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Biomedical subjects

P Taggart

Publications and source records attributed to P Taggart.

At least 55 records · Page 3Linked to original sources
PubMed1988

Simultaneous endocardial and epicardial monophasic action potential recordings during brief periods of coronary artery ligation in the dog: influence of adrenaline, beta blockade and alpha blockade.

Local differences in the time course of recovery of excitability during the early phase of myocardial ischaemia are important in the genesis of arrhythmias. Catecholamines are known to encourage the formation of arrhythmias and adrenergic blockade is a recognised therapeutic regime. The purpose of this study was to compare the effect of short periods of coronary artery ligation on endocardial and epicardial repolarisation time, to assess any disparity between the two surfaces, and investigate the influence of catecholamines and adrenergic blockade. Simultaneous left ventricular endocardial and epicardial monophasic action potentials (MAPs) were recorded during short periods of left anterior descending coronary artery (LAD) ligation in 9 open chested dogs. Recordings were made during two 90 s periods of LAD ligation. Two further ligations were made during infusion of adrenaline (1 microgram.kg-1.min-1). Subsequently ligations were made after beta blockade with propranolol (0.25 mg.kg-1) and then in the presence of a combination of alpha blockade (phentolamine, 0.15 mg.kg-1) and beta blockade. MAP duration was measured at 90% repolarisation. LAD ligation produced a marked shortening of MAP duration epicardially with only minimal shortening endocardially, which resulted in a highly significant difference between the repolarisation times on the two surfaces. The disparity between surfaces tended to be augmented by adrenaline and was significantly minimised by either beta blockade alone or in combination with alpha blockade. Our results show rapid development of substantial regional differences in repolarisation time between endocardium and epicardium in response to "ischaemia".(ABSTRACT TRUNCATED AT 250 WORDS)

Action Potentials↗
PubMed1988

Monophasic action potentials at discontinuation of cardiopulmonary bypass: evidence for contraction-excitation feedback in man.

Mechanical dysfunction is the strongest predictor of sudden cardiac death due to arrhythmia. Contraction-excitation feedback whereby changes in myocardial length/tension influence the time course of repolarization and excitability would provide a possible mechanism. Such a relationship has been shown in animals but has yet to be demonstrated in man. A useful model for studying this relationship is provided by the process of weaning off cardiopulmonary bypass after routine coronary artery surgery. During this weaning period of approximately 1 min, the heart is converted from being partially empty and flaccid (i.e., a "nonworking" state) to being filled and stretched to support the circulation (i.e., a "working" state). Monophasic action potentials (MAPs) were recorded from the left ventricular epicardium as a measure of repolarization time in 16 patients at discontinuation of cardiopulmonary bypass. Systolic pressure was recorded from the radial artery line. Measurements were made at three stages that related to different dynamic states of the heart: (1) starting to come off bypass ("minimally working"), defined as the time of first appearance of an inflection on the arterial pressure trace indicating the start of left ventricular ejection and valve opening, when arterial pressures represent left ventricular pressure, (2) half off bypass ("partially working"), and (3) off bypass ("wholly working"). During the process of discontinuing bypass MAP duration shortened, while systolic pressure increased. MAP duration at 90% and 60% repolarization (MAP D90, MAP D60) decreased from 288.0 +/- 29.5 msec (mean +/- SEM) and 235.0 +/- 27.9 msec in the minimally working heart to 274.5 +/- 30.2 msec and 224.2 +/- 27.3 msec in the partially working heart (p less than .001), with a subsequent decrease to 261.0 +/- 28.8 and 214.0 +/- 28.7 when the heart was wholly working (p less than .001). Systolic pressure increased from 54.1 +/- 9.3 mm Hg in the minimally working heart to 65.9 +/- 13.8 mm Hg in the partially working heart (p less than .001) and subsequently increased to 75.5 +/- 13.3 mm Hg when the heart was wholly working (p less than .001). Mean heart rates did not change significantly. A strong correlation was obtained between absolute MAP duration and systolic pressure. Regression analysis revealed: MAP D90 vs systolic pressure (p less than .001) and MAP D60 vs systolic pressure (p less than .01).(ABSTRACT TRUNCATED AT 400 WORDS)

Action Potentials↗
PubMed1987

Modifications of electrode design for recording monophasic action potentials in animals and humans.

