Atrial Stretch Research Articles

Fetal and neonatal atrial arrhythmias: an association with maternal diabetes and neonatal macrosomia

To determine if the incidence of maternal diabetes mellitus or neonatal macrosomia is more frequent in fetuses and neonates with atrial arrhythmias than the general population. Fetuses and neonates <30 days of age with atrial flutter or ectopic atrial tachycardia and structurally normal hearts were identified retrospectively through the cardiology databases. Electrocardiograms, echocardiograms, and medical records of mothers and infants were reviewed. Thirty-one patients (15 fetuses, 12 diagnosed in-utero) were identified. Infants with atrial flutter or ectopic atrial tachycardia were more likely to be macrosomic or to be born to diabetic mothers than the general population. Two had left atrial dimension z-scores above +2, and two had interventricular thickness z-scores above +2. Eighteen of 19 had abnormal mitral E/A ratios, suggesting left ventricular diastolic dysfunction. Fetuses and neonates with atrial flutter or ectopic atrial tachycardia were more likely to be macrosomic or be born to diabetic mothers than the general population. Postnatal echocardiography suggests that there may be abnormal diastolic left ventricular filling in some babies with these arrhythmias. Independent of ventricular hypertrophy, we speculate that isolated, non-recurrent fetal or neonatal atrial flutter, or ectopic atrial tachycardia may be caused by cardiac diastolic dysfunction and atrial stretch in utero.

Would right atrial stretch inhibit sodium intake following GABAA receptor activation in the lateral parabrachial nucleus?

The knowledge of the mechanisms underlying circulating volume control may be achieved by stretching a balloon placed at the junction of the superior vena cava–right atrial junction (SVC–RAJ). We investigated whether the inflation of a balloon at the SVC–RAJ inhibits the intake of 0.3M NaCl induced by GABAA receptor activation in the lateral parabrachial nucleus (LPBN) in euhydrated and satiated rats. Male Wistar rats (280–300g) with bilateral stainless steel LPBN cannulae and balloons implanted at the SVC–RAJ were used. Bilateral injections of the GABAA receptor agonist muscimol (0.5ηmol/0.2l) in the LPBN with deflated balloons increased intake of 0.3M NaCl (30.1±3.9 vs. saline: 2.2±0.7)ml/210min, n=8) and water (17.7±1.9 vs. saline: 2.9±0.5ml/210min). Conversely, 0.3M NaCl (27.8±2.1ml/210min) and water (22.8±2.3ml/210min) intake were not affected in rats with inflated balloons at the SVC–RAJ. The results show that sodium and water intake induced by muscimol injected into the LPBN was not affected by balloon inflation at the SVC–RAJ. We suggest that the blockade of LPBN neuronal activity with muscimol injections impairs inhibitory mechanisms activated by signals from cardiopulmonary volume receptors determined by balloon inflation.

Myocardial Infarction and Atrial Fibrillation

Background— Myocardial infarction (MI) is associated with the development of atrial fibrillation (AF). We aimed to characterize the atrial abnormalities because of MI and determine the role of ischemia to the AF substrate. Methods and Results— Forty-four sheep were studied. MI was induced by occlusion of the left circumflex artery (LCX) or left anterior descending artery (LAD). Excluding 11 with fatal arrhythmias, equal groups of animals (LCX; LAD; and sham-operated) underwent sequential electrophysiology study for 45 minutes to determine atrial effective refractory periods, conduction velocity, conduction heterogeneity index, and AF inducibility. Postmortem evaluation was performed with 2,3,5 triphenyl tetrazolium chloride staining. MI resulted in greater left ventricular dysfunction ( P &lt;0.05), LA pressure ( P &lt;0.0003), and reduction in atrial effective refractory periods ( P &lt;0.0001) compared with control. 2,3,5 triphenyl tetrazolium chloride staining demonstrated that the left circumflex artery, and not the LAD, group had atrial infarction. The left circumflex artery group demonstrated the following compared with the LAD or control groups: greater slowing in atrial conduction velocity ( P &lt;0.0001 and P &lt;0.001); increased absolute range of conduction phase delay ( P &lt;0.001 and P &lt;0.001); increased conduction heterogeneity index ( P &lt;0.0001 and P &lt;0.001); greater AF vulnerability ( P &lt;0.05 for both); and longer AF duration ( P &lt;0.05 for both). LAD group had modest but significant slowing in conduction velocity ( P &lt;0.01) but no change in conduction heterogeneity index or AF duration compared with control. Conclusions— Left ventricular infarction, which is known to result in atrial stretch, hemodynamic change, and neurohumoral activation, contributes partially to the atrial abnormalities in MI. Atrial ischemia/infarction results in greater atrial electrophysiological changes and propensity for AF forming the dominant substrate for AF in MI.

