Changes In Atrial Volume Research Articles

Ursolic acid accentuates contractile and secretory functions in beating rabbit atria

Aim of studyUrsolic acid (UA) is a well known hydroxyl pentacyclic triterpenoic acid and has been found in vegetarian foods and medicinal herbs. However, the effects of UA on cardiac functions have not well been documented. The purpose of the present study was, therefore, to address whether UA has contractile and secretory effects in perfused beating rabbit atria.Materials and MethodsThe UA‐induced changes in atrial mechanical dynamics, pulse pressure and stroke volume, cAMP efflux, and ANP secretion were measured in perfused beating rabbit atria.ResultsUA increased atrial dynamics and ANP secretion in a concentration‐dependent manner without changes in atrial cAMP levels. The UA‐induced increase in atrial dynamics was not changed by inhibition of the L‐type Ca2+ channels and SR system. On the other hand, UA‐induced increase in ANP secretion was attenuated by inhibition of L‐type Ca2+ channels.ConclusionThese results indicate that UA accentuates atrial ANP secretion concomitantly with increase of atrial dynamics and also suggest that the accentuation of ANP secretion is related with changes in cellular Ca2+ metabolism.

Effects of urotensin II on hypoxia‐induced ANP secretion in rats

Urotensin II (UII) is a vasoactive peptide with many potent effects in the cardiovascular system through a G‐protein‐coupled receptor termed UT. The synthesis and secretion of atrial natriuretic peptide (ANP) are increased during hypoxic condition and plays an important role in adaptation to hypoxia and in the pathogenesis of cardiopulmonary diseases. The present study was to investigate the effects of human UII (hUII) on ANP secretion in hypoxia condition in vitro and in vivo experiments. Hypoxia caused an increase in ANP secretion compared to normoxia in isolated perfused beating rat atria. hUII (10‐10 M) decreased hypoxia‐induced ANP secretion whereas hUII receptor antagonist, urantide (10‐6 M), increased it. However, there were no significant changes in atrial contractility, stroke volume, and extracellular fluid (ECF) translocation by hUII in hypoxia condition. The pretreatment with urantide attenuated the effect of hUII on hypoxia‐induced ANP secretion. Monocrotaline‐treated (MCT, 60mg/kg, sc., 4weeks) rats increased UII level in plasma. In vivo experiment, hUII (5*10‐6 M injection plus 2.5*10‐6 M infusion for 15 min) was infused into MCT‐treated and control rats anesthetized with ketamine. hUII increased blood pressure and heart rate in both groups without significant difference. Interestingly, intravenous infusion of hUII decreased plasma concentration of ANP in MCT‐treated rats whereas hUII increased plasma concentration of ANP in control rats. The ANP generation may protect against the hypoxia and pulmonary hypertension. These results suggest that hUII may play a pathophysiological role in the regulation of ANP secretion in hypoxic condition. Supported by the KOSEF (R13‐2008‐005‐00000‐0).

Rapid Reversal of Left Ventricular Hypertrophy and Intracardiac Volume Overload in Patients With Resistant Hypertension and Hyperaldosteronism

We have shown previously that patients with resistant hypertension and hyperaldosteronism have increased brain natriuretic peptide suggestive of increased intravascular volume. In the present study, we tested the hypothesis that hyperaldosteronism contributes to cardiac volume overload. Thirty-seven resistant hypertensive patients with hyperaldosteronism (urinary aldosterone > or = 12 microg/24 hours and plasma renin activity < or = 1.0 ng/mL per hour) and 71 patients with normal aldosterone status were studied. Both groups had similar blood pressure and left ventricular mass, whereas left and right ventricular end-diastolic volumes measured by cardiac MRI were greater in high versus normal aldosterone subjects (P<0.05). Spironolactone treatment (19 patients in the high aldosterone group and 15 patients from the normal aldosterone group participated in the follow-up) resulted in a significant decrease in clinic systolic blood pressure, right and left ventricular end diastolic volumes, left atrial volume, left ventricular mass, and brain natriuretic peptide at 3 and 6 months of follow-up in patients with high aldosterone, whereas in those with normal aldosterone status, spironolactone decreased blood pressure and left ventricular mass without changes in ventricular or atrial volumes or plasma brain natriuretic peptide. Hyperaldosteronism causes intracardiac volume overload in patients with resistant hypertension in spite of conventional thiazide diuretic use. Mineralocorticoid receptor blockade induces rapid regression of left ventricular hypertrophy irrespective of aldosterone status. In subjects with high aldosterone, mineralocorticoid receptor blockade induces a prominent diuretic effect compared with a greater vasodilatory effect in subjects with normal aldosterone status.

