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.     

Biventricular pacing in the early postoperative period after cardiac surgery

Cardiac resynchronization therapy is not commonly used in the early postoperative period in patients undergoing cardiac surgery who have left ventricular (LV) dysfunction and a history of heart failure. We performed a prospective randomized clinical trial to compare atrial synchronous right ventricular (DDD RV) and biventricular (DDD BIV) pacing within 72 hours after cardiac surgery in patients with an EF ≤35 %, a QRS interval longer than 120 msec and who had LV dyssynchrony detected by real-time three-dimensional echocardiography (RT3DE). Epicardial pacing was provided by a modified Medtronic INSYNC III pacemaker. An LV epicardial pacing lead was implanted on the latest activated segment of the LV based on RT3DE. The study included 18 patients with ischemic heart disease, with or without valvular heart disease (14 men, 4 women, average age 71 years). Patients undergoing DDD BIV pacing had a statistically significant greater CO and CI (CO 6.7±1.8 l/min, CI 3.4±0.7 l/min/m(2)) than patients undergoing DDD RV pacing (CO 5.5±1.4 l/min, CI 2.8±0.7 l/min/m(2)), p<0.001. DDD BIV pacing in the early postoperative period after cardiac surgery corrects LV dyssynchrony and has better hemodynamic results than DDD RV pacing.     

Noninvasive quantification of left ventricular elastance and ventricular-arterial coupling using three-dimensional echocardiography and arterial tonometry

Most techniques previously used to assess left ventricular (LV) end-systolic elastance (E(es)) and ventricular-arterial coupling (C(LV-A)) relied on invasive measurements and data acquisition over a wide range of loading conditions. Our goals were to 1) assess the feasibility of noninvasive assessment of E(es) and C(LV-A) using real-time three-dimensional echocardiography (RT3DE) and arterial tonometry; 2) test the ability of this approach to detect changes in LV contractility; and 3) study its reproducibility. We studied pharmacologically induced changes in inotropic state (5 and 10 μg·kg(-1)·min(-1) dobutamine) in normal volunteers (N = 8) and compared 10 normal volunteers with 10 patients with dilated cardiomyopathy (DCM; ejection fraction < 35%). RT3DE LV images, calibrated carotid artery tonometry, and Doppler tracings were obtained to noninvasively estimate E(es) and C(LV-A), using two alternative calculations. Dobutamine caused a significant stepwise increase in blood pressure, heart rate, ejection fraction, and E(es) and a decreased C(LV-A). In patients with DCM, E(es) was significantly reduced and C(LV-A) elevated, compared with controls. Both inter- and intraobserver variability were good for all measured parameters, as reflected by intraclass correlation coefficients (>0.8) and coefficients of variation (<20%). While both E(es) estimates showed significant differences between DCM patients and controls, one estimate resulted in no overlap and better reproducibility (interobserver intraclass correlation coefficient: 0.83 vs. 0.47, coefficients of variation: 20 vs. 29%). This is the first study to test the feasibility of using RT3DE-derived LV volumes in conjunction with arterial tonometry to noninvasively quantify LV elastance and C(LV-A). This approach was found to be sensitive enough to detect expected differences in LV contractility and reproducible. Due to its noninvasive nature, this methodology may have clinical implications in various disease states.     

Rapid microcomputed tomography suggests cardiac enlargement occurs during conductance catheter measurements in mice

