cyclic-gmp and Atrial-Fibrillation

Investigations into the mixed muscle-secretory phenotype of cardiomyocytes from the atrial appendages of the heart led to the discovery that these cells produce, in a regulated manner, two polypeptide hormones - the natriuretic peptides - referred to as atrial natriuretic factor or atrial natriuretic peptide (ANP) and brain or B-type natriuretic peptide (BNP), thereby demonstrating an endocrine function for the heart. Studies on the gene encoding ANP (NPPA) initiated the field of modern research into gene regulation in the cardiovascular system. Additionally, ANP and BNP were found to be the natural ligands for cell membrane-bound guanylyl cyclase receptors that mediate the effects of natriuretic peptides through the generation of intracellular cGMP, which interacts with specific enzymes and ion channels. Natriuretic peptides have many physiological actions and participate in numerous pathophysiological processes. Important clinical entities associated with natriuretic peptide research include heart failure, obesity and systemic hypertension. Plasma levels of natriuretic peptides have proven to be powerful diagnostic and prognostic biomarkers of heart disease. Development of pharmacological agents that are based on natriuretic peptides is an area of active research, with vast potential benefits for the treatment of cardiovascular disease.

Topics: Animals; Atrial Appendage; Atrial Fibrillation; Atrial Natriuretic Factor; Atrial Remodeling; Biomarkers; Cyclic GMP; Diabetes Mellitus; Fibrosis; Gene Expression Regulation, Developmental; Heart Atria; Heart Failure; Humans; Hypertension; Lipid Metabolism; Metabolic Syndrome; Mice; Myocardium; Myocytes, Cardiac; Natriuretic Peptide, Brain; Obesity; Peptide Fragments; Prognosis; Protein Processing, Post-Translational; Pulmonary Arterial Hypertension; Receptors, Guanylate Cyclase-Coupled; Secretory Vesicles; Ventricular Remodeling; Water-Electrolyte Balance

Atrial fibrillation (AF) is the commonest sustained cardiac arrhythmia, which confers a high risk of mortality and morbidity from stroke and thromboembolism. The precise mechanisms by which AF causes thromboembolism and subsequent cerebrovascular events have attracted much research interest, and are yet to be fully elucidated. Nonetheless, it is well recognised that AF fulfils Virchow's triad for thrombogenesis, with abnormal flow conditions with loss of atrial contractility and an irregularly irregular cardiac output, (i. e. flow abnormalities), as well as structural heart disease with endocardial damage (i. e. abnormal vessel wall) and abnormalities in platelet and haemostatic variables (i. e. abnormal blood constituents). This review is to summarise the evidence so far for the role of coagulation and fibrinolytic components, platelets and inflammation (that is blood constituents) in the generation of the prothrombotic state in AF, with particular focus on the endothelium and AF.

Topics: Atrial Fibrillation; Cyclic GMP; Endothelium, Vascular; Fibrinolysis; Hemostasis; Humans; Nitric Oxide; Stroke; Thromboembolism; Thromboplastin; von Willebrand Factor

Both ambulatory atrial fibrillation (AF) and post-operative AF (poAF) are associated with substantial morbidity and mortality. Analyzing the tissue-specific gene expression in the left atrium (LA) can identify novel genes associated with AF and further the understanding of the mechanism by which previously identified genetic variants associated with AF mediate their effects.. LA free wall samples were obtained intraoperatively immediately prior to mitral valve surgery in 62 Caucasian individuals. Gene expression was quantified on mRNA harvested from these samples using RNA sequencing. An expression quantitative trait loci (eQTL) analysis was performed, comparing gene expression between different genotypes of 1.0 million genetic markers, emphasizing genomic regions and genes associated with AF.. Comparison of whole-genome expression between patients who later developed poAF and those who did not identified 23 differentially expressed genes. These included genes associated with the resting membrane potential modified by potassium currents, as well as genes within Wnt signaling and cyclic GMP metabolism. The eQTL analysis identified 16,139 cis eQTL relationships in the LA, including several involving genes and single nucleotide polymorphisms (SNPs) linked to AF. A previous relationship between rs3744029 and MYOZ1 expression was confirmed, and a novel relationship between rs6795970 and the expression of the SCN10A gene was identified.. The current study is the first analysis of the human LA expression landscape using high-throughput RNA sequencing. Several novel genes and variants likely involved in AF pathogenesis were identified, thus furthering the understanding of how variants associated with AF mediate their effects via altered gene expression.. ClinicalTrials.gov ID: NCT00833313 , registered 5. January 2009.

Topics: Aged; Atrial Fibrillation; Carrier Proteins; Cyclic GMP; Female; Gene Expression Regulation; Genetic Association Studies; Genetic Predisposition to Disease; Heart Atria; High-Throughput Nucleotide Sequencing; Humans; Male; Membrane Potentials; Middle Aged; Muscle Proteins; NAV1.8 Voltage-Gated Sodium Channel; Polymorphism, Single Nucleotide; Postoperative Period; Quantitative Trait Loci; Sequence Analysis, RNA; Signal Transduction; White People

Atrial fibrillation (AF) affects >30 million individuals worldwide. However, no genetic mutation from human patients with AF has been linked to inflammation. Here, we show that AF-associated human variant p.Ile138Thr in natriuretic peptide A (

Topics: Animals; Atrial Fibrillation; Atrial Natriuretic Factor; Cells, Cultured; Cyclic GMP; Female; Fibrosis; HEK293 Cells; Humans; Immunity, Innate; Interleukin-1beta; Male; Mutation, Missense; Myofibroblasts; NF-kappa B; Rats; Rats, Sprague-Dawley; Signal Transduction; Tumor Necrosis Factor-alpha

Nitric oxide (NO) synthesized by cardiomyocytes plays an important role in the regulation of cardiac function. Here, we studied the impact of NO signalling on calcium influx in human right atrial myocytes and its relation to atrial fibrillation (AF).. Right atrial appendages (RAAs) were obtained from patients in sinus rhythm (SR) and AF. The biotin-switch technique was used to evaluate endogenous S-nitrosylation of the α1C subunit of L-type calcium channels. Comparing SR to AF, S-nitrosylation of Ca(2+) channels was similar. Direct effects of the NO donor S-nitroso-N-acetyl-penicillamine (SNAP) on L-type calcium current (ICa,L) were studied in cardiomyocytes with standard voltage-clamp techniques. In SR, ICa,L increased with SNAP (100 µM) by 48%, n/N = 117/56, P < 0.001. The SNAP effect on ICa,L involved activation of soluble guanylate cyclase and protein kinase A. Specific inhibition of phosphodiesterase (PDE)3 with cilostamide (1 µM) enhanced ICa,L to a similar extent as SNAP. However, when cAMP was elevated by PDE3 inhibition or β-adrenoceptor stimulation, SNAP reduced ICa,L, pointing to cGMP-cAMP cross-regulation. In AF, the stimulatory effect of SNAP on ICa,L was attenuated, while its inhibitory effect on isoprenaline- or cilostamide-stimulated current was preserved. cGMP elevation with SNAP was comparable between the SR and AF group. Moreover, the expression of PDE3 and soluble guanylate cyclase was not reduced in AF.. NO exerts dual effects on ICa,L in SR with an increase of basal and inhibition of cAMP-stimulated current, and in AF NO inhibits only stimulated ICa,L. We conclude that in AF, cGMP regulation of PDE2 is preserved, but regulation of PDE3 is lost.

