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Effects of subacute exposure to noise on the noradrenergic innervation of the cardiovascular system in young and aged rats: a morphofunctional study.

The effects of subacute noise stress on the noradrenergic pattern and receptor-mediated responses were examined in aorta and atria of young and aged rats. Noise exposure increased the density of noradrenergic fibres and responses to the beta-adrenergic agonist isoprenaline in the cardiac tissue of young animals. In aged rats, the stressing stimulus markedly increased the maximal response to the alpha-agonist on the aortic musculature; on the contrary, a reduced responsiveness to the beta-agonist was observed at the cardiac level, without any noteworthy changes in the noradrenergic pattern in comparison to aged controls. The present results indicate that subacute noise stress induces both morphological and functional modifications of the noradrenergic nervous system and also that after subacute noise stress, morphological changes do not necessarily correspond exactly to functional data; the latter show responses that are more widely differentiated than the morphological ones.

Aging↗

Velocity-encoded cine MRI in the evaluation of left ventricular diastolic function: measurement of mitral valve and pulmonary vein flow velocities and flow volume across the mitral valve.

Left ventricular diastolic function has been evaluated by means of analysis of the flow pattern through the mitral valve. Velocity-encoded cine magnetic resonance imaging (VEC-MR) is a new method for characterizing flow patterns in the heart. The feasibility of using VEC-MR to measure early diastolic (E) and atrial systolic (A) peak flow velocities and E/A ratios in the mitral inflow, as well as systolic (X), early diastolic (Y), and atrial systolic (Z) peak flow velocities and X/Y ratios in the pulmonary vein, was evaluated in 10 normal volunteers. The VEC-MR-derived velocities and indexes were compared with Doppler-derived results. Volumetric flow across the mitral valve was also used to measure stroke volume, cardiac output, and the left atrial contribution of left ventricular filling. VEC-MR yielded lower peak velocities than Doppler echocardiography. The velocities of the two measurements showed a significant linear correlation (Doppler E velocity = 1.30 x VEC-MR + 1.6 cm/sec, r = 0.68; Doppler A velocity = 1.83 x VEC-MR - 5.2 cm/sec, r = 0.83; and Doppler X velocity = 0.45 x VEC-MR + 0.09 cm/sec, r = 0.74). Consequently the E/A and X/Y ratios measured by these two methods showed statistically significant linear correlations with r values of 0.94 and 0.83. The volume of blood flow across the mitral valve measured by VEC-MR (5610 +/- 620 ml/min) was not statistically different from the cardiac output measured from the ascending aorta by VEC-MR (5670 +/- 590 ml/min) or by left ventricular cine magnetic resonance imaging (5440 +/- 614 ml/min). The left atrial contribution to left ventricular filling was 25.9 +/- 7.5%. Our results indicate that VEC-MR can be used not only for evaluation of left ventricular diastolic filling from the mitral valve and pulmonary vein flow velocities but also for quantitative measurement of the volume of blood flow across the mitral valve.

Adult↗

Racial variation in the prevalence of atrial fibrillation among patients with heart failure: the Epidemiology, Practice, Outcomes, and Costs of Heart Failure (EPOCH) study.

OBJECTIVES: This study was designed to determine the association between race and atrial fibrillation (AF) among patients with heart failure (HF). BACKGROUND: Atrial fibrillation is known to complicate HF, but whether its prevalence varies by race, and the reasons why, are not well understood. METHODS: We identified adults hospitalized with confirmed HF within a large integrated healthcare delivery system. We obtained information on demographics, comorbidity, vital signs, medications, and left ventricular systolic function status. "Atrial fibrillation" was defined as AF or atrial flutter documented by electrocardiogram or prior physician-assigned diagnoses. We evaluated the independent relationship between race and AF using multivariable logistic regression. RESULTS: Among 1,373 HF patients (223 African Americans, 1,150 Caucasians), the prevalence of AF was 36.9% (95% confidence interval [CI] 34.3% to 39.5%). Compared with Caucasians, African Americans were younger (mean age 67 vs. 74 years, p < 0.001) and more likely to have hypertension (86.6% vs. 77.7%, p < 0.01) and prior diagnosed HF (79.4% vs. 70.7%, p < 0.01). African Americans had less prior diagnosed coronary disease, revascularization, hypothyroidism, or valve replacement. Atrial fibrillation was much less prevalent in African Americans (19.7%) than Caucasians (38.3%, p < 0.001). After adjustment for risk factors for AF and other potential confounders, African Americans had 49% lower odds of AF (adjusted odds ratio 0.51, 95% CI 0.35 to 0.76). CONCLUSIONS: In a contemporary HF cohort, AF was significantly less common among African Americans than among Caucasians. This variation was not explained by differences in traditional risk factors for AF, HF etiology and severity, and treatment.