Conductance catheters (CC) represent an established method of determining cardiac function in mice; however, the potentially detrimental effects a catheter may have on the mouse heart have never been evaluated. The present study takes advantage of rapid three-dimensional (3D) microcomputed tomography (CT) to compare simultaneously acquired micro-CT and CC measurements of left ventricular (LV) volumes in healthy and infarcted mice and to determine changes in LV volume and function associated with CC insertion. LV volumes were measured in C57BL/6 mice (10 healthy, 10 infarcted, 2% isoflurane anesthesia) using a 1.4-Fr Millar CC. 3D micro-CT images of each mouse were acquired before CC insertion as well as during catheterization. Each CT scan produced high-resolution images throughout the entire cardiac cycle in <1 min, enabling accurate volume measurements as well as direct visualization of the CC within the LV. Bland-Altman analysis demonstrated that CC measurements underestimate volume compared with CT measurements in both healthy [bias of -18.4 and -28.9 μl for end-systolic (ESV) and end-diastolic volume (EDV), respectively] and infarcted mice (ESV = -51.6 μl and EDV = -71.7 μl); underestimation was attributed to the off-center placement of the catheter. Individual evaluation of each heart revealed LV dilation following CC insertion in 40% of mice in each group. No change in ejection fraction was observed, suggesting the enlargement was caused by volume overload associated with disruption of the papillary muscles or chords. The enlargement witnessed was not significant; however, the results suggest the potential for CC insertion to detrimentally affect mouse myocardium, necessitating further investigation.     

Effects of hydralazine on blood pressure, pressor mechanisms, and cardiac hypertrophy in two-kidney, one-clip hypertensive rats

In 2-kidney, 1-clip hypertensive rats, the time course of changes in blood pressure (BP), heart rate, activity of the sympathetic nervous system and the renin-angiotensin system, plasma and blood volumes, left ventricular (LV) and right ventricular (RV) weight, and LV dimensions were evaluated during treatment with hydralazine 80 and 120 mg/L drinking water for 2 days or 1, 2, 3, 5, and 8 weeks. Hydralazine induced initially a clear antihypertensive effect (mean BP from 170-180 down to 135-145 mmHg (1 mmHg = 133.32 Pa], subsequently tolerance developed. Heart rate, plasma catecholamines, and the blood pressure response to hexamethonium were not affected by treatment. Significant increases in plasma renin activity occurred during the initial 1-3 weeks of treatment. Plasma and blood volumes showed only small increases with prolonged treatment. RV weight and LV internal diameter showed significant increases at 3, 5, and 8 weeks of treatment, LV weight at 5 and 8 weeks. LV wall thickness did not change significantly. Thus, treatment with the arterial vasodilator hydralazine causes both RV hypertrophy and eccentric LV hypertrophy. Intravascular volume expansion, associated possibly with redistribution of blood volume to the central compartment, may play a major role in these cardiac effects. Increased renin release but not a generalized increase in sympathetic tone may play a role in the development of tolerance to the antihypertensive effect.     

Changes in Doppler mitral inflow patterns during parabolic flight

Aim of the study was to evaluate by transthoracic Doppler the alterations in mitral inflow velocity pattern caused by acute changes in loading conditions occurring during parabolic flights. Each parabola included normogravity (1 Gz, 1 min), mild hypergravity (1.8 Gz, 20 sec), microgravity (0 Gz, 24 sec) and mild hypergravity (1.8 Gz, 20 sec) phases. Pulsed-Doppler images were digitally acquired in 11 unmedicated subjects (46 +/- 5 years), in standing upright position and supine resting. Doppler profiles were semi-automatically traced and inflow parameters extracted and averaged onto three consecutive beats. Only in standing position, significant alterations during microgravity (p<0.05) were noted in several parameters.     

A Pig Model of Ischemic Mitral Regurgitation Induced by Mitral Chordae Tendinae Rupture and Implantation of an Ameroid Constrictor

