Structural atrial remodeling alters the substrate and spatiotemporal organization of atrial fibrillation: a comparison in canine models of structural and electrical atrial remodeling

Several animal models of atrial fibrillation (AF) have been developed that demonstrate either atrial structural remodeling or atrial electrical remodeling, but the characteristics and spatiotemporal organization of the AF between the models have not been compared. Thirty-nine dogs were divided into five groups: rapid atrial pacing (RAP), chronic mitral regurgitation (MR), congestive heart failure (CHF), methylcholine (Meth), and control. Right and left atria (RA and LA, respectively) were simultaneously mapped during episodes of AF in each animal using high-density (240 electrodes) epicardial arrays. Multiple 30-s AF epochs were recorded in each dog. Fast Fourier transform was calculated every 1 s over a sliding 2-s window, and dominant frequency (DF) was determined. Stable, discrete, high-frequency areas were seen in none of the RAP or control dogs, four of nine MR dogs, four of six CHF dogs, and seven of nine Meth dogs in either the RA or LA or both. Average DFs in the Meth model were significantly greater than in all other models in both LA and RA except LA DFs in the RAP model. The RAP model was the only one with a consistent LA-to-RA DF gradient (9.5 +/- 0.2 vs. 8.3 +/- 0.3 Hz, P < 0.00005). The Meth model had a higher spatial and temporal variance of DFs and lower measured organization levels compared with the other AF models, and it was the only model to show a linear relationship between the highest DF and dispersion (R(2) = 0.86). These data indicate that structural remodeling of atria (models known to have predominantly altered conduction) leads to an AF characterized by a stable high-frequency area, whereas electrical remodeling of atria (models known to have predominantly shortened refractoriness without significant conduction abnormalities) leads to an AF characterized by multiple high-frequency areas and multiple wavelets.     

Direction-dependent conduction abnormalities in a canine model of atrial fibrillation due to chronic atrial dilatation

Chronic rapid atrial pacing (RAP) leads to changes that perpetuate atrial fibrillation (AF). Chronic atrial dilatation due to mitral regurgitation (MR) also increases AF inducibility, but it is not clear whether the underlying mechanism is similar. Therefore, we have investigated atrial electrophysiology in a canine MR model (mitral valve avulsion, 1 mo) using high-resolution optical mapping and compared it with control dogs and with the canine RAP model (6-8 wk of atrial pacing at 600 beats/min, atrioventricular block, and ventricular pacing at 100 beats/min). At followup, optical action potentials were recorded using a 16 x 16 photodiode array from 2 x 2-cm left atrial (LA) and right atrial (RA) areas in perfused preparations, with pacing electrodes around the field of view to study direction dependency of conduction. Action potential duration at 80% repolarization (APD(80)) was not different between control and MR but was reduced in RAP atria. Conduction velocities during normal pacing were not different between groups. However, the MR LA showed increased conduction heterogeneity during pacing at short cycle lengths and during premature extrastimuli, which frequently caused pronounced regional conduction slowing. Conduction in the MR LA during extrastimulation also displayed a marked dependence on propagation direction. These phenomena were not observed in the MR RA and in control and RAP atria. Thus both models form distinctly different AF substrates; in RAP dogs, the decrease in APD(80) may stabilize reentry. In MR dogs, regional LA conduction slowing and increased directional dependency, allowing unidirectional conduction block and preferential paths of conduction, may account for increased AF inducibility.     

Echocardiographic [correction of Ehocardiographic] evaluation of regional left atrial function after rapid atrial pacing

Rapid regular atrial pacing (RAP) produces changes in atrial function similar to those caused by atrial fibrillation in animal models. Left atrial appendage (LAA) function represents regional atrial function. The aim of our study was to investigate the influence of RAP on left atrial regional function and to evaluate the reversibility of changes after termination of pacing in a canine model. Eight dogs were subjected to RAP (400 bpm) for 16 days. Transesophageal echocardiography was performed at baseline, immediately after RAP and 4 weeks after the termination of RAP. The LAA peak late emptying velocity (LAA-E) and filling wave (LAA-f) were measured. LAA-E velocities were significantly reduced and filling wave velocities (LAA-f) were significantly less negative after RAP compared with the baseline values. Four weeks after termination of pacing, the LAA-E and LAA-f velocities were normal. RAP results in impaired regional atrial systolic and diastolic function. The changes were completely reversible 4 weeks after termination of pacing. These results suggest that the LAA is mechanically stunned after RAP.     

