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Functional and physical properties of chick atrial and ventricular GTP-binding proteins: relationship to muscarinic acetylcholine receptor-mediated responses.

Activation of muscarinic acetylcholine receptors in chick atria, but not ventricles, causes an increase in K+ permeability. Because of suggestions that this difference in muscarinic receptor-mediated physiological responses may be due to changes in the guanine nucleotide regulatory proteins (termed Go and Gi) associated with the receptor, we compared the functional and biochemical properties of these proteins in atria and ventricles from 8-day chick embryos. The affinity of agonist for the muscarinic receptor in either the absence or presence of guanine nucleotides was the same in membranes from atria and ventricles; similar concentrations of guanyl-5'-yl imidodiphosphate were required to regulate agonist binding in both tissues (EC50 of 2.7 X 10(-8) and 2.0 X 10(-8) M for atria and ventricles, respectively). Forskolin-stimulated adenylate cyclase activity in atria and ventricles was equally sensitive to inhibition by guanyl-5'-yl imidodiphosphate. In addition, the muscarinic agonist carbachol inhibited adenylate cyclase in ventricles with an IC50 similar to that observed in atria, although the magnitude of inhibition was slightly less in ventricles. The physical properties of the alpha subunits of the guanine nucleotide regulatory proteins were examined after covalent modification by islet activating protein. Two [32P]ADP-ribosylated polypeptides were detected by one dimensional gel electrophoresis, with molecular weights equal to those reported for Go and Gi from other tissues. Similar amounts of both proteins were found in atrial and ventricular membranes. Peptide mapping demonstrated that although the 39 and 42 kD proteins had nonidentical peptide maps, atrial and ventricular peptide maps were identical.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Diphosphate Ribose↗

Assessment of right atrial (RA) and right ventricular (RV) function by gated blood pool scan with krypton-81m: RA and RV pressure-volume loops with simultaneous pressure data.

We developed a new method of analyzing right atrial (RA) and right ventricular (RV) function by Krypton-81m gated blood pool scan (Kr-81m-GBPS). Pressure data were recorded simultaneously with a modified Swan-Ganz catheter. Krypton-81m (Kr-81m) is ideally suited to hemodynamic study of the right heart because of the following characteristics: physical half-life of 13 seconds; high photon yield and gamma ray energy of 190 KeV; low radiation exposure; and deployment during exhalation when the left heart is not active. A computerized method for list mode data acquisition was developed to collect data from the gamma camera, ECG wave, and RA and RV pressure simultaneously. RA and RV volume curves were obtained by calibrating the time-activity curves with end-diastolic volumes and cardiac output. Ejection fraction (EF) was used in the calculation of volume and cardiac output (CO) was measured by the thermodilution method. From RA and RV pressure and volume curves, RA and RV pressure-volume (P-V) loops were created simultaneously and displayed on the same plane. One spanning cardiac cycle of RV beats was separated into four phases: the ventricular emptying phase, the early ventricular filling phase, equilibrium, and the late ventricular filling phase. One spanning cardiac cycle of RA beats also was separated into four phases as follows: the atrial filling phase, the early atrial emptying phase, equilibrium, and the late atrial emptying phase. P-V loops of RA and RV were shifted after sublingual nitroglycerin administration. This new method is potentially useful in the study of right heart hemodynamics.

Atrial Function, Right↗

Cardioversion of atrial fibrillation and its effect on right ventricular function as assessed by tricuspid annular motion.

In patients with atrial fibrillation, the reduced right ventricular function determined by tricuspid annular motion before cardioversion returns to normal 1 month after successful cardioversion to sinus rhythm. The simplicity of recording the tricuspid annular motion provides an easy opportunity to assess right ventricular function following electroconversion of atrial fibrillation to sinus rhythm.

Aged↗

Pulmonary vein encircling ablation alters the atrial electrophysiologic response to autonomic stimulation.

OBJECTIVE: Pulmonary vein encircling ablation is often effective in the treatment of atrial fibrillation (AF). The success of the procedure does not depend upon creation of continuous lines of block. Thus mechanisms by which pulmonary vein encircling can cure AF remain unclear. Stimulation of cardiac autonomic ganglia alters atrial refractoriness and potentiates AF. We hypothesized that pulmonary vein encircling alters atrial autonomic function and that these alterations account in part for prevention of AF recurrences following ablation. METHODS: Atrial effective refractory periods (ERP) and AF inducibility were quantified in ten dogs before and during central autonomic nerve stimulation. Pulmonary vein encircling ablation was then performed and electrophysiologic testing repeated. In two dogs subjected to sham procedures measurements were repeated without performance of ablation. Hearts were examined histologically. RESULTS: Autonomic nerve stimulation led to decreased atrial refractoriness and increased AF inducibility and duration. Each of these effects were attenuated following pulmonary vein encircling (e.g., mean ERP decreased before (-23.7 +/- 1.8, p < 0.001) but not after ablation (-2.3 +/- 1.9, p = 0.25); AF inducibility increased by 26% before vs. 5% after ablation). No attenuation was seen in the sham operated animals. Histologic analysis following pulmonary vein encircling demonstrated destruction of some but not all autonomic ganglia. CONCLUSION: Autonomic stimulation shortens atrial refractory periods and potentiates AF. Pulmonary vein encircling ablation partially destroys atrial autonomic inputs, attenuates the refractory period shortening effect of autonomic stimulation and decreases AF inducibility. Destruction of autonomic ganglia may contribute to the anti-fibrillatory effects of pulmonary vein encircling and warrants further investigation.