A miniature pig model of ischemic mitral regurgitation (IMR) was developed by posterior mitral chordae tendinae rupture and implantation of an ameroid constrictor. A 2.5-mm ameroid constrictor was placed around the left circumflex coronary artery (LCX) of male Tibetan miniature pigs to induce ischemia, while the posterior mitral chordae tendinae was also ruptured. X-ray coronary angiography, ECG analysis, echocardiography, and magnetic resonance imaging (MRI) were used to evaluate heart structure and function in pigs at baseline and one, two, four and eight weeks after the operation. Blood velocity of the mitral regurgitation was found to be between medium and high levels. Angiographic analyses revealed that the LCX closure was 10–20% at one week, 30–40% at two weeks and 90–100% at four weeks subsequent ameroid constrictor implantation. ECG analysis highlighted an increase in the diameter of the left atria (LA) at two weeks post-operation as well as ischemic changes in the left ventricle (LV) and LA wall at four weeks post-operation. Echocardiography and MRI further detected a gradual increase in LA and LV volumes from two weeks post-operation. LV end diastolic and systolic volumes as well as LA end diastolic and systolic volume were also significantly higher in pig hearts post-operation when compared to baseline. Pathological changes were observed in the heart, which included scar tissue in the ischemic central area of the LV. Transmission electron microscopy highlighted the presence of contraction bands and edema surrounding the ischemia area, including inflammatory cell infiltration within the ischemic area. We have developed a pig model of IMR using the posterior mitral chordae tendineae rupture technique and implantation of an ameroid constrictor. The pathological features of this pig IMR model were found to mimic the natural history and progression of IMR in patients.     

Effect of changing the gravity vector on respiratory output and control.

We studied the respiratory output in five subjects exposed to parabolic flights [gravity vector 1, 1.8 and 0 gravity vector in the craniocaudal direction (Gz)] and when switching from sitting to supine (legs bent at the knees). Despite differences in total respiratory compliance (highest at 0 Gz and in supine and minimum at 1.8 Gz), no significant changes in elastic inspiratory work were observed in the various conditions, except when comparing 1.8 Gz with 1 Gz (subjects were in the seated position in all circumstances), although the elastic work had an inverse relationship with total respiratory compliance that was highest at 0 Gz and in supine posture and minimum at 1.8 Gz. Relative to 1 Gz, lung resistance (airways plus lung tissue) increased significantly by 52% in the supine but slightly decreased at 0 Gz. We calculated, for each condition, the tidal volume changes based on the energy available in the preceding phase and concluded that an increase in inspiratory muscle output occurs when respiratory load increases (e.g., going from 0 to 1.8 Gz), whereas a decrease occurs in the opposite case (e.g., from 1.8 to 0 Gz). Despite these immediate changes, ventilation increased, going to 1.8 and 0 Gz (up to approximately 23%), reflecting an increase in mean inspiratory flow rate, tidal volume, and respiratory frequency, while ventilation decreased (approximately -14%), shifting to supine posture (transition time approximately 15 s). These data suggest a remarkable feature in the mechanical arrangement of the respiratory system such that it can maintain the ventilatory output with small changes in inspiratory muscle work in face of considerable changes in configuration and mechanical properties.     

Time-variant spectral analysis of heart rate variability during parabolic flight with and without LBNP

Modifications of autonomic activity during parabolic flight were studied by a time-variant model able to estimate low (LF, 0.04-0.14 Hz) and high (HF, 0.14-0.35 Hz) frequency spectral components on a beat-to-beat basis. Ten subjects were studied with and without lower body negative pressure (LBNP). ECG and Gz load were digitized (500 Hz) and RR interval variability series extracted. Beat-to-beat mean RR, variance, LF and HF power were obtained. One-way ANOVA (p<0.01) was used to compare values obtained during starting 1Gz (I), first 1.8Gz (II), 0Gz (III), second 1.8Gz (IV), ending 1Gz (V). Without LBNP, total and LF power increased during 0Gz to 1.69 +/- 1.41 and 2.87 +/- 4.66 respectively (mean +/- SD, normalized by phase I value). With LBNP, their change during 0Gz (1.38 +/- 1.37 and 1.54 +/- l.04 respectively) reached significance only with phase II and phase V. Phase I HF power was higher than in the other phases, both without and with LBNP.     

Continuous monitoring of right ventricular volume changes using a conductance catheter in the rabbit.