Left atrial dilatation resulting from chronic mitral regurgitation decreases spatiotemporal organization of atrial fibrillation in left atrium

Atrial conduction properties have been shown to differ among animal atrial fibrillation (AF) models of rapid atrial pacing (RAP), chronic mitral regurgitation (MR), and control. We hypothesized that these conduction differences would continue with the onset of AF, which would affect AF spatiotemporal organization, resulting in model-specific characteristics of AF. With frequency domain analysis of electrograms acquired from high-density optical mapping, AF from the right (RA) and left (LA) atrium in animals with RAP and MR were compared with control animals. At follow-up, the hearts were excised and perfused, and optical action potentials were recorded from a 2 x 2-cm area each of the RA and LA free wall with a 16 x 16 photodiode array. AF was induced with extra stimuli, several 2.4-s AF episodes were recorded in each dog, and a fast Fourier transform was calculated. The dominant frequency (DF) was determined, and the organization (organization index, OI) was calculated as the ratio of the area under the dominant peak and its harmonics to the total area of the spectrum. All possible pairs of electrograms for each episode were cross-correlated. LA AF in the chronic MR model showed an increase in the highest DF, the number of DF domains, and in frequency gradient compared with AF in control or RAP models. In addition, there was a decrease in OI and in the correlation coefficients in the LA of the MR model. These results suggest that the AF substrate in the MR model may be different from that of control or RAP models.     

Differential modulation of right ventricular strain and right atrial mechanics in mild vs. severe pressure overload

Increased right atrial (RA) and ventricular (RV) chamber volumes are a late maladaptive response to chronic pulmonary hypertension. The purpose of the current investigation was to characterize the early compensatory changes that occur in the right heart during chronic RV pressure overload before the development of chamber dilation. Magnetic resonance imaging with radiofrequency tissue tagging was performed on dogs at baseline and after 10 wk of pulmonary artery banding to yield either mild RV pressure overload (36% rise in RV pressure; n = 5) or severe overload (250% rise in RV pressure; n = 4). The RV free wall was divided into three segments within a midventricular plane, and circumferential myocardial strain was calculated for each segment, the septum, and the left ventricle. Chamber volumes were calculated from stacked MRI images, and RA mechanics were characterized by calculating the RA reservoir, conduit, and pump contribution to RV filling. With mild RV overload, there were no changes in RV strain or RA function. With severe RV overload, RV circumferential strain diminished by 62% anterior (P = 0.04), 42% inferior (P = 0.03), and 50% in the septum (P = 0.02), with no change in the left ventricle (P = 0.12). RV filling became more dependent on RA conduit function, which increased from 30 ± 9 to 43 ± 13% (P = 0.01), than on RA reservoir function, which decreased from 47 ± 6 to 33 ± 4% (P = 0.04), with no change in RA pump function (P = 0.94). RA and RV volumes and RV ejection fraction were unchanged from baseline during either mild (P > 0.10) or severe RV pressure overload (P > 0.53). In response to severe RV pressure overload, RV myocardial strain is segmentally diminished and RV filling becomes more dependent on RA conduit rather than reservoir function. These compensatory mechanisms of the right heart occur early in chronic RV pressure overload before chamber dilation develops.     

