Myocardial reperfusion injury: experimental evidence and clinical relevance.
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Humans↗
Biomedical subjects
P Taggart
Publications and source records attributed to P Taggart.
Mechano-electric feedback in the human heart.
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Animals↗
Repolarization gradients derived by subtraction of monophasic action potential recordings in the human heart. Studies incorporating altered mechanical loading and ischemia.
Information derived from the analysis of the electrocardiographic waveform remains one of the most valuable diagnostic aids in modern cardiology. Paradoxically, although changes in the ST-T segment probably have the widest clinical application, it is the analysis of this repolarization phase that has been surrounded by the greatest difficulties in interpretation.
Action Potentials↗
Nuclear translocation of aflatoxin B1 - protein complex.
The in vitro binding of [3H]-AFB1 to various proteins was studied by equilibrium dialysis. At 23 +/- 1 degree C, [3H]-AFB1 binding activity (mmol/mol) decreased as follows: pyruvate kinase > albumin-NLS > albumin > carbonic anhydrase > RNase > histones. The nuclear translocation and activation of AFB1 and AFB-protein complexes was investigated using isolated rat liver nuclei in the presence of ATP and a NADPH regenerating system. Proteins containing NLS such as histones and albumin-NLS facilitated AFB1 translocation into the nucleus where activation and adduct formation took place.
Aflatoxin B1↗
Biotelemetric investigation of morphine's thermic and kinetic effects in rats.
A biotelemetric procedure was used to investigate the thermic and kinetic responses of rats to a range of doses (0.0-30.0 mg/kg) of morphine sulphate. Both responses demonstrated a biphasic dose-response pattern, with depressant effects (hypothermia and hypokinesis) predominant at high doses, and excitatory effects (hyperthermia and hyperkinesis) predominant at low doses. The time-courses of the thermic and kinetic responses were found to be uncorrelated. With repeated doses of morphine, the depressant effects were attenuated (tolerance) while the excitatory effects were augmented (sensitization). These results are interpreted in the light of current views of opiate function. The value of biotelemetry as a means of avoiding the confounding effects of drug-induced thermic responses and thermic responses induced by stressful temperature-assessment procedures is discussed.
Animals↗
Characterization of a G-protein from the mandibular organ of the lobster Homarus americanus (Nephropidae, Decapoda).
1. GTP-binding activity was found in both calf brain and male lobster mandibular organ (MO). There was approximately two to three times as much binding in the calf brain. 2. The GTP-binding activity could be extracted from the calf brain with sodium cholate, but not from the MOs. 3. Using ADP-ribosylation catalyzed by pertussis toxin, GTP-binding was shown to be the result of the presence of G-protein. In the lobster MO the G-protein alpha subunit has a molecular weight of about 42 kDa and may be of the Go or Gi varieties.
Adenosine Diphosphate Ribose↗
Interaction between ventricular loading and repolarisation: relevance to arrhythmogenesis.
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Arrhythmias, Cardiac↗
Monophasic action potential recordings during acute changes in ventricular loading induced by the Valsalva manoeuvre.
OBJECTIVE: The strong association between ventricular arrhythmia and ventricular dysfunction is unexplained. This study was designed to investigate a mechanism by which a change in ventricular loading could alter the time course of repolarisation and hence refractoriness. A possible mechanism may be a direct effect of an altered pattern of contraction on ventricular repolarisation and hence refractoriness. This relation has been termed contraction-excitation feedback or mechano-electric feedback. METHODS: Monophasic action potentials were recorded from the left ventricular endocardium as a measure of the time course of local repolarisation. The Valsalva manoeuvre was used to change ventricular loading by increasing the intrathoracic pressure and impeding venous return, and hence reducing ventricular pressure and volume (ventricular unloading). PATIENTS: 23 patients undergoing routine cardiac catheterisation procedures: seven with no angiographic evidence of abnormal wall motion or history of myocardial infarction (normal), five with a history of myocardial infarction but with normal wall motion, and 10 with angiographic evidence of abnormal wall motion--with or without previous infarction. One patient was a transplant recipient and was analysed separately. SETTING: Tertiary referral centre for cardiology. RESULTS: In patients with normal ventricles during the unloading phase of the Valsalva manoeuvre (mean (SD)) monophasic action potential duration shortened from 311 (47) ms to 295 (47) ms (p less than 0.001). After release of the forced expiration as venous return was restored the monophasic action potential duration lengthened from 285 (44) ms to 304 (44) ms (p less than 0.0001). In the group with evidence of abnormal wall motion the direction of change of action potential duration during the strain phase was normal in 7/21 observations, abnormal in 6/21, and showed no clear change in 8/21. During the release phase 11/20 observations were normal, five abnormal, and four showed no clear change. In those with myocardial infarction four out of five patients had changes that resembled those with normal ventricles but the changes were less pronounced. There were no differences in any of the three groups between the changes in monophasic action potential duration in patients taking beta blockers and those who were not. The changes in monophasic action potential duration in the transplanted heart resembled those in the group with normal ventricles. Inflections on the repolarisation phase of the monophasic action potential consistent with early afterdepolarisations were seen in three of the patients with abnormal wall motion and in none of those with normal wall motion. CONCLUSIONS: These results are further evidence that changes in ventricular loading influence repolarisation. When wall motion was abnormal the effects on regional endocardial repolarisation were often opposite in direction to those when it was normal. Thus regional differences in wall motion could generate local electrophysiological inhomogeneity which may be relevant to the association of arrhythmia with impaired left ventricular function.