An Ag-AgCl electrode for recording monophasic action potentials by pressure contact is described. The electrode is mounted in a hand-held support designed for epicardial recordings during open-heart surgery from both the anterior and lateral walls of the left ventricle with minimal displacement of the heart. The support allows the electrode to be manipulated without the need for direct vision by the surgeon to any desired position while ensuring perpendicular apposition of the electrode without risk of damage to the myocardium. The permanently mounted electrode is also suitable for animal experiments. The electrode may be used for endocardial recordings in animals by direct puncture. Either a straight or curved electrode may be chosen as dictated by the recording site. The monophasic action potentials recorded by this electrode are of a high quality in terms of configuration, lack of drift, and amplitude.

Action Potentials↗
PubMed1986

Use of monophasic action potential recordings during routine coronary-artery bypass surgery as an index of localised myocardial ischaemia.

In 8 patients undergoing routine coronary-artery bypass surgery, monophasic action potentials (MAPs) were measured by means of a hand-held pressure contact electrode to provide an index of local ischaemic changes. 4 patients received left internal mammary anastomoses (LIMA), and there were a total of 27 saphenous vein grafts (SVG). After completion of all grafts blood-flow to the myocardium was reduced for 90 s by means of different permutations of SVG and LIMA occlusion, either on or off bypass. In all patients MAPs indicated typical ischaemic changes. The high sensitivity of the method enables the study to be completed quickly and without hazard to the patient. The technique provides a new means to assess local ischaemia, the viability of specific areas of myocardium, and the efficiency of individual grafts during surgery.

Action Potentials↗
PubMed1986

Effect of sotalol on human atrial action potential duration and refractoriness: cycle length dependency of class III activity.

Using intracardiac electrophysiological techniques the effects of sotalol hydrochloride were studied in the right atrium in eight patients with paroxysmal supraventricular atrial arrhythmias. Atrial action potential duration was recorded from two well separated standard sites via endocardial contact electrodes before and for 30 minutes after intravenous sotalol (1 mg X kg-1). Atrial effective refractory period and vulnerability to atrial arrhythmia initiation were assessed by premature extrastimulation. All patients developed a prolonged action potential duration (mean +6%, p less than 0.01 in high atrial site; +8%, p less than 0.01 in low atrial site), with similar increases in atrial effective refractory period (mean +9%, p less than 0.01). The small regional difference in action potential duration detected between these well separated recording sites was minimally decreased, indicating no tendency towards increased regional inhomogeneity of repolarisation. The relatively refractory zone as denoted by the gap between atrial effective refractory period and action potential duration was slightly reduced, and transient repetitive atrial depolarisations, initially provoked by extrastimuli in two patients, were abolished. The relation between atrial interval and duration, investigated using two modes of paced cycle length modification, showed that a gradual reduction in pacing cycle length was more potent in shortening action potential duration than was isolated premature extrastimulation. Sotalol was significantly more effective in opposing shortening of the action potential duration caused by progressive cycle length reduction than that caused by isolated extrastimulation. The class III antiarrhythmic activity of sotalol, confirmed in the atrium, is dependent on cycle length and mode of cycle length alteration. Under study conditions, there was no tendency to increase atrial vulnerability or regional non-uniformity of repolarisation.

Action Potentials↗
PubMed1986

Multiple aflatoxin B1 binding proteins exist in rat liver cytosol.

The in vitro binding of aflatoxin B1 to rat liver cytosolic proteins was investigated. Aflatoxin B1 binding activity was assayed with protein purified by gel permeation chromatography, ammonium sulfate fractionation, and DEAE-cellulose chromatography. Twenty-five percent of the total binding activity was associated with proteins eluted by 0 and 0.1 M NaCl. Over 50% of the total binding activity was associated with protein present in the 0.2 M NaCl fraction. Glutathione S-transferase activity was also monitored and found only in the low salt (less than 0.2 M NaCl) fractions. The proteins eluted by 0.2 M NaCl were further purified by hydroxylapatite column chromatography and binding was found predominantly in a single fraction. The protein purification steps resulted in a 20-fold increase in the specific binding activity over that initially observed in the cytosol. These results indicate that multiple proteins are capable of binding aflatoxin B1 in rat liver cytosol.

Aflatoxin B1↗
PubMed1985

d-Sotalol: a new potent class III anti-arrhythmic agent.