A novel framework of circulatory equilibrium

A novel framework of circulatory equilibrium was developed by extending Guyton's original concept. In this framework, venous return (CO(V)) for a given stressed volume (V) was characterized by a flat surface as a function of right atrial pressure (P(RA)) and left atrial pressure (P(LA)) as follows: CO(V) = V/W - G(S)P(RA) - G(P)P(LA), where W, G(S), and G(P) denote linear parameters. In seven dogs under total heart bypass, CO(V), P(RA), P(LA), and V were varied to determine the three parameters in each animal with use of multivariate analysis. The coefficient of determination (r(2) = 0.92-0.99) indicated the flatness of the venous return surface. The averaged surface was CO(V) = V/0.129 - 19.61P(RA) - 3.49P(LA). To examine the invariability of the surface parameters among animals, we predicted the circulatory equilibrium in response to changes in stressed volume in another 12 dogs under normal and heart failure conditions. This was achieved by equating the standard surface with the individually measured cardiac output (CO) curve. In this way, we could predict CO [y = 0.90x + 5.6, r(2) = 0.95, standard error of the estimate (SEE) = 8.7 ml.min(-1).kg(-1)], P(RA) (y = 0.96x, r(2) = 0.98, SEE = 0.2 mmHg), and P(LA) (y = 0.89x + 0.5, r(2) = 0.98, SEE = 0.8 mmHg) reasonably well. We conclude that the venous return surface accurately represents the venous return properties of the systemic and pulmonary circulations. The characteristics of the venous return surface are invariable enough among animals, making it possible to predict circulatory equilibrium, even if those characteristics are unknown in individual animals.     

Left Ventricular Diastolic Dysfunction Assessment with Dual-Source CT

PurposeTo assess the impact of left ventricular (LV) diastolic dysfunction on left atrial (LA) phasic volume and function using dual-source CT (DSCT) and to find a viable alternative prognostic parameter of CT for LV diastolic dysfunction through quantitative evaluation of LA phasic volume and function in patients with LV diastolic dysfunction.ResultsLA ejection fraction (LAEF), LA contraction, reservoir, and conduit function in patients in impaired relaxation group were not different from those in the normal group, but they were lower in patients in the pseudonormal and restrictive LV diastolic dysfunction groups (P < 0.05). For LA conduit function, there were no significant differences between the patients in the pseudonormal group and restrictive filling group (P = 0.195). There was a strong correlation between the indexed maximal left atrial volume (LAVmax, r = 0.85, P < 0.001), minimal left atrial volume (LAVmin, r = 0.91, P < 0.001), left atrial volume at the onset of P wave (LAVp, r = 0.84, P < 0.001), and different stages of LV diastolic function. The LAVi increased as the severity of LV diastolic dysfunction increased.ConclusionsLA remodeling takes place in patients with LV diastolic dysfunction. At the same time, LA phasic volume and function parameters evaluated by DSCT indicated the severity of the LV diastolic dysfunction. Quantitative analysis of LA phasic volume and function parameters using DSCT could be a viable alternative prognostic parameter of LV diastolic function.     

Metformin regulates adiponectin signalling in epicardial adipose tissue and reduces atrial fibrillation vulnerability

Epicardial adipose tissue (EAT) remodelling is closely related to the pathogenesis of atrial fibrillation (AF). We investigated whether metformin (MET) prevents AF‐dependent EAT remodelling and AF vulnerability in dogs. A canine AF model was developed by 6‐week rapid atrial pacing (RAP), and electrophysiological parameters were measured. Effective refractory periods (ERP) were decreased in the left and right atrial appendages as well as in the left atrium (LA) and right atrium (RA). MET attenuated the RAP‐induced increase in ERP dispersion, cumulative window of vulnerability, AF inducibility and AF duration. RAP increased reactive oxygen species (ROS) production and nuclear factor kappa‐B (NF‐κB) phosphorylation; up‐regulated interleukin‐6 (IL‐6), tumour necrosis factor‐α (TNF‐α) and transforming growth factor‐β1 (TGF‐β1) levels in LA and EAT; decreased peroxisome proliferator‐activated receptor gamma (PPARγ) and adiponectin (APN) expression in EAT and was accompanied by atrial fibrosis and adipose infiltration. MET reversed these alterations. In vitro, lipopolysaccharide (LPS) exposure increased IL‐6, TNF‐α and TGF‐β1 expression and decreased PPARγ/APN expression in 3T3‐L1 adipocytes, which were all reversed after MET administration. Indirect coculture of HL‐1 cells with LPS‐stimulated 3T3‐L1 conditioned medium (CM) significantly increased IL‐6, TNF‐α and TGF‐β1 expression and decreased SERCA2a and p‐PLN expression, while LPS + MET CM and APN treatment alleviated the inflammatory response and sarcoplasmic reticulum Ca²⁺ handling dysfunction. MET attenuated the RAP‐induced increase in AF vulnerability, remodelling of atria and EAT adipokines production profiles. APN may play a key role in the prevention of AF‐dependent EAT remodelling and AF vulnerability by MET.     