Cardiac mast cells regulate myocyte ANP release via histamine H 2 receptor in beating rabbit atria

It has been shown that histamine inhibits atrial natriuretic peptide (ANP) release. Because cardiac mast cells are the principal source of histamine in the heart, we hypothesized that cardiac mast cells are involved in the regulation of atrial ANP release. To test the hypothesis, experiments were performed in perfused beating rabbit atria allowing atrial pacing and measurements of changes in atrial stroke volume, intraatrial pulse pressure and myocyte ANP release. Mast cell degranulation with Compound 48/80 decreased atrial myocyte ANP release, and the response was blocked by a selective histamine H 2 receptor blocker, cimetidine, indicating that histamine was responsible for the decrease in ANP release. Mast cell stabilization with cromolyn blocked the Compound 48/80-induced decrease in ANP release. These data suggest that mast cell-derived histamine is involved in the regulation of cardiac ANP release. Thus, the cardiac mast cell–cardiomyocyte communication via the histamine–ANP pathway may implicate in the cardiac disorder associated with mast cell degranulation such as in acute coronary syndrome or cardiac hypertrophy.

Size and function of the atria

Size and function of the atria

Right atrial function: still underestimated in clinical cardiology

As already described in several studies, the left and right atrium acts as a reservoir during ventricular systole to transport blood from, respectively, the caval veins and the pulmonary veins to the right and left ventricle, respectively. However, atrial volume and function is also associated with clinical outcome. In a multivariate risk model for the prediction of age-related events an indexed left atrial volume above 32 ml/m2 was an independent risk factor for the prediction of the first age related cardiovascular event [1]. Although clinical outcome was corrected for age we have to realize that left atrial size and volume could be influenced by age with larger volumes found in the elderly population [2]. However, this finding has been debated in recent studies in which normal younger and elderly individuals were compared as left atrial volume is concerned [3]. Increase of left atrial volume if people get older could be related to increase of cardiac pathology at an older age: atrial fibrillation and diastolic and systolic heart failure. In contrast to the left atrium, right atrial volume and function are less well studied. This could be related to the difficulties one encounters with measuring right atrial volumes and function with 2D echocardiography [4]. Freehand 3D echocardiography and cardiac magnetic resonance imaging showed better results as level of agreement and intra-observer and inter-observer variability is concerned [5]. Right atrial volume and function can be described by atrial filling from the point of minimal atrial volume, at the onset of ventricular systole until maximal atrial flow. It is the sum of forward caval flow and reversed flow through the tricuspid annulus. From maximal right atrial volume until atrial volume at the P-wave is described as passive emptying volume. This occurs during ventricular diastole. The active emptying volume occurs during atrial contraction until minimal atrial volume and closure of the tricuspid valve. The different phases are given in Fig. 1. Fig. 1 Right atrial volume change over time The study of Willens et al [6] in the current issue of the International Journal of Cardiac Imaging shows, that in a limited number of healthy subjects right atrial passive emptying volume and passive emptying fraction decreases with age and active emptying volume and active right atrial ejection fraction increase with age. This could indicate that with increasing age right ventricular diastolic function deceases irrespective of the occurrence of cardiac disease. In patients with pulmonary arterial hypertension right atrial function was even more impaired with larger right atrial maximal volume, minimal volume and volumes at the P-wave, lower passive right atrial emptying fraction and higher active right atrial emptying volume and active right atrial emptying fraction pulmonary artery systolic pressure correlated fairly with active emptying volume The study of Willens gives a nice insight in right atrial mechanics and volumes in healthy individuals and patients with pulmonary hypertension. We have to take in account, that this study has several limitations. First, it is a very small study with a very limited number of patients with pulmonary hypertension included. A more serious limitation is due to the sometimes poor acoustic window of ultrasound and therefore poor definition of the right atrial endocardium and the geometric assumptions, which have been made using single plane planimetry method of discs to calculate right atrial volumes and right atrial function. As indicated, measurement of right atrial function with 3D echo or with cardiac magnetic resonance imaging in a larger cohort of normal individuals and patients could make the results more valid. The results are not without any impact. In the next decades we will see a growing number of patients with right ventricular and right atrial dysfunction: Patients with chronic pulmonary diseases, after pulmonary embolism, after right ventricular infarction, chronic heart failure, valvular heart disease and atrial fibrillation. Especially in a population with a growing number of elderly people and diseases related to higher age as atrial fibrillation and pulmonary hypertension and right ventricular dysfunction right ventricular and right atrial function has to be determined more frequently. Thus proper treatment can be initiated more accurately and the effects of treatment on the right atrium and right ventricle can be evaluated. For this, 3D echocardiography and magnetic resonance imaging are the preferred imaging tools. If these techniques are not available reasonable evaluation of right atrial function can be done with 2D echocardiography.