To assess the reliability of conductance (G) catheter for evaluating right ventricular (RV) volume changes, a miniature (3.5F) six-electrode catheter was developed and tested in 11 New Zealand rabbit hearts. In five animals the heart was excised; in six it was left in the thorax. RV conductance was recorded while the RV was filled with blood in 0.25-ml steps at different left ventricular (LV) volumes. Linear correlation of measured conductance vs. reference volumes was computed. RV conductance was highly correlated with reference volume [correlation coefficient (r) ranging from 0.991 to 0.999]. Slope of regression lines was not significantly affected by LV volume variations in 1-ml steps or by acute conductance changes of structures surrounding the heart, whereas the intercept was affected only by the 0- to 1-ml LV volume change. In four rabbits, RV conductance changes during a cardiac cycle [stroke volume- (SV) G] were compared in vivo with electromagnetic flow probe-derived estimates of SV (SVem) as stroke volume was varied by graded inferior vena caval occlusion. SV-G correlated well with SVem (r ranging from 0.92 to 0.96). This correlation persisted after the thorax was filled with saline; however, significant differences were found in individual slopes (P < 0.001). These results show that the conductance catheter has a potential to reliably monitor in vivo relative RV volume changes in small-animal hearts.     

The role of ANG II and endothelin-1 in exercise-induced diastolic dysfunction in heart failure

The diastolic dysfunction present at rest in congestive heart failure (CHF) is exacerbated during exercise (Ex). Increases in circulating ANG II and endothelin-1 (ET-1) during Ex may contribute to this response. We assessed the effect of Ex on circulating plasma levels of ANG II and ET-1 and left ventricular (LV) dynamics before and after pacing-induced CHF at rest and during Ex in nine conscious, instrumented dogs. Before CHF, there were modest increases in circulating levels of ANG II (but not ET-1) during Ex. LV diastolic performance was enhanced during Ex with decreases in the time constant of LV relaxation (tau), LV end-systolic volume (V(ES)), and LV minimum pressure with a downward shift of the LV early diastolic portion of the pressure-volume (P-V) loop. This produced an increase in peak LV filling rate without an increase in mean left atrial (LA) pressure. After CHF, the resting values of ANG II and ET-1 were elevated and increased to very high levels during Ex. After CHF, mean LA pressure, tau, and LV minimum pressure were elevated at rest and increased further during Ex. Treatment with L-754,142, a potent ET-1 antagonist, or losartan, an ANG II AT(1)-receptor blocker, decreased these abnormal Ex responses in CHF more effectively than an equally vasodilatory dose of sodium nitroprusside. Combined treatment with both ANG II- and ET-1-receptor blockers was more effective than either agent alone. We conclude that in CHF, circulating ANG II and ET-1 increase to very high levels during Ex and exacerbate the diastolic dysfunction present at rest.     

Abstracts from the 3rd Annual A-CURE Symposium

Background

Patients after aortic coarctation (CoA) repair show impaired aortic bioelasticity and altered left ventricular (LV) mechanics, predisposing diastolic dysfunction. Our purpose was to assess aortic bioelasticity and LV properties in CoA patients who underwent endovascular stenting or surgery using cardiovascular magnetic resonance (CMR) imaging.

Methods

Fifty CoA patients (20.5 ± 9.5 years) were examined by 3-Tesla CMR. Eighteen patients had previous stent implantation and 32 had surgical repair. We performed volumetric analysis of both ventricles (LV, RV) and left atrium (LA) to measure biventricular volumes, ejection fractions, left atrial (LA) volumes, and functional parameters (LAEF_Passive, LAEF_Contractile, LAEF_Reservoir). Aortic distensibility and pulse wave velocity (PWV) were assessed. Native T1 mapping was applied to examine LV tissue properties. In twelve patients post-contrast T1 mapping was performed.

Results

LV, RV and LA parameters did not differ between the surgical and stent group. There was also no significant difference for aortic distensibility, PWV and T1 relaxation times. Aortic root distensibility correlated negatively with age, BMI, BSA and weight (p < 0.001). Native T1 values correlated negatively with age, weight, BSA and BMI (p < 0.001). Lower post-contrast T1 values were associated with lower aortic arch distensibility and higher aortic arch PWV (p < 0.001).

