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Biomedical subjects

D Lacroix

Publications and source records attributed to D Lacroix.

At least 19 recordsLinked to original sources

Signal-averaged electrocardiography and detection of heart transplant rejection: comparison of time and frequency domain analyses.

To evaluate the role of the signal-averaged electrocardiogram (ECG) in the detection of heart transplant rejection, findings on 277 ECGs were compared with those in 218 endomyocardial biopsy specimens in 25 patients followed up for a median duration of 5.2 months (range 7 days to 17.5 months). Signal-averaged ECGs obtained at intervals of 16.4 +/- 22.3 days were analyzed in the time domain before and after high pass filtering at 25 and 70 Hz. Frequency domain analysis was performed with use of a fast Fourier transform algorithm. Sixteen severe rejection episodes requiring treatment were observed. These episodes induced significant decreases in peak and root-mean-square voltages of both filtered and unfiltered QRS complexes, as well as in the total spectral area. Conversely, QRS duration and 50- to 250-Hz or 70- to 110-Hz spectral areas were not significantly altered. In 14 cases mild rejection episodes were observed that did not significantly alter any of the variables studied. The root-mean-square voltage of the 70-Hz high pass filtered QRS complex was found to be the most accurate variable in detecting rejection. Moreover, this variable was also the most reproducible in 10 healthy control subjects. The optimal rejection criterion was defined as an 11% decrease in voltage between two consecutive recordings. It provided 87.5% sensitivity with 78.4% specificity. In conclusion, the signal-averaged ECG is helpful in the management of heart transplant rejection. Frequency domain analysis of the QRS complex does not increase the accuracy of the technique compared with the time domain approach.

Adult

Effects of consecutive administration of central and peripheral anticholinergic agents on respiratory sinus arrhythmia in normal subjects.

Respiratory sinus arrhythmia is thought to be vagally mediated, since it disappears after atropine, but the site of action of the drug (central vs. peripheral) accounting for this effect has not been elucidated. To investigate the effects of anticholinergic agents on respiratory arrhythmia, ten healthy subjects received an intravenous bolus of tropatepine (a presumed central antagonist) at a dose of 0.08 mg per kg of body weight, then, 7 min later, prifinium (a peripheral antagonist) at a dose of 0.1 mg per kg of body weight. Respiratory sinus arrhythmia during controlled breathing was evaluated as the area under the high-frequency peak of the heart rate variability spectrum coinciding with the respiratory frequency +/- 0.02 Hz. The power of this high-frequency peak decreased by 55% after tropatepine (P less than 0.05) with a concomitant increase of the mean RR interval from 930 to 1072 ms (P less than 0.01). When prifinium was added, a further but non-significant decrease of respiratory arrhythmia was observed, while the mean RR interval decreased from 1072 to 714 ms (P less than 0.01). The low-frequency components (0.05 to 0.15 Hz) of the power spectrum, significantly decreased (P less than 0.05) after infusion of both drugs. In conclusion, tropatepine depresses respiratory sinus arrhythmia with a paradoxical concomitant bradycardia. This suggests that tropatepine acts like a pure central muscarinic antagonist, in support of the hypothesis that a central cholinergic receptor is involved in the respiratory modulation of heart rate.

Adult

Thinking with images or thinking with language: a pilot EEG probability mapping study.

This pilot EEG mapping study was designed to explore thinking processes using complex mental imagery and thought processes. EEG was recorded with 19 electrodes (10/20 system against averaged ear lobe signals) while volunteers (n = 42) performed two separate tasks: visualization of an abstract concept and interpretation of a painting. Average spectral parameters such as amplitude, local and interhemispheric coherences were computed for five frequency bands (theta, alpha, beta 1, 2 and 3). Results indicate that the frontal regions are strongly involved during these tasks as evidenced by coherence changes. Changes are also present in temporal, parietal and occipital regions and are discussed in relation to information processing with the frontal regions considering the different cognitive functions required by the tasks.

Adolescent

Evaluation of arrhythmic causes of syncope: correlation between Holter monitoring, electrophysiologic testing, and body surface potential mapping.