We have compared the effect of a new drug d-sotalol which has minimal beta-blocking action with the parent (beta-blocking) compound dl-sotalol on monophasic action potential (MAP) duration in open-chested dogs. In seven experiments d-sotalol was administered in intravenous bolus doses of 1.5, 3 and 6 mg/kg given at 10 min intervals. In a further seven experiments dl-sotalol was administered using the same dosage regimen. The animals were anaesthetized with chloralose and urethane. Atrioventricular block was created by injection of the bundle of His with 0.1 ml of 40% formalin in order to ensure capture by ventricular pacing. After prior beta-blockade with propranolol (0.25 mg/kg), simultaneous epicardial and endocardial MAP were recorded at paced heart rates of 100 and 150 beats/min after each bolus injection. d-Sotalol and dl-sotalol showed similar prolongation of MAP duration (measured at 90% repolarization) in both endocardial and epicardial recording at both paced heart rates. These results show that the dextro-isomer of sotalol possesses similar class III action to the parent compound and that this action is homogeneous with respect to left ventricular endocardium and epicardium at heart rates of 100 beats/min and 150 beats/min over a wide dose range. d-Sotalol may be a useful anti-arrhythmic agent in man.

Action Potentials↗
PubMed1984

Effect of nitroglycerin on the electrical changes of early or subendocardial ischaemia evaluated by monophasic action potential recordings.

Intracavitary recording of monophasic action potentials (MAP) is a sensitive means of detecting the electrophysiological effects of early or subendocardial ischaemia. The effects of nitroglycerin (NTG) on the MAP was evaluated during pacing-induced angina in seven patients with localised, reversible ischaemia. Recordings from the ischaemic zone demonstrated a decrease in MAP amplitude and an abnormal rate-corrected shortening of MAP repolarisation. The "control" right ventricular MAP showed only the expected rate-dependent decrease in duration throughout the pacing stress test. The ischaemic MAP were unchanged following the intracoronary administration of NTG (100 micrograms). In contrast, intravenous NTG (200 to 300 micrograms) produced a normalisation of MAP amplitude and duration in spite of continuous pacing at the angina-provoking rate. These changes were preceded by a fall in aortic pressure (from mean 123/84 to 96/62) and subsequent lowering of the rate-pressure product. The major beneficial effects of NTG on the early electrical changes of pacing-induced ischaemia are thus related to decreased oxygen demand due to reduction in cardiac preload.

Action Potentials↗
PubMed1984

Class III action of beta-blocking agents.

We have studied the effect of the intravenous administration of the following drugs on ventricular refractoriness in 35 experiments in open chested beagle dogs: atenolol 0.2 mg X kg-1; nadolol 0.05 mg X kg-1; oxprenolol 0.2 mg X kg-1; pindolol 0.04 mg X kg-1; propranolol 0.2 mg X kg-1; sotalol 0.6 mg X kg-1 and timolol 0.1 mg X kg-1. The animals were anaesthetised with chloralose and urethane. Measurements were made of left ventricular epicardial monophasic action potentials (MAP) (n = 35) and the left ventricular paced evoked response (PER) (n = 25) at a fixed paced cycle length of between 220 and 310 ms. The animals were initially beta-blocked with iv pindolol or propranolol and the drug under study then administered iv 10 min later. The results were as follows: (control and post drug administration) MAP: nadolol 151 +/- 12 SD to 172 +/- 13 SD (p less than 0.001); oxprenolol 153 +/- 21 to 178 +/- 20 (p less than 0.001); sotalol 153 +/- 19 to 176 +/- 20 (p less than 0.001); atenolol 152 +/- 25 to 153 +/- 23 (NS); pindolol 149 +/- 11 to 152 +/- 10 (NS); propranolol 152 +/- 26 to 155 +/- 26 (NS); timolol 144 +/- 23 to 144 +/- 21 (NS). PER: nadolol 172 +/- 14 to 190 +/- 20 (p less than 0.001); oxprenolol 164 +/- 16 to 188 +/- 15 (p less than 0.001); propranolol 166 +/- 22 to 173 +/- 18 (NS).(ABSTRACT TRUNCATED AT 250 WORDS)

Action Potentials↗
PubMed1984

Differential effects of ischaemia and hyperkalaemia on myocardial repolarization and conduction times in the dog.