Conclusions

CoA patients after surgery or stent implantation did not show significant difference of aortic elasticity. Thus, presumably other factors like intrinsic aortic abnormalities might have a greater impact on aortic elasticity than the approach of repair. Interestingly, our data suggest that native T1 values are influenced by demographic characteristics.

     

Regional left ventricular performance during normal and obstructed spontaneous respiration

To clarify the effects of respiration on left ventricular (LV) dimensions and shortening, we studied chronically instrumented dogs with endocardial sonomicrometer crystals in the anterior-posterior (AP), septal to lateral (SL), and long axes (LA) following pericardiectomy. Ten anesthetized dogs were examined during spontaneous unobstructed respiration, partial inspiratory obstruction (PIO), and Mueller maneuvers (MM). During unobstructed inspiration, end-diastolic dimensions (EDD) demonstrated a significant increase in the AP and a similar decrease in the SL axis (i.e., noncongruent shape changes). During PIO only the SL EDD diminished significantly, while no significant changes occurred in any EDD during MM. Individual dogs also demonstrated noncongruent shape changes at end systole during inspiration. However, the end-systolic dimensions for the entire group demonstrated a significant increase in one dimension during each inspiratory mode with no significant changes in the other two axes suggesting an increased ventricular volume. Regional shortening declined only in the SL axis during both unobstructed respiration and PIO. Spontaneous sighs with large tidal volumes, yet smaller changes in pleural pressure than during the MM, were associated with marked noncongruent shape changes in both diastole and systole. We conclude that 1) estimates of LV volumes during respiration based on only one or two axes and assuming regional congruent shape changes may be misleading; and 2) lung volume changes can affect LV geometry independently of changes in pleural pressure.     

MRI assessment of LV relaxation by untwisting rate: a new isovolumic phase measure of tau

Most noninvasive measures of diastolic function are made during left ventricular (LV) filling and are therefore subject to "pseudonormalization," because variation in left atrial (LA) pressure may confound the estimation of relaxation rate. Counterclockwise twist of the LV develops during ejection, but untwisting occurs rapidly during isovolumic relaxation, before mitral opening. We hypothesized that the rate of untwisting might reflect the process of relaxation independent of LA pressure. Recoil rate (RR), the velocity of LV untwisting, was measured by tagged magnetic resonance imaging and regressed against the relaxation time constant (tau), recorded by catheterization, in 10 dogs at baseline and after dobutamine, saline, esmolol, and methoxamine treatment. RR correlated closely (average r = -0.86) with tau and was unaffected by elevated LA pressure. Multiple regression showed that tau, but not LA or aortic pressure, was an independent predictor of RR (P < 0.0001, P = 0.99, and P = 0.18, respectively). The rate of recoil of torsion, determined wholly noninvasively, provides an isovolumic phase, preload-independent assessment of LV relaxation. Use of this novel parameter should allow the detailed study of diastolic function in states known to affect filling rates, such as aging, hypertension, and congestive heart failure.     

Estimation of left ventricular operating stiffness from Doppler early filling deceleration time in humans

Shortened early transmitral deceleration times (E(DT)) have been qualitatively associated with increased filling pressure and reduced survival in patients with cardiac disease and increased left ventricular operating stiffness (K(LV)). An equation relating K(LV) quantitatively to E(DT) has previously been described in a canine model but not in humans. During several varying hemodynamic conditions, we studied 18 patients undergoing open-heart surgery. Transesophageal echocardiographic two-dimensional volumes and Doppler flows were combined with high-fidelity left atrial (LA) and left ventricular (LV) pressures to determine K(LV). From digitized Doppler recordings, E(DT) was measured and compared against changes in LV and LA diastolic volumes and pressures. E(DT) (180 +/- 39 ms) was inversely associated with LV end-diastolic pressures (r = -0.56, P = 0.004) and net atrioventricular stiffness (r = -0.55, P = 0.006) but had its strongest association with K(LV) (r = -0.81, P < 0.001). K(LV) was predicted assuming a nonrestrictive orifice (K(nonrest)) from E(DT) as K(nonrest) = (0.07/E(DT))(2) with K(LV) = 1.01 K(nonrest) - 0.02; r = 0.86, P < 0.001, DeltaK (K(nonrest) - K(LV)) = 0.02 +/- 0.06 mm Hg/ml. In adults with cardiac disease, E(DT) provides an accurate estimate of LV operating stiffness and supports its application as a practical noninvasive index in the evaluation of diastolic function.     