Adult↗

Results following physiological repair for tricuspid atresia.

Fourteen patients underwent a physiological operation for tricuspid atresia. Seven patients survived up to 3 years after operation. Six patients underwent hemodynamic studies 2 to 34 months postoperatively (mean, 15 months). Average age at the time of operation was 14 years (range, 5 to 25 years). Postoperative studies showed 4 patients to be in sinus rhythm and 2 in junctional rhythm. Right atrial pressure was elevated an average of 17 mm Hg (range, 10 to 34 mm Hg). All patients showed good atrial transport function regardless of their rhythm. Two had a right atrium-left pulmonary artery gradient of 1.5 to 10 mm Hg across the conduit. Average arterial saturation was 92% (range, 87 to 97%), on improvement of 13% over preoperative values. Residual hypoexmia was due to pulmonary vein desaturation and to atrial right-to-left shunting early postoperatively and later, to atrial right-to-left shunting alone.

Adolescent↗

Modeling of diastole.

Modeling methods have been employed to further characterize the physical and physiologic processes of filling and diastolic function. They have led to more detailed understanding of the effect of alteration of physiologic parameters on the Doppler E-wave contour as well as pulmonary vein flow. Depending on the modeling approach, different aspects of the filling process have been considered from AV gradient and net compliance to atrial appendage function to the mechanical suction pump attribute of the heart. The models have been applied for further characterization of diastolic function and elucidation of novel basic physiologic relations. We trust that readers recognize that this article could not serve as a comprehensive and global review of the state-of-the-art in physiologic modeling, but rather as a selective overview, with emphasis on the main modeling principles and options currently in use. Modeling of systems physiology, especially as it relates to the function of the four-chamber heart, remains a fertile area of investigation. Future progress is likely to have profound influence on (noninvasive) diagnosis and quantitation of the effect of therapy and lead to continued discovery of "new" (macroscopic, cellular, and molecular biologic) physiology.

Animals↗

Comparison of velocity and volumetric indexes of left ventricular filling during increased heart rate with exercise and amyl nitrite.

Physiologic variables, such as heart rate, affect the noninvasive indexes of left ventricular filling, complicating the interpretation of these indexes for clinical assessment of diastolic function. We compared the effect in normal subjects of increased heart rate provoked by both exercise and amyl nitrite on noninvasive velocity and volumetric indexes of left ventricular filling. Velocity indexes were affected in a different pattern with exercise compared with amyl nitrite because peak E wave velocity and relative atrial contribution to filling increased with exercise. In contrast, the volumetric index of rapid left ventricular filling increased similarly with both mechanisms. These findings demonstrate the importance of recognizing the different effects on indexes of left ventricular filling when heart rate is increased by different methods.

Adult↗

Comparison of left ventricular function and volumes during transesophageal atrial pacing combined with two-dimensional echocardiography in patients with syndrome X, atherosclerotic coronary artery disease, and normal subjects.

Nine patients with syndrome X were compared with 2 groups of patients known to have coronary artery disease (CAD) (8 patients who developed regional wall motion abnormalities [group ECHO+] and 6 patients who showed only ST depression at echo-pacing [group ECG+]) and with 6 healthy volunteer control subjects. Left ventricular function at rest was normal in all patients. End-diastolic and end-systolic volumes (ml/m2) and ejection fraction were calculated at baseline and at peak of echo-pacing using a Simpson's biplane method. No regional wall motion abnormalities were observed during the echo-pacing in patients with syndrome X or in the volunteers. End-diastolic volume decreased in patients with syndrome X, in the volunteers (from 47 +/- 11 to 30 +/- 12 and from 72 +/- 7 to 38 +/- 6, respectively, p <0.01 for both), and in ECG+ patients (from 48 +/- 10 to 33 +/- 6, p <0.05), whereas it did not change in ECHO+ patients. End-systolic volume decreased in patients with syndrome X and in the volunteers (from 17 +/- 5 to 11 +/- 4 and from 28 +/- 6 to 16 +/- 4, respectively, p <0.01 for both), whereas it did not change or else slightly increased in patients with CAD (from 18 +/- 10 to 16 +/- 5 for ECG+ patients and from 19 +/- 5 to 24 +/- 9 for ECHO+ patients, p = NS for both), regardless of whether regional wall motion abnormalities appeared. Ejection fraction decreased in ECG+ and ECHO+ patients (from 64 +/- 12 to 52 +/- 11 and from 62 +/- 9 to 44 +/- 13, respectively, p <0.01 for both), whereas it did not change in patients with syndrome X and in the volunteers (from 64 +/- 8 to 61 +/- 8 and from 61 +/- 7 to 58 +/- 7, respectively, p = NS for both). During echo-pacing in syndrome X patients no regional wall motion was detected. Left ventricular volumes and ejection fraction showed the same patterns of variation in these patients as they did in the healthy control subjects, in contrast with those patients with CAD, whether or not regional wall motion abnormalities appeared in the latter.