Left atrial Frank–Starling law assessed by real-time, three-dimensional echocardiographic left atrial volume changes

Background:The Frank–Starling law describes the relation between left ventricular volume and function. However, only a few studies have described the relation between left atrial volume (LAV) and function.Objective:To describe an...

Characterization of the Electroanatomical Substrate in Human Atrial Fibrillation: The Relationship between Changes in Atrial Volume, Refractoriness, Wavefront Propagation Velocities, and AF Burden

Progressive remodeling occurs in experimental models of AF whereby slowing of conduction, shortening of refractoriness, and atrial dilatation are associated with an increased vulnerability to atrial fibrillation (AF). This study investigates the relative changes in atrial geometry and electrophysiology with increasing AF burden in humans. Patients undergoing ablation of AF or left-sided accessory pathways were recruited. Atrial volumes were determined by echocardiography. Wavefront propagation velocities (WPV), specifically in the direction of activation, were calculated from pre-ablation activation (Carto) maps of both atria. Dispersion, adaptation of, and effective refractoriness (ERP) were measured at 3 sites. A composite arrhythmogenic index (Atrial Volume/WPV x ERP) was derived to compare the degree of electroanatomical remodeling with AF burden. Fifty-nine patients (22 paroxysmal AF, 19 recurrent persistent AF, and 18 controls) were recruited. AF subjects had slower right atrial WPV (P = 0.01), but no difference in left atrial WPV compared with controls. ERP was reduced globally (P < 0.05), with increased dispersion (P < 0.05). WPV and ERP did not distinguish between patients with paroxysmal or persistent AF. Biatrial volumes were greater only in patients with persistent AF (P < 0.01). There was a stepwise increase in the AI with increasing AF burden (P < 0.0001). An arrhythmogenic substrate exists in human AF, characterized by globally decreased refractoriness with greater dispersion, slower right atrial conduction, and atrial dilatation. Persistence of AF is not accompanied by any further electrical remodeling, but only atrial dilatation. The degree of electroanatomical remodeling is associated with the clinical pattern of AF.