Topics: Atrial Fibrillation; Calcium; Calcium Channels, L-Type; Cyclic AMP; Cyclic GMP; Humans; Myocardium; Nitric Oxide; Patch-Clamp Techniques; Phosphodiesterase 3 Inhibitors; Quinolones

To determine changes in plasma brain natriuretic peptide (BNP) after direct current cardioversion (DC) and to evaluate the relationship between plasma atrial natriuretic peptide (ANP) and BNP and the recurrence of atrial fibrillation (AF) after DC in patients with mild congestive heart failure (CHF), plasma ANP and BNP were measured before and after DC in 71 patients with mild CHF and then followed. In 65 patients with successful DC, both ANP and BNP decreased 15 min after DC. Cox stepwise multivariate analysis among 14 variables such as age, history of AF, echocardiographic parameters, medication and ANP and BNP revealed that only low ANP (p=0.005) and high BNP before DC (p=0.0002) were independent predictors of recurrent AF. A ratio of ANP to BNP less than 0.44 was a significant risk factor for AF recurrence by Kaplan-Meier analysis (p=0.02). BNP began to decrease immediately after successful DC. High BNP and relatively low ANP compared with BNP were independent risk factors of AF recurrence in patients with mild CHF.

Topics: Adult; Aged; Aged, 80 and over; Atrial Fibrillation; Atrial Natriuretic Factor; Biomarkers; Cyclic GMP; Electric Countershock; Female; Heart Failure; Humans; Male; Middle Aged; Multivariate Analysis; Natriuretic Peptide, Brain; Recurrence

The aim of the present study was to assess whether cGMP release to ANP stimulation can be a biochemical marker of subsequent successful electrical cardioversion of lone atrial fibrillation to sinus rhythm. For this purpose, we studied 13 patients with chronic, lone atrial fibrillation of less than one year's duration who presented to our laboratory for electrical therapy of their arrhythmia. Prior to electrical cardioversion, peripheral venous cGMP levels were assessed at baseline and following an intravenous challenge of 50 Ug human ANP. Venous blood samples for cGMP assessment were taken a) at baseline, b) 5 and 10 mins after the end of ANP infusion. ANOVA of repeated measures was used for statistical analysis. Eight of the study patients were successfully cardioverted to sinus rhythm, while the remaining 5 were not. Although no difference was noted between the two groups regarding the mean time of arrhythmia duration as well as left atrial and ventricular dimensions, ANP stimulation provoked significantly greater cGMP release in patients whose arrhythmia reverted to sinus rhythm, when compared with that of patients whose arrhythmia persisted (p < 0.001). Therefore, cGMP levels following ANP challenge might discriminate between patients with chronic AF who are going to be successfully cardioverted and those who are not. These findings imply that the underlying atrial disease might be different in extent/nature between patients with lone AF responsive to cardioversion and those with resistant arrhythmia.

Topics: Atrial Fibrillation; Atrial Natriuretic Factor; Biomarkers; Case-Control Studies; Cyclic GMP; Electric Countershock; Female; Humans; Male; Middle Aged; Stimulation, Chemical; Time Factors

Patients with atrial fibrillation have been reported to exhibit abnormal hemostasis. Since nitric oxide (NO) exerts antithrombotic effects and attenuates platelet function, we evaluated two indicators of plasma NO levels, the plasma levels of nitrite and nitrate (NOx), and the levels of cGMP in platelets. We also examined whether indicators of plasma NO levels were associated with abnormalities in parameters related to platelet function, blood coagulation, and fibrinolysis. We evaluated 45 patients with chronic sustained atrial fibrillation (33 men and 12 women, age range 63 +/- 2 years) compared with 45 sex- and age- (+/- 2 years) matched nonhospitalized subjects with sinus rhythm. There were no significant differences between the two groups in the incidence of risk factors for stroke except for ischemic heart disease or in echocardiographic parameters. Plasma levels of NOx measured using the Greiss reagent (mean [interquartile range]: 15.6 [9.5 to 25.7] versus 24.1 [14.2 to 40.8] mumol/L, n = 45) and the platelet cGMP levels (0.33 [0.16 to 0.67] versus 0.63 [0.31 to 1.29] pmol/10(9) platelets, n = 9) were significantly (P < .05) lower in the patients with atrial fibrillation than in the control subjects. Plasma levels of D-dimer, beta-thromboglobulin, and fibrinogen were significantly (P < .05) higher in the patients with atrial fibrillation. The two groups did not differ as to the plasma levels of tissue plasminogen activator or plasminogen activator inhibitor-1. Our findings suggest that a decrease in plasma NO levels may account for the hemostatic abnormalities observed in patients with atrial fibrillation.