Adipose Tissue↗

Clinical utility of tissue Doppler imaging in prediction of atrial fibrillation after coronary artery bypass grafting.

BACKGROUND: Atrial systolic dysfunction in patients with coronary artery disease might influence the development of atrial fibrillation after coronary artery bypass grafting (CABG). Tissue Doppler imaging of the mitral annulus during atrial systole has proved to quantify, accurately, left atrial contractile function. Therefore, the aim of the present study was to investigate the correlation between preoperative left atrial dysfunction assessed by tissue Doppler and postoperative atrial fibrillation after CABG. METHODS: We studied a total of 96 patients (mean age 67 +/- 6 years; range, 55 to 81) undergoing CABG who were preoperatively in sinus rhythm. All patients underwent a preoperative transthoracic echocardiography with tissue Doppler evaluation. Until the day of discharge, all patients were monitored with continuous electrocardiographic telemetry. RESULTS: There were no hospital deaths. Postoperative atrial fibrillation was recorded in 24 of 96 patients (25%). Patients with postoperative atrial fibrillation were significantly older (70 +/- 6 vs 65 +/- 8 years; p = 0.006), had a preoperative larger left atrium diameter (38 +/- 5 vs 36 +/- 4 mm; p = 0.045), a larger left atrium area (13.2 +/- 3.4 vs 11.5 +/- 2.3 cm2; p = 0.007), and a lower peak atrial systolic mitral annular tissue Doppler velocity (10 +/- 3 vs 13 +/- 5 cm/second; p = 0.01). Stepwise logistic regression analysis showed that age 70 years or greater (p = 0.02; odds ratio [OR] 2.0), preoperative medication with beta-blockers (p = 0.04; OR 0.7), left atrium area 13 cm2 or greater (p = 0.02; OR 2.5), and peak atrial systolic mitral annular tissue Doppler velocity 9 cm/second or less (p = 0.03; OR 1.8) were independently related with the incidence of postoperative atrial fibrillation. CONCLUSIONS: Tissue Doppler is useful for assessing preoperative atrial dysfunction and predicting atrial fibrillation after CABG. Further studies are needed to confirm this finding.

Aged↗

Right-to-left interatrial shunt after pneumonectomy.

BACKGROUND: Platypnea and Orthodeoxia have been described with congenital heart and severe lung diseases. METHODS: We report 4 patients in whom platypnea and orthodeoxia developed after pneumonectomy. In these patients the mean oxygen saturation on room air was 65% (range, 45% to 79%) in the supine position. On O2 therapy it improved to 94% (range, 80% to 99%). When the patients assumed the erect position and were receiving O2 therapy the saturation dropped to a mean of 76% (range, 56% to 82%) and the patients complained of shortness of breath. Cardiac catheterization revealed a mean pulmonary capillary wedge pressure of 11.6 mm Hg (range, 7 to 18 mm Hg). All patients had normal right atrial pressure. A right-to-left interatrial shunt through a patent foramen ovale was documented by transesophageal echocardiography and dynamic ultrafast magnetic resonance imaging. The patients underwent surgical closure of the patent foramen ovale. RESULTS: In the erect position, the room air O2 saturation improved to a mean of 95% (range, 92% to 99%), and the shortness of breath disappeared. CONCLUSIONS: Postpneumonectomy patients complaining of shortness of breath should be assessed for platypnea and orthodeoxia. A right-to-left interatrial shunt through a patent foramen ovale can occur even in the absence of elevated right heart pressures, especially after right pneumonectomy, and is accentuated in the upright posture. Surgical correction of the patent foramen ovale can produce dramatic improvement.

Aged↗

Positive inotropy mediated via CGRP receptors in isolated human myocardial trabeculae.