Holter monitoring, electrocardiographic (ECG) signal-averaging, body surface potential mapping (BSPM) for PQRST isoarea maps, and electrophysiologic study (EPS) were performed in 100 patients with syncope. Coronary artery disease (CAD) was found in 46 patients and other heart disease was found in 19. EPS was diagnostic in 44 patients, while Holter monitoring suggested a diagnosis in only 21 patients. Abnormal BSPM was frequently seen (56%), especially in CAD (70%), or with inducible ventricular tachycardia (VT) (87%). Late potentials were recorded in 13 patients with CAD; five had inducible VT. In seven other patients with VT, they were either absent or bundle branch block (BBB) was found. Thirteen deaths (three sudden) occurred in our series. EPS-guided therapy resulted in a low rate of total cardiac death. In conclusion, EPS had a higher diagnostic yield than Holter monitoring regardless of cardiac pathology. ECG signal-averaging was useful in predicting VT only in patients with CAD without BBB. BSPM was abnormal in most patients with cardiac disease, but poorly predicted VT.

Arrhythmias, Cardiac

Bipolar atrial triggered pacing to restore normal chronotropic responsiveness in an orthotopic cardiac transplant patient.

A not uncommon arrhythmia in cardiac orthotopic transplantation patients is sinus node dysfunction with chronotropic incompetence. This is a result of the surgical procedure that denervates the donor heart while the native sinus node may be normal but isolated in the remnant of the recipient atrial wall that serves as the anastomotic site. We were able to restore "normal sinus node function" in a heart transplant patient utilizing a bipolar single chamber pacemaker programmed to the triggered mode. A single unipolar active fixation lead was positioned in each atria. Both leads were connected to a bipolar AAT pulse generator utilizing a Y adaptator. The native atrium with its innervated intact sinus node effectively drove the donor atrium and thus the heart.

Arrhythmia, Sinus

Effects of long-term desipramine administration on noradrenergic neurotransmission: electrophysiological studies in the rat brain.

The present studies were undertaken to assess in vivo the effects of repeated administration of the norepinephrine (NE) reuptake blocker desipramine (DMI) (5 or 10 mg/kg/day x 14 days) on five subsets of adrenoceptors and on the effectiveness of the NE reuptake process in the rat central nervous system. These receptors were: 1) the postsynaptic alpha-2 adrenoceptors which signal the suppressant effect of microiontophoretically applied NE on the firing activity of dorsal hippocampus pyramidal neurons; 2) the postsynaptic alpha-1 adrenoceptors which mediate the short-latency suppressant effect of endogenous NE, released by the electrical stimulation of the locus ceruleus (LC), on the firing activity of these same neurons; 3) the postsynaptic beta adrenoceptors which mediate the long-latency excitatory effect of LC stimulation on hippocampus pyramidal neurons; 4) the alpha-2 autoreceptors located on NE terminals in the hippocampus; and 5) the alpha-2 autoreceptors located on the cell body of LC NE neurons. The suppressant effect of microiontophoretic applications of NE on dorsal hippocampus pyramidal neurons was not changed by the long-term DMI treatments. The recovery time of the firing activity of these neurons after microiontophoretic application of NE, an index of the activity of the NE reuptake process, was the same in control and DMI-treated rats. However, the prolongation of this recovery time by the acute i.v. administration of DMI reached a plateau at a lower cumulative dose in long-term DMI-treated than in control rats. These results thus suggest that long-term administration of DMI did not affect the function of the NE transporter but reduced the number of DMI binding sites. The effectiveness of the 1 Hz stimulation of the LC in suppressing of the firing activity of pyramidal neurons was unchanged by either long-term DMI treatment (5 or 10 mg/kg/day), whereas that of the 5 Hz stimulation was enhanced only in rats on the 10-mg/kg regimen. This suggests that the function of terminal alpha-2 autoreceptors was decreased after this latter DMI regimen, because the reduction of the efficacy of the stimulation obtained by increasing the frequency from 1 to 5 Hz has been shown to be due to the activation of terminal alpha-2 adrenergic autoreceptors. In keeping with this interpretation, the reduction of the effectiveness of the stimulation of the LC by the systemic administration of the alpha-2 adrenoceptor agonist clonidine was attenuated in rats treated with the 10-mg/kg/day regimen of DMI, but not in those with the 5-mg/kg/day regimen.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals

[Prolongation of the CAST study.Is it justified to consider another trial?].

