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BackgroundPulmonary vein (PV) ablation is unsuccessful in atrial fibrillation (AF) patients with high left atrial (LA) pressure. Increased atrial stretch by increased pressure is proarrhythmic for AF, and myocardial scar alters wall deformation. We hypothesized that localized PV scar is proarrhythmic for AF in high LA pressure.MethodsRadiofrequency energy was delivered locally in the right PV of healthy sheep. The sheep recovered for 4 months. Explanted hearts (n = 9 PV scar, n = 9 controls) were perfused with 1:4 blood:Tyrode’s solution in a four-chamber working heart setup. Programmed PV stimulation was performed during low (∼12 mmHg) and high (∼25 mmHg) LA pressure. An AF inducibility index was calculated based on the number of induction attempts and the number of attempts causing AF (run of ≥ 20 premature atrial complexes).ResultsIn high LA pressure, the presence of PV scar increased the AF inducibility index compared with control hearts (0.83 ± 0.20 vs. 0.38 ± 0.40 arb. unit, respectively, p = 0.014). The diastolic stimulation threshold in high LA pressure was higher (108 ± 23 vs. 77 ± 16 mA, respectively, p = 0.006), and its heterogeneity was increased in hearts with PV scar compared with controls. In high LA pressure, the refractory period was shorter in PV scar than in control hearts (178 ± 39 vs. 235 ± 48 ms, p = 0.011).ConclusionLocalized PV scar only in combination with increased LA pressure facilitated the inducibility of AF. This was associated with changes in tissue excitability remote from the PV scar. Localized PV ablation is potentially proarrhythmic in patients with increased LA pressure.

Background: Pulmonary vein (PV) ablation is unsuccessful in atrial fibrillation (AF) patients with high left atrial (LA) pressure. Increased atrial stretch by increased pressure is proarrhythmic for AF, and myocardial scar alters wall deformation. We hypothesized that localized PV scar is proarrhythmic for AF in high LA pressure. Methods: Radiofrequency energy was delivered locally in the right PV of healthy sheep. The sheep recovered for 4 months. Explanted hearts (n = 9 PV scar, n = 9 controls) were perfused with 1:4 blood:Tyrode's solution in a four-chamber working heart setup. Programmed PV stimulation was performed during low (∼12 mmHg) and high (∼25 mmHg) LA pressure. An AF inducibility index was calculated based on the number of induction attempts and the number of attempts causing AF (run of ≥ 20 premature atrial complexes). Results: In high LA pressure, the presence of PV scar increased the AF inducibility index compared with control hearts (0.83 ± 0.20 vs. 0.38 ± 0.40 arb. unit, respectively, p = 0.014). The diastolic stimulation threshold in high LA pressure was higher (108 ± 23 vs. 77 ± 16 mA, respectively, p = 0.006), and its heterogeneity was increased in hearts with PV scar compared with controls. In high LA pressure, the refractory period was shorter in PV scar than in control hearts (178 ± 39 vs. 235 ± 48 ms, p = 0.011). Conclusion: Localized PV scar only in combination with increased LA pressure facilitated the inducibility of AF. This was associated with changes in tissue excitability remote from the PV scar. Localized PV ablation is potentially proarrhythmic in patients with increased LA pressure. [ABSTRACT FROM AUTHOR]

This investigation was aimed to identify gene profiles in human atrial myocardium in response to chronic mechanical stretch. Right atrial appendages from 21 patients were divided into 2 groups based on the size of right atrial volume. The microarray DATA analyses differentially identified 335 genes (> 2.0-fold, corrected P < 0.05) including "functionally unknown genes". This study identified 26 up-regulated genes (natriuretic peptide B, G protein subunit gamma 13, thyroid stimulating hormone beta, etc.) and 23 down-regulated genes (oligodendrocyte transcription factor 1, carbonic anhydrase 12, etc.), which could be responsible for chronic stretch-mediated structural remodeling in the atrium. [ABSTRACT FROM AUTHOR]