Invited commentary

This is another elegant investigation from the Cleveland Clinic cardiovascular surgical experience and the Atrial Fibrillation Innovation Center [1Koch C.G. Li L. Van Wagoner D.R. Duncan A.I. Gillinov A.M. Blackstone E.H. Red cell transfusion is associated with an increased risk for postoperative atrial fibrillation.Ann Thorac Surg. 2006; 82: 1747-1757Abstract Full Text Full Text PDF PubMed Scopus (128) Google Scholar]. It brings together two of the most vexing postoperative care issues in cardiac surgery, namely, the need for red blood cell (RBC) transfusion and the occurrence of postoperative atrial fibrillation. That they may be linked, as suggested by this investigation, has not been previously established. Table 1 illustrates that overall, the patients who have postoperative atrial fibrillation (AF) develop have received more in quantity and type of blood products, including RBCs, fresh frozen plasma, and platelets. These patients also manifest the usual preoperative risk factors for AF (age, prior AF, valve procedures, chronic obstructive pulmonary disease), and had higher inotropic requirements. Preoperative hematocrit was higher in the non-AF cohort. The multivariate regression analysis demonstrated that intraoperative RBC transfusion, female gender, and preoperative statin use were protective against the development of postoperative AF. The propensity analysis for on-pump cases demonstrated that postoperative RBC transfusion is an independent risk factor for AF. As the number of RBC units increased, so did the likelihood of AF. In the off-pump comparison, female gender, but not intraoperative RBC transfusion, ameliorated the postoperative transfusion impact on AF. Although the cohort number is small, this propensity analysis also demonstrated an effect from postoperative RBC transfusion. Time is the confounding variable here, because to fully understand this relationship requires the linking of events separated by as much as 72 to 96 hours. Data support the authors’ hypothesis that this link may be mediated by the inflammatory effect of RBC transfusion. Alternatively a major contributing factor here may be the need for intracardiac volume resuscitation in the patients who receive RBCs, and the effect of atrial volume changes on atrial stretch and nonuniform dispersion of refractoriness leading to postoperative AF. The findings in the off-pump coronary artery bypass cohort suggest that factors in addition to inflammation may be contributing to this link. Of course the indication for RBC transfusion (low oxygen carrying capacity vs bleeding vs volume requirement) is not available, so that at present the mechanism for this link remains unknown. Importantly the recommendation to carefully consider the indications and benefits and risks associated with transfusions in cardiac surgery patients is further strengthened by this investigation. Additional studies examining the link established in this analysis may ultimately provide new information to address each of these remaining thorny issues in adult cardiac surgery. Red Cell Transfusion is Associated With an Increased Risk for Postoperative Atrial FibrillationThe Annals of Thoracic SurgeryVol. 82Issue 5PreviewAtrial fibrillation (AF) is a common complication after cardiac surgery and is associated with increased resource utilization. Recent evidence supports a role of inflammation in the development of AF. It is also known that red blood cell transfusion modulates inflammation by increasing plasma levels of inflammatory markers. Therefore, we tested the hypothesis that red blood cell transfusion increases the risk of postoperative AF for patients undergoing cardiac surgery. Full-Text PDF

Left atrial systolic function in primary and familial amyloidosis: assessment from left atrial volume change.