A possible prolongation of the CAST would be another trial of the same type, (CAST II), designed for high risk patients (1 year mortality over 20%). The aim of this study would be to confirm the hypothesis that the ratio efficacy/undesirable side effects of antiarrhythmic drugs is beneficial in this type of patient. The most important selection criteria would be an ejection fraction of less than 40%, the presence of repetitive arrhythmias, especially ventricular tachycardia on Holter monitoring and the recording of late ventricular potentials on surface averaging ECG. The patients would be included at about the 20th day after myocardial infarction in order to exclude as much as possible unstable coronary artery disease and ventricular arrhythmias on successive Holter recordings because this would make interpretation of the efficacy of antiarrhythmic drugs impossible. The ideal number of patients would be about 5,000 but this is unrealistic because the trial would only include high risk cases and there would be difficulties in recruiting this number even in a multicenter trial. During follow-up of 2 to 3 years, the surveillance of the therapeutic efficacy of the antiarrhythmics would have to be better than in the CAST. The most delicate methodological problem would be the randomization of patients as the formation of a placebo group is unethical in high risk coronary patients with severe or malignant ventricular arrhythmias. The use of the only proved cardioprotector drugs, the betablockers, in all these high risk patients would be one solution, even if it might introduce a bias in the results.(ABSTRACT TRUNCATED AT 250 WORDS)

Anti-Arrhythmia Agents

[Prognostic value and development of late potentials after aortocoronary bypass. A prospective study of 100 patients].

Ventricular late potentials are post-infarction markers of the risk of ventricular tachycardia and sudden death. In order to assess their prognostic value and evolution after coronary bypass surgery, 100 patients underwent signal-averaged electrocardiographic recordings 24 hours before and 9 days after surgery, and were then prospectively followed up for 40 +/- 8 months. Patients who displayed late ventricular potentials underwent an additional recording at 5 months with 24 hour Holter monitoring. The average age of the patients was 57.0 +/- 8.4 years; 55 had previous myocardial infarction; 32 had triple vessel disease; the mean left ventricular ejection fraction was 59.7 +/- 12.4%. Ventricular late potentials were recorded in 17 patients before surgery and their left ventricular ejection fraction was significantly lower (51.4 +/- 11.5% vs 61.4 +/- 11.9%: p less than 0.05). There was one operative death in a patient with late ventricular potentials. After surgery, late ventricular potentials were only recorded in 6 patients: at the 9th postoperative day in 3 cases and at the 5th postoperative day in 3 cases. Ventricular late potentials appeared postoperatively in 5 patients, 4 of whom had suffered perioperative myocardial infarction. The recordings became normal at the 5th month in 2 of these 5 patients. Holter monitoring at the 5th month compared with a control group, showed a significant correlation between left ventricular potentials and frequent repetitive or polymorphic ventricular extrasystoles. The 40 month survival rate was excellent: 2 patients were lost to follow-up; there were 3 cardiac deaths, one of which was sudden and 4 non-cardiac deaths. All patients with late ventricular potentials were still alive. These results show that late ventricular potentials persist after coronary bypass surgery in 2/3 of patients; their prognostic significance is not obvious. The low incidence of postoperative sudden death could be attributed to the favourable overall effects of revascularisation rather than on the arrhythmogenic substrate.

Adult

[Unwanted cardiovascular effects of anti-arrhythmia agents].