Atrial fibrillation (AF) is the most common arrhythmia in adults; it affects approximately 0.8 million patients in Japan alone. Yet despite many years of basic and clinical research, the exact mechanisms underlying the initiation and maintenance of AF remain poorly understood. In this review article, we summarize recent high-resolution optical mapping studies in isolated sheep hearts, which have provided new insights into the dynamics and mechanisms of AF. We focus on 3 models of AF. First, we discuss results from experiments on AF induced by atrial stretch that revealed the presence of spatio-temporally organized waves emerging from the posterior wall of the left atrium. In the presence of adreno-cholinergic stimulation and stretch, AF was governed by evolving interactions between reentry and spontaneous focal discharges. Next, we outline the results obtained from a persistent AF model (average AF duration: 21.3 day) induced by intermittent rapid atrial pacing. By using simultaneous optical mapping of epicardial and endocardial activation patterns, we demonstrated that AF in this model was maintained by 3-dimensional scroll waves with I-shaped filaments anchored to junctions between thin and thick myocardium. Numerical simulation results predicted that wall thickness-dependent activation of stretch-activated channels and the filament tension dynamics were sufficient to explain the specific localization of the I-shaped filament. In a final set of studies discussed herein, we investigated AF in sheep with tachypacing-induced heart failure and found that micro-reentry in the left atria was a major mechanism of AF maintenance, although focal discharges at the pulmonary vein area also played a role. Large fibrotic patches in failing hearts may serve as potential anchoring sites for micro-reentry in this model. Thus, the 3 different experimental results in isolated sheep hearts presented here clearly suggest that self-sustained rotors do exist in the atria and that such rotors are in fact the high frequency sources that determine the complex patterns of activation that characterize AF.

Background Ranolazine is evaluated for antiarrhythmic therapy of atrial fibrillation ( AF). The electrophysiologic mechanisms of ranolazine in combination with class III drugs were studied in an isolated whole-heart model of stretch-related AF. Methods and Results Thirty rabbits were fed with amiodarone (50 mg/kg/day, n = 10), dronedarone (50 mg/kg/day, n = 10), or placebo (n = 10) for 6 weeks. Subsequently, in isolated hearts, AF was induced by high-rate atrial pacing and acute atrial dilatation. In placebo-treated hearts, d,l-sotalol (50 μM) was acutely administered. Ranolazine (10 μM) was additionally infused in all groups. Chronic amiodarone (+26 ± 7 ms, P < 0.05) or dronedarone (+22 ± 4 ms, P < 0.05) as well as acute application of d,l-sotalol (+20 ± 3 ms, P < 0.05) increased atrial action potential duration (a APD90). Additional treatment with ranolazine did not significantly change a APD90 ( P = ns). Class III drugs did not affect interatrial conduction time, while ranolazine significantly increased it (amiodarone group: +15 ± 3 ms, dronedarone group: +11 ± 3 ms, sotalol group: +15 ± 6 ms; P < 0.05 each). Ranolazine led to an additional increase in atrial effective refractory period (a ERP), thus leading to an enhanced atrial postrepolarization refractoriness (a PRR, +17 ± 6 ms, +21 ± 4 ms and +16 ± 8 ms, P < 0.05, respectively). Acute atrial dilatation increased AF incidence compared with baseline. Amiodarone-pretreated hearts showed a lower incidence of AF. Additional infusion of ranolazine further diminished AF. Dronedarone or acute infusion of sotalol did not significantly suppress AF, while additional treatment with ranolazine in these groups also reduced AF incidence. Conclusion In this study, ranolazine on top of class III antiarrhythmic therapy had a beneficial effect. The increase in interatrial conduction time and marked atrial a PRR suppressed AF. These results shed further light on a potential therapeutic benefit of ranolazine on top of conventional antiarrhythmic therapy for rhythm control in AF. [ABSTRACT FROM AUTHOR]