Transient outward potassium current in rabbit atrium is depressed after short-time rapid atrial pacing but recovers after a longer pacing period

In rabbit, after short-time rapid atrial pacing (RAP), atrial ion currents are reduced similarly as in human chronic atrial fibrillation (AF). Using the rabbit model, time-course of transient outward potassium current (I(to)) remodeling due to RAP was studied. RAP (600 bpm) was applied via an atrial lead for 0 (control), 24 and 120 h, n = 4 animals/group. Using patch clamp technique in whole-cell mode, current densities and biophysical properties were measured in isolated atrial myocytes. After 24 h of RAP, a reduction of peak I(to) (mean +/- SEM, test potential +50 mV, +37 degrees C) was observed (60.3 +/- 5.4 pA/pF (control, n = 20) vs. 28.0 +/- 2.5 pA/pF (24 h, n = 21)). Inactivation of I(to) was slower after 24 h, other biophysical properties were unaltered. However, I(to) recovered after 120 h: 51.7 +/- 4.5 pA/pF (n = 26, p = n.s. vs. control). Inactivation tended to also recover to initial values but was still different to control. Early I(to) remodeling due to RAP in rabbits seems to be more complex than previously thought: a time course of I(to) remodeling with swayings has to be considered when using the rabbit model of RAP in order to study early remodeling or rather its therapeutic manipulation.     

山羊房颤模型中左心房与肺静脉外膜碎裂电位的动态比较

目的:比较在持续性房颤发生、发展过程中,房颤模型山羊左心房与肺静脉外膜碎裂电位(CFAEs)的变 化,以期探讨肺静脉外膜碎裂电位(CFAEs)在持续性房颤中的作用.方法:选取10只雌性山羊,使用左心房快速刺激,发送输出电压为6 V、周长为20 ms的脉冲1 s,间隔2 s后重复发放,以此方法建立持续性房颤模型(房颤持续...     

The impact of baseline artery diameter on flow-mediated vasodilation: a comparison of brachial and radial artery responses to matched levels of shear stress

An inverse relationship between baseline artery diameter (BAD) and flow-mediated vasodilation (FMD) has been identified using reactive hyperemia (RH) to create a shear stress (SS) stimulus in human conduit arteries. However, RH creates a SS stimulus that is inversely related to BAD. The purpose of this study was to compare FMD in response to matched levels of SS in two differently sized upper limb arteries [brachial (BA) and radial (RA) artery]. With the use of exercise, three distinct, shear rate (SR) stimuli were created (SR = blood velocity/vessel diameter; estimate of SS) in the RA and BA. Artery diameter and mean blood velocity were assessed with echo and Doppler ultrasound in 15 healthy male subjects (19-25 yr). Data are means ± SE. Subjects performed 6 min of adductor pollicis and handgrip exercise to increase SR in the RA and BA, respectively. Exercise intensity was modulated to achieve uniformity in SR between arteries. The three distinct SR levels were as follows: steady-state exercise 39.8 ± 0.6, 57.3 ± 0.7, and 72.4 ± 1.2 s(-1) (P < 0.001). %FMD and AbsFMD (mm) at the end of exercise were greater in the RA vs. the BA at each shear level [at the highest level: RA = 15.7 ± 1.5%, BA = 5.4 ± 0.8% (P < 0.001)]. The mean slope of the within-subject SR-%FMD regression line was greater in the RA (RA = 0.33 ± 0.04, BA = 0.13 ± 0.02, P < 0.001), and a strong within-subjects relationship between %FMD and SR was observed in both arteries (RA: r(2) = 0.92 ± 0.02; BA: r(2) = 0.90 ± 0.03). Within the RA, there was a significant relationship between baseline diameter and %FMD; however, this relationship was not present in the BA (RA: r(2) = 0.76, P < 0.001; BA: r(2) = 0.03, P = 0.541). These findings suggest that the response to SS is not uniform across differently sized vessels, which is in agreement with previous studies.     

