The classical Guyton view that mean systemic pressure, right atrial pressure, and venous resistance govern venous return is/is not correct.
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The purpose of our investigation was to identify the transcriptional basis for ultrastructural and functional specialization of human atria and ventricles. Using exploratory microarray analysis (Affymetrix U133A+B), we detected 11,740 transcripts expressed in human heart, representing the most comprehensive report of the human myocardial transcriptome to date. Variation in gene expression between atria and ventricles accounted for the largest differences in this data set, as 3.300 and 2.974 transcripts showed higher expression in atria and ventricles, respectively. Functional classification based on Gene Ontology identified chamber-specific patterns of gene expression and provided molecular insights into the regional specialization of cardiomyocytes, correlating important functional pathways to transcriptional activity: Ventricular myocytes preferentially express genes satisfying contractile and energetic requirements, while atrial myocytes exhibit specific transcriptional activities related to neurohumoral function. In addition, several pro-fibrotic and apoptotic pathways were concentrated in atrial myocardium, substantiating the higher susceptibility of atria to programmed cell death and extracellular matrix remodelling observed in human and experimental animal models of heart failure. Differences in transcriptional profiles of atrial and ventricular myocardium thus provide molecular insights into myocardial cell diversity and distinct region-specific adaptations to physiological and pathophysiological conditions. Moreover, as major functional classes of atrial- and ventricular-specific transcripts were common to human and murine myocardium, an evolutionarily conserved chamber-specific expression pattern in mammalian myocardium is suggested.
Chronic obstructive pulmonary disease has been associated with a high frequency of arrhythmias. Few studies have analysed the role of reduced lung function in predicting atrial fibrillation (AF). The aim of the present study was to investigate the relationship between forced expiratory volume in one second (FEV1) and risk of first episode of AF in a prospective study. Data from 13,430 males and females without previous myocardial infarction, who participated in the Copenhagen City Heart Study, were analysed. New AF was assessed at re-examination after 5 yrs and by hospital admission for AF during a period of 13 yrs. Multivariate analyses were used with adjustment for cardiopulmonary risk factors. There were 62 new cases of AF at 5-yr follow-up (0.58%) and 290 cases (2.20%) diagnosed at hospitalisations. Risk of new AF at re-examination was 1.8-times higher for FEV1 between 60-80% of predicted compared with FEV1 > or = 80% after adjustment for sex, age, smoking, blood pressure, diabetes and body mass index. The risk of AF hospitalisation was 1.3-times higher for FEV1 between 60-80% and 1.8-times higher for FEV1 < 60% compared with FEV1 > or = 80%, when additional adjustment was made for education, treatment with diuretics and chest pain at activity. The authors conclude that reduced lung function is an independent predictor for incident atrial fibrillation.
BACKGROUND: The characteristics of transmembrane potential (TMP) at the core of functional reentry in the atrium are not well understood. METHODS AND RESULTS: In protocol 1 (11 dogs), isolated perfused canine right atria were mapped from the endocardial surface while simultaneous TMPs were recorded from the epicardial surface. Episodes of reentry (n=64) were induced in the presence of 1 to 5 micromol/L acetylcholine. Successful simultaneous TMP recordings and activation maps were made in 8 episodes. The TMP was "near the core" if it was within 3.2 mm of the core; otherwise, it was considered to be "in the periphery." The mean cycle length of reentry was 110+/-35 ms. The TMP amplitude, duration (90% repolarization), and (dV/dt)max near the core (n=106) were 58+/-22 mV, 46+/-14 ms, and 33+/-20 V/s, respectively, significantly less than those in the periphery (n=241): 70+/-8 mV, 94+/-32 ms, and 55+/-10 V/s (P<0.001 for all). In 2 episodes of reentry, the cell at the core remained unexcited at its resting membrane potential. In protocol 2 (2 dogs), we performed simultaneous high-density mapping in 4 episodes of reentry and showed synchronous activation patterns on both surfaces with similar locations of the core. CONCLUSIONS: During meandering functional reentry in isolated canine right atria, (1) TMPs of cells near the core have a reduced amplitude, duration, and (dV/dt)max, and (2) cells at the core may remain unexcited at their resting membrane potential. These findings are compatible with the spiral wave concept of functional reentry in the atrium.