The role of increased extracellular K+ concentration ([K+]o) in the production of the early electrophysiological changes induced by myocardial ischaemia, was evaluated by recordings of monophasic action potentials and the paced endocardial evoked response. Changes in the duration of local repolarization and conduction time were evaluated during ischaemia, K+ infusion and hypoxia. Raising [K+]o levels in systemic arterial blood from 3.4 +/- 0.5 mmol l-1 to 5.9 +/- 1.5 mmol l-1 produced a similar shortening of repolarization as was seen during ischaemia. Prolongation of conduction time occurred only when the [K+]o levels rose to 8.8 +/- 1.3 mmol l-1. The conduction time slowing during acute ischaemia was always greater and occurred at lower [K+]o levels than that produced by K+ infusion at rates equivalent to the post-ischaemic myocardial venous effluent. Monophasic action potential amplitude and upstroke velocity were reduced in ischaemia but not markedly affected by the increase in [K+]o. Absolute reduction in repolarization time during K+ infusion was more marked at the apex than at the base in the epicardial recordings. The superimposition of hypoxia on hyperkalaemia resulted in marked slowing of repolarization and conduction time. Many but not all of the early electrophysiological abnormalities of acute ischaemia in the intact heart can be related to raised [K+]o.

Action Potentials↗
PubMed1984

Recordings of the local pacing-induced myocardial activation and repolarization.

We have studied the endocardial ventricular evoked response which follows delivery of a unipolar stimulus down the sensing electrode. The system uses the same lead for both pacing and sensing and permits recordings of the evoked T wave representing a dominantly local repolarization which follows a pacing-induced depolarization at the same site. In 12 animal experiments and in the course of electrophysiological investigations in 19 patients, we evaluated changes in the morphology and duration of the paced evoked response following drug interventions which alter myocardial refractoriness and repolarization time. These changes paralleled results obtained by simultaneous, paced monophasic action potential recordings, and suggest that myocardial repolarization can be accurately assessed by this new technique, which could overcome some of the difficulties in comparing 'in vivo' experiments with the clinical effects of drugs in man.

Action Potentials↗
PubMed1984

Study of electrophysiological ischemic events during coronary angioplasty.

The electrophysiological and mechanical events that follow transient therapeutic coronary artery balloon occlusion were analyzed in five patients. A marked (mean, 60 msec) decrease in the repolarization time of the left ventricular ischemic zone (assessed indirectly from endocardial monophasic action potential [MAP] recordings) ensued within 6 to 10 beats of occlusion. Abnormalities in left ventricular relaxation occurred almost simultaneously and preceded contraction abnormalities. A shift in the ST segment in the electrocardiogram (ECG) usually followed within the next 5 to 10 beats. An increase in heart rate (approximately 10 beats per minute) appeared last in the sequence of events. Angina was a variable parameter, frequently absent. Thus, intracavitary recordings of the electrical and mechanical changes are sensitive indicators of the early ischemic changes that follow coronary occlusion, and may be used to assess the effects of therapeutic interventions on events resulting from a myocardial perfusion deficit.

Journal Article↗
PubMed1983

Some effects of emotion on the normal and abnormal heart.

Increased heart rate and catecholamine secretion are induced by certain emotions. Automobile driving in busy city traffic, racing driving, speaking before an audience, and parachute jumping are associated with sinus tachycardia 120-180 per minute, and increase in the plasma levels of adrenaline and/or noradrenaline. Electrocardiographic changes, chiefly ST depression, may occur in a small proportion of persons without ischemic symptoms and with normal resting tracings. Patients with clinical coronary disease, angina, and ischemic ST changes and arrhythmias may be induced by the emotional stimuli associated with car driving and public speaking; plasma catecholamine levels are increased in proportion to the intensity of the stimulus. beta-blockade reduces the tachycardia, and prevents in whole or in part the ST changes, arrhythmia and symptoms associated with emotional challenge to the heart. We would like to leave the reader with a final morsel of food for thought. Emotion may parallel exercise in its ability to accelerate the heart rate up to 180 per minute in healthy subjects, comparable to the maximum reached during physical exertion. Thus, there are good grounds to advise persons at risk not only against violent exercise but also against exposing themselves to intense emotion. At the same time, we would not advocate emotional overprotection, and we believe our ideas would be misinterpreted if healthy persons were to be deterred on the grounds of apprehension or nervousness from facing up to reasonable everyday professional or social challenges.

Adult↗
PubMed1983

Study of the electrophysiological effects of early or subendocardial ischaemia with intracavitary electrodes in the dog.