SAFE Combinations Fail to Open the Door to Atrial Fibrillation Prevention

The prevalence of atrial fibrillation (AF) in the entire US population is ≈1%.1 The prevalence of AF increases substantially with age, with ≤9% of patients over the age of 80 years developing AF. The population presenting with permanent pacing requirements also increases with age, and the cumulative lifetime risk of developing paroxysmal AF in pacemaker patients may be as high as 40%.2 Article see p 687 Mechanisms for AF initiation and maintenance are multiple but are widely accepted to be a result of triggered initiation by atrial premature beats, and maintenance within the atrial substrate on the basis of multiple wavelets of reentry and rotors that depend on inhomogeneous atrial refractory periods and atrial conduction velocities. Atrial pacing may prevent both AF triggers and atrial substrate changes by suppressing atrial premature beats and inducing a more homogenous atrial landscape of refractory periods and conduction velocities. Atrial-based pacing is clearly superior to ventricular pacing alone in preventing atrial fibrillation with an 18% relative risk reduction with atrial-based pacing over a 3-year follow-up.3 This treatment effect has been postulated to be the result of atrial premature beat suppression and changes in atrial refractory periods and atrial conduction velocities as a result of atrial stretch attributed to higher atrial pressure from AV dyssynchronous pacing. The atrial changes associated with atrial-based pacing could possibly be enhanced by atrial overdrive pacing algorithms or by alternative site atrial pacing, such as the atrial septum. The role of alternative-site atrial pacing …

Fibroblasts, electrophysiological changes, and atrial fibrillation: Focus on the arrhythmogenic properties of fibroblasts

Atrial fibrosis is one of the fundamental mechanisms for the pathogenesis of atrial fibrillation (AF), but the underlying electrophysiological changes involved are not completely understood. Aging, neurohumoral activation, and chronic atrial stretch due to structural heart disease activate various signaling pathways that lead to cellular hypertrophy, fibroblast proliferation, and complex alterations of the extracellular matrix (ECM), such as tissue fibrosis; these may lead to disruption of the electrical side-toside junctions between muscle bundles [1], resulting in electrical dissociation. Cardiomyocytes and cardiac fibroblasts are 2 major myocardial cell types, which constitute o50% and 40–60% of the total cell population, respectively [2,3]. In normal adult hearts, quiescent fibroblasts substantially outnumber myocytes, and in response to hemodynamic stress or injury, these fibroblasts differentiate into myofibroblasts that proliferate, secrete collagen, and synthesize new proteins such as α-smooth muscle actin (α-SMA), stretch-sensitive ion channels, and connexins [4]. Fibroblasts have arrhythmogenic properties such as those involved in blocking impulse propagation and differentiation into myofibroblasts, which have contractility, have electrical connectivity and stimulate electrical impulse. The alteration of fibroblast-induced electrical impulses depends on the number of fibroblasts: small numbers of fibroblasts lead to slow impulse conduction whereas large numbers of fibroblasts lead to conduction block [5]. Recently,

Abstract 180: Differential Role of Endothelin-1 in Mitral Stenosis and Atrial Fibrillation

Background Chronic atrial stretch due to mitral stenosis is a major substrate for the development of atrial fibrillation (AF). It is well established that rhuematic mitral stenosis and AF are associated with an increased risk of thromboembolic events. Endothelin-1 (ET-1) is a potent vasoconstrictor and modulator of vascular function, and is known to play a role in thrombus formation. We therefore sought to compare ET-1 levels between patients with rheumatic mitral stenosis and AF. Methods We measured plasma levels of ET-1 in blood samples from the femoral vein (FV), right atria (RA) and left atria (LA) obtained from 19 patients with rheumatic mitral stenosis, 12 patients with lone AF and 10 subjects with supraventricular tachycardia (reference subjects [REF]). Plasma ET-1 levels were measured by conventional ELISA techniques. Results The FV concentrations of ET-1 were significantly higher in rheumatic mitral stenosis patients than in AF patients or REF subjects (Figure). However, there was no significant difference in the concentrations of ET-1 between AF patients and REF subjects. In rheumatic mitral stenosis patients and REF subjects there were no differences in concentrations of ET-1 between the FV, RA and LA. In contrast, ET-1 levels were highest in the femoral vein of AF patients (FV vs RA p&lt;0.03 and FV vs LA p&lt;0.06). Conclusion Patients with rheumatic mitral stenosis have significantly higher ET-1 levels than AF patients. These data suggest that ET-1 plays a differential role in the pathophysiology of thrombus formation in mitral stenosis and AF. It highlights the importance of the underlying substrate to the risk of developing thrombus within the atria.