The severity of left ventricular involvement may differ between primary (PA) and familial amyloidosis (FA). This study examined whether differences in left atrial (LA) systolic function are also present. Twenty-eight patients (18 men, 10 women, aged 59 +/- 12 years) with PA, 17 (11 men, 6 women, aged 40 +/- 11 years) with FA, and 25 normal controls (18 men, 7 women, aged 56 +/- 14 years) underwent transthoracic M-mode, two-dimensional, and Doppler echocardiography. Left atrial volumes were determined at mitral valve (MV) opening (maximal, Vmax), electrocardiographic P wave (onset of atrial systole, Vp), and MV closure (minimal, Vmin) from the apical two-and four-chamber views using the biplane area-length method. Left atrial systolic function was assessed with the LA active emptying volume (ACTEV) = Vp-Vmin and fraction (ACTEF) = ACTEV/Vp. The E/A ratio was increased (1.34 +/- 0.93 vs. 0.89 +/- 0.3), whereas deceleration time was decreased (168.1 +/- 33.7 vs. 196.2 +/- 34.2 ms) in PA compared with FA (p<0.05). Vmax and Vp were similar in PA and FA and greater than in the controls (46.6 +/- 14 vs. 40 +/- 11.4 vs. 27.1 +/- 6.3 cm3/m2, p<0.01, and 33.4 +/- 11.6 vs. 29.7 +/- 10.8 vs. 16.8 +/- 3.8 cm3/m2, p<0.01, respectively). The ACTEV was lower in PA and in the controls than in FA (6.7 +/- 2 vs. 6.2 +/- 2.2 vs. 8.5 +/- 3.3, respectively, p<0.05). The ACTEF was lower in PA than in FA and both were lower than those in the controls (20 +/- 5% vs. 28 +/- 7% vs. 36 +/- 11%, respectively, p<0.01). Despite a similar increase in LA volume, LA systolic dysfunction is more pronounced in PA than in FA. This is most likely due to the restrictive left ventricular physiology possibly associated with depressed LA contractility in the former.

Diverse regulation of atrial natriuretic peptide secretion by serotonin receptor subtypes.

Serotonin (5-hydroxytryptamine [5-HT]) receptors are located in peripheral tissues as well as in the central nervous system. Serotonin receptors mediate positive inotropic and chronotropic effects in atria. The aim of this study was to investigate physiological role of endogenous serotonin on the regulation of atrial natriuretic peptide (ANP) secretion from the atria. An isolated perfused nonbeating rat atrial model was used. Changes in atrial volume induced by increasing intra-atrial pressure were measured. The concentration of ANP was measured by radioimmunoassay and the translocation of ECF was measured by [3H]-inulin clearance. Serotonin, an endogenous 5-HT receptor agonist, caused concentration-dependent suppressions of stretch-induced ANP secretion, which were less pronounced than those caused by alpha-methyl-5-HT maleate, a 5-HT(2) receptor selective agonist. The suppression of stretch-induced ANP secretion due to serotonin and alpha-methyl-5-HT maleate was attenuated by ketanserin, a 5-HT(2) receptor antagonist, and accentuated by RS23597-190, a 5-HT(4) receptor antagonist. The suppressive effect of serotonin on ANP secretion was attenuated by neomycin, staurosporine, and chelerythrine. In contrast, 2-[1-(4-piperonyl)piperazinyl]benzothiazole, a 5-HT(4) receptor selective agonist, caused an accentuation of stretch-induced ANP secretion, which was completely blocked by RS23597-190 and SB203186 HCl but not by ketanserin. This effect was not affected by MDL12330, KT-5720, or H-89. The intracellular Ca(2+) concentration in single atrial myocytes was not changed by serotonin and agonist for either 5-HT(2) or 5-HT(4) receptor. These results suggest that atrial 5-HT(2) and 5-HT(4) receptor agonists have opposite actions on the regulation of ANP secretion and the suppressive effect of serotonin on the ANP secretion may act through 5-HT(2) receptor and phospholipase C pathway.

Stretch-activated atrial natriuretic peptide secretion in atria with heat shock protein 70 overexpression.

The mechanical overload of the heart is known to induce the expression of atrial natriuretic peptide (ANP) and heat-shock protein 70 (HSP70) in the heart. However, the relationship between these two substances remains unknown. In the present study, we characterized ANP secretion from mouse atria and examined a possible role that HSP70 may play in the regulation of ANP synthesis and secretion by using atria in transgenic mice in which HSP70 was overexpressed. We generated transgenic mice harboring the human HSP70gene under the transcriptional control of human myosin heavy-chain promoter. In these mice, the transgene was overexpressed in the heart. Both atrial ANP messenger RNA and its concentration in the HSP70 transgenic mice were measured; these were not significantly different from those in wild-type mice. In isolated perfused nonbeating atria, basal secretion of ANP was similar in both groups. When atrial volume was increased by changing atrial pressure, extracellular fluid (ECF) translocation and ANP secretion proportionately increased. Changes in atrial volume and ECF translocation and ANP secretion were positively correlated. However, these parameters did not significantly differ between the two groups. Endothelin-1 (ET-1), the strongest paracrine stimulus of ANP secretion, accentuated stretch-activated ANP secretion without significantly changing mechanically stimulated ECF translocation, as compared with that in the wild-type mice. The increased ANP secretion due to ET-1 in the transgenic mice was similar to that in the wild-type mice. The results suggest that both atrial stretching and ET-1 are important stimuli to ANP secretion from mouse atria, and the responsiveness of the ANP system to those stimuli are unlikely coupled to the pathway involving HSP70.