Left atrial strain - an early marker of left ventricular diastolic dysfunction in patients with hypertension and paroxysmal atrial fibrillation

Background

2D strain imaging of the left atrium (LA) is a new echocardiographic method which allows us to determine contractile, conduit and reservoir functions separately. This method is particularly useful when changes are subtle and not easily determined by traditional parameters, as it is in arterial hypertension and atrial fibrillation (AF). The aims of our study were: to determine LA contractile, conduit and reservoir function by 2D strain imaging in patients with mild arterial hypertension and paroxysmal AF; to assess LA contractile, conduit and reservoir functions’ relation with LV diastolic dysfunction (DD) parameters.

Methods

LA contractile, conduit and reservoir functions together with echocardiographic signs of LV DD were assessed in 63 patients with arterial hypertension and paroxysmal AF. Patients were grouped according to number of signs showing LV DD (annular e’ velocity: septal e’?<?7 cm/s, lateral e’?<?10 cm/s, average E/e’ ratio?>?14, LA volume index >?34 ml/m², peak tricuspid regurgitation velocity?>?2.8 m/s) present. Number of patients with 0 signs – 17, 1 sign – 26, 2 signs – 19. Contractile, conduit and reservoir functions were compared between the groups.

Results

Mean contractile, conduit and reservoir strains in all the patients were???14.14 (± 5.83) %, 15.98 (± 4.85) % and 31.03 (± 7.64) % respectively. Contractile strain did not differ between the groups. Conduit strain was higher in patients with 0 signs compared with other groups (p =?0.016 vs 1 sign of LV DD and p =?0.001 vs 2 signs of LV DD). Reservoir strain was higher in patients with 0 signs compared with other groups (p =?0.014 vs 1 sign of LV DD and p <?0.001 vs 2 signs of LV DD).

Conclusions

The patients with paroxysmal AF and primary arterial hypertension have decreased reservoir, conduit and pump LA functions even in the absence of echocardiographic signs of LV DD. With increasing number of parameters showing LV DD, LA conduit and reservoir functions decrease while contractile does not change. LA conduit and reservoir functions decrease earlier than the diagnosis of LV DD can be established according to the guidelines in patients with primary arterial hypertension and AF.

     

Eleven fetal echocardiographic planes using 4-dimensional ultrasound with spatio-temporal image correlation (STIC): a logical approach to fetal heart volume analysis

Background

Real time three dimensional (RT3D) echocardiography is an accurate and reproducible method for assessing left ventricular shape and function.

Aim

assess the feasibility and reproducibility of RT3D stress echocardiography (SE) (exercise and pharmacological) in the evaluation of left ventricular function compared to 2D.

Methods and results

One hundred eleven patients with known or suspected coronary artery disease underwent 2D and RT3DSE. The agreement in WMSI, EDV, ESV measurements was made off-line. The feasibility of RT-3DSE was 67%. The inter-observer variability for WMSI by RT3D echo was higher during exercise and with suboptimal quality images (good: k = 0.88; bad: k = 0.69); and with high heart rate both for pharmacological (HR < 100 bpm, k = 0.83; HR ≥ 100 bpm, k = 0.49) and exercise SE (HR < 120 bpm, k = 0.88; HR ≥ 120 bpm, k = 0.78). The RT3D reproducibility was high for ESV volumes (0.3 ± 14 ml; CI 95%: -27 to 27 ml; p = n.s.).

Conclusions

RT3DSE is more vulnerable than 2D due to tachycardia, signal quality, patient decubitus and suboptimal resting image quality, making exercise RT3DSE less attractive than pharmacological stress.     