Isometric contractile force were studied on isolated human myocardial trabeculae that were paced at 1.0 Hz in tissue baths. Alpha calcitonin gene-related peptide (alpha-CGRP) had a potent positive inotropic effect in most trabeculae from both the right atrium and left ventricle, and this effect was partially antagonized by the CGRP(1) receptor antagonist alpha-CGRP-(8-37) (10(-6) M). Amylin and the CGRP(2) receptor agonist [Cys(acetylmethoxy)(2, 7)]CGRP had a positive inotropic effect in some trabeculae, whereas adrenomedullin had no inotropic effect. Using reverse transcriptase-polymerase chain reaction (PCR) mRNAs encoding the human calcitonin receptor-like receptor and the receptor associated modifying proteins (RAMPs) RAMP1, RAMP2, and RAMP3 were detected in human myocardial trabeculae from both the right atrium and left ventricle. In conclusion, functional CGRP(1) and CGRP(2) receptors may mediate a positive inotropic effect at both the atrial and ventricular level of the human heart. mRNAs for calcitonin receptor-like receptor and specific RAMPs further support the presence of CGRP receptors.

Adrenomedullin↗

A technique for measurement of the extent of spatial organization of atrial activation during atrial fibrillation in the intact human heart.

Atrial fibrillation (AF) is a common clinical problem, associated with considerable morbidity and mortality, for which effective management strategies have yet to be devised. The absence of objective measures to guide selection of antiarrhythmic drug therapy for maintenance of sinus rhythm leaves only clinical endpoints (either beneficial or detrimental) for assessment of drug action, with occasional catastrophic consequences. As part of an attempt to provide an objective framework for the assessment of antiarrhythmic drug action on the electrophysiologic determinants of atrial fibrillation, we have developed a measure of the spatial organization of atrial activation processes during atrial fibrillation. By recording activation sequences at multiple equally spaced locations on the endocardial surface of the atria during atrial fibrillation in humans and determining the degree of correlation between these activation sequences as a function of distance, we have been able to construct spatial correlation functions for atrial activation. We have found that atrial activation remains well-correlated, independent of distance during normal sinus rhythm and atrial flutter. During atrial fibrillation, correlation decays monotonically with distance and the space-constant for this decay may be used to describe the relative spatial organization of atrial fibrillation. We provide examples of the impact of antiarrhythmic agents on the space-constant and suggest that assessment of the relative spatial organization of atrial activation using this methodology may potentially provide an objective framework to guide therapy in patients with AF.

Adenosine↗

Radiographic assessment of atrial dipole position in single pass lead VDD and DDD pacing. The Multicenter Study Group.

Atrial electrode position was determined by radiographic analysis in 160 patients paced in single-lead VDD for second- or third-degree A-V block, implanted > 1 year with Phymos single pass leads and Phymos 3D pacemakers. The packing lead features an atrial dipole with a 30-mm electrode interspace. In 44% of patients, the upper atrial electrode was positioned within a band of 20 mm centered at the level of the superior vena caval insertion (junctional area) and was in the inferior vena cava or in the atrium in 35% and 21% of cases, respectively. In spite of these different dipole locations, all patients had stable atrium-driven pacing at routine follow-up visits. With the electrode in the junctional area, unipolar stimulation of up to 5 V for 1 ms resulted in stable atrial capture in 63% and 59% of the patients in supine and upright positions, respectively. With the electrode in the atrium, corresponding success rates were 45% and 54%. In the atrium, however, the prevalence of diaphragmatic stimulation was significantly lower than at the junction (10% vs 42% in supine position; 21% vs 47% upright). Though atrial sensing function proved adequate in a wide range of positions, these results suggest that the Phymos lead atrial dipole should be positioned within the atrium, as close as possible to the atrial wall, to maximize the number of VDD patients who might benefit from single-lead DDD pacing.

Cardiac Pacing, Artificial↗

Morphologic-echocardiographic correlates of Ebstein's malformation.

The cross-sectional echocardiographic findings were analysed retrospectively in 26 patients with Ebstein's malformation in the light of studies of autopsied specimens from different patients showing this lesion. The salient anatomical feature in diagnosis is the finding of the hinge point of the septal and mural leaflets of the valve within the inlet component of the right ventricle rather than at the atrioventricular junction. The other important feature is the nature of the distal attachment of the leaflets, particularly the anterosuperior one, which can either be in focal or linear fashion. The hinge point of the septal leaflet was noted echocardiographically to be displaced in 19 patients but, significantly, the leaflet was absent in the other seven. Also significant was that the hinge point of the mural leaflet at the crux had been visualized in only 15 of the patients. The anterosuperior leaflet had a distal linear attachment in 20 of the patients, with the anteroseptal commissure becoming a keyhole in six of these through which blood passed to the functional right ventricle. The valve remained a competent structure, even though closing at the junction of atrialized and functional components of the right ventricle rather than at the atrioventricular junction. Cross-sectional echocardiography is the technique of choice with which to display the salient morphological features of Ebstein's malformation.