Oleanolic acid increases plasma ANP levels via an accentuation of cardiac ANP synthesis and secretion in rats

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.

Atrial and brain natriuretic peptide changes in an experimental model of intra-abdominal hypertension

BackgroundIntra-abdominal hypertension (IAH) can have a profound impact on the cardiovascular system. We hypothesized that natriuretic peptides (Nt-pro-ANP and Nt-pro-BNP) are produced in response to the cardiovascular changes observed in an experimental model of IAH. Materials and methodsEleven female pigs were enrolled in this study. Four experimental phases were created: a baseline phase for instrumentation (T1); two subsequent phases (T2 and T3), in which helium pneumoperitoneum was established at 20 and 35 mm Hg, respectively; and the final phase (T4), in which abdominal desufflation took place. Hemodynamic parameters and concentrations of Nt-pro-ANP and Nt-pro-BNP were measured. ResultsCentral venous pressure and pulmonary capillary wedge pressure increased significantly during the elevation of intra-abdominal pressure (IAP) and returned to baseline after abdominal desufflation. Right and left transmural pressures remained unaffected by the elevation of IAP. Cardiac output decreased in phases T2 and T3 and was restored to baseline levels after abdominal desufflation. Systemic and pulmonary vascular resistances increased significantly with IAH and decreased after abdominal desufflation. Nt-pro-ANP did not change significantly in comparison to baseline. Nt-pro-BNP increased significantly in comparison to baseline at T3 and T4. Peak Nt-pro-BNP levels at T3 (peak IAP) correlated positively with indices of afterload at this time point, that is, systemic vascular resistance and pulmonary vascular resistance (r2 = 0.38, P = 0.042 and r2 = 0.55, P = 0.009, respectively). A strong negative correlation between Nt-pro-BNP and cardiac output at T3 was also demonstrated (r2 = 0.58, P = 0.006). ConclusionsIAH resulted in cardiovascular compromise. The unchanged Nt-pro-ANP concentrations might reflect unaltered atrial stretch with IAH, despite the elevation of right atrial filling pressure. The significant increase of Nt-pro-BNP in response to high levels of IAP may reflect left ventricular strain and dysfunction due to the severe IAH and provide an alternative marker in the monitoring of IAH.

Phospholipase C signaling tonically represses basal atrial natriuretic factor secretion from the atria of the heart

The cardiac hormone atrial natriuretic factor (ANF or ANP) plays significant, well-established roles in a large number of physiological and pathophysiological processes, including water and electrolyte balance, blood pressure regulation, and cardiovascular growth. Understanding the regulation of its production and secretion by atrial cardiomyocytes is incomplete. We have previously established a significant role of G(i/o) protein signaling in modulating ANF secretion as promoted by stretch of the atrial myocardium. In the present study, we investigated the role of G(q) protein signaling and its relationship to G(i/o) protein signaling using pharmacological manipulation of proximal effectors of G(αq) in an ex vivo model of spontaneously beating rat atria. Phospholipase C (PLC) and protein kinase C (PKC) inhibitors dramatically increased basal secretion of ANF. Furthermore, although atrial wall stretch is a potent stimulus for secretion, stretch unexpectedly reduced ANF secretion to basal levels under PLC and PKC inhibitory conditions. Inhibition of the inositol triphosphate receptor did not appear to affect basal secretion but dose-dependently blocked stretch-secretion coupling. The results obtained demonstrate that the PLC and PKC signaling cascades play important albeit unexpected roles in the regulation of basal and stimulated ANF secretion and suggest interplay between the G(q) and G(i/o) protein signaling pathways.

Angiotensin III stimulates high stretch-induced ANP secretion via angiotensin type 2 receptor

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.

Sodium channel block by ranolazine in an experimental model of stretch-related atrial fibrillation: prolongation of interatrial conduction time and increase in post-repolarization refractoriness

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. 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. 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.

