolinium having a non-specific action via the calcium channel, or Na(+)-Ca2+ exchange, and are consistent with the possibility that stretch-activated channels contribute to length-dependent activation in cardiac muscle, and thus to 'Starling's Law of the Heart'.

Animals↗
PubMed1994

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↗