Action Potentials↗
Effect of abrupt changes in ventricular loading on repolarization induced by transient aortic occlusion in humans.
We have investigated the influence of ventricular loading on repolarization from beat to beat in the human heart. Sixteen patients undergoing routine coronary artery surgery were studied. Left ventricular epicardial monophasic action potentials and local electrograms were recorded during acute changes in ventricular loading induced by transient aortic occlusion. Monophasic action potential duration shortened (P less than 0.0001) and returned to control values within one or two beats after release (P less than 0.0001). Values at 90% repolarization were 325 +/- 31 ms preocclusion, 311 +/- 29 ms during occlusion, 326 +/- 32 ms postocclusion. The Q-T interval of the local epicardial electrogram shortened during occlusion (P less than 0.001) and returned to control values after release (P greater than 0.0001): 396 +/- 44 ms preocclusion, 379 +/- 41 ms during occlusion, and, 399 +/- 42 ms postocclusion. A significant correlation was obtained between changes in peak systolic pressure and changes in monophasic action potential duration (R = 0.96; P less than 0.0001 at 90% repolarization). A significant correlation was also observed between changes in peak systolic pressure and the Q-T interval of the local electrogram (R = 0.91; P less than 0.0001). This study shows that abrupt changes in ventricular loading from one beat to the next induce significant changes in the timing of ventricular repolarization. These results may well be relevant to the initiation of arrhythmia by a single ventricular ectopic beat, particularly under pathological conditions.
Action Potentials↗
Alternans of epicardial repolarization as a localized phenomenon in man.
Electrophysiological alternans (beat-to-beat alternation of the configuration of the action potential and/or electrocardiogram) may be important in the causation of ventricular arrhythmias. We recorded monophasic action potentials from the left ventricular epicardium in patients undergoing routine cardiac surgery. We set out to determine: (a) whether a small increase in atrial pacing rate could elicit electrophysiological alternans; (b) whether different phases of the operation influence the incidence and; (c) whether electrical alternans was a localized phenomenon. Thirty-six patients were studied, and alternans of action potential duration was observed in 14 (39%). The difference between alternate long and short action potential durations ranged from 4 to 112 ms. The mean differences during each stage of the protocol were: pacing before bypass 33.3 +/- 22.7 ms (three of 17 patients); pacing after bypass 46.7 +/- 37.8 ms (nine of 36 patients); pacing during transient graft occlusion 28.0 +/- 23.1 ms (five of 17 patients); pacing following release of the grafts 29.6 +/- 30.0 ms (five of 17 patients). None of the patients showed any evidence of alternans in the electrocardiogram or mechanical alternans in radial artery pressure. In seven of the 14 patients showing alternans, recordings were made in closely adjacent (approximately 1 cm) areas showing that alternans could be a localized phenomenon. The findings indicate that electrical alternans was a frequent occurrence in this study (39% of patients) and may be a localized phenomenon.
Action Potentials↗
Interaction of circadian rhythm and opiate-induced thermic and kinetic responses: a biotelemetric investigation.
The thermic and kinetic effects of a low dose of morphine sulphate (5mg/kg) were monitored using a remote biotelemetric procedure. Drug and control (saline) injections were administered at two times of day, during the high and low phases of the circadian temperature/activity cycle respectively. Standard measures of the responses revealed that the effect of a dose of morphine differs significantly according to the phase of the circadian rhythm in which it is administered. In contrast to previous studies employing standard stress-inducing rectal probing techniques of temperature measurement, the direction and time-course of thermic and kinetic responses were uncorrelated. The implications for research on physiological and behavioral drug effects and for theories of drug tolerance/dependence are considered.