Topics: Aged; Atrial Fibrillation; beta-Thromboglobulin; Blood Platelets; Blood Proteins; Cerebrovascular Disorders; Comorbidity; Cyclic GMP; Diabetes Mellitus; Echocardiography; Female; Fibrinogen; Hemodynamics; Humans; Hyperlipidemias; Hypertension; Male; Middle Aged; Myocardial Ischemia; Nitrates; Nitric Oxide; Nitrites; Risk Factors; Smoking; Thrombophilia

The aim of this study was to evaluate clinical, adrenergic and endocrine factors that could predict sinus rhythm maintenance after direct current cardioversion in chronic atrial fibrillation. Nineteen patients with chronic non-rheumatic atrial fibrillation (mean duration 6 +/- 5 months) were studied. They were exercised 24 h before cardioversion at maximum effort with the Naughton protocol. Heart rate and blood pressure at rest and exercise were recorded and blood samples were taken for the assessment of adrenergic activity, by measuring cyclic adenosine monophosphate, heart endocrine function, atrial natriuretic peptide and its second messenger, cyclic guanosine monophosphate. Fifteen of the 19 patients were initially converted to sinus rhythm (eight patients with external and seven patients with internal DC shocks). After 3 months eight patients remained in sinus rhythm and 11 had relapsed, most of them within the first month. On exercise the chronotropic response was lower in the group who remained in sinus rhythm than in the group in atrial fibrillation (peak heart rate 147 +/- 11 beats.min-1 vs 165 +/- 24 beats.min-1 P = 0.02). During exercise, the systolic blood pressure in the sinus group reached higher values than in the group who relapsed (192 +/- 17 mmHg vs 176 +/- 18 mmHg, P = 0.03). Cyclic adenosine monophosphate increased significantly from rest to peak exercise in the sinus rhythm group (from 23 +/- 9 pmol.ml-1 to 31 +/- 15 mol.ml-1, P = 0.02) while it remained unchanged in the atrial fibrillation group (25 +/- 10 pmol.ml-1 to 24 +/- 8 pmol.ml-1, P = 0.02). For all 19 patients the difference in cyclic adenosine monophosphate between rest and exercise was negatively correlated with maximum heart rate (r = 0.58, P = 0.009). Atrial natriuretic peptide increased from rest to peak exercise in the sinus rhythm group (from 129 +/- 58 fmol.ml-1 to 140 +/- 66 fmol.ml-1) while it remained unchanged in the group in which atrial fibrillation persisted or recurred (from 112 +/- 58 fmol.ml-1 to 111 +/- 53 fmol.ml-1, P = 0.002). A significant correlation between atrial natriuretic peptide and cyclic guanosine monophosphate levels at exercise before cardioversion was found for the sinus rhythm group only (r = 0.76, P = 0.02). In patients with non-rheumatic chronic atrial fibrillation evaluation of clinical parameters such as heart rate and blood pressure changes during maximal exercise can be useful in the choice of suitable therapy. An inadequate increase

Topics: Aged; Atrial Fibrillation; Atrial Natriuretic Factor; Biomarkers; Blood Pressure; Chronic Disease; Cyclic AMP; Cyclic GMP; Discriminant Analysis; Electric Countershock; Exercise Test; Female; Heart Rate; Humans; Male; Middle Aged; Prognosis; Treatment Outcome