Atrial stretch delays gastric emptying of liquids in awake rats

AimsWe previously reported that mechanical atrial stretch (AS) by balloon distention increased gastric tonus in anesthetized rats. The present study evaluated the effect of AS on the gastric emptying of a liquid test meal in awake rats and its underlying neural mechanisms. Main methodsAnesthetized male rats received a balloon catheter into the right atrium and a gastrostomy cannula. The next day, mean arterial pressure (MAP), heart rate (HR), central venous pressure (CVP), and cardiac output (CO) were continuously monitored. After the first 20min of monitoring (basal interval), the balloon was either distended or not (control) with 30, 50, or 70μl saline for 5min. Fifteen minutes later, the rats received the test meal (glucose solution with phenol red), and fractional gastric dye retention was determined 10, 20, or 30min later. Key findingsHeart rate and CVP values were transiently increased by 50 or 70μl AS but not 30μl AS, whereas gastric emptying was slower after 30, 50, or 70μl AS than after sham distention. Subdiaphragmatic vagotomy or splanchnicotomy+celiac ganglionectomy and capsaicin, ondansetron, hexamethonium, L-NAME, and glibenclamide treatment prevented the AS-induced delay in gastric emptying, whereas atropine and guanethidine treatment failed to prevent it. SignificanceAtrial stretch inhibited the gastric emptying of liquid via non-adrenergic and non-cholinergic pathways that activate nitric oxide-K+ATP channels.

Improvements in Left Atria and Vascular Function 24 h Following the Reversal of Chronic Atrial Stretch

Improvements in Left Atria and Vascular Function 24 h Following the Reversal of Chronic Atrial Stretch

Impact of Atrial Fibrillation On Cardiovascular Mortality in the Setting of Myocardial Infarction.

Atrial fibrillation (AF) commonly occurs in patient with acute myocardial infarction (AMI). Potential triggers for AF development in this setting includes reduced left ventricular function, advanced diastolic dysfunction and mitral regurgitation leading to elevated left atrial pressures and atrial stretch. Other triggering mechanisms include inflammation and atrial ischemia. Multiple studies have shown that AF in patients with is associated with increased mortality. However, whether AF is a risk marker or a causal mediator of death remains controversial. There is relative dearth of data with regard to optimal management of AF in the setting of acute coronary syndromes. Patients with AMI who develop AF are at increased risk of stroke. However, the issue of the most appropriate antithrombotic regimens is complex given the need to balance stroke prevention against recurrent coronary events or stent thrombosis and the risk of bleeding. Presently, 'triple therapy' consisting of dual antiplatelet agents plus oral anticoagulants for 3-6 months or longer has been recommended for patients at moderate-high risk of stroke. Atrial fibrillation (AF), the most common sustained arrhythmia seen in clinical practice, often coincides with acute myocardial infarction (AMI), with a reported incidence ranging between 7% and 21%.[1] The development of atrial fibrillation in the acute phase of AMI may aggravate ischemia and heart failure, lead to clinical instability and adversely affect outcome. In the following we will review the pathophysiology, clinical characteristics and importance, and management of AF occurring in the setting of AMI.

Heart Failure

See related article, pp 327–332 Atrial and brain natriuretic peptides (ANP and BNP) possess important regulatory cardiorenal functions, such as promoting natriuresis, diuresis, vasodilatation, and activation of antihypertrophic responses on pathophysiological stress. Release of ANP and BNP is significantly increased in response to atrial and ventricular stretch, respectively. Both ANP and BNP are produced and stored as prohormones and are present in the circulation as a mixture of propeptide and active 28- and 32-amino acid, carboxyl-terminal peptide hormones, respectively.1 Both ANP and BNP bind to the natriuretic peptide receptor-A, which is coupled to particulate guanylate cyclase to generate cGMP, the primary second messenger mediating downstream signaling cascades in target tissues. Despite stimulation of the same receptor, the physiological effects of ANP and BNP are somewhat different: ANP predominantly regulates sodium-water homeostasis and blood pressure, whereas BNP has more antihypertrophic effects, although there is substantial overlap.1 In theory, increases in generation of ANP and BNP in response to myocardial stretch should occur as part of compensatory mechanism(s) to restore homeostatic balance. However, the lusitropic, antihypertrophic, and natriuretic effects of ANP and BNP are significantly attenuated in congestive heart failure despite a considerable apparent increase in plasma concentrations. It is now increasingly accepted that the key reason for this discrepancy is because of variable activation/processing of natriuretic peptides, resulting in much greater proportion …