Pericardium modulates left and right ventricular stroke volumes to compensate for sudden changes in atrial volume.

The pericardium may modulate acute compensatory changes in stroke volumes seen with sudden changes in cardiac volume, but such a mechanism has never been clearly demonstrated. In eight open-chest dogs, we measured left and right ventricular pressures, diameters, stroke volumes, and pericardial pressures during rapid (approximately 300 ms) systolic infusions or withdrawals of approximately 25 ml blood into and out of the left atrium and right atrium. Control beats, the infusion/withdrawal beat, and 4-10 subsequent beats were studied. With infusions, ipsilateral ventricular end-diastolic transmural pressure, diameter, and stroke volume increased. With the pericardium closed, there was a compensatory decrease in contralateral transmural pressure, diameter, and stroke volume, mediated by opposite changes in transmural end-diastolic pressures. The sum of the ipsilateral increase and contralateral decrease in stroke volume approximated the infused volume. Corresponding changes were seen with blood withdrawals. This direct ventricular interaction was diminished when pericardial pressure was <5 mmHg and absent when the pericardium was opened. Pericardial constraint appears essential for immediate biventricular compensatory responses to acute atrial volume changes.

Analysis of Left Atrial Volume Change Rate for Evaluation of Left Ventricular Diastolic Functio

OBJECTIVES: To define the role of left atrial (LA) volume change rate, as indicated by posterior aortic wall motion during the left ventricular (LV) diastolic phase, in the assessment of LV diastolic function.

Compensatory changes in atrial volumes with normal aging: is atrial enlargement inevitable?

ObjectivesThe aim of this study was to evaluate left atrial volume and its changes with the phases (active and passive) of atrial filling, and to examine the effect of normal aging on these parameters and pulmonary vein (PV) flow patterns. BackgroundAtrial volume change with normal aging has not been adequately described. Pulmonary vein flow patterns have not been volumetrically evaluated in normal aging. Combining atrial volumes and PV flow patterns obtained using transthoracic echocardiography could estimate shifts in left atrial mechanical function with normal aging. MethodsA total of 92 healthy subjects, divided into two groups: Group Y (young <50 years) and Group O (old ≥50 years), were prospectively studied. Maximal (Volmax) and minimal (Volmin) left atrial volumes were measured using the biplane method of discs and by three-dimensional echocardiographic reconstruction using the cubic spline interpolation algorithm. The passive filling, conduit, and active emptying volumes were also estimated. Traditional measures of atrial function, mitral peak A-wave velocity, velocity time integral (VTI), atrial emptying fraction, and atrial ejection force were measured. ResultsAs age increased, Volmax, Volmin, and total atrial contribution to left ventricle (LV) stroke volume were not significantly altered. However, the passive emptying volume was significantly higher (14.2 ± 6.4 ml vs. 11.6 ± 5.7 ml; p = 0.03) whereas the active emptying volume was lower (8.6 ± 3.7 ml vs. 10.2 ± 3.8 ml; p = 0.04) in Group Y versus Group O. Pulmonary vein flow demonstrated an increase in peak diastolic velocity (Group Y vs. Group O) with no corresponding change in diastolic VTI or systolic fraction. ConclusionsNormal aging does not increase maximum (end-systolic) atrial size. The atrium compensates for changes in LV diastolic properties by augmenting active atrial contraction. Pulmonary vein flow patterns, although diastolic dominant using peak velocity, demonstrated no volumetric change with aging.