The response of atrial natriuretic peptide (ANP) release to haemodynamic influences after cardioversion of atrial fibrillation has not been fully examined. We measured plasma concentrations of ANP and assessed haemodynamic changes 60-120 min after DC cardioversion in 22 patients with non-valvular chronic atrial fibrillation. Passive leg elevation to enhance volume expansion was performed 60 min after DC cardioversion. Sinus rhythm was restored in 18 of the 22 patients (successful DC cardioversion group). The control group consisted of seven patients with non-valvular chronic atrial fibrillation who did not undergo DC cardioversion (atrial fibrillation control group). In the successful DC cardioversion group, the mean pulmonary artery wedge pressure decreased significantly 15 min after cardioversion (P < 0.05) and then remained unchanged. Plasma concentrations of ANP also decreased significantly 15 min after cardioversion (P < 0.05). Furthermore, there was an additional significant decrease in ANP levels for up to 60 min after cardioversion (P < 0.05 from 15 min). Passive leg elevation for 15 min led to an increase in the mean pulmonary artery wedge pressure (P < 0.01) and right atrial pressure (P < 0.05), but did not result in increased plasma concentrations of ANP (47.1 +/- 27.6 vs 43.9 +/- 34.4 pg.ml-1, mean +/- SD, P = ns). In the atrial fibrillation control group, passive leg elevation increased the mean pulmonary artery wedge pressure (P < 0.01), the mean right atrial pressure (P < 0.05) and plasma concentrations of ANP (139.9 +/- 85.8 vs 168.1 +/- 108.2, P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Aged; Atrial Fibrillation; Atrial Natriuretic Factor; Cardiac Output; Chronic Disease; Cyclic GMP; Electric Countershock; Female; Hemodynamics; Humans; Male; Middle Aged; Pulmonary Wedge Pressure; Treatment Outcome

Plasma immunoreactive atrial natriuretic peptide (ANP) and cyclic guanosine monophosphate (cGMP), serum thyroxine (T4), triiodothyronine (T3), and thyrotropin (TSH) concentrations were measured in 11 patients with thyrotoxicosis and atrial fibrillation (group 1), in 5 patients with thyrotoxicosis and sinus cardiac rhythm (group 2) and in 8 healthy subjects in comparable age. Patients with thyrotoxicosis were studied before and after treatment with methimazole (3 x 20 mg daily) during 10 days. During treatment sinus cardiac rhythm returned in 6 patients with initial fibrillation (group 1a) while 5 patients still presented atrial fibrillation at the end of the study (group 1b). All patients from group 2 maintained a sinus cardiac rhythm throughout the study. Median plasma concentrations of ANP and cGMP before treatment in patients from group 1 were higher: 43.8 pmol/l and 11.0 nmol/l, respectively than in patients from group 2: 20.0 pmol/l (p < 0.005) and 6.5 nmol/l (p < 0.01), respectively. In all groups of patients methimazole treatment resulted in a significant decrease of plasma ANP and cGMP concentrations in parallel to a reduction of serum T3 and T4 levels. After therapy, plasma ANP and cGMP levels in patients from group 1a were not significantly different from those in patients from group 2, while in patients from group 1b remained slightly elevated. Presented results suggest that atrial fibrillation in patients with thyrotoxicosis represents an important factor augmenting plasma ANP and cGMP levels, in addition to the stimulatory effect exerted by thyroid hormones. However, the marked reduction of serum thyroid hormones produced by short-term methimazole treatment in patients with thyrotoxicosis was associated with parallel decrease of plasma ANP and cGMP levels toward normal values. Therefore, the influence of thyroid hormones on plasma ANP and cGMP concentrations seems relatively more important than the effect of atrial fibrillation.