Resetting the baroreflex during snoring: Role of resistive loading and intra-thoracic pressure

Baroreflex sensitivity (BRS) is reduced during snoring in humans and animal models. We utilised our rabbit model to examine the contribution of increased upper airway resistance to baroreflex resetting during snoring, by comparing BRS and baroreflex operating point (OP) values during IS to those obtained during tracheostomised breathing through an external resistive load (RL) titrated to match IS levels of peak inspiratory pleural pressure (Ppl). During both IS and RL, BRS decreased by 45% and 49%. There was a linear relationship between the change in Ppl and the decrease in BRS, which was similar for IS and RL. During both RL and IS, there was a shift in OP driven by ∼16% increase in HR and no change in arterial pressure. Snoring related depression of BRS is likely mediated via a HR driven change in OP, which itself may be the outcome of negative intra-thoracic pressure mediated effects on right atrial wall stretch reflex control of heart rate.

Abstract 19395: Increased Multiple Firing of Single Muscle Vasoconstrictor Neurons during Lower Body Positive Pressure in Human Heart Failure

Introduction: Functionally specific efferent renal sympathetic nerves fire selectively in response to distinct hemodynamic afferent inputs. Using norepinephrine spillover, our group detected a heart failure (HF)-specific cardio-cardiac sympathoexcitatory reflex stimulated by high atrial pressure. Efferent discharge directed at other vascular beds similarly activated by atrial stretch might not be detected by multi-unit sympathetic recordings. Hypothesis: In contrast to healthy controls (CON), in HF some muscle sympathetic fibers respond paradoxically (i.e. increase firing) to increases in filling pressure. Methods: Single-unit muscle sympathetic nerve activity (sMSNA; microneurography) and peripheral venous pressure (PVP; forearm catheter) were recorded from 11 CON and 10 treated HF (LVEF 27±6%) patients at baseline and during non-hypotensive lower body negative pressure (LBNP; -10mmHg) and non-hypertensive lower body positive pressure (LBPP; +10mmHg). sMSNA firing frequency and incidence, and the percentage of multiple within-burst firing was calculated for each condition. Results: PVP was reduced with LBNP (p&lt;0.05) and increased with LBPP (p&lt;0.05) in both groups, with PVP greater in HF across each condition (p&lt;0.05). Blood pressure and heart rate were unchanged by LBNP or LBPP in both groups (p&gt;0.05). We identified 26 and 22 single-units in CON and HF patients, respectively. sMSNA firing frequency was similar (p&gt;0.05) in CON and HF at baseline (30±18 vs. 35±15 spikes/min) and during LBNP (45±24 vs. 42±23 spikes/min) but higher in HF during LBPP (28±17 vs. 40±22 spikes/min, p=0.05). sMSNA firing incidence was similar (p&gt;0.05) in both groups across each condition. The percentage of within-burst multiple spike firing was similar (p&gt;0.05) in CON and HF during baseline (24±9% vs. 24±7%) and LBNP (25±11% vs. 28±14%) but higher in HF during LBPP (17±8% vs. 34±16%, p&lt;0.001). Conclusions: In HF, increases in PVP with non-hypertensive LBPP cause a paradoxical increase in muscle sympathetic single-unit firing frequency and multiple within-burst firing, compared to CON. This provides evidence of a sympathoexcitatory cardiac-skeletal muscle vasoconstrictor reflex in human HF that may be attenuated by normalizing filling pressures.

Electrophysiological effects of acute atrial stretch on persistent atrial fibrillation in patients undergoing open heart surgery