The early electrophysiological patterns of regional subendocardial ischaemia were studied by using the paced endocardial evoked response and simultaneous endocardial monophasic action potential recordings in 16 experiments in open chested dogs. Ischaemia was produced by transient (1-3 min) coronary artery occlusion. Regional subendocardial isochaemia caused asynchronous activation due to differential conduction delay and shortened repolarization as evaluated by the duration of the paced evoked response from 175 +/- (SD) 18.7 ms to 167 +/- 16 ms (P less than 0.001). These changes occurred within 60 s of occlusion and reversed rapidly after release of the occlusion. In simultaneous endocardial monophasic action potentials there was a decrease in plateau amplitude and the duration of repolarization shortened from 180 +/- (SD) 21.2 ms to 167 +/- 20.4 ms (P less than 0.001). The delay in endocardial activation after 2 min ischaemia was 5.5 ms, which is considerably shorter than the conduction delay previously reported in the subepicardial layers. The calcium-channel blocking drug verapamil (infused at 0.4 mg/kg) altered the rate at which shortening of repolarization and asynchronous activation occurred during ischaemia in six experiments. These experiments suggest that intracavitary electrodes could provide earlier and more sensitive detection of regional subendocardial ischaemia and may permit the assessment of therapy on the early electrical changes in the intact heart.

Action Potentials↗
PubMed1983

Observations on the biphasic nature of digitalis electrophysiological actions in the human right atrium.

Cardiac electrophysiological effects of a digitalis glycoside have been investigated by right atrial intracardiac stimulation and recording in 12 patients with paroxysmal supraventricular tachyarrhythmias. Measurements were made of atrial effective refractoriness by pacing together with programmed premature extrastimulation. Simultaneous recordings of atrial action potential duration from a site close to the sinoatrial node and from a more distal atrial site were made using an endocardial contact-injury potential technique. All subjects received methyldigoxin 10.0 micrograms X kg-1 intravenously, while half were also pretreated with atropine. A biphasic response to methyldigoxin was observed, with initial action potential prolongation, maximal at 20 min post-infusion, followed by significant action potential shortening which persisted to the end of the study period at 40 min. The initial phase, that of prolongation, was associated with smaller increases in atrial effective refractoriness and increased vulnerability to atrial tachyarrhythmia initiation. During the subsequent phase of action potential shortening, the gap between the termination of effective refractoriness and completion of action potential repolarisation was narrowed, coinciding with diminished vulnerability to tachyarrhythmias. Slight but significant atrioventricular conduction delay was apparent 30 to 40 min after glycoside infusion, indicating enhanced vagal activity during the phase of action potential shortening. Prior atropinisation reduced the magnitude of both early and late components of the biphasic action potential response to digitalis, supporting the proposition that both components are mediated via cardiac muscarinic receptors. Since vagal effects on the atrioventricular junction appeared during the later phase, it is suggested that initial action potential prolongation by digitalis may have been effected via local acetylcholine release, while subsequent action potential shortening may have been caused by a combination of vagally and locally mediated activity.

Action Potentials↗
PubMed1983

Intracardiac electrode detection of early ischaemia in man.

We have evaluated an intracardiac technique for the study of the electrophysiological patterns of early or subendocardial ischaemia in man. Simultaneous recordings of the paced endocardial evoked response and monophasic action potentials were obtained during pacing stress testing in 10 patients with reversible myocardial ischaemia. Early patterns of change occurred in both these recordings in response to regional ischaemia. Abnormal rate corrected shortening of the local repolarisation time in the paced endocardial evoked response from the left ventricular ischaemic zone diverging from control non-ischaemic values by a mean of 10.6% was paralleled by decreases in the simultaneous paced monophasic action potentials duration. A differential delay in the local activation time and conduction was also documented by the paced endocardial evoked response and monophasic action potential electrodes. Non-ischaemic control zones showed no changes in the pattern of activation and repolarisation. Disparate repolarisation times and asynchronous activation within the myocardium were thus consistently demonstrated during regional ischaemia. These changes in the endocardial paced evoked response and monophasic action potentials always preceded the appearance and regression of the clinical ischaemia. Intracavitary recordings may thus provide earlier and more sensitive detection of regional ischaemia during cardiac catheterisation or coronary artery surgery. The study of the patterns of activation and response could permit the assessment of interventions on the early electrical changes of ischaemia, and may bridge the gap between in vitro studies and the electrophysiological studies performed upon the intact heart.

Action Potentials↗