The aim of this study was to investigate the activity of the parasympathetic limb of the baroreflex arch in a canine model of obesity-related hypertension. Twelve male beagle dogs were randomized into 2 groups. Six dogs were fed with normal canine food and 6 were submitted to a 10-week high-fat diet (HFD). We have evaluated the consequences of HFD on heart rate (HR) and blood pressure (BP) circadian cycles and methylscopolamine dose-response curves. Binding of [(3)H]-AF-DX 384 and adenylyl cyclase activity were investigated to determine the density and functionality of M(2)-cholinoceptors on right atrial membranes from control and HFD dogs. HFD induced a significant increase in body weight (15+/-1 vs 12+/-1 kg), systolic BP (161+/-5 vs 145+/-4 mm Hg), diastolic BP (92+/-3 vs 79+/-2 mm Hg), and HR (96+/-4 vs 81+/-3 bpm). Circadian rhythms of HR and BP observed in the baseline period were abolished after 9 weeks of HFD. After propranolol (1 mg/kg) pretreatment, the dose of methylscopolamine able to induce 50% maximum tachycardia was significantly increased after 9 weeks of HFD (7.4+/-0.3 vs 4.7+/-0.1 microg/kg). In the control group, the experimental period failed to modify these parameters. The numbers of M(2)-cholinoceptors measured in right atrial membranes were significantly lower in HFD than in control groups (54+/-6 vs 27+/-6 fmol/mg protein). The ability of carbachol to inhibit isoproterenol-stimulated adenylyl cyclase activity was significantly lower in HFD than in control groups (IC(50)=47+/-12 vs 6.4+/-1.4 micromol/L). However, the basal activity of adenylyl cyclase was unchanged by HFD. HFD decreases M(2)-cholinoceptor number and function in cardiomyocytes. This could explain the abolition of circadian rhythm of HR and the changes in chronotropic effect brought about by methylscopolamine.
Pulmonary venous flow as assessed by transesophageal echocardiography (TEE) is influenced by changes in left atrial pressure and function. In mitral stenosis (MS), normal left atrial hemodynamics are altered because there is a prolonged decay in diastolic pressure from the left atrium to the left ventricle and atrial function may be altered because of atrial fibrillation. To assess the effect of the prolonged atrial diastolic pressure decay caused by MS on pulmonary venous flow, we studied 27 patients with MS (mitral valve range 0.7 to 2.4 cm2) by pulsed-wave Doppler TEE of the left or right upper pulmonary vein, and compared results with those of 13 normal subjects. Of the 27 subjects with MS, 61% showed a blunted systolic flow pattern and 39% showed a normal flow pattern with greater systolic to diastolic flow ratio. Patients with atrial fibrillation had a predominantly blunted pattern, whereas patients with normal sinus rhythm exhibited both blunted and normal flow patterns. Patients with MS had a lower pulmonary venous peak systolic flow velocity and a longer diastolic pressure halftime than control subjects. Pulmonary venous peak systolic flow velocity was significantly decreased in the presence of atrial fibrillation (p = 0.004). The mitral valve pressure halftime significantly correlated with pulmonary venous diastolic pressure halftime (r = 0.54; p = 0.004) mitral valve area (r = -0.46; p = 0.02). In conclusion, it was found that MS alters pulmonary venous flow patterns, showing a decreased pulmonary venous systolic flow and a prolonged diastolic flow, which may be useful in assessing the hemodynamics of MS.
BACKGROUND: The Cox Maze III procedure is the standard operation for the surgical cure of atrial fibrillation. Its wide spread use is limited by the extensive nature of the procedure. The surgical diathermy device is a radio frequency generator and can be used to create surgical lesions, which cause interruption of the basic flutter cycle that initiates/maintains atrial fibrillation. METHODS: We describe the initial results in 25 cases where we used an ordinary surgical diathermy unit to create bi-atrial lesions creating an electrocautery maze during concomitant mitral valve surgery. RESULTS: There was a 96% conversion to sinus rhythm. This has remained stable over a follow-up of a mean of 3.5 years. There has been an associated return of left atrial transport function and a significant reduction in left atrial size. CONCLUSION: The electrocautery maze appears to be a simple, effective, and quick method to cure atrial fibrillation.
A family of biologically active peptides (atrial natriuretic factor - ANF) has recently been identified in mammalian heart atria. The peptides derive from a common 152 amino acid precursor and at least 1% of total messenger RNA activity is specific for the factor. When injected intravenously ANF is hypotensive and natriuretic. Data indicate that atrial natriuretic factor represents a newly discovered hormone involved in the regulation of blood pressure and volume. Cellular release of ANF does not require the activation of the adenylate cyclase system, but is associated with receptor-mediated activation of the cellular polyphosphoinositide mechanism. The natriuretic effect includes increased glomerular filtration rate and specific inhibition of normal sodium reabsorption from the medullary collecting duct. The mechanism of this transport inhibition is not yet known.
