atrial-natriuretic-factor and Aortic-Valve-Insufficiency

The effect of hANP (atrial natriuretic peptide) was investigated clinically in 40 patients who underwent isolated valve replacement. Patients were divided into four groups: aortic regurgitation (AR), aortic stenosis (AS), mitral regurgitation (MR) and mitral stenosis (MS). Each group was divided into two subgroups: one was administered hANP after the operation until leaving ICU, and the other was not administered hANP. We measured the levels of hANP and c-GMP and blood pressure, pulmonary artery pressure, central venous pressure and levels of Na, K of urine and blood prcoperatively, immediately postoperatively and 1, 2, 4, 6 hours after operation. First, to examine the relationship between preoperative level of hANP and cardiac function, the relationship between preoperative level of hANP and history of cardiac failure and pulmonary artery wedge pressure (PAWP) were evaluated. Also, we evaluated the relationship between preoperative level of hANP and each dimension on echocardiography. There was a weak statistical relationship between hANP and PAWP (row = 0.39 (p = 0.04) Pearson correlation method) and there was no statistical relationship between hANP and duration of cardiac failure (row = 0.00445 (p = 0.98) Pearson correlation method). Preoperatively Left atrial diameter (LAD) showed a statistical relationship with level of hANP in every group using Spearman correlation method. Other dimensions such as left ventricular diastolic diameter (LVDd) and left ventricular systolic diameter (LVDs) and also fractional shortening (FS) did not show a strong correlation with preoperative level of hANP. Especially, in AS group there was a strong relationship between every dimension and preoperative level of hANP. Only in MS group LAD and the level of hANP were negatively related. This finding suggests that atrial dilatation results in reduction of secretion of hANP in cases of MS on long term follow up. Finally, hNAP therapy was shown to have a continuous diuretic effect, with stable hemodynamics.

Topics: Adult; Aortic Valve Insufficiency; Aortic Valve Stenosis; Atrial Natriuretic Factor; Female; Heart Valve Diseases; Heart Valve Prosthesis Implantation; Humans; Male; Middle Aged; Mitral Valve Insufficiency; Mitral Valve Stenosis; Pulmonary Wedge Pressure

The development of left ventricular hypertrophy and dysfunction in aortic regurgitation (AR) has only been sparsely studied experimentally. In a new model of chronic AR in rats, we examined activation of molecular pathways involved in myocardial hypertrophy. Chronic AR was produced by damaging one or two valve cusps, resulting in eccentric remodeling and left ventricular dysfunction, with no increase in overall fibrosis. Western blotting showed increased activation of Akt and p38 at 12 weeks and of c-Jun amino-terminal kinase at 2 weeks, decreased activation of extracellular regulated kinase 5 at both 2 and 12 weeks, while activation of calcium/calmodulin-dependent protein kinase II and extracellular regulated kinase 1/2 was unchanged. Expression of calcineurin and ANF was also unchanged. Eccentric hypertrophy and early cardiac dysfunction in experimental AR are associated with a pattern of activation of intracellular pathways different from that seen with pathological hypertrophy in pressure overload, and more similar to that associated with benign physiological hypertrophy.

Topics: Animals; Aortic Valve Insufficiency; Atrial Natriuretic Factor; Calcineurin; Calcium-Calmodulin-Dependent Protein Kinase Type 2; Chronic Disease; Disease Models, Animal; Echocardiography, Doppler, Color; Extracellular Signal-Regulated MAP Kinases; Hypertrophy, Left Ventricular; JNK Mitogen-Activated Protein Kinases; Male; Myocardium; p38 Mitogen-Activated Protein Kinases; Phosphorylation; Proto-Oncogene Proteins c-akt; Rats; Rats, Sprague-Dawley; Signal Transduction; Time Factors; Ventricular Dysfunction, Left; Ventricular Function, Left

Aortic regurgitation (AR) is a chronic disease for which there is currently no approved medical treatment. We previously reported in an animal model that β-blockade with metoprolol exerted beneficial effects on left ventricular remodeling and survival. Despite the recent publication of promising human data, β-blockade in chronic AR remains controversial. More data are needed to support this potentially new treatment strategy. We hypothesized that carvedilol might be another safe treatment option in chronic AR, considering its combined β-blocking and α-blocking effects and proven efficacy in patients with established heart failure.. The effects of a 6-month treatment with carvedilol 30 mg/kg/d orally were evaluated in adult Wistar rats with severe AR. Sham-operated and untreated AR animals were used as controls. Carvedilol treatment resulted in less left ventricular hypertrophy and dilatation. Ejection fraction was improved and filling pressures were reduced by carvedilol. β1-Receptor expression was also improved as well as myocardial capillary density. Those beneficial effects were noted despite the presence of drug-induced bradycardia.. Carvedilol exerted protective effects against volume-overload cardiomyopathy in this model of aortic valve regurgitation with preserved ejection fraction. These results suggest a protective class effect of β-blockers. Combined with the recent publication of promising human data, our findings support the need to carefully design a prospective study in humans to evaluate the effects of β-blockers in chronic aortic valve regurgitation.

Topics: Administration, Oral; Adrenergic beta-Antagonists; Animals; Aortic Valve Insufficiency; Atrial Natriuretic Factor; Bradycardia; Capillaries; Carbazoles; Carvedilol; Chronic Disease; Disease Models, Animal; Extracellular Matrix Proteins; Follistatin-Related Proteins; Gene Expression Regulation; Heart Rate; Hypertrophy, Left Ventricular; Male; Natriuretic Peptide, Brain; Propanolamines; Rats; Rats, Wistar; Receptors, Adrenergic; RNA, Messenger; Stroke Volume; Time Factors; Ultrasonography; Ventricular Function, Left; Ventricular Pressure

This study measured plasma atrial natriuretic peptide (ANP) concentration in horses with heart valve regurgitations (HVR) with and without atrial and ventricular dilatation.. In humans and small animals, plasma ANP concentration is increased in heart disease and correlates with the severity of clinical signs and heart enlargement.. Ten healthy horses (control) and 36 horses with HVR were evaluated by auscultation, electrocardiography, echocardiography, and determination of plasma ANP.. Control horses demