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PubMedDate not supplied

[Atrial fibrillation. New views on an old disease].

Atrial fibrillation (Afib) is clinically the most common arrhythmia. Its main complications are recurrent embolic events and a variable deterioration of functional class. Atrial fibrillation induces changes in cellular ionic channels that self-perpetuate the arrhythmia. The pharmacologic treatment of Afib is directed toward correction of those changes and return to sinus rhythm. It is also intended to maintain adequate heart rates and prevent embolic events through anticoagulation or platelet antiagregation. There are presently several class IC or class III antiarrhythmics available for attempting a return to sinus rhythm. The success rates are irregular, the best achieved with flecainide or propafenone among patients without structural heart disease. Amiodarone is the best choice when there is such a problem. The combination possibilities are huge, so that each case must be individualized. The new class III antiarrhythmics are very effective, but have a relatively high rate of side effects including torsade de pointes. Anticoagulation should be the preferred treatment among the majority of patients, but each case should be individually evaluated. New therapies such as focal or linear catheter ablation techniques, atrial or biatrial programmed stimulation, and atrial cardioverter-defibrillator need longer follow-up and experience to be objectively evaluated, although there are reasons to be optimistic in the future, even if patients need antiarrhythmic support at present. Surgery has high morbi-mortality rates, so it is not the preferred approach.

Algorithms↗
PubMed1991

Characterization of novel mRNAs encoding enzymes involved in peptide alpha-amidation.

The COOH-terminal alpha-amidation of bioactive peptides is a 2-step process catalyzed by two separable enzymatic activities both derived from the peptidylglycine alpha-amidating monooxygenase (PAM) precursor. Two forms of PAM mRNA (rPAM-1 and -2), differing by the presence or absence of optional Exon A, were previously characterized; both encode precursors predicted to have an NH2-terminal signal sequence, an intragranular domain containing both enzymatic activities, and a single transmembrane domain followed by a short, cytoplasmic COOH-terminal domain. In this report, two novel types of PAM mRNA were identified in adult rat atrium. A cDNA of each type was sequenced, and the results indicate that rPAM-3 and -4 could be related to each other and to the previously characterized rat PAM cDNAs by alternative mRNA splicing. Deletion of a 258-nucleotide segment (optional Exon B) encoding the transmembrane domain from rPAM-3 and the presence of a novel 3'-exon in rPAM-4 mean that both rPAM-3 and -4 mRNAs encode precursor proteins that have an NH2-terminal signal peptide but lack a transmembrane domain. The rPAM-4 precursor protein lacks the region of the PAM precursor catalyzing the second step in the alpha-amidation reaction. Low levels of rPAM-3 and -4 type mRNA were detected in atrium. Utilizing the polymerase chain reaction, two major patterns of distribution of forms of PAM mRNA were found. In the heart and central nervous system, PAM mRNAs both containing and lacking optional Exon A were prevalent and almost all of the PAM mRNAs detected contained optional Exon B. In the pituitary and submaxillary glands, PAM mRNAs lacking optimal Exon A were prevalent, as were PAM mRNAs lacking all or part of optional Exon B. Since the distribution of PAM activity between soluble and membrane fractions is tissue-specific and developmentally regulated and since rPAM-4 lacks an enzymatic portion of the PAM precursor, the tissue-specific expression of these forms of rat PAM mRNA is expected to be of functional significance.

Amino Acid Sequence↗
PubMed1994

[Functional anatomy of the junction of the left atrium and the pulmonary veins].

PURPOSE: To study the spatial arrangement of the bundles of myocardial fibers presents in the left atrial-venous junctions and in the wall of the pulmonary veins. METHODS: The study was made on 24 human adult hearts, together with pulmonary vessels, fixed in 10% formaldehyde solution. Each specimen was cleared of remnants of pericardium to expose the myocardial fibers as clearly as possible. Particular attention was paid to the atrial-venous junction and the extension of the myocardial fibers in the pulmonary veins. The specimens were embedded in celloidin and cut serially at a thickness of 70 mu and stained by methods of Azan's trichrome. RESULTS: The myocardial bundles leave the atrial wall around the openings of all pulmonary veins forming a sphincter-like structure. These fibers are continuous in the adventitial coat running in oblique or spiral directions. Some bundles, more external, leaving from the atrial wall, surround the ostium of the veins and return to the atrium, forming true loops. CONCLUSION: The extremities of the pulmonary veins and their junctions with the atrium have a morphological substract which may be of physiological importance in the control of the pulmonary venous pressure and blood flow.

Adult↗
PubMed1990

Atrial natriuretic factor and autonomic nervous system function in man.

To delineate a possible interaction of atrial natriuretic peptide ANF-(99-126) with autonomic nervous system function in humans, a spectrum of indices were assessed in 10 healthy young men during a 90 min iv administration of a) synthetic ANF-(99-126) 50 micrograms bolus followed by 0.025 micrograms.kg-1.min-1, b) the potent vasodilator sodium nitroprusside (SNP) 0.35 micrograms.kg-1. min-1, or c) vehicle 0.9% NaCl40 ml and 20% albumin 5 ml, in random sequence. Plasma immunoreactive ANF (irANF) rose from 32 to 1700 pg.ml-1 during the ANF-(99-126) infusion and was stable during SNP or vehicle. Infusion of ANF-(99-126) and SNP, but not vehicle, decreased diastolic blood pressure (BP) on average by -9 and -7.5%, respectively; systolic BP was largely unchanged. Heart rate (HR, + 15 and 12%) or plasma norepinephrine (NE) rose similarly during ANF-(99-126) and SNP infusions, and the systolic BP response to orthostasis was similar (-18 mmHg). The following autonomic indices did not differ significantly after the 3 infusions: responses of HR and NE to orthrostasis; reflex bradycardic response to phenylephrine (PE)-induced rise in systolic BP (+ 20 mmHg); responses of BP to hyperventilation, PE, or 3 min of sustained handgrip; and beat-to-beat variation (R-R interval) during deep breathing. The immediate orthostatic HR response (30/15 R-R interval ratio) fell similarly during infusion of ANF-(99-126) or nitroprusside. The findings indicate that in healthy men the function of the autonomic nervous system is not notably impaired by high circulating ANF levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMedDate not supplied

Color and pulsed Doppler studies of atrial flow dynamics in normals and adult patients with uncomplicated atrial septal defects.

Left and right atrial flow dynamics were compared by means of color and pulsed Doppler in order to study whether color Doppler could reliably provide differentiation between normals [15] and patients without atrial shunt at catheterization [12], vs patients with confirmed atrial septal defect [12]. The procedure consisted of sequential analysis of colored images throughout the cardiac cycle using an apical approach. In addition pulsed Doppler indices were calculated from both annular traces, relating diastolic early (E) and late (A) filling waves at each annulus (E/A); E and A waves were also summed (E + A), and the sum was related between both annuli (Tricuspid/Mitral ratio). Sequential analysis had a 100% sensitivity and specificity for the diagnosis of atrial septal defect, showing an asymmetrical pattern with predominant images in the right atrium, from the 2nd half of systole till End-diastole, vs the symmetrical 'Horseshoe' pattern found over both atria for control subjects. It avoided diagnostic errors due to overriding septal images in systole in 44% of controls. There also was a significant increase of the Tricuspid/Mitral ratios, (for duration and velocity time integral of waves) in patients with atrial septal defect. The correlation coefficient between ratios and values of the Pulmonary/Systemic flow ratio invasively calculated for 10 patients was respectively 0.6 and 0.7 (p less than 0.01). Sequential analysis of colored images appears highly reliable for the diagnosis of atrial septal defect; anomalies of ratios, although of moderate value for predicting shunt magnitude, substantiate the inequality of atrial fillings.

Adolescent↗
PubMed1997

Prejunctional neuropeptide Y receptors in human kidney and atrium.

The aim of our study was to characterize functionally prejunctional neuropeptide Y (NPY) receptors in human and rabbit renal cortex, as well as in human right atrium. Segments of human atrial appendages and of human and rabbit renal cortex were preincubated with [3H]noradrenaline, superfused with Krebs-Henseleit solution and stimulated electrically in superfusion chambers. The stimulation-induced outflow of radioactivity was taken as an index of endogenous noradrenaline release. The effects of subtype-selective NPY analogs on the stimulation-induced noradrenaline release were studied. NPY, its endogenous analog, peptide YY, and its C-terminal fragment, NPY13-36, but not its analog, [Leu31,Pro34]NPY, concentration dependently (1-100 nM) inhibited [3H]noradrenaline release in all tissues studied. NPY-induced inhibition of [3H]noradrenaline release in human and rabbit kidney was abolished by pretreatment with pertussis toxin. We conclude that prejunctional inhibition of noradrenaline release in human heart and human and rabbit kidney occurs through NPY receptors of the Y2 subtype, which appear to couple to a pertussis toxin-sensitive G protein.

Animals↗
PubMed1991

Incessant ectopic atrial tachycardia and sudden death.

A patient with refractory and incessant ectopic atrial tachycardia (IEAT) is reported in whom it was possible to document, during ECG (Holter) the occurrence of aborted sudden death by spontaneous ventricular fibrillation (VF). Following the second of two attempts at surgical ablation of the origin of the IEAT, the patient has been asymptomatic without antiarrhythmic drugs and in sustained sinus rhythm for 24 months. Although we cannot exclude the residual action of amiodarone and flecainide (proarrhythmia) or the residual peripartum cardiomyopathy it is probable that the observed VF was a true complication of a cardiomyopathy induced by a chronically increased heart rate (HR). Although unclear, this VF might be considered as a form of adrenergic-dependent long QT syndrome due to early afterdepolarization in the presence of predisposing myocardial conditions.

Adult↗
PubMed1990

Raised plasma concentrations of atrial natriuretic peptide are independent of left atrial dimensions in patients with chronic atrial fibrillation.

The aim of the present study was to determine whether left atrial size--a likely indicator of atrial stretching--correlates with the plasma concentration of atrial natriuretic peptide and whether this relation is different in patients in sinus rhythm and in those with atrial fibrillation. Arterial plasma concentrations of immunoreactive atrial natriuretic peptide (ir-ANP), adrenaline, noradrenaline, aldosterone, and vasopressin were measured in 13 patients in sinus rhythm without apparent heart failure and in 13 patients in atrial fibrillation. The two groups were matched for left atrial diameter and the ratio of the left atrial diameter to the diameter of the aortic root (assessed by echocardiography). There were no significant differences in age, heart rate, blood pressure, or left ventricular end diastolic diameter between the two groups. Left atrial diameters varied from 33 to 60 mm. The mean (SD) plasma concentration of ir-ANP was significantly higher (35 (21) pmol/l) in the patients with atrial fibrillation than in those in sinus rhythm (12 (11) pmol/l). The concentration of plasma aldosterone was also higher in patients with atrial fibrillation (831 (366) v 523 (211) pmol/l). Concentrations of adrenaline, noradrenaline, and vasopressin were similar in both groups. None of the hormone concentrations correlated with left atrial dimensions. These results indicate that plasma concentrations of ir-ANP and aldosterone are highly sensitive indicators of changes in haemodynamic function during atrial fibrillation. They also underscore the difficulties of correlating echocardiographic assessment of patients with plasma concentrations of a vasoactive hormone.

Aldosterone↗
PubMed1997

Physical and physiological determinants of pulmonary venous flow: numerical analysis.

To study the physical and physiological determinants of transmitral and pulmonary venous flow, a lumped-parameter model of the cardiovascular system has been created, modeling the instantaneous pressure, volume, and influx/efflux of the pulmonary veins, left atrium and ventricle, systemic arteries and veins. right atrium and ventricle, and pulmonary arteries. Initial validation has been obtained by direct comparison with transesophageal echocardiographic recordings of mitral and pulmonary venous velocity for the following clinical situations: normal diastolic function, delayed ventricular relaxation, restrictive filling due to severe systolic dysfunction, severe mitral regurgitation before and after valve repair surgery, and premature atrial contraction occurring during ventricular systole. Sensitivity analysis has been performed with a Jacobian matrix, representing the proportional change in a group of output indexes (yi) in response to isolated changes in input parameters (xj), [(delta yi/yi)/ ([delta xj/xj)], demonstrating the complementary nature of mitral and pulmonary venous A-wave velocity for predicting ventricular stiffness and atrial systolic function. This unified numerical-experimental programming environment should facilitate model refinement and physiological data exploration, in particular guiding more accurate interpretations of Doppler echocardiographic data.

Animals↗
PubMed1999

Digoxin delays recovery from tachycardia-induced electrical remodeling of the atria.

BACKGROUND: Atrial fibrillation (AF) induces electrical remodeling, which is thought to be responsible for the low success rate of antiarrhythmic treatment in AF of longer duration. Electrical remodeling seems to be related to tachycardia-induced intracellular calcium overload. Due to its vagomimetic action, digoxin is widely used to control the ventricular rate during AF, but it also increases intracellular calcium. On the basis of these characteristics, we hypothesized that digoxin would aggravate tachycardia-induced electrical remodeling. METHODS AND RESULTS: We analyzed the atrial effective refractory period (AERP) at cycle lengths of 430, 300, and 200 ms during 24 hours of rapid atrio/ventricular (300/150 bpm) pacing in 7 chronically instrumented conscious goats treated with digoxin or saline. Digoxin decreased the spontaneous heart rate but had no other effects on baseline electrophysiological characteristics. In addition to a moderate increase in the rate of electrical remodeling during rapid pacing, digoxin significantly delayed the recovery from electrical remodeling after cessation of pacing (at 430, 300, and 200 ms: P=0. 001, P=0.0015, and P=0.007, respectively). This was paralleled by an increased inducibility and duration of AF during digoxin. Multivariate analysis revealed that both a short AERP and treatment with digoxin were independent predictors of inducibility (P=0.001 and P=0.03, respectively) and duration (P=0.001 for both) of AF. CONCLUSIONS: Dioxin aggravates tachycardia-induced atrial electrical remodeling and delays recovery from electrical remodeling in the goat, which increases the inducibility and duration of AF.

Animals↗
PubMedDate not supplied

Quantitative assessment of diastolic filling function: a new Doppler echocardiographic method and in vitro validation.

The effects of changes in preload and chamber compliance on the transmitral flow pattern was investigated with a fluid dynamics model. A decrease in compliance led to a steepening of the deceleration slope and a shortening of the pressure half-time in both restricted and nonrestricted valves. An increase in the preload led to a longer pressure half-time but did not affect the slope in the restricted valve. However, increased preload led to a shorter pressure half-time and a steeper slope in the nonrestricted valve. A mathematically derived method to measure the net atrioventricular compliance (-[annular area] va/[pvt [flow deceleration rate]]), where va and vt are flow velocities at the mitral anulus and the mitral tip levels) was then proposed. The values obtained by this method showed a strong correlation with true values (r2 = 0.89). A possibility of noninvasive quantitative assessment of diastolic filling function was implied.

Atrial Function↗
PubMed2000

Altered transient outward current in human atrial myocytes of patients with reduced left ventricular function.

INTRODUCTION: Electrophysiologic remodeling is involved in the self-perpetuation of atrial fibrillation. To define whether differences in atrial electrophysiology already are present in patients with increased susceptibility for atrial fibrillation, we compared patients in sinus rhythm with and without heart failure. METHODS AND RESULTS: Atrial specimens were obtained from patients with reduced left ventricular ejection fraction (LVEF; n = 10) and normal LVEF (n = 16) who were undergoing aortocoronary bypass surgery and from donor hearts (n = 4). Enzymatically isolated atrial myocytes were investigated by whole cell, patch clamp techniques. Total outward current was significantly larger in myocytes of hearts with low LVEF than normal LVEF (19.4 +/- 1.3 vs 15.1 +/- 1.2 pA/pF at pulses to +60 mV, respectively). Analysis of inactivation time courses of different outward current components revealed that the observed current difference is due to the transient calcium-independent outward current I(to1) which is twice as large in the low LVEF group than in the normal LVEF group (9.4 +/- 0.9 vs 4.7 +/- 0.4 pA/pF at pulses to +60 mV, respectively). I(to1) recovery from inactivation was significantly more rapid in myocytes of hearts with low LVEF, and action potential plateau in these cells was significantly shorter. The results of I(to1) and action potential measurements in atrial myocytes of donor hearts were very similar to the results of patients with preserved heart function. CONCLUSION: I(to1) in human atrial myocytes of patients with reduced LVEF has an increased density and altered kinetics in sinus rhythm. These differences in outward current may explain the reduced plateau phase of action potentials.

4-Aminopyridine↗
PubMed1978

Ultrastructural alterations of atrial myocardium induced by adriamycin in chronically treated animals.