Myocardial function defined by strain rate and strain during alterations in inotropic states and heart rate

For porcine myocardium, ultrasonic regional deformation parameters, systolic strain (epsilon(sys)) and peak systolic strain rate (SR(sys)), were compared with stroke volume (SV) and contractility [contractility index (CI)] measured as the ratio of end-systolic strain to end-systolic wall stress. Heart rate (HR) and contractility were varied by atrial pacing (AP = 120-180 beats/min, n = 7), incremental dobutamine infusion (DI = 2.5-20 microg. kg(-1). min(-1), n = 7), or continuous esmolol infusion (0.5 mg. kg(-1). min(-1)) + subsequent pacing (120-180 beats/min) (EI group, n = 6). Baseline SR(sys) and epsilon(sys) averaged 5.0 +/- 0.4 s(-1) and 60 +/- 4%. SR(sys) and CI increased linearly with DI (20 microg. kg(-1). min(-1); SR(sys) = 9.9 +/- 0.7 s(-1), P < 0.0001) and decreased with EI (SR(sys) = 3.4 +/- 0.1 s(-1), P < 0.01). During pacing, SR(sys) and CI remained unchanged in the AP and EI groups. During DI, epsilon(sys) and SV initially increased (5 microg. kg(-1). min(-1); epsilon(sys) = 77 +/- 6%, P < 0.01) and then progressively returned to baseline. During EI, SV and epsilon(sys) decreased (epsilon(sys) = 38 +/- 2%, P < 0.001). Pacing also decreased SV and epsilon(sys) in the AP (180 beats/min; epsilon(sys) = 36 +/- 2%, P < 0.001) and EI groups (180 beats/min; epsilon(sys) = 25 +/- 3%, P < 0.001). Thus, for normal myocardium, SR(sys) reflects regional contractile function (being relatively independent of HR), whereas epsilon(sys) reflects changes in SV.     

A modified regimen of extracorporeal cardiac shock wave therapy for treatment of coronary artery disease

Background

Radiofrequency catheter ablation of atrial fibrillation (AF) has been proved to be effective and to prevent progressive left atrial (LA) remodeling. Cryoballoon catheter ablation (CCA), using a different energy source, was developed to simplify the ablation procedure. Our hypothesis was that successful CCA can also prevent progressive LA remodeling.

Methods

36 patients selected for their first CCA because of nonvalvular paroxysmal AF had echocardiography before and 3, 6 and 12 months after CCA. LA diameters, volumes (LAV) and LA volume index (LAVI) were evaluated. LA function was assessed by: early diastolic velocities of the mitral annulus (Aa_sept, Aa_lat), LA filling fraction (LAFF), LA emptying fraction (LAEF) and the systolic fraction of pulmonary venous flow (PVSF). Detailed left ventricular diastolic function assessment was also performed.