Abstract: Oleanolic acid is known to have beneficial effects on the regulation of cardiovascular homeostasis. The present study was designed to identify the effects of oleanolic acid on plasma levels and atrial synthesis and secretion of atrial natriuretic peptide (ANP). Experiments were performed in rats and isolated perfused beating rat atria. ANP was measured using a selective radioimmunoassay. ANP mRNA expression was measured using real-time quantitative polymerase chain reaction. Administration of oleanolic acid increased plasma ANP levels in a dose-related manner. Similarly, oleanolic acid increased atrial ANP content and ANP mRNA expression. To evaluate the effects of oleanolic acid on ANP secretion, atrial stretch and muscarinic acetylcholine receptor activation were applied to the atria from rats chronically treated with oleanolic acid. Baseline levels of ANP secretion were higher in the atria from rats treated with oleanolic acid compared to rats treated with vehicle. Furthermore, oleanolic acid treatment enhanced the stretch-induced increase in ANP secretion. Acetylcholine in the presence of isoproterenol increased ANP secretion. The acetylcholine-induced increase in ANP secretion was also enhanced in the atria from rats treated with oleanolic acid compared to atria from rats treated with vehicle. The present findings indicate that oleanolic acid increases plasma ANP levels via increased ANP synthesis and secretion in rats. It is proposed that an accentuation of the ANP system is involved in the beneficial effects of oleanolic acid on the regulation of cardiovascular homeostasis. [Copyright &y& Elsevier]

Aims In several clinical and pre-clinical studies, application of ranolazine (RAN) led to suppression of atrial fibrillation (AF). The aim of the present study was to investigate whether RAN can suppress AF in an experimental rabbit whole heart model, in which acute haemodynamic changes trigger AF. Ranolazine was compared with flecainide and sotalol as established antiarrhythmic agents. Methods and results In 60 Langendorff-perfused, isolated rabbit hearts, AF episodes were evoked by burst pacing with a fixed number of stimuli at baseline and following acute atrial stretch. Data were obtained in the absence and presence of acute dilatation of the left atrium (20 mmHg) at baseline and after drug application (RAN 10 µM, n = 10; flecainide 2 µM, n = 10; sotalol 50 µM, n = 10). Application of sotalol, but not RAN or flecainide increased the atrial action potential duration at 90% repolarization (aAPD90); however, both RAN (+8 ms) and flecainide (+13 ms) increased interatrial conduction time. All three drugs caused a significant increase in atrial effective refractory period (aERP) and, thus, an increase in atrial post-repolarization refractoriness (aPRR: +11 ms each, P < 0.05). Acute dilatation of the left atrium reduced aAPD90 and aERP. The described drug effects were preserved in the setting of acute atrial dilatation. Acute atrial dilatation significantly increased the incidence of AF. Ranolazine and flecainide, but not sotalol, decreased the number of responses. Conclusion Ranolazine-related sodium channel block is preserved upon acute atrial stretch. Ranolazine suppresses stretch-induced AF by increasing interatrial conduction time and aPRR. These results shed further evidence on the potential role of RAN in the prevention of AF. This might also apply to clinical conditions that are associated with haemodynamic or mechanical disorders, leading to acute dilatation of the atria. [ABSTRACT FROM PUBLISHER]