Analysis of Variance↗
Monophasic action potential recordings in response to rapid transient elevation of extracellular potassium and their modification by beta-adrenoceptor blockade in the anaesthetized dog.
1. Monophasic action potentials (MAPs) were recorded simultaneously from the endocardium and the epicardium in open-chested dogs (n = 16) during bolus intravenous injections of potassium chloride at 0.1 mmol/kg and 0.2 mmol/kg. MAP duration was measured at 90% repolarization. Local conduction was measured as the delay between the pacing artefact and upstroke of the MAP. 2. The animals were anaesthetized with alpha-chloralose and urethane. Heart block was created by atrioventricular nodal ablation with 0.1% (v/v) formalin. Infra-nodal pacing was established. 3. Bolus injections of potassium chloride at 0.1 mmol/kg shortened MAP duration. The effect was maximal at 15 s after the injection [epicardium: 171.5 +/- 3.0 (control) and 148.9 +/- 5.2 ms at 15 s (P less than 0.001); endocardium: 178.7 +/- 4.4 (control) and 165.6 +/- 5.3 ms (P less than 0.001)]. The shortening on the epicardium was significantly greater than on the endocardium (P less than 0.05). 4. Local conduction time showed no significant change [epicardium: 37.8 +/- 1.8 (control) and 41.2 +/- 2.4 at 15 s; endocardium: 41.1 +/- 1.6 (control) and 45.0 +/- 3.4 at 15 s]. 5. After beta-adrenoceptor blockade, MAP duration shortened, exhibiting a maximum effect at 20 s after a bolus injection of potassium chloride at 0.1 mmol/kg [epicardium: 184.7 +/- 7.1 (control) and 130.7 +/- 9.0 ms at 20 s (P less than 0.001); endocardium 192.0 +/- 7.4 (control) and 148.6 +/- 10.8 ms at 20 s (P less than 0.001)]. The greater shortening observed on the epicardial surface did not reach statistical significance.(ABSTRACT TRUNCATED AT 250 WORDS)
Action Potentials↗
Interplay between adrenaline and interbeat interval on ventricular repolarisation in intact heart in vivo.
STUDY OBJECTIVE: The aim was to examine the hypothesis that an interaction between adrenaline and change in heart rate may alter the normal time sequence of ventricular repolarisation (and hence refractoriness) in a manner that (1) may favour arrhythmia formation, (2) may partly explain conflicting reports of the effect of adrenaline, ie, there are two opposing effects on action potential duration, and (3) be relevant to T wave abnormalities that sometimes occur in normal people. DESIGN: As a measure of the time course of repolarisation, monophasic action potentials were recorded simultaneously from three epicardial sites in the porcine heart (left ventricular apex, left ventricular base, and mid right ventricle). During steady state pacing, test pulse intervals were interposed at progressively shorter intervals in order to construct restitution curves. MEASUREMENTS AND MAIN RESULTS: Adrenaline infusion (0.4-1.5 micrograms.kg-1.min-1) resulted in earlier repolarisation in the beats after shorter interbeat intervals, and delayed repolarisation after longer interbeat intervals, tending to turn the restitution curve anticlockwise (ie, there were two opposing effects on action potential duration). The effects were not homogeneous between regions. To show this inhomogeneity, pairs of monophasic action potentials from different regions were subtracted using a differential input amplifier to produce an ECG like waveform at the amplifier output. The resulting T wave was thereby a measure of the time difference in repolarisation between the monophasic action potentials from which it was derived. The inhomogeneity of repolarisation induced by adrenaline and rate change was reflected in the morphology of this derived T wave, particularly at early (premature) beats. These T wave changes correlated closely with the true T wave changes in bipolar electrograms recorded between the same recording sites (R = 0.89; p less than 0.0001). CONCLUSIONS: These results show that adrenaline altered the normal relationship between interbeat interval and the timing of repolarisation. The effect was not homogeneous and when regional differences were observed they were reflected in changes in T wave morphology. These were marked at short intervals. It is possible that in addition to increased excitability observed with adrenaline, a combination of raised sympathetic activity and early beats predisposes to arrhythmias by exaggerating dispersion of repolarisation.
Action Potentials↗
The epicardial electrogram: a quantitative assessment during balloon angioplasty incorporating monophasic action potential recordings.