Results

Excluding recurrences in the first 3-month blanking period, the clinical success rate was 64%. During one-year of follow-up, recurrent atrial arrhythmia was found in 21 patients (58%). In the recurrent group at 12 months after ablation, minimal LAV (38 ± 19 to 44 ± 20 ml; p < 0.05), maximal LAV (73 ± 23 to 81 ± 24 ml; p < 0.05), LAVI (35 ± 10 to 39 ± 11 ml/m²; p = 0.01) and the maximal LA longitudinal diameter (55 ± 5 to 59 ± 6 mm; p < 0.01) had all increased. PVSF (58 ± 9 to 50 ± 10%; p = 0.01) and LAFF (36 ± 7 to 33 ± 8%; p = 0.03) had decreased. In contrast, after successful cryoballoon ablation LA size had not increased and LA function had not declined. In the recurrent group LAEF was significantly lower at baseline and at follow-up visits.

Conclusions

In patients whose paroxysmal atrial fibrillation recurred within one year after cryoballoon catheter ablation left atrial size had increased and left atrial function had declined. In contrast, successful cryoballoon catheter ablation prevented progressive left atrial remodeling.     

Deceleration time of systolic pulmonary venous flow: a new clinical marker of left atrial pressure and compliance.

The curvilinearity of the atrial pressure-volume curve implies that atrial compliance decreases progressively with increasing left atrial (LA) pressure (LAP). We predicted that reduced LA compliance leads to more rapid deceleration of systolic pulmonary venous (PV) flow. With this rationale, we investigated whether the deceleration time (t dec) of PV systolic flow velocity reflects mean LAP. In eight patients during coronary surgery, before extracorporeal circulation, PV flow by ultrasonic transit time and invasive LAP were recorded during stepwise volume loading. The t dec was calculated using two methods: by drawing a tangent through peak deceleration and by drawing a line from peak systolic flow through the nadir between the systolic and early diastolic flow waves. LA compliance was calculated as the systolic PV flow integral divided by LAP increment. Volume loading increased mean LAP from 11 +/- 3 to 20 +/- 5 mmHg (P < 0.001) (n = 40), reduced LA compliance from 1.16 +/- 0.42 to 0.72 +/- 0.40 ml/mmHg (P < 0.004) (n = 40), and reduced t dec from 320 +/- 50 to 170 +/- 40 ms (P < 0.0005) (n = 40). Mean LAP correlated well with t dec (r = 0.84, P < 0.0005) (n = 40) and LA compliance (r = 0.79, P < 0.0005) (n = 40). Elevated LAP caused a decrease in LA compliance and therefore more rapid deceleration of systolic PV flow. The t dec has potential to become a semiquantitative marker of LAP and an index of LA passive elastic properties.     

星状神经节电刺激建立交感神经介导的急性房颤犬模型

目的建立交感神经张力异常介导的急性房颤动物模型的方法学。方法将16只随意来源犬分为三组：对照组（n=4）,右侧星状神经节（aSG）组（n=6）和左侧星状神经节（LSG）组（n=6）,测定心房和肺静脉不同部位的房颤诱发率、房颤持续时间。结果RSG刺激显著增加右心房（RA）的房颤诱发率和持续时间（P〈0．05）,LSG刺激显著增加左心房（LA）、左上肺静脉（LSPV）、左下肺静脉（LIPV）的房颤诱发率和持续时间（P〈0．05）;与刺激时相比,RSG切除显著降低RA的房颤诱发率和持续时间（P〈0．05）;LSG切除显著降低LA、LSPV、LIPV的房颤诱发率和持续时间（P〈0．05）。结论星状神经节电刺激同时快速心房起搏6h可成功建立交感神经介导的急性房颤犬模型,星状神经节电刺激使心房和肺静脉部位的房颤诱发率显著升高,房颤持续时间显著延长,去星状神经节支配可减少房颤的发生和维持。     

Clinical impact of atrial fibrillation in patients with pulmonary hypertension

Background

Pulmonary hypertension (PH) is associated with progressive impairment of right ventricular function, reduced exercise capacity and a poor prognosis. Little is known about the prevalence, clinical manifestation and impact of atrial fibrillation (AF) on cardiac function in PH.