Aged↗

Verapamil sustained-release in renal parenchymal hypertension: effect on blood pressure, kidney function, angiotensin II, aldosterone, arginine vasopressin, atrial natriuretic peptide, and lipoproteins.

In 14 patients with arterial hypertension secondary to chronic renal parenchymal disease and impaired renal function, 24-h ambulatory blood pressure, casual blood pressure, plasma concentrations of angiotensin II, aldosterone, arginine vasopressin and atrial natriuretic peptide, serum creatinine, plasma lipids and lipoproteins, and body weight were determined at the end of two consecutive 3-week periods; placebo was administered in the first period and verapamil sustained-release 240 mg was given in the second period. Verapamil reduced mean 24-h ambulatory blood pressure from 152/104 mm Hg (means) to 142/97 mm Hg. Blood pressure was reduced significantly during the daytime, in the evening, and in the early morning, but not at night. Casual blood pressure was also significantly reduced from 176/106 mm Hg to 154/96 mm Hg. No significant changes were determined in the hormones, serum creatinine, plasma lipids and lipoproteins, heart rate, or body weight. Atrial natriuretic peptide was correlated significantly with serum creatinine (p = 0.733, n = 14, p less than 0.01). We conclude that verapamil sustained-release 240 mg in one daily dose has a moderate blood-pressure-lowering effect in patients with chronic renal disease and hypertension without inducing tachycardia, activation of the renin-angiotensin-aldosterone system, or increase in body weight, and without altering renal function and plasma lipids and lipoproteins. The positive correlation between atrial natriuretic peptide and serum creatinine may support the hypothesis that extracellular volume increases during progression of renal disease.

Adult↗

Functional characterization of the human atrial essential myosin light chain (hALC-1) in a transgenic rat model.

Most patients with hypertrophic cardiomyopathy and congenital heart diseases express the atrial essential myosin light chains (ALC-1) in their ventricles, partially replacing the ventricular essential light chains (VLC-1). This VLC-1/ALC-1 isoform shift is correlated with an increase in cross-bridge cycling kinetics as measured using skinned fibers from the hypertrophied ventricles of human hearts. To study the functional importance of hALC-1 in the intact perfused heart, we generated a transgenic rat model (TGR) overexpressing hALC-1 in the heart. Twelve-week-old TGR rats expressed 17 +/- 4 microg hALC-1 per mg of whole SDS-soluble protein. Their perfused heart contractility parameters were evaluated using the Langendorff preparation. Expression of hALC-1 was accompanied by statistically significant improvements (P<0.001) in the contractile parameters of the hearts of the TGR compared to the age matched control (WKY) animals, represented by increases from 20.8 +/- 2.3 to 45.1 +/- 3.6 mmHg/g heart weight in the developed left ventricular pressure, 1,035.7 +/- 89.8 to 2,181 +/- 135.4 mmHg/s in the contraction rate, and 713 +/- 60.2 to 1,364 +/- 137.4 mmHg/s in the relaxation rate in the WKY and the TGR groups respectively. Characterizing the functional effects of hALC-1 at the whole organ level represents a step towards gene therapy of heart failure.

Amino Acid Sequence↗

Left ventricular diastolic dysfunction in lone atrial fibrillation determined by Doppler tissue imaging of mitral annular motion.

In this study, we sought evidence for an underlying atrial or ventricular myopathy in patients with paroxysmal lone atrial fibrillation using standard echocardiographic parameters in addition to Doppler tissue imaging of mitral annular motion. No impairment in atrial contractile function was found, but there was evidence for impaired diastolic function in these patients.

Adult↗

Iodoaminopotentidine and related compounds: a new class of ligands with high affinity and selectivity for the histamine H2 receptor.