An electrogram was recorded from the angioplasty catheter guide wire when coronary blood flow was interrupted in 20 patients undergoing percutaneous transluminal coronary angioplasty. Monophasic action potentials were recorded from the right ventricular septum together with the routine electrocardiogram. The patients were studied during angioplasty for lesions in the left anterior descending (12), circumflex (3), and right coronary arteries (6). ST elevation in the electrogram recorded in the left anterior descending and circumflex systems was usually more obvious than that in the electrocardiogram. Signals obtained from the right coronary artery were of very low amplitude and registered only minimal ST changes. The ST elevation developed in the electrogram during insertion of the catheter before inflation of the balloon in 11 of the 15 patients undergoing angioplasty of the left system. In eight of the patients showing pre-inflation ST elevation the ST shift lessened after successive inflations. Monophasic action potential recordings were obtained during 45 balloon inflations in 19 patients. In those patients undergoing angioplasty for lesions of the circumflex coronary artery the monophasic action potential showed no change during balloon inflation. In patients undergoing angioplasty for the right coronary artery the mean normalised duration at 60 seconds' occlusion was 99.6 (1.5)% of control. Of a total of 25 occlusions in the patients undergoing angioplasty for the left anterior descending coronary artery 19 showed shortening of less than 5%, five showed shortening between 5 and 10%, and one showed a shortening of 16.4% in the monophasic action potential. The QT interval was satisfactorily measured in the electrogram during 36 balloon inflations, and in 24 of these it was also measured in the electrocardiogram. QT changes in the electrogram tended to be the opposite of those in the electrocardiogram. When changes in RR interval were minimal (less than 20 ms) during the balloon inflation 14 of 17 electrograms showed QT prolongation but only one of 12 electrocardiograms showed prolongation. Conversely one of 17 electrograms showed shortening compared with eight of 12 electrocardiograms. There was angiographic evidence of the development of collaterals in six of 15 patients undergoing angioplasty of the left system. ST segment elevation in both the electrogram and electrocardiogram was less pronounced in these patients than in those without evidence of the development of collaterals. ST segment changes recorded from the angioplasty guide wire provide a more sensitive index of ischaemia than the surface 12 lead electrocardiogram, and fall in ST segments on balloon deflation is a prognostic index of a good angiographic result in the left anterior descending and circumflex arteries, but not in the right coronary artery.
Action Potentials↗
Monophasic action potential recordings in response to graded hyperkalemia in dogs.
Recent interest in sudden cardiac death during exercise in normal healthy people has highlighted the possible role of swings of extracellular potassium in arrhythmogenesis in conditions other than ischemia. Regional differences in action potential duration and conduction may be important. We have recorded monophasic action potentials (MAPs) from the endocardium and epicardium in nine open-chest dogs during graded intravenous infusion of potassium up to a plasma level of 9 mM. The animals were anesthetized with alpha-chloralose and urethan. Continuous, online arterial potassium monitoring was employed. MAP duration showed a biphasic response with initial shortening up to 7 mM, which tended to be more obvious on the epicardium. Regional activation time was measured as the difference between the onset of depolarization of the endocardial and epicardial MAP. Regional activation time also showed a biphasic response with initial shortening and subsequent delay. The QRS width of the scalar lead II electrocardiogram also showed biphasic changes, and the T wave amplitude progressively decreased. Our results suggest that regional differences in repolarization time may develop in the nonischemic myocardium in response to increased extracellular potassium levels mainly as a result of local changes in regional activation time rather than as a result of a direct effect on action potential duration.
Action Potentials↗
Intraoperative assessment of myocardial revascularisation for the relief of ischaemia using monophasic action potential recordings.
We have been concerned with developing a method of assessing regional myocardial perfusion which is simple, quick and without hazard to the patient. Monophasic action potential (MAP) recordings provide a highly sensitive measure of localised myocardial ischaemia. We have developed a hand-held pressure contact silver/silver chloride electrode for recording MAP signals from the left ventricular epicardium. The design enables it to slide within the pericardium on the left ventricle/epicardium with minimal displacement of the heart. Three protocols were adopted providing different permutations of atrial pacing and graft occlusion. Protocol 1: after discontinuing bypass, atrial pacing was established. After 90 s, all grafts were occluded for a period of 90 s. Protocol 2: after discontinuing bypass, all grafts were occluded for 90 s in the absence of pacing. Protocol 3: atrial pacing was established for 60 s before grafting and bypass and repeated subsequent to grafting and discontinuing bypass. Our results show that the most promising method is protocol 3. The most important results were that when heart rate is taken into account, the ischaemic changes in the MAP were significantly less impressive (P less than 0.05) following grafting. With further refinement, this technique may be applicable to the assessment of individual grafts.
Action Potentials↗