Topics: Adult; Atrial Fibrillation; Atrial Natriuretic Factor; Cyclic GMP; Female; Humans; Methimazole; Middle Aged; Thyroid Hormones; Thyrotoxicosis

We investigated atrial natriuretic peptide (ANP) and cyclic guanosine monophosphate (cGMP) in patients undergoing elective direct current cardioversion (CV group) due to atrial fibrillation (n = 9) or atrial flutter (n = 3). Anesthesia for cardioversion (CV) was induced with propofol 1.5 mg/kg. Conversion was achieved in all patients. Before CV all patients had elevated ANP and cGMP plasma levels. After CV the concentrations of ANP and cGMP decreased significantly within 15 and 30 minutes (p less than 0.01), respectively. Only one patient in the CV group showed increasing ANP and cGMP levels although his heart rate had decreased after CV and his blood pressure remained stable. High concentrations of ANP and cGMP might possibly be a compensatory mechanism of cardiac dysfunction. To study the influence the anesthetic agent on plasma levels of ANP and cGMP, we investigated six patients anesthetized with propofol for high-density radiation (HDR group). The data from this control group showed that propofol did not influence the plasma levels of ANP and cGMP. ANP correlated statistically significantly (p less than 0.05) with cGMP in both groups (r = 0.88 and 0.76 in the HDR and CV groups, respectively). In addition, we found a cGMP release of 149.6 +/- 17.6 per mol ANP in the HDR group, in the CV group the release was 109 +/- 54.2 cGMP per mol ANP. This phenomenon could be due to minor response of target cells to ANP stimulation (receptor down-regulation) in patients with heart disease. In conclusion, ANP and cGMP levels decreased after successful cardioversion.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Aged; Anesthesia, Intravenous; Atrial Fibrillation; Atrial Flutter; Atrial Natriuretic Factor; Blood Pressure; Cyclic GMP; Electric Countershock; Female; Hemodynamics; Humans; Male; Middle Aged; Propofol

To study the relation between plasma atrial natriuretic factor (ANF) and cardiac pressures, we measured plasma ANF in 24 patients with mitral stenosis 30 minutes before and 20 minutes after balloon mitral valvulotomy. All patients were without physical signs of congestive heart failure. Normal sinus rhythm was present in 15 (group 1), whereas the other nine (group 2) had permanent atrial fibrillation. There were no significant differences between groups for basal mean pressures in right atrium (RA), left atrium (LA), and pulmonary artery (PA). Valvulotomy resulted in a fall in both groups (p less than 0.001) in LA and PA mean pressures, whereas heart rate, cardiac index, and RA and aorta (AO) pressures did not change significantly. Basal ANF was not different in either group in RA (240 +/- 43 vs. 266 +/- 35 pg/ml) or AO (441 +/- 92 vs. 643 +/- 70 pg/ml) but tended to be higher in group 2 in LA (428 +/- 88 vs. 682 +/- 84 pg/ml; p = 0.059) and PA (488 +/- 93 vs. 759 +/- 92 pg/ml; p = 0.057). Plasma ANF was the highest in PA, and about 50% ANF was extracted in the systemic circulation. After valvulotomy, plasma ANF was greater (p less than 0.05) in group 2 (372 +/- 90, 755 +/- 152, 805 +/- 134, and 707 +/- 144 pg/ml) than in group 1 (206 +/- 36, 386 +/- 47, 429 +/- 66, and 421 +/- 49 pg/ml), regardless of the site of blood collection (RA, LA, PA, and AO, respectively). PA ANF was correlated with LA pressure (p less than 0.05) in group 1 before as well as after valvulotomy, whereas there was no such correlation in group 2. Cyclic GMP (cGMP) in LA was correlated (p less than 0.01) with PA ANF in group 1, and LA cGMP (10.0 +/- 1.2 and 9.1 +/- 1.8 pmol/ml in groups 1 and 2, respectively) was higher (p less than 0.05) than PA cGMP (9.1 +/- 1.0 and 8.0 +/- 1.5 pmol/ml in groups 1 and 2, respectively) before valvulotomy, which suggests the presence of ANF receptors in the pulmonary circulation. Taken together, these results indicate that in patients in sinus rhythm with mitral stenosis, there is an increase in ANF secretion depending on LA pressure. ANF secretion is also high in patients with mitral stenosis and atrial fibrillation but does not respond appropriately to changes in LA pressure.(ABSTRACT TRUNCATED AT 400 WORDS)