The synthesis and biological evaluation of a new class of histamine H2 antagonists with N-cyano-N'-[omega-[3-(1-piperidinylmethyl)phenoxy] alkyl]guanidine partial structure are described as part of an extensive research program to find model compounds for the development of new radioligands with high H2 affinity and specific activity. High receptor affinity is achieved by an additional (substituted) aromatic ring, which is connected with the third guanidine N by a carbon chain spacer and an amine, carboxamide, ester, or sulfonamide link ("polar group"). In functional studies for H2 antagonistic activity and other pharmacological actions [e.g. H1 antihistaminic, antimuscarinic, antiadrenergic (alpha 1, beta 1), 5-HT2 blocking activity] in the isolated guinea pig atrium and ileum and rat aorta and tail artery, the compounds proved to be highly potent and selective histamine H2 receptor antagonists. The H2 antagonistic activity is mainly depending on the length of both the N'-alkyl chain (chain A) and the N"-spacer (chain B). Compounds with a C3 chain A and a C2 chain B are most potent in the preferred group of substances, i.e., the carboxamide series. A wide variety of substituents at the aromatic ring is tolerated, among them iodine, amino, and azido groups. These compounds are up to 32 times more potent than cimetidine in the isolated guinea pig right atrium. The replacement of the carboxamide by an ester group (44c) is well tolerated, while replacement of the cyanoguanidine by an urea group results in nearly 100-fold decrease in activity (46c,e). The iodinated benzamides are among the most potent H2 antagonists known so far. The [125I]-labeled form of 31f ([125I]iodoaminopotentidine, [125I]-N-[2-(4-amino-3-iodobenzamido) ethyl]-N'-cyano-N"-[3-[3-(1-piperidinylmethyl) phenoxy]propyl]guanidine) and its photolabile analogue 31h ([125I]iodoazidopotentidine, [125I]-N-[2-(4-azido-3- iodobenzamido)ethyl]-N'-cyano-N"-[3-[3-(1-piperidinyl-methyl)pheno xy] propyl]guanidine) proved to be useful probes for reversible and irreversible labeling of the histamine H2 receptor. Radioligand binding studies in guinea pig cerebral membranes revealed considerably higher H2 receptor affinity for 31f (pKi = 9.15), 31h (pKi = 8.58), and some analogues than functional experiments (guinea pig atrium), presumably reflecting an easier access to the H2 receptors in membranes.

Aniline Compounds↗

Development of a numerical simulation model of the cardiovascular system.

A numerical simulation model of the cardiovascular system has been developed. It consists of a model of the left atrium, the left ventricle, the coronary vascular system, the aorta, the arterial system, and the venous system. The input of the complete model is the elastance (pressure/volume ratio) developed by the left ventricle. The shape of this elastance is constant in different circumstances. Left ventricular (LV) myocardial oxygen consumption and the amount of oxygen offered to the left ventricle can be calculated with the model. The model has been validated using data from a patient suffering from coronary artery disease. The measured clinical hemodynamical waveforms could be fitted to those generated by the model. With the numerical simulation model, it is possible to predict the functioning of the left ventricle under different circumstances. This makes it possible to study in vitro various pathological clinical situations.

Aorta↗

Functional and morphological evidence for a ventricular conduction system in zebrafish and Xenopus hearts.

Zebrafish and Xenopus have become popular model organisms for studying vertebrate development of many organ systems, including the heart. However, it is not clear whether the single ventricular hearts of these species possess any equivalent of the specialized ventricular conduction system found in higher vertebrates. Isolated hearts of adult zebrafish (Danio rerio) and African toads (Xenopus laevis) were stained with voltage-sensitive dye and optically mapped in spontaneous and paced rhythms followed by histological examination focusing on myocardial continuity between the atrium and the ventricle. Spread of the excitation wave through the atria was uniform with average activation times of 20 +/- 2 and 50 +/- 2 ms for zebrafish and Xenopus toads, respectively. After a delay of 47 +/- 8 and 414 +/- 16 ms, the ventricle became activated first in the apical region. Ectopic ventricular activation was propagated significantly more slowly (total ventricular activation times: 24 +/- 3 vs. 14 +/- 2 ms in zebrafish and 74 +/- 14 vs. 35 +/- 9 ms in Xenopus). Although we did not observe any histologically defined tracts of specialized conduction cells within the ventricle, there were trabecular bands with prominent polysialic acid-neural cell adhesion molecule staining forming direct myocardial continuity between the atrioventricular canal and the apex of the ventricle; i.e., the site of the epicardial breakthrough. We thus conclude that these hearts are able to achieve the apex-to-base ventricular activation pattern observed in higher vertebrates in the apparent absence of differentiated conduction fascicles, suggesting that the ventricular trabeculae serve as a functional equivalent of the His-Purkinje system.