The aim of this study was to evaluate the use of intraventricular dispersion of the peak diastolic flow velocity as a marker of left ventricular diastolic dysfunction in patients with atrial fibrillation. Regional diastolic flow velocity patterns at 1, 2, and 3 cm away from the mitral tip toward the apex were simultaneously recorded with the mitral flow velocity pattern by using pulsed Doppler echocardiography in 24 patients with atrial fibrillation before electrical or medical cardioversion. Echocardiographic examination was repeated after 10 to 30 days (ie, at the time of recovery of left atrial mechanical functions) after cardioversion of atrial fibrillation in all patients. Thirteen patients were found to have diastolic dysfunction; the remaining 11 patients with a normal E/A ratio constituted the control group. Afterward, the data recorded before the cardioversion were analyzed for each patient. In subjects with normal diastolic function, the peak diastolic flow velocity (PDFV) at the mitral tips also was maintained at the positions 1 to 3 cm away from the tip in the left ventricular cavity (PDFV at the mitral tips: 0.84 m/s, PDFV at 3 cm: 0.85 m/s; P =.34). In contrast, the regional PDFV progressively decreased toward the apex in patients with diastolic dysfunction (PDFV at the mitral tips: 0.82 m/s, PDFV at 3 cm: 0.63 m/s; P =.0004). Only 77% of the initial velocity was maintained at 3 cm away from the mitral tips in patients with diastolic dysfunction, whereas almost 100% of the initial velocity was preserved in patients with normal diastolic function (P <.001). These findings suggest that the assessment of the intraventricular decrease in mitral PDFV may be used as a reliable marker of diastolic dysfunction in patients with atrial fibrillation.
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This study was undertaken to investigate the effect of chronic right ventricular (RV) volume overload on left ventricular (LV) diastolic function. Twelve patients with atrial septal defect and 7 age-matched normal controls were examined. Patients with atrial septal defect were divided into 2 groups based on their Qp/Qs values (ASD1:Qp/Qs < or = 3, n = 7; ASD2:Qp/Qs > 3, n = 5). The LV volume curve and its first derivative were derived by a frame-by-frame analysis of the left ventriculogram. The peak filling rate was defined by the peak positive first derivative of the LV volume curve. We measured the time constant, isovolumetric relaxation time, stiffness constant and compliance at LV end-diastole. The time constant was significantly prolonged in the ASD2 group compared with the controls, and the isovolumetric relaxation time in both atrial septal defect groups was also prolonged compared with the controls. The peak filling rate, which was normalized by end-diastolic volume, was lower in the ASD2 group than in the controls. Although the stiffness constant and the compliance at LV end-diastole in the controls were not significantly different from those in the atrial septal defect group, an upward and leftward displacement of the left ventricular pressure-volume curve was observed in patients with atrial septal defect. Moreover, a significant correlation (r = 0.78, p < 0.01) was observed between the time constant and RV end-diastolic pressure. Thus, these results suggest that chronic RV volume overload affects left ventricular diastolic function.