Abstract: Angiotensin III (Ang III) is metabolized from Ang II by aminopeptidase (AP) A and in turn, Ang III is metabolized to Ang IV by APN. Ang III is known to have a similar effect to Ang II on aldosterone secretion, but the effect of Ang III on atrial natriuretic peptide (ANP) secretion from cardiac atria is not known. The aim of the present study is to define the effect of Ang III on ANP secretion and its receptor subtype using isolated perfused beating atria. The volume load was achieved by elevating the height of outflow catheter connected with isolated atria from 5cmH2O to 7.5cmH2O. Atrial stretch by volume load increased atrial contractility and ANP secretion. Ang III stimulated stretch-induced ANP secretion in a dose-dependent manner without change in atrial contractility. The stimulated effect of Ang III (1μM) on stretch-induced ANP secretion was blocked by the pretreatment of Ang II type 2 (AT2) receptor antagonist but not by AT1 or Mas receptor antagonist. Pretreatment with inhibitor of phosphoinositide 3-kinase (PI3K), Akt, nitric oxide synthase, soluble guanylyl cyclase, or protein kinase G (PKG) attenuated Ang III-stimulated ANP secretion. When Ang III (40nM) or Ang II (4nM) was infused for 10min into anesthetized rats, mean arterial pressure was increased about 10%. However, Ang III increased plasma ANP level by 35.81±10.19% but Ang II decreased plasma ANP level by 30.41±7.27%. Therefore, we suggest that Ang III, opposite to Ang II, stimulated stretch-induced ANP secretion through AT2 receptor/PI3K/Akt/nitric oxide/PKG pathway. [Copyright &y& Elsevier]

Abstract: Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia in human beating hearts. AF initiates self-perpetuating changes in electrophysiology, structure and functional properties of the atria, a phenomenon known as atrial remodeling. Hypertension, heart failure, valvular heart disease, sleep apnea, congenital heart disease are well known risk factors for AF that contribute to the development of atrial substrate. There is some evidence that reversal of atrial remodeling is possible with correction of antecedent conditions, however the timing of the intervention or upstream therapy may be critical. This review will describe the pathophysiology of atrial remodeling as it pertains to AF. We will describe components of remodeling including changes in atrial refractoriness, conduction and atrial structure, in addition to autonomic changes and anatomic factors that predispose to remodeling. We will discuss our current understanding of the electrophysiological changes that contribute to AF persistence. We will describe nature of atrial and pulmonary vein remodeling in the context of different forms of AF, with and without predisposing risk factors. We will describe the nature of remodeling over time following therapeutic interventions such as AF ablation in order to show that it does not necessarily improve and may worsen. [Copyright &y& Elsevier]

Aims There is increasing evidence of the role direction-dependent conduction plays in the arrhythmogenic interaction between ectopic triggers and abnormal atrial substrates. We thus sought to characterize direction-dependent conduction in chronically stretched atria. Methods and results Twenty-four patients with chronic atrial stretch due to mitral stenosis and 24 reference patients with left-sided accessory pathways were studied. Multipolar catheters placed at the lateral right atrium, crista terminalis, and coronary sinus (CS) characterized direction-dependent conduction along linear catheters and across the crista terminalis. Bi-atrial electroanatomic maps were created in both sinus rhythm and an alternative wavefront direction by pacing from the distal CS. This allowed an assessment of conduction velocities, electrogram, and voltage characteristics during wavefronts propagating in different directions. While differing wavefront directions caused changes in both chronic atrial stretch and reference patients (P< 0.001 for all), these direction-dependent changes were greater in chronic atrial stretch compared with reference patients, who exhibited greater slowing in conduction velocities (P= 0.09), prolongation of bi-atrial activation time (P= 0.04), increase in number (P< 0.001) and length (P< 0.001) of lines of conduction block, increase in fractionated electrograms (P< 0.001), and decrease in voltage (P= 0.08) during left-to-right compared with right-to-left atrial activation. These direction-dependent changes were associated with a greater propensity for chronically stretched atria to develop atrial fibrillation (P= 0.02). Conclusions Atrial remodelling in chronic atrial stretch exacerbates physiological direction-dependent conduction characteristics. Our data suggest that the greater direction-dependent conduction seen in patients with chronic atrial stretch may promote arrhythmogenesis due to ectopic triggers from the left atrium. [ABSTRACT FROM PUBLISHER]

Abstract: Atrial fibrillation (AF) is the most common arrhythmia in adults; it affects approximately 0.8 million patients in Japan alone. Yet despite many years of basic and clinical research, the exact mechanisms underlying the initiation and maintenance of AF remain poorly understood. In this review article, we summarize recent high-resolution optical mapping studies in isolated sheep hearts, which have provided new insights into the dynamics and mechanisms of AF. We focus on 3 models of AF. First, we discuss results from experiments on AF induced by atrial stretch that revealed the presence of spatio-temporally organized waves emerging from the posterior wall of the left atrium. In the presence of adreno-cholinergic stimulation and stretch, AF was governed by evolving interactions between reentry and spontaneous focal discharges. Next, we outline the results obtained from a persistent AF model (average AF duration: 21.3 day) induced by intermittent rapid atrial pacing. By using simultaneous optical mapping of epicardial and endocardial activation patterns, we demonstrated that AF in this model was maintained by 3-dimensional scroll waves with I-shaped filaments anchored to junctions between thin and thick myocardium. Numerical simulation results predicted that wall thickness-dependent activation of stretch-activated channels and the filament tension dynamics were sufficient to explain the specific localization of the I-shaped filament. In a final set of studies discussed herein, we investigated AF in sheep with tachypacing-induced heart failure and found that micro-reentry in the left atria was a major mechanism of AF maintenance, although focal discharges at the pulmonary vein area also played a role. Large fibrotic patches in failing hearts may serve as potential anchoring sites for micro-reentry in this model. Thus, the 3 different experimental results in isolated sheep hearts presented here clearly suggest that self-sustained rotors do exist in the atria and that such rotors are in fact the high frequency sources that determine the complex patterns of activation that characterize AF. [Copyright &y& Elsevier]

Abstract: Caveolae may act as mechanosensors and function as binding sites for calcium ions. The intracaveolar localization of atrial natriuretic peptide (ANP) derived from the direct interaction of atrial granules with caveolae has been demonstrated. The aim of this study was to define the effect of caveolae on ANP secretion induced by stretch and angiotensin II. The isolated perfused beating atria from Sprague-Dawley rats were used. To disrupt caveolae, 10mM methyl-β-cyclodextrin (MbCD) was applied for 1h and the number of caveoli were markedly decreased. MbCD increased basal ANP secretion and atrial diastolic pressure. The molecular profile of ANP in perfusate from control atria showed mainly one major peak corresponded to synthetic ANP whereas that from MbCD-treated atria showed two major immunoreactive peaks corresponded to synthetic rat ANP and proANP. High atrial stretch induced by elevating the height of outflow catheter from 5cmH2O to 7.5cmH2O increased atrial contractility and ANP secretion. The response of ANP secretion to high stretch was attenuated in MbCD-pretreated atria. Pretreatment with MbCD abolished angiotensin II-induced suppression and losartan-induced stimulation of ANP secretion. However, the effect of angiotenisin (1-7) on ANP secretion was not altered by MbCD treatment. The expression of angiotensin II type 1 receptor protein was reduced by MbCD treatment. These data suggest that caveolae are essential for angiotensin II type 1 receptor-mediated ANP secretion and relate to the processing of proANP. [Copyright &y& Elsevier]

Abstract: Angiotensin II (Ang II) is released by stretch of cardiac myocytes and has paracrine and autocrine effects on cardiac myocytes and fibroblasts. However, the direct effect of Ang II on the secretion of atrial natriuretic peptide (ANP) is unclear. The aim of the present study is to test whether Ang II affects stretch-induced ANP secretion. The isolated perfused beating atria were used from control and two-kidney one-clip hypertensive (2K1C) rats. The volume load was achieved by elevating the height of outflow catheter connected with isolated atria from 5cmH2O to 7.5cmH2O. Atrial stretch by volume load caused increases in atrial contractility by 60% and in ANP secretion by 100%. Ang II suppressed stretch-induced ANP secretion and tended to increase atrial contractility whereas losartan stimulated stretch-induced ANP secretion. Neither PD123319 nor A779 had direct effect on stretch-induced ANP secretion. The suppressive effect of Ang II on stretch-induced ANP secretion was blocked by the pretreatment of losartan but not by the pretreatment of PD123319 or A779. In hypertrophied atria from 2K1C rats, stretch-induced ANP concentration attenuated and atrial contractility augmented. The response of stretch-induced ANP secretion to Ang II and losartan augmented. The expression of AT1 receptor protein and mRNA increased but AT2 and Mas receptor mRNA did not change in 2K1C rat atria. Therefore, we suggest that Ang II generated endogenously by atrial stretch suppresses stretch-induced ANP secretion through the AT1 receptor and alteration of Ang II effect in 2K1C rat may be due to upregulation of AT1 receptor. [ABSTRACT FROM AUTHOR]

Background: Atrial stretch is thought to play a role in the development of atrial fibrillation (AF). However, the precise mechanism by which stretch contributes to AF maintenance in humans is unknown. Objective: The purpose of this study was to determine the impact of left atrial (LA) pressure on AF frequency in patients undergoing catheter ablation of AF. Methods: The subjects of this study were 58 consecutive patients with persistent AF (n = 40) or paroxysmal AF (n = 18) undergoing LA ablation. LA pressure was measured before ablation. Both atria and the coronary sinus were mapped, and regional dominant frequency (DF) was determined. Results: Mean LA pressure in the persistent AF group was significantly higher than in the paroxysmal AF group (18 ± 5 vs 10 ± 4 mmHg, P <.0001). Mean DF in the persistent AF group was also higher than in the paroxysmal AF group (6.36 ± 0.51 Hz and 5.83 ± 0.54 Hz, P = .0006). In patients with persistent AF, there was a significant correlation between LA pressure and DF at the LA appendage (r = 0.55, P = .0002). DFmax was found at the LA appendage region in 24 (60%) of the 40 patients with persistent AF (P = .0006). In multivariate analysis, LA pressure was the only independent predictor of DFmax in the LA appendage (P = .04, odds ratio 1.41, 95% confidence interval 1.02–1.94). Conclusion: Higher LA pressure in patients with persistent AF implies that these patients are more vulnerable to stretch-related remodeling than are patients with paroxysmal AF. The DF of AF was directly related to LA pressure in patients with persistent AF. This finding suggests that atrial stretch may contribute to the maintenance of AF in humans by stabilizing high-frequency sources. [ABSTRACT FROM AUTHOR]

Background: The posterior left atrium (LA) is involved in the initiation and maintenance of atrial fibrillation (AF). Objective: The purpose of this study was to compare conduction patterns on the posterior LA in patients with mitral regurgitation (MR), with and without AF. Methods: Epicardial mapping of the posterior LA was performed in 23 patients undergoing cardiac surgery. Patients were included in one of three groups: Group A—patients in sinus rhythm with normal left ventricular function undergoing coronary artery bypass grafting, Group B—patients in sinus rhythm with MR undergoing mitral valve surgery, or Group C—patients in persistent AF with MR undergoing mitral valve surgery. Conduction patterns, regional conduction velocity, conduction heterogeneity, conduction anisotropy, and complex fractionated atrial electrograms (CFAEs) were assessed. Results: LA diameter was greater in patients in Groups C (57 ± 4mm) and B (54 ± 6mm) than in Group A (39 ± 7mm, P <0.01). Patients in Group C had a greater number of lines of conduction delay than Groups A and B (2.0 ± 0.8 vs 1 ± 0 and 1 ± 0, P <0.05). The extent of conduction delay and conduction heterogeneity was greater in Group C than in Group B, which was greater than in Group A (P <0.05). The percentage of CFAEs that remained stable during AF was 61% ± 17%. There was a significant correlation between CFAEs during AF and regions of slow conduction during pacing (R = 0.36, P <0.001). Conclusion: Patients with MR, LA enlargement, and AF have more extensive regions of conduction slowing in the posterior LA. Anatomically constant lines of conduction delay in this region lead to circuitous wavefront propagation. During persistent AF, fractionated electrograms in the posterior LA are distributed to regions demonstrating slow conduction, and the majority remain stable over time. [Copyright &y& Elsevier]

Abstract: The progressive nature of atrial fibrillation (AF) has been demonstrated in numerous experimental as well as clinical investigations. Electrical remodeling (shortening of atrial refractoriness) develops within the first days of AF and contributes to the increase in stability of the arrhythmia. However, “domestication of AF” must also depend on other mechanisms since the stability of AF continues to increase after electrical remodeling has been completed. Chronic atrial stretch induces activation of numerous signaling pathways leading to cellular hypertrophy, fibroblast proliferation and tissue fibrosis. The resulting electro-anatomical substrate is characterized by increased non-uniform anisotropy and local conduction heterogeneities facilitating reentry in the dilated atria. Atrial fibrosis may lead to disruption of the electrical side-to-side junctions between muscle bundles. This can result in electrical dissociation between neighboring muscle bundles, i.e. they become activated out-of-phase. Recent mapping studies in goats with persistent AF showed that electrical dissociation can not only occur between neighboring muscle bundles but also in the third dimension, i.e. between the epicardial layer and the endocardial bundle network. Such endo-epicardial dissociation will significantly increase the number of wavefronts which can simultaneously be present in the atrial wall. This article reviews data suggesting a role of endo-epicardial dissociation in dilated and fibrillating atria, for the self-perpetuating nature of AF as well as its possible implications for therapeutic interventions. [Copyright &y& Elsevier]

Study objective – The aim was to investigate the pattern of release of atrial natriuretic factor induced by mechanical and adrenergic stimulation from atria of rats with or without congestive heart failure.Design – Monocrotaline, a pyrrolizidine alkaloid, was given to rats to cause severe pulmonary hypertension, leading to a marked degree of right ventricular hypertrophy and failure. Measurements of noradrenaline and atrial natriuretic factor were performed in each cardiac chamber and in plasma. Right and left atria of control rats and rats with congestive heart failure were isolated and subjected to mechanical or adrenergic stimulation to study the in vitro release of atrial natriuretic factor.Materials – Studies were performed on plasma, ventricles, and isolated right and left atria of 276 male Wistar rats, 80-100 g weight, with or without congestive heart failure.Measurements and main results – In monocrotaline rats right and left ventricular concentrations of noradrenaline were significantly reduced. In the same rats concentrations of atrial natriuretic factor fell to 15.2% in the right atria and to 65.5% in the left atria. Whole heart content of atrial natriuretic factor was diminished, while plasma concentrations were increased sevenfold. Isolated hypertrophied right atria of failing hearts did not release atrial natriuretic factor in response to stretch or to isoprenaline (10−9 M) and they were insensitive to the inotropic action of isoprenaline. On the other hand, nonhypertrophied left atria from the same animals released increased amounts of atrial natriuretic factor under basal conditions and after both stimuli, despite reduced tissue stores of the peptide.Conclusions – Heart failure may deplete cardiac stores of noradrenaline and atrial natriuretic factor, especially in hypertrophied chambers, and can result in a decrease in the release of atrial natriuretic factor from atrial tissue in response to mechanical and adrenergic stimulation. [ABSTRACT FROM PUBLISHER]

The effect of pericardiocentesis on the plasma concentration of atrial natriuretic peptide was studied in a patient with cardiac tamponade. Plasma atrial natriuretic peptide concentrations rose sharply from 42 pmoll1 to a maximum of l50 pmol l1 with a corresponding fall in mean right atrial pressure from 20 mmHg to 6 mmHg. Our results suggest that atrial ‘stretch’ (or transmural pressure) rather than atrial pressure per se, is the primary stimulus for atrial natriuretic peptide release in man. [ABSTRACT FROM PUBLISHER]