Arsenic contamination of groundwater and prevalence of arsenical dermatosis in the Hetao plain area,Inner Mongolia,China

The present study determined cardiac chamber-specific alterations of the expression of the atrial and brain natriuretic peptide (ANP and BNP) genes with a small increase in age beyond adulthood and with systemic hypertension of intermediate duration. The expression distributions of these genes was determined using in situ hybridization in the right and left atria (RA and LA), and the right and left ventricles (RV and LV) in Wistar Kyoto rats (WKY) and age-matched Spontaneously Hypertensive rats (SHR) at ages 6 months (adult) and 8 months (advanced-age beyond adulthood).In all rat groups, both genes were expressed (ANP > BNP) in the LA and LV, and were not expressed in the RA and RV. The genes were expressed in the LA in all rat groups; the ANP, but not the BNP, expression increased with advancing age and with superimposed hypertension. They were expressed in the LV of the advanced-age WKY, adult and advanced-age SHR, but not in the adult WKY. The ANP mRNA labeling in the LA was diffuse and interspersed with dense accumulations, whereas BNP labeling was diffuse. The labeling of both genes in the form of sparse clusters was seen in the LV of the advanced-age SHR. Our study showed that ANP and BNP expression in left heart chambers increased with a small increase in age, with hypertension of intermediate duration, and with modest left ventricular hypertrophy. The chamber-specific expression distribution could be due to special groups of cardiac cells, or to local chamber-specific factors.     

Analysis of right ventricular function in healthy mice and a murine model of heart failure by in vivo MRI

Because of its complex geometry, assessment of right ventricular (RV) function is more difficult than it is for the left ventricle (LV). Because gene-targeted mouse models of cardiomyopathy may involve remodeling of the right heart, the purpose of this study was to develop high-resolution functional magnetic resonance imaging (MRI) for in vivo quantification of RV volumes and global function in mice. Thirty-three mice of various age were studied under isoflurane anesthesia by electrocardiogram-triggered cine-MRI at 7 T. MRI revealed close correlations between RV and LV stroke volume and cardiac output (r = 0.97, P < 0.0001 each). Consistent with human physiology, murine RV end-diastolic and end-systolic volumes were significantly higher compared with LV volumes (P < 0.05 each). MRI in mice with LV heart failure due to myocardial infarction revealed significant structural and functional changes of the RV, indicating RV dysfunction. Hence, MRI allows for the quantification of RV volumes and global systolic function with high accuracy and bears the potential to evaluate mechanisms of RV remodeling in mouse models of heart failure.     

Age is an independent risk factor for left atrial dysfunction: results from an observational study

Introduction. The degenerative changes of myocardial tissue are thought to influence left atrial (LA) function. Changes of left atrial function are generally due to changes in left ventricle (LV) compliance. But valvular dysfunction and hypertension as comorbidity cannot be ignored. Women have a different clinical profile compared with men concerning the risk of heart failure. We investigated the influence of increasing age and gender corrected for comorbidity, on left atrial function. Methods. Using an open access echocardiography database, supplemented with additional LA function measurements, we defined three different LA function parameters. Odds ratios (OR) were calculated to reproduce the relation between age, gender and LA function. The association between age, gender and LA function was estimated, and corrected for comorbid conditions as valve disease, high blood pressure and LV dysfunction, using logistic regression. Results. Higher age was positively correlated with increased LA volume, decreased ejection fraction and increased LA kinetic energy. Age per decade increase, corrected for comorbidity, resulted in an increased risk of LA dysfunction (OR between 1.5 and 1.9). Gender had little influence on LA function parameters except for LA maximal volume. Men had a significantly larger LA maximal volume compared with women. Conclusions. In this open access echocardiography database, increasing age was correlated with LA dysfunction. Age per decade increase, corrected for comorbid conditions such as mitral and aortic valve disease, hypertension and heart failure, is an independent risk factor for LA dysfunction. The gender influence on LA dysfunction seems to be limited. (Neth Heart J 2010;18:243-7.)