BACKGROUND AND METHODS: The correlations between continuous positive-pressure ventilation-induced antidiuresis/antinatriuresis, atrial transmural pressure, and atrial natriuretic peptide concentrations have not been clarified. The purpose of the present study was to use aggressive hydration to restore atrial transmural pressure during continuous positive-pressure ventilation and to test for correlations of atrial transmural pressure, atrial natriuretic peptide concentration, diuresis, and natriuresis during this intervention. An intrapleural catheter was used to measure atrial transmural pressure in three ways: a) right atrial pressure minus intrapleural pressure, b) left ventricular end-diastolic pressure minus intrapleural pressure, and c) pulmonary artery occlusion pressure minus intrapleural pressure. Hemodynamic, atrial natriuretic peptide concentrations, and renal measurements were made in 12 anesthetized closed-chest dogs during baseline (intermittent positive-pressure ventilation), during continuous positive-pressure ventilation), during continuous positive-pressure ventilation with 10 cm H2O end-expiratory pressure, and during continuous positive-pressure ventilation plus aggressive hydration (approximately 60 mL/kg lactated Ringer's solution). Pearson's correlation matrix was used to generate all possible correlation coefficients between the three atrial transmural pressures, atrial natriuretic peptide concentrations, urine output, and urine sodium excretion. RESULTS: Application of continuous positive-pressure ventilation resulted in a 60% decrease in right atrial transmural pressure (p less than .05), a 51% decrease in left ventricular end-diastolic transmural pressure (p less than .05), and a 26% decrease in pulmonary artery occlusion transmural pressure (p less than .05) from baseline. Plasma atrial natriuretic peptide concentration decreased from 80 +/- 12 (SEM) pg/mL at baseline to 49 +/- 8 pg/mL during continuous positive-pressure ventilation (p less than .05). Both urine output and sodium excretion decreased by 81% (p less than .05). After aggressive hydration with lactated Ringer's solution during continuous positive-pressure ventilation, to restore atrial transmural pressure to baseline, plasma atrial natriuretic peptide concentration returned to baseline values (81 +/- 12 pg/mL) as did urine output and sodium excretion. Correlation indices (r2 values) between transmural pressure, atrial natriuretic peptide concentration, urine output, and sodium excretion ranged from .835 to .994. Multivariate analysis of covariance demonstrated significant (p less than .05) temporal dependence between the three transmural pressures, atrial natriuretic peptide concentration, urine output, and sodium excretion. CONCLUSIONS: The results demonstrate that aggressive hydration during continuous positive-pressure ventilation will restore diuresis and natriuresis and that this response correlates significantly with atrial transmural filling pressure and plasma atrial natriuretic peptide concentration.
OBJECTIVE: To assess the feasibility of measuring left atrial (LA) function with acoustic quantification (AQ) and then assess the effects of age and sex on LA reservoir, conduit, and booster pump function. PATIENTS AND SETTING: 165 subjects without cardiovascular disease, 3-79 years old, were enrolled by six tertiary hospital centres. INTERVENTIONS: Continuous LA AQ area data were acquired and signal averaged to form composite waveforms which were analysed off-line. MAIN OUTCOME MEASURES: Parameters of LA performance according to age and sex. RESULTS: Signal averaged LA waveforms were sufficiently stable and detailed to allow automated analysis in all cases. An age related increase in LA area was noted. LA reservoir function did not vary with age or sex. All parameters of LA passive and active emptying revealed a significant age dependency. Overall, the passive emptying phase accounted for 66% of total LA emptying ranging from 76% in the youngest to 44% in the oldest decade. LA contraction accounted for 34% of atrial emptying in all subjects combined with the older subjects being more dependent on atrial booster pump function. When adjusted for atrial size, there were no sex related differences in LA function. CONCLUSIONS: LA reservoir, conduit, and booster pump function can be assessed with automated analysis of signal averaged LA area waveforms. As LA performance varies with age, establishment of normal values should enhance the evaluation of pathologic states in which LA function is important.
OBJECTIVE: The aim of the study is to find out the efficacy of radiofrequency catheter atrial ablation (RF) simultaneously done with mitral valve replacement (MVR) surgery in patients having rheumatic mitral valve disease with chronic atrial fibrillation and to evaluate the short-term postoperative results. METHODS: Seventeen patients underwent MVR surgery, and intraoperative RF procedures were done simultaneously with MVR to eight of these patients, whereas remaining nine of them were assigned to control group. Patients were assessed preoperatively, at time of discharge, and 1st, 6th and 12th months controls. Atrial and ventricular functions were evaluated with echocardiography, serum atrial natriuretic peptide (ANP) levels were investigated and electrocardiograms were recorded in all patients. RESULTS: Demographically there were no significant differences between two groups. Radiofrequency ablation group had longer aortic cross-clamping and cardiopulmonary bypass times. Sinus rhythm was established in seven patients of RF group at postoperative 12th month. However, all patients of this group experienced sinus rhythm at postoperative sixth month whereas 'atrial kick' was detected in five of them. Significantly increased ejection fraction, decreased pulmonary artery pressure and decreased left atrial diameter were observed in RF group compared to control group. Serum ANP levels were found to be significantly decreased as compared to preoperative periods in both groups. CONCLUSION: Although RF ablation has higher costs, this technique is efficient and useful to restore the sinus rhythm and to recover the atrial functions back in patients having rheumatic mitral valve disease.
Anatomic indexes of the LAA are dependent on the plane in which the appendage is viewed. Greater LAA neck width and cross-sectional area are observed at 135 degrees than at 45 degrees or 90 degrees, consistent with the characteristic 3-dimensional ungular shape of this structure. Appendage ejection and inflow velocity measurements are independent of the imaging plane.