Topics: Aldosterone; Atrial Fibrillation; Atrial Natriuretic Factor; Catheterization; Coronary Circulation; Cyclic GMP; Female; Hemodynamics; Humans; Male; Mitral Valve Stenosis; Renin; Veins

To investigate the mechanisms of polyuria associated with tachycardia, we measured plasma concentrations of alpha-human atrial natriuretic polypeptide (alpha-hANP) and cGMP in 6 patients with paroxysmal tachycardia. Plasma concentrations of immunoreactive alpha-hANP and cGMP increased by +69% (p less than 0.05) and +100% (p less than 0.05), respectively, during both paroxysmal atrial tachycardia and atrial fibrillation. To examine whether tachycardia per se raises the secretion of alpha-hANP, we also determined plasma concentrations of alpha-hANP and cGMP in 5 patients during rapid atrial pacing. The pacing-induced tachycardia also increased both of the plasma concentrations. Further, the examinations of cardiac and renal functions in patients with complete atrioventricular block during rapid pacing revealed that each of the increases in atrial pressures, urinary sodium excretion and creatinine clearance were in parallel with the change in plasma concentration of alpha-hANP. These results suggest that an increase in plasma concentration of alpha-hANP during paroxysmal tachycardia is mainly due to elevation of atrial pressure and that this increase in alpha-hANP contributes to tachycardia polyuria.

Topics: Atrial Fibrillation; Atrial Natriuretic Factor; Cardiac Pacing, Artificial; Cyclic GMP; Heart; Heart Block; Humans; Kidney; Middle Aged; Radioimmunoassay; Tachycardia, Paroxysmal; Time Factors

To investigate the role of cyclic nucleotides in the genesis and/or the persistence of atrial fibrillation (AF), plasma levels of cyclic GMP (c-GMP) and cyclic AMP (c-AMP) were measured in dogs with electrically induced AF, and in dogs subjected to high frequency (230 or 410/min) atrial pacing. The atrial fibrillation threshold (AFT) after intravenous administration of a dibutyryl derivative of c-GMP (Dbc-GMP), and the effect of atropine (0.1 mg/kg) on AFT were determined. Plasma levels of c-GMP and c-AMP were also measured in patients during paroxysmal AF and sinus rhythm. The c-GMP level increased significantly 15 min after the onset of artificial AF, and gradually increased during the course of the experiment. The c-GMP level began to increase significantly 15 min after the initiation of pacing at the higher rate (410/min) but not at the lower rate, compared to the prepacing value. The c-GMP level continued to rise until the end of pacing in the animals paced at 410/min. Although Dbc-GMP induced a dose-dependent decrease in AFT, atropine did not prevent the decrease in AFT by Dbc-GMP. In contrast, c-AMP levels were not significantly affected in any of these experiments. Clinical assessment revealed that patients had almost four times higher c-GMP level during AF than during sinus rhythm, though c-AMP levels in these patients did not change significantly during the attack of AF. These results suggest that the increase in c-GMP plays an important role in the maintenance and/or the genesis of AF.

Topics: Animals; Atrial Fibrillation; Atropine; Cardiac Pacing, Artificial; Cyclic AMP; Cyclic GMP; Dibutyryl Cyclic GMP; Dogs; Humans

Topics: Adult; Animals; Atrial Fibrillation; Cardiac Complexes, Premature; Cyclic AMP; Cyclic GMP; Humans; Male; Middle Aged; Prognosis; Rats

The variations in the content of endogenic prostanoids and cyclic nucleotides in the blood plasma of the coronary sinus and ascending aorta were studied in patients with the idiopathic stable form of atrial fibrillation before and after sinus rhythm recovery effected by electroimpulse therapy. Changes in the levels and ratios of these compounds in the coronary venous and arterial blood were found to be opposite in their trends. A significant elevation in TxB2 levels and the TxB2/6-keto-PGF1 ratio as well as increased cGMP concentrations in the plasma of the coronary venous blood appear to be suggestive of an unfavourable prognosis because patients with such changes developed atrial fibrillation recurrences soon after electroimpulse therapy.