Antiarrhythmic drugs can cause many undesirable side effects affecting a number of organs and functions. Of those which affect the cardiovascular system, the proarrhythmic and negative inotropic effects are the most serious. Proarrhythmic effects, suggested by an aggravation of an arrhythmia or the induction of a previously undocumented arrhythmia, may be favorised by the presence of an arrhythmogenic substrate (unidirectional lock, delayed conduction, dual conduction pathways, low thresholds of depolarisation or fibrillation, presence of zones of hyperautomaticity...), "triggering" mechanisms (extrasystoles, variations of heart rate, after-depolarisation) and by changes in the cardiac environment (variations of autonomic nervous tone and hormonal changes, electrolytic or metabolic disorders...). An antiarrhythmic may have a beneficial action on one of these factors (for example, suppression of extrasystoles) but an aggravating effect on others (for example, an increase in the heart rate, creation of zones of reentry). This probably explains the fact that, for the moment, only molecules which have multifactorial modes of action have been shown to be beneficial in arrhythmias after myocardial infarction. Negative inotropic effects may be directly responsible for a deterioration in the hemodynamic status of patients on antiarrhythmics and indirectly responsible for aggravating arrhythmia by altering the anatomical substrate, so favorising proarrhythmic effects. The negative inotropic action may be related to ionic mechanisms (lowering intracellular calcium concentration due to blockade of the sodium channel by Class I antiarrhythmics) or to indirect mechanisms (reduced sympathetic tone, non-specific beta inhibition, calcium channel blockade, decreased left ventricular compliance, vasoconstrictor effects...).(ABSTRACT TRUNCATED AT 250 WORDS)

Anti-Arrhythmia Agents

[Circumferential laser thermo-exclusion of post-infarction ventricular tachycardia. Apropos of 11 cases].

Circumferential laser thermoexclusion was assessed in the treatment of postinfarction ventricular tachycardia resistant to drug therapy in 11 patients between December 1986 and April 1989. There were 10 men and 1 woman with an average age of 63.7 +/- 5.6 years whose ventricular tachycardia occurred 10.7 +/- 7.5 years after infarction. All had left ventricular aneurysm or an akinetic plaque. Circumferential thermoexclusion was carried out by Mesnildrey's method, systematically associated with resection of the aneurysm or, when this was not feasible, with coronary revascularisation. Programmed ventricular stimulation was performed before and after surgery in 8 patients. Sustained ventricular tachycardia remained inducible in 4 patients after surgery but the prescription of antiarrhythmic drugs in 2 of these cases resulted in tachycardia becoming non-inducible. The increase in the left ventricular ejection fraction after surgery was not statistically significant (36.9 +/- 9.4% to 44.4 +/- 12.8%). After an average follow-up of 16.7 +/- 10.6 months, there were 2 cardiac deaths not related to arrhythmias (18%), 1 early at the 20th postoperative day and 1 late, 10 months after surgery. There were 2 recurrences of tachycardia (18%) controlled by antiarrhythmic therapy. Late ventricular potentials were recorded in 9 out of the 11 patients before surgery but in only 3 of these cases (33%) after surgery. Circumferential laser thermoexclusion guided visually in the border zone of the infarct scar would seem to be a simple, safe, rapid and therefore attractive, surgical antiarrhythmic technique, the efficacy of which should be evaluated by programmed ventricular stimulation. This should be undertaken on a large scale in order to define the indications and results of this method.

Aged

[Late potentials].

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Arrhythmias, Cardiac

Alternative splicing of mRNA encoding rat liver cytochrome P450e (P450IIB2).

Cytochrome P450e (P450IIB2) is a phenobarbital(PB)-inducible member of the rat liver P450IIB subfamily. Among P450 cDNA clones previously isolated from a cDNA library made from the liver of a single rat were several that contained P450e inserts, including PB13, PB16, and PB22. By nucleotide sequence analysis, the PB16 and PB22 inserts have now been found to contain an additional 24-bp segment not present in the PB13 insert or in previously reported P450e-coding sequences. According to the published P450e genomic sequence, the 24-bp segment is exactly at the junction of the fifth and the sixth exons and its sequence is identical to the first 24 bp of the fifth intron. Translation of this segment would add 8 amino acid residues to the P450e protein. To detect the alternatively spliced P450e mRNA, a synthetic oligodeoxyribonucleotide (oligo) corresponding to 18 of the 24 bp of the intronic sequence found in the PB16 and PB22 inserts was made. This oligo hybridized with a 2.1-kb RNA on Northern blots of liver RNA from PB- or Aroclor 1254-treated rats. Taken together, these results indicate that individual rats can possess both forms of P450e mRNA and that an alternative splicing mechanism is responsible for their formation.

Amino Acid Sequence

Spatial domain analysis of late ventricular potentials. Intraoperative and thoracic correlations.