Animals↗

Superior vena cava obstruction after Mustard repair of d-transposition of the great arteries.

Superior vena caval obstruction following Mustard repair of d-transposition of the great arteries is usually relieved by partial or complete revision of the intra-atrial repair. We employed a different approach in a patient with isolated total obstruction of the superior vena caval pathway, who suffered from fatigue, venous congestion in the upper part of the body and mild hydrocephalus. A 12 mm polytetrafluoroethylene tube was interposed between the left innominate vein and the left (functionally right) atrial appendage. Early and medium-term relief was demonstrated by repeat catheterization of the right heart and computed tomography brain scan three months postoperatively. The rationale for use of prosthetic material in the venous system is discussed and the need for long-term follow-up is stressed.

Blood Vessel Prosthesis↗

A semi-immobilization of a partial auricle induces hypertrophy and ultrastructural alteration of cardiomyocytes.

Semi-immobilization of a partial area of the ventral edge, lateral epicardium of the left auricle (ventrolateral of left auricle), by using quick adhesion glue induces moderate hypertrophy of myocytes with an average increase of 34% in cross-sectional area. Intercellular connective tissues increased, and cellular sizes varied markedly. The ultrastructure of immobilized (semi-immobilized) myocytes commonly exhibited degenerating features in myofibrils, various cytoplasmic organelles including mitochondrial cristae and sarcoplasmic reticulum (SR) were disrupted, and T-tubules disappeared. Z-line streaming and widening (hypertrophic Z-line, rod bodies) and increase of metabolic particle deposition are typical phenomena in addition to intercalated disc (Id) disorganization. The results suggest that semi-immobilization of the auricle induces hypertrophy of myocytes in association with degeneration and disruption of myofibrils and other cytoplasmic organelles, and an increase of intercellular connective tissues, rather than increase of myofibril mass. This is the first study to immobilize only a part of the heart rather than the whole animal. Our results using artificial immobilization of cardiac myocytes were extremely significant since the structural alterations obtained were similar to that observed in cardiomyopathies. This suggests that myocytes progressing to heart failure are also subjected to inhibition of movement. Therefore, this experiment may prove very useful as a model for studying the functional effect of heart failure observed in cardiomyopathy.

Anatomy, Cross-Sectional↗

Echocardiography of the right side of the heart.

Echocardiography has not only revealed the morphologic aspects of the right-sided cardiac structure but has, through the use of pulsed and color Doppler imaging, provided a whole new level of certainty in the diagnosis of cardiac disease. The structure and function of the right-sided chambers are now far better appreciated since this technique has become more widely used for early clinical diagnosis of right-sided cardiac disease.

Atrial Function, Right↗

Regional differences in cardiac effects of pituitary adenylate cyclase-activating polypeptide-27 in the isolated dog heart.

Recent observations indicate that several neuropeptides may be involved in the regulation of cardiac function, but the effects of these peptides on the atrium are not always the same as those on the ventricle. To compare the effect of pituitary adenylate cyclase-activating polypeptide (PACAP)-27 on the atrium with that on the ventricle, we investigated the effects of PACAP-27 on the sinus rate and atrial and ventricular contractility in isolated, blood-perfused dog heart preparations. PACAP-27 (0.01-0.3 nmol) caused transient positive followed by negative chronotropic and inotropic responses in a dose-dependent manner in the isolated right atrium, whereas it caused only a dose-dependent positive inotropic response in the left ventricle. After atropine treatment, PACAP-27 caused only positive cardiac responses in isolated atria. The order of the increase in response to PACAP-27 was atrial contractile force > sinus rate > or = ventricular contractile force. Tetrodotoxin blocked the negative chronotropic and inotropic responses to PACAP-27 in isolated atria. Propranolol did not affect the positive response. PACAP-(6-27), a type I PACAP receptor antagonist, attenuated the positive responses similarly in the atropine-treated right atrium and the left ventricle. Thus, we demonstrated that (1) PACAP-27 caused negative cardiac effects in the atrium and sinoatrial node by activation of intracardiac parasympathetic nerves, but had no negative effect on the ventricle; (2) PACAP-27 had positive effects in the atrium, sinoatrial node and ventricle mediated by type I PACAP receptors, but PACAP-27 was more effective in the atrium and sinoatrial node than in the ventricle of the dog heart.

Animals↗