Analysis of left atrial volume change rate during left ventricular diastolic phase with M-mode echocardiography for differentiation between normal and pseudonormal mitral inflow

Pseudonormalization of mitral inflow is a diagnostic problem in clinical practice. An excellent correlation exists between the change in the left atrial (LA) angiographic area and posterior aortic wall motion. Therefore, we sought to define the role of LA wall motion, indicating LA volume change rate, in patients with normal and pseudonormal mitral inflow. We performed echocardiography after cardiac catheterization in 62 patients with a velocity ratio of early-to-late mitral inflow (E/A ratio) >1. Study patients were classified into 2 groups according to the response of mitral inflow to phase II of the Valsalva maneuver: patients with E/A >1 after the Valsalva maneuver (n = 31, control group), and patients with <1 after the Valsalva maneuver (n = 31, pseudonormal group). The slopes (slope E and A) of early diastolic and late diastolic motion of the LA wall were derived from M-mode analysis together with the time constant of left ventricular (LV) isovolumic relaxation from cardiac catheterization. The values of slope E (41 ± 11 vs 61 ± 12 mm/s, p <0.001) and slope E/A (0.69 ± 0.13 vs 1.32 ± 0.35, p <0.001) were significantly lower in the pseudonormal group and were inversely correlated with the time constant of LV isovolumic relaxation (r = 0.64, p <0.001 and r = 0.73, p <0.001, respectively). Using slope E/A <1 as an indicator of relaxation abnormality, the sensitivity, specificity, positive predictive value, and negative predictive value for the detection of pseudonormalization were 94%, 100%, 100%, and 94%, respectively. The slope of LA wall motion, indicating LA volume change rate, during the LV diastolic phase is useful for evaluating pseudonormal LV diastolic dysfunction in the selected patient population.

Attenuation of negatively regulated ANP secretion by calcium in hypertrophied atria.

Abnormal intracellular Ca(2+)-handling has been described in various heart diseases associated with cardiac hypertrophy. The crucial role of Ca(2+) in the excitation-secretion coupling in atrial cardiomyocytes is not well established. To investigate modulation of atrial natriuretic peptide (ANP) secretion regulated by Ca(2+) in hypertrophied atria, responsiveness of stretch-induced ANP to Ca(2+) was studied using isolated perfused quiescent hypertrophied rat atria. Male Sprague-Dawley rats were given a single subcutaneous injection of 50 mg/kg monocrotaline (MCT) and were sacrificed at 5-6 weeks. In isolated perfused hypertrophied right atria from MCT rats, changes in atrial volume induced by increased atrial pressure caused proportional increases in mechanically stimulated extracellular fluid (ECF) translocation and stretch-induced ANP secretion. Stretch-induced ANP secretion was markedly increased by the depletion of extracellular Ca(2+). However, an accentuation of stretch-induced ANP secretion by Ca(2+) depletion was markedly attenuated in hypertrophied right atria, as compared to control right atria. Therefore, stretch-induced ANP secretion in terms of ECF translocation by Ca(2+) depletion in hypertrophied atria was significantly lower than in control right atria. However, no significant differences were observed between nonhypertrophied and control left atria. Depletion of extracellular Ca(2+) caused a decrease in intracellular calcium in single beating atrial myocytes, which was significantly attenuated in hypertrophied atrial myocytes. The results suggest that attenuation of Ca(2+)-induced negative regulation of ANP secretion in hypertrophied atria may be due to the disturbance of intracellular Ca(2+) regulation.