Methods

In a four year single-centre retrospective analysis 225 patients with confirmed PH of various origins were enrolled to investigate the prevalence of AF, and to assess the clinical manifestation, 6-minute walk distance, NT-proBNP levels, echocardiographic parameters and hemodynamics obtained by right heart catheterization in PH with AF.

Results

AF was prevalent in 31.1%. In patients with PH and AF, parameters of clinical deterioration (NYHA/WHO functional class, 6-minute walk distance, NT-proBNP levels) and renal function were significantly compromised compared to patients with PH and sinus rhythm (SR). In the total PH cohort and in PH not related to left heart disease occurrence of AF was associated with an increase of right atrial pressure (RAP) and right atrial dilatation. While no direct association was found between pulmonary artery pressure (PAP) and AF in these patients, right ventricular function was reduced in AF, indicating more advanced disease. In PH due to left heart failure the prevalence of AF was particularly high (57.7% vs. 23.1% in other forms of PH). In this subgroup, left atrial dilatation, increase of pulmonary capillary wedge pressure, PAP and RAP were more pronounced in AF than in SR, suggesting that more marked backward failure led to AF in this setting.

Conclusion

PH is associated with increased prevalence of AF. Occurrence of AF in PH indicates clinical deterioration and more advanced disease.     

Left atrial conduit volume is generated by deviation from the constant-volume state of the left heart: a combined MRI-echocardiographic study

Although modeling the four-chambered heart as a constant-volume pump successfully predicts causal physiological relationships between cardiac indexes previously deemed unrelated, the real four-chambered heart slightly deviates from the constant-volume state by ventricular end systole. This deviation has consequences that affect chamber function, specifically, left atrial (LA) function. LA attributes have been characterized as booster pump, reservoir, and conduit functions, yet characterization of their temporal occurrence or their causal relationship to global heart function has been lacking. We investigated LA function in the context of the constant-volume attribute of the left heart in 10 normal subjects using cardiac magnetic resonance imaging (MRI) and contemporaneous Doppler echocardiography synchronized via ECG. Left ventricular (LV) and LA volumes as a function of time were determined via MRI. Transmitral flow, pulmonary vein (PV) flow, and lateral mitral annular velocity were recorded via echocardiography. The relationship between the MRI-determined diastolic LA conduit-volume (LACV) filling rate and systolic LA filling rate correlate well with the relationship between the echocardiographically determined average flow rate during the early portion of the PV D wave and the average flow rate during the PV S wave (r = 0.76). We conclude that the end-systolic deviation from constant volume for the left heart requires the generation of the LACV during diastole. Because early rapid filling of the left ventricle is the driving force for LACV generation while the left atrium remains passive, it may be more appropriate to consider LACV to be a property of ventricular diastolic rather than atrial function.     

Impact of pericardial restraint on right atrial mechanics during acute right ventricular pressure load

Optimization of right atrial (RA) mechanics is important for maintaining right ventricular (RV) filling and global cardiac output. However, the impact of pericardial restraint on RA function and the compensatory role of the right atrium to changes in RV afterload remain poorly characterized. In eight open-chest sheep, RA elastance (contractility) and chamber stiffness were measured (RA pressure-volume relations) at baseline and during partial pulmonary artery (PA) occlusion. Data were collected before and after pericardiotomy. With the pericardium intact and partial PA occlusion, RA elastance increased by 28% (P < 0.04), whereas RA stiffness tended to rise (P = 0.08). However, after pericardiotomy, there was a significant fall in both RA elastance (54%, P < 0.04) and stiffness (39%, P < 0.04), and subsequent PA occlusion failed to induce a change in elastance (P > 0.19) or stiffness (P > 0.84). After pericardiotomy, RA elastance and stiffness fell dramatically, and the compensatory response of the right atrium to elevated RV afterload was lost. The ability of the right atrium to respond to changes in RV hemodynamics is highly dependent on pericardial integrity.     