Adolescent↗

Atrial natriuretic factor modulates nitric oxide production: an ANF-C receptor-mediated effect.

OBJECTIVES: To investigate the possible immunomodulatory and regulatory functions of atrial natriuretic factor (ANF) and the natriuretic peptide C (NPR-C) receptor in the control of cytokine-stimulated nitric oxide production in primary cultures of human proximal tubular cells. METHODS: Freshly prepared human proximal tubular cells were seeded on plastic plates and allowed to reach confluence. The confluent cells were then incubated with ANF or cyclic(4-23)ANF (c(4-23)ANF) alone, or preincubated with ANF or c(4-23)ANF before incubation with the nitric oxide-stimulating combination of cytokines interleukin-1 beta (10 u/ml), tumour necrosis factor-alpha (10 ng/ml) and interferon-gamma (100 u/ml). RESULTS: In the present series of experiments we have found that incubation of primary cultures of human proximal tubular cells with ANF or c(4-23)ANF stimulates nitric oxide production dose-dependently. Paradoxically, ANF acting via the NPR-C receptor also inhibits cytokine activation of the enzyme-inducible nitric oxide synthase via a cyclic GMP-independent mechanism. Both of these effects were reproduced by the NPR-C receptor-specific ligand c(4-23)ANF. CONCLUSIONS: These findings represent novel actions of ANF mediated via the NPR-C receptor. The results also provide a simple model system in which to study the subcellular mechanisms of NPR-C receptor activation.

Atrial Natriuretic Factor↗

Cardiac electrical stunning is a common feature of cardiac arrhythmias.

There are many published papers focused on the topic of atrial electrical remodeling, which defined as the shortening and dispersion of effective refractory period (ERP) in patients with paroxysmal or persistent tachyarrhythmias or in animals with long-term rapid atrial pacing. Heart failure could produce the electrical remodeling of sinus node, manifesting the prolongation of corrected sinus node recovery time and sinus cycle length. It might be attributed to decreased hyperpolarization-activated cyclic nucleotide expression of sinus node. Rapid atrial pacing for only 10-15 min, simulating transient atrial tachyarrhythmias, alters sinus node function in human. Termination of atrial flutter by ablation induces reversible changes in sinus node function. After atrial fibrillation (AF) ablation, there was a significant improvement of sinus node function, with an increase in the mean heart rate, maximal heart rate and heart rate range significantly. Reverse electrical remodeling of the ERP occurs at different rates in different regions of the atrium. Previous experiments showed that electrical remodeling of atrial myocardium could be induced by autonomic nervous transmitters and suggested that autonomic nerve activity was an important factor to promote AF episodes. We postulated that electrical remodeling and reverse electrical remodeling are common features of the heart, including atrium, ventricle, sinus node, and conductive system. Inappropriate very rapid or slow electrical depolarization may cause electrical remodeling of the heart, but appropriate rates of electrical depolarization and cessation of rapid stimulation may contribute to the reverse electrical remodeling. So, we forward that a concept defined as cardiac electrical stunning, including electrical remodeling and reverse electrical remodeling, should be a common characteristic and mechanism of cardiac arrhythmias.

Animals↗

Measurement of atrial volumes by magnetic resonance imaging in healthy volunteers and in patients with myocardial infarction.

Magnetic resonance imaging was used to measure atrial volumes and emptying fractions in healthy volunteers to establish normal ranges and also in patients with myocardial infarction. Fourteen healthy volunteers (age mean +/- SD, 47 +/- 13 years) and 14 patients (age 56 +/- 9) with previous myocardial infarction were studied. All patients were in sinus rhythm, had competent cardiac valves and no heart failure. Atrial and ventricular volumes were measured from a set of cardiac gated transverse spin echo images (TE 40 ms) covering the heart and acquired at the end of ventricular systole and diastole. Ventricular ejection fractions and atrial emptying fractions were calculated. In patients with myocardial infarction, left atrial end-diastolic and systolic volumes were significantly higher (P < 0.001), and the emptying fraction significantly lower (P < 0.001) than in the control group. The right atrial end-diastolic volume was also significantly higher (P < 0.05) and the emptying fraction significantly lower (P < 0.01) than those in the control group. These findings are likely to be due to abnormal left ventricular long axis dynamics caused by damage to the myocardium, and reflect the abnormal systolic and diastolic functions of the left ventricle which contribute to atrial filling and emptying, respectively. Changes in atrial volumes can be measured non-invasively by magnetic resonance imaging. Using this method we have studied the normal ranges and demonstrated abnormalities in patients with myocardial infarction. Thus this imaging method may prove to be useful for studying atrial function under different physiological and pathological conditions and for evaluating the effect of therapeutic interventions on atrial function.

Adult↗