For investigation of late potentials seen on the signal-averaged electrocardiogram, intracardiac and thoracic distributions of terminal activity were analyzed in 16 patients undergoing cryosurgery for ventricular tachycardia after remote myocardial infarction. The body surface potentials measured with 63 time-averaged unipolar leads were compared with epicardial and endocardial potential maps in six patients without and 10 patients with bundle-branch block. Intracardiac post-QRS activity, defined as extending beyond the thoracic QRS offset, was found in five of six patients without bundle-branch block (83%) and in five of 10 patients with bundle-branch block (50%), corresponding to 4 +/- 5% of the total number of electrograms in each patient. Fragmentation, double deflections, and single deflections were observed in 27%, 34%, and 39%, respectively, of these post-QRS electrograms. Post-QRS activation patterns that were stable from beat to beat showed slow propagation around or within areas of conduction block. Post-QRS activity was most often observed on both epicardial and endocardial surfaces (five of 10 patients). In the six patients without post-QRS activity, an area of late activity displaying low-amplitude deflections that were masked by the terminal activation of the normal myocardium was identified. Isopotential maps of the high-pass-filtered (55-Hz) thoracic and intracardiac signals demonstrated a close spatial correlation between the location, amplitude, and orientation of the potential extrema observed over the thoracic, epicardial, or endocardial surfaces during post-QRS activity. The thoracic patterns were generally dipolar with close extrema for anteroseptal or apical sites of post-QRS activity and more distant extrema for other sites.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

[The origin of late potentials in patients with ventricular tachycardia after myocardial infarction].

In order to study the origin of late potentials, their distribution was analyzed in 16 patients who had undergone surgery for arrhythmia due to ventricular tachycardia following myocardial infarction. The potentials were measured in sinus rhythm using 63 unipolar leads placed on the chest before the operation, then on the epicardium and endocardium during the operation. Epicardial and/or endocardial activity extending beyond the QRS complex measured from unfiltered chest signals and characterized by slowed propagation at the edge or inside of necrotic regions, stable from one beat to the next, and showing simple (39 per cent), double (34 per cent) or fragmented (27 per cent) deflections on the electrocardiograms were observed in 5/6 patients without bundle-branch block and in 5/10 patients with block. Similar activity but which did not extend after the QRS was detected in the 6 other patients. For signals filtered at 55 Hz, a close correlation between the distribution of chest, epicardial and endocardial potentials was observed, thus allowing approximate location of the origin of late potentials from the chest. Anterior or apical sites corresponded to close extrema in the precordial region, whereas the other sites were associated with more distant extrema. An analysis of potential distribution thus gives a better understanding of the electrogenesis of late potentials as well as their detection on the chest.

Aged

Electrophysiological effects of methylphenidate on the coeruleo-cortical noradrenergic system in the rat.

The effect of methylphenidate on noradrenergic neurotransmission was investigated in urethane-anesthetized rats. The spontaneous activity of locus coeruleus noradrenergic neurons was the same in rats treated for 7 days with methylphenidate as in the controls. In control rats, i.v. methylphenidate induced a reduction of locus coeruleus neuronal firing whereas in rats treated for 7 days with methylphenidate, the same dose of methylphenidate failed to induce any change in locus coeruleus activity. At this time, clonidine induced a lesser reduction of locus coeruleus neuronal firing than in the controls, indicating that their autoreceptors had become desensitized. Following electrical stimulation of the locus coeruleus, most of the spontaneously firing cortical neurons were inhibited but the percentage of such neurons was reduced and the neurons showed a decreased responsiveness after methylphenidate treatment. The responsiveness of cortical neurons to microiontophoretic applications of NA as assessed by the I.T50 method was reduced after 7 days of treatment with methylphenidate. These findings suggest that the efficacy of cortical NA neurotransmission is markedly reduced following methylphenidate treatment.

Animals

[New inotropic drugs in chronic cardiac insufficiency: progress or wrong track].

The first results of the long-term treatment of chronic heart failure with inotrope positive medications are disappointing, especially in that survival is not prolonged and even a greater mortality is suggested. Is it because of the regular failure of specific medications, of a class of medications or because the overall concept of inotropism stimulation during chronic heart failure should be condemned? The mechanisms of inotropism of normal muscles or muscles in human chronic heart failure are reviewed as well as the various pharmacological means available to stimulate inotropism.

Cardiotonic Agents