Accentuation of ANP secretion to endothelin-1 in hypertrophied atria

To investigate modulation of ANP secretion by atrial hypertrophy, the secretion of ANP in response to stretch and endothelin-1 was studied using isolated perfused quiescent atria from rats treated with monocrotaline (MCT). Male Sprague-Dawley rats were given a single subcutaneous injection of 50 mg/kg MCT or saline and were sacrificed at 6 weeks. Rats with right heart hypertrophy showed an increase in ANP mRNA and decrease in tissue concentration of ANP in hypertrophied atria and a marked increase in plasma concentration of ANP. In isolated perfused hypertrophied right atria from MCT rats, changes in atrial volume induced by increased atrial pressure caused proportional increases in mechanically stimulated extracellular fluid (ECF) translocation and stretch-activated ANP secretion. Changes in atrial volume and mechanically stimulated ECF translocation in hypertrophied right atria were not different from those in control right atria. The stretch-activated ANP secretion was suppressed without significant difference in basal ANP secretion, as compared to control right atria. Therefore, the stretch-activated ANP secretion from hypertrophied right atria into the atrial lumen in relation to the ECF translocation (ANP concentration in the interstitium) was lower than that from control atria. A positive correlation between the stretch-activated ANP secretion in relation to the ECF translocation and tissue ANP content was found in control atria but not in hypertrophied atria. Endothelin-1 caused increases in stretch-activated ANP secretion in a dose-dependent manner, which were accentuated in hypertrophied right atria. Therefore, we suggest that atrial hypertrophy causes an attenuated response to stretch and accentuated response to endothelin-1 of ANP secretion.

Assessment of mulibrey nanism cardiopathy with functional magnetic resonance imaging.

It has been proposed that thickened pericardium is the main cause of the cardiac malfunction in Mulibrey nanism cardiopathy. In contrary, we showed that the pericardial thickness was normal in all our patients. Diastolic 1/3 filling was rapid, but in normal limits when taking into account the young age of our patient population. Although, LV time volume curves did not show remarkable pathologic changes, a restrictive physiology cannot be definitively excluded. LV end diastolic volumes and cardiac output were clearly reduced in our patients. It could be possible that in the course of time the reduced cardiac output affects clinical pattern of heart failure despite of normal systolic function. The reduced LA largest volume and atrial cyclic volume change may partly contribute to the low cardiac output observed in our patients.

Echocardiographic determination of left atrial function and its application for assessment of mitral flow velocity pattern

We determined left atrial (LA) volume changes to evaluate LA function, and to correlate the Doppler-determined mitral flow velocity (MFV) pattern. Twenty-four patients with ischemic heart disease who showed ‘normal’ MFV pattern by pulsed Doppler echocardiography were studied. The patients were divided into 14 patients with left ventricular end diastolic pressure <18 mmHg (true normals) and 10 patients with ≥18 mmHg (pseudo normals). The changes in LA volume were determined by echocardiography from apical two- and four-chamber views with modified Simpson’s method. The volume measurements were done at the time of mitral valve opening ( V max), at onset of atrial systole ( V a) and at mitral valve closure ( V min). Then the passive LA emptying volume was calculated by subtracting V a from V max, and the active LA emptying volume by subtracting V min from V a. The LA ejection fraction was calculated by the formula: {( V a− V min) V a}×100. There was no significant difference in LA ejection fraction in pseudo normal (39±6%) and in true normal (41±13%) patients. Although the passive LA emptying volume was 16±4 ml/beat in true normal and was 11±3 ml/beat in pseudo normal (NS), the active LA emptying volume was significantly greater in pseudo normals (22±4 m/beat) than in true normals (12±2 ml/beat, P<0.001). Thus, the ratio of passive and active LA emptying volume was markedly greater in true normals (1.28±0.35) than in pseudo normals (0.52±0.19, P<0.001), facilitating the differentiation of these two groups. These results indicate that two-dimensional echocardiographic measurement of LA volume can be valuable in assessing the LA function, providing an alternative method for differentiating pseudo normal from true normal MFV pattern in clinical settings, although several technological shortcomings should be resolved.