BACKGROUND: Although there have been many studies on the effects of atrial fibrillation (AF) on cardiac function, few studies have been done on its effects on endothelial function. The present study was designed to examine the effects of AF on endothelial function in human subjects. METHODS AND RESULTS: Changes in forearm blood flow (FBF) induced by acetylcholine and nitroglycerin were measured by using plethysmography in 14 patients with lone AF, 13 patients with AF and underlying heart disease, and 12 normal control subjects. In the patients, these measurements were repeated after cardioversion. Although baseline FBF was the same in the 3 groups, acetylcholine-induced increases in FBF were significantly smaller in both patient groups than in the control group, and FBF increases were particularly depressed in AF patients with underlying heart disease. After restoration of sinus rhythm by cardioversion, FBF response to the highest dose of acetylcholine increased by 46% in patients with lone AF (n = 10) and by 90% in AF patients with underlying heart disease (n = 11). Nitroglycerin-induced vasodilatation was the same in all 3 groups and was not affected by cardioversion. CONCLUSIONS: These findings suggest that endothelium-dependent vasodilatation is impaired by AF and improves after sinus rhythm is restored.
We have investigated the role of the lungs in the extraction of atrial natriuretic factor (ANF) by measuring plasma levels in samples taken from the central circulation in 12 patients (mean age 59 years; range 43 to 68) undergoing cardiac surgery. We also investigated the effects of cardiopulmonary bypass on ANF levels. ANF levels (mean +/- SD) were lower in pulmonary venous samples (41 +/- 20 pg/ml) than in pulmonary arterial samples (54 +/- 18 pg/ml; p less than 0.001), demonstrating 24% extraction of ANF by the lungs. Both left atrial (47 +/- 23 pg/ml) and systemic arterial levels (52 +/- 22 pg/ml) were higher than pulmonary venous levels (both p less than 0.05), indicating secretion of ANF into the left side of the heart. During cardiopulmonary bypass, plasma ANF concentration fell from 68 +/- 23 pg/ml before aortic cross-clamping to 35 +/- 13 pg/ml 10 minutes after and 28 +/- 9 40 minutes after the application of clamps (both p less than 0.001). A rebound rise to 122 +/- 33 pg/ml followed the release of the clamp (p less than 0.001). This study demonstrates that ANF is extracted by the lungs and secreted directly into the left side of the heart. The considerable fall in plasma levels that was observed during aortic cross-clamping might contribute to the neurohumoral activation and increased peripheral resistance observed after prolonged cardiopulmonary bypass and to the risk of renal ischemic injury.
BACKGROUND: We assessed the effects of pacing-induced chronic atrial fibrillation (AF) on sinus node function, intra-atrial conduction, and atrial refractoriness. METHODS AND RESULTS: In 15 mongrel dogs (20 to 30 kg), AV nodal block was produced by radiofrequency catheter ablation, and a ventricular-inhibited (VVI) pacemaker (Minix 8330, Medtronic) was implanted and programmed to pace at 80 pulses per minute. In 11 of these dogs, right atrial endocardial pacing leads were connected to a pulse generator (Itrel 7432, Medtronic) and set at a rate of 20 Hz to induce AF. Corrected sinus node recovery time, P-wave duration, 24-hour Holter ECG to assess AF duration, maximal heart rate in response to isoproterenol (10 micrograms/min), intrinsic heart rate after administration of atropine (0.04 mg/kg) and propranolol (0.1 mg/kg), and atrial effective refractory periods (ERPs) were obtained at baseline (EPS-1) and after 2 to 6 weeks (EPS-2) of VVI pacing alone (n = 4) or VVI pacing and rapid atrial pacing (n = 11). At EPS-2, corrected sinus node recovery time and P-wave duration were prolonged, maximal heart rate and intrinsic heart rate were decreased, atrial ERPs were shortened, and the duration of AF was increased significantly compared with EPS-1. These changes partially reversed toward baseline 1 week after conversion to sinus rhythm. Sinus node function and AF inducibility observed in the control dogs that underwent ventricular pacing alone (n = 4) did not change. CONCLUSIONS: Pacing-induced chronic AF induces sinus node dysfunction, prolongs intra-atrial conduction time, shortens atrial refractoriness, and perpetuates AF, changes that reverse gradually after termination of AF.