Ca(2+) handling in isolated human atrial myocardium

Physiologically, human atrial and ventricular myocardium are coupled by an identical beating rate and rhythm. However, contractile behavior in atrial myocardium may be different from that in ventricular myocardium, and little is known about intracellular Ca(2+) handling in human atrium under physiological conditions. We used rapid cooling contractures (RCCs) to assess sarcoplasmic reticulum (SR) Ca(2+) content and the photoprotein aequorin to assess intracellular Ca(2+) transients in atrial and ventricular muscle strips isolated from nonfailing human hearts. In atrial myocardium (n = 19), isometric twitch force frequency dependently (0. 25-3 Hz) increased by 78 +/- 25% (at 3 Hz; P < 0.05). In parallel, aequorin light signals increased by 111 +/- 57% (P < 0.05) and RCC amplitudes by 49 +/- 13% (P < 0.05). Similar results were obtained in ventricular myocardium (n = 13). SR Ca(2+) uptake (relative to Na(+)/Ca(2+) exchange) frequency dependently increased in atrial and ventricular myocardium (P < 0.05). With increasing rest intervals (1-240 s), atrial myocardium (n = 7) exhibited a parallel decrease in postrest twitch force (at 240 s by 68 +/- 5%, P < 0.05) and RCCs (by 49 +/- 10%, P < 0.05). In contrast, postrest twitch force and RCCs significantly increased in ventricular myocardium (n = 6). We conclude that in human atrial and ventricular myocardium the positive force-frequency relation results from increased SR Ca(2+) turnover. In contrast, rest intervals in atrial myocardium are associated with depressed contractility and intracellular Ca(2+) handling, which may be due to rest-dependent SR Ca(2+) loss (Ca(2+) leak) and subsequent Ca(2+) extrusion via Na(+)/Ca(2+) exchange. Therefore, the influence of rate and rhythm on mechanical performance is not uniform in atrial and ventricular myocardium.     

Left Atrial Systolic and Diastolic Dysfunction in Patients with Chronic Constrictive Pericarditis: A Study Using Speckle Tracking and Conventional Echocardiography

Background

Left atrial (LA) function plays an important role in the maintenance of cardiac output, however, in patients with constrictive pericarditis (CP), whether pericardial restriction and adhesion can lead to LA dysfunction, and the characteristics of LA function remain unclear. The aim of the study is to compare the left atrial (LA) function of patients with CP to that of healthy study participants using speckle tracking echocardiography (STE) and conventional echocardiography.

Methods and Results

Thirty patients with CP and 30 healthy volunteers (controls) were enrolled in the study. The underlying cause of CP was viral pericarditis in 24 (80%) patients and unknown in 6 (20%) patients. The LA maximum volume (Vmax), LA minimal volume (Vmin), and LA volume before atrial contraction (Vpre-a) were measured using biplane modified Simpson’s method. The LA expansion index (LA reservoir function) was determined as follows: ([LAVmax - LAVmin]/LAVmin) ×100. The passive emptying index (LA conduit function) was calculated as follows: ([LAVmax - LAVpre-a]/LAVmax) ×100, and the active emptying index (booster pump function) was calculated as follows: ([LAVpre-a - LAVmin]/LAVpre-a) ×100. All the patients underwent two-dimensional STE. The LA global systolic strain (S), systolic strain rate (SrS), early diastolic strain rate (SrE) and late diastolic strain rate (SrA) were measured. The LA expansion index, passive emptying index, the active emptying index and the LA global S, SrS, SrE, SrA were found to be significantly lower in patients with CP than in the control participants (P <0.001). LA function was correlated with the early diastolic velocity of the lateral mitral annulus (P <0.05).

Conclusions

Although left ventricular systolic function was preserved in patients with CP, the LA reservoir, conduit, and booster functions were impaired. Pericardial restriction and impairment of the LA myocardium may play an important role in the reduction of LA function in patients with CP.