The clinical use of adriamycin (AM) is limited by a possible dose-dependent myocardiopathy. Severe lesions of ventricular myocardium widely described by electron microscopy have been correlated to irreversible congestive heart failure. On the other hand, the atrial contractile elements which differ from the ventricular ones because of the presence of the so-called specific granules have rarely been considered. In the work described in this paper, adriamycin was injected into rabbits and mice according to schedules of chronic toxicity. At the end of the treatment the atrial myocells presented diffuse ultrastructural lesions of mitochondria, sarcoplasmic reticulum and myofibrillar bundles. These alterations might be caused by the ribonucleoprotein synthesis inhibition, by a direct drug toxicity or by an energetic crisis due to early mitochondrial lesions. Besides, adriamycin produces a decrease of the specific atrial granules that play a hypothetic role in the metabolism of myocardial cells. However, lack of information about the contents and the exact function of atrial granules does not allow us to conclude that their decrease in treated animals has a pathogenetic significance in myocardiopathy induced by adriamycin.

Animals↗
PubMed2005

Atrial natriuretic peptide reverses the negative functional effects of stunning in rabbit myocardium.

We tested the hypothesis that atrial natriuretic peptide (ANP) would decrease both the effects of myocardial stunning and oxygen consumption in rabbit hearts. In two groups of anesthetized open-chest rabbits, myocardial stunning was produced by two 15 min occlusions of the left anterior descending (LAD) artery separated by 15 min of reperfusion. Either ANP (0.2 mg) or vehicle (lactated Ringers) was then injected into the affected area of the left ventricle. In a third group, ANP was injected into the LAD region of non-stunned rabbits. Hemodynamic (heart rate, aortic and left ventricular pressures) and functional (wall thickening (WT), delay of onset of WT, and rate of WT) parameters were measured. Coronary blood flow (microspheres) and O2 extraction (microspectrophotometry) were used to determine myocardial O2 consumption. Stunning was demonstrated by an increase in the time delay to contraction and depressed WT. In the control group, baseline delay to contraction was 25+/-7 ms, and this increased to 84+/-16 following stunning and vehicle administration. In the ANP group, baseline delay was 20+/-6 at baseline and after stunning and ANP administration it was 30+/-7. Wall thickening decreased by approximately 30% with stunning and vehicle but only 8% in the ANP treated hearts. Stunning did not affect regional O2 consumption (6.0+/-1.1 stunned vs. 7.4+/-1.2 mlO2/min/100g non-stunned). ANP administration did not affect O2 consumption (7.3+/-1.7 stunned vs. 6.4+/-1.0 non-stunned). We therefore concluded that ANP administration reversed the effects of stunning without alteration in local O2 consumption in stunned myocardium.

Analysis of Variance↗
PubMed1987

Design of a multi-point laser scanned optical monitor of cardiac action potential propagation: application to microreentry in guinea pig atrium.

A system is described that uses a scanned laser beam to excite voltage-dependent fluorescence in cardiac muscle and thereby monitors propagation of the action potential. Details of the optical and electronic design are presented along with descriptions of the system performance. The scanner can monitor membrane voltage activity from 64 points simultaneously at a sample rate of 1000 samples/sec. Results are presented from a laser scan of arrhythmic guinea pig left atrium showing the complete evolution, from initiation to termination, of a functional microreentry induced by a premature stimulus.

Action Potentials↗
PubMed1989

Assessment of right atrial pressure-volume relations in patients with and without an atrial septal defect.

Assessment of the complex relations between pressure and volume in the right atrium has been hampered in the past by difficulties in the measurement of atrial volume. Accordingly, in the present study the dynamics of right atrial pressure-volume relations were examined (with the use of an impedance catheter to measure right atrial volume) in patients with and without an atrial septal defect. Right atrial pressure and impedance volume were measured in 16 patients at the time of cardiac catheterization with the use of a multi-electrode impedance catheter to provide continuous, on-line, pressure-volume data. Eleven patients without evidence of an interatrial shunt were examined during normal respiration and during the Valsalva maneuver and contrasted with five patients with an atrial septal defect documented by oxygen saturation step-up and echocardiographic studies. Right atrial pressure-volume diagrams in patients without an atrial septal defect exhibited the normal figure eight pattern, with an A loop (atrial contraction) and a V loop (passive filling), corresponding to the A wave and V wave of right atrial pressure, respectively. During inspiration, mean right atrial pressure decreased and mean right atrial volume increased, consistent with augmented venous return. With the Valsalva maneuver, right atrial pressure increased and both right atrial stroke volume and mean right atrial volume decreased compared with baseline. Patients with an atrial septal defect demonstrated baseline pressure-volume diagrams similar to those of patients without an interatrial shunt. However, no change in mean right atrial volume occurred with either respiration or the Valsalva maneuver despite changes in right atrial pressure similar to those seen inpatients without an atrial septal defect.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