Topics: Adult; Aorta, Thoracic; Atrial Fibrillation; Coronary Vessels; Cyclic AMP; Cyclic GMP; Dinoprost; Epoprostenol; Female; Humans; Male; Middle Aged; Prostaglandins; Prostaglandins E; Prostaglandins F; Thromboxane A2; Thromboxanes

We examined the histologic, hemodynamic and metabolic factors associated with rheumatic mitral stenosis. Eighteen patients comprised three groups: Group I - 7 patients in sinus rhythm; Group II - 5 patients in intermittent atrial fibrillation; Group III - 6 patients in chronic atrial fibrillation. The left atrial dimension was determined by echocardiography. Left atrial pressure, mitral valve gradient, mitral valve area and the presence or absence of calcium in the mitral valve were determined at catheterization. The left atrial appendage was removed during open heart surgery and the tissue was analyzed for cell size, percent fibrosis and content of cyclic AMP and GMP. There was no difference between the groups in pulmonary capillary wedge pressure, mitral valve gradient, mitral valve area or the presence of calcium. The Group I left atrial dimension (51 +/- 2 mm, means +/- SE) was significantly smaller than that of Group III (56 +/- 2 mm, P less than 0.05). Group II was not different from Groups I or III. Although the concentration of cyclic AMP did not differ among the groups, the cyclic GMP was significantly depressed in Group III (0.15 +/- 0.02 fmol/microgram protein) when compared to Group I (0.24 +/- 0.05 fmol/microgram protein, P less than 0.01). Group II had intermediate values which did not differ from Groups I or III. The percent fibrosis was greatest in Group III (34.8 +/- 1.8%) and least in Group I (27.2 +/- 2.8%, P less than 0.05). There was no difference in cell size among the groups. Although atrial fibrillation may lead to some of these irregularities, a depressed cyclic GMP, increased fibrosis and increased left atrial dimension may play a role in the pathogenesis of irreversible atrial fibrillation.

Topics: Adult; Atrial Fibrillation; Calcium; Cyclic AMP; Cyclic GMP; Echocardiography; Heart Atria; Hemodynamics; Humans; Male; Middle Aged; Mitral Valve; Mitral Valve Stenosis; Rheumatic Heart Disease

Plasma concentration of cyclic nucleotides in patients with paroxysmal atrial fibrillation was determined by ultrasensitive radioimmunoassay on the day of attack and also the next day, following recovery to sinus rhythmus. The concentration of cyclic GMP in the plasma of patients with attacks of paroxysmal atrial fibrillation was significantly higher than in those with sinus rhythmus, but no significant difference in plasma concentration of cyclic AMP was observed.

Topics: Atrial Fibrillation; Cyclic AMP; Cyclic GMP; Female; Humans; Male; Middle Aged

The concentrations of plasma cyclic nucleotides in patients with atrial fibrillation and in dogs with aconitine-induced atrial fibrillation were measured. Radioimmunoassay was used for the determination of cyclic nucleotides. The concentration of plasma cGMP in dogs with aconitine-induced atrial fibrillation was significantly elevated at 30 and 60 min after the onset of atrial fibrillation, whereas that of plasma cAMP showed no significant changes. After the injection of atropine in dogs with atrial fibrillation and with increased plasma cGMP, the plasma levels decreased to the normal level at 60 min after the conversion to sinus rhythmus. In patients with paroxysmal atrial fibrillation, a significantly increased concentration of plasma cGMP was demonstrated on attacks of atrial fibrillation compared with those with sinus rhythmus, but no significant changes of plasma cAMP levels were observed in these patients. Thus, these results showed that the enhanced parasympathetic nervous activity had been maintained by the atrial fibrillation.

Topics: Aconitine; Aconitum; Animals; Atrial Fibrillation; Cyclic AMP; Cyclic GMP; Dogs; Electrocardiography; Heart Atria; Heart Rate; Humans; Myocardium