The electrophysiologic effects of acute atrial dilatation and dedilatation in humans with chronic atrial fibrillation remains to be elucidated. To study the electrophysiological effects of acute atrial dedilatation and subsequent dilatation in patients with long-standing persistent atrial fibrillation (AF) with structural heart disease undergoing elective cardiac surgery. Nine patients were studied. Mean age was 71 ± 10 years, and left ventricular ejection was 46% ± 6%. Patients had at least moderate mitral valve regurgitation and dilated atria. After sternotomy and during extracorporal circulation, mapping was performed on the beating heart with 2 multielectrode arrays (60 electrodes each, interelectrode distance 1.5 mm) positioned on the lateral wall of the right atrium (RA) and left atrium (LA). Atrial pressure and size were altered by modifying extracorporal circulation. AF electrograms were recorded at baseline after dedilation and after dilatation of the atria afterward. At baseline, the median AF cycle length (mAFCL) was 184 ± 27 ms in the RA and 180 ± 17 ms in the LA. After dedilatation, the mAFCL shortened significantly to 168 ± 13 ms in the RA and to 168 ± 20 ms in the LA. Dilatation lengthened mAFCL significantly to 189 ± 17 ms in the RA and to 185 ± 23 ms in the LA. Conduction block (CB) at baseline was 14.3% ± 3.6% in the RA and 17.3% ± 5.5% in the LA. CB decreased significantly with dedilatation to 7.4% ± 2.9% in the RA and to 7.9% ± 6.3% in the LA. CB increased significantly with dilatation afterward to 15.0% ± 8.3% in the RA and to 18.5% ± 16.0% in the LA. Acute dedilatation of the atria in patients with long-standing persistent AF causes a decrease in the mAFCL in both atria. Subsequent dilatation increased the mAFCL. The amount of CB decreased with dedilatation and increased with dilatation afterward in both atria.

Estimated glomerular filtration rate and proteinuria are associated with persistent form of atrial fibrillation: Analysis in Japanese patients

BackgroundSeveral reports have identified that decline in renal function and presence of proteinuria are closely associated with incidence of atrial fibrillation (AF). However, it is still unclear whether these kidney-related markers are associated with the progression of AF from paroxysmal to persistent form. Methods and resultsAmong the new patients who visited the Cardiovascular Institute Hospital between 2004 and 2010 (Shinken Database 2004–2010, n=15,227), both estimated glomerular filtration rate (eGFR) and proteinuria were measured in 1074 AF patients (paroxysmal/persistent 579/495, respectively), who were divided into tertiles of eGFR (the borderlines were 60.07 and 73.67ml[min−1]1.73[m−2], respectively), and then further divided into the two categories with/without proteinuria. The average value of eGFR was lower (63.1ml[min−1]1.73[m−2] vs. 68.8ml[min−1]1.73[m−2], p<0.001) and the detection rate of proteinuria was higher (13.7% vs. 8.5%, p=0.006) in patients with persistent AF than in those with paroxysmal AF, respectively. In the multivariate analysis without parameters of echocardiography [left ventricular ejection fraction (LVEF) and left atrial dimension (LAD)], both eGFR and proteinuria were independently associated with persistent AF, but the association was abolished when the model included LAD and LVEF. ConclusionsIn the present analysis with cross-sectional design, both eGFR and proteinuria were apparently linked to the persistent form of AF, but their role in the pathogenesis does not seem to exceed the atrial stretch and remodeling, represented by LAD and LVEF.

Could Plugging the Oxidation-Mediated Ca 2+ Leak Stem the Tide of the Atrial Fibrillation Epidemic?

As the most common sustained arrhythmia, atrial fibrillation (AF) afflicts >2 million patients in the United States alone, and this number is predicted to double by the year 2050.1 Although AF is not life-threatening, it is linked to a 2-fold increase in mortality when present as a comorbidity in heart disease patients.2,3 AF can have devastating consequences, such as stroke, impaired cardiac performance, and promotion of cardiomyopathy. The treatment of AF can also produce life-threatening side effects, such as ventricular arrhythmias and hemorrhage. AF patients are generally classified as paroxysmal (episodes lasting 7 days but treated to restore sinus rhythm), or permanent (no attempt to restore sinus rhythm).2,3 AF is usually secondary to other conditions such as hypertension, heart failure, valvular disease, sleep apnea, hyperthyroidism, and diabetes. Most of these AF-inducing conditions are associated with elevated atrial pressure and atrial stretch, as well as increased oxidative stress and inflammation, which lead to structural and electric changes (remodeling) that create a substrate for supporting AF induction and maintenance.4,5 Article, see p 708 Although the majority of AF patients have preexisting cardiovascular disease, an important subpopulation do not and are therefore referred to as “lone AF” patients. Besides the obvious increase in stroke risk, a major concern with lone AF patients is their predisposition to develop persistent or permanent AF, because bouts of AF appear to promote more AF (ie, AF begets AF), which leads to chronic AF and its associated complications. It has long been suspected that many lone AF patients, particularly those afflicted at a relatively young age, have underlying genetic factors predisposing to AF. Indeed, many single-gene mutations and some polymorphisms are linked to electric and structural changes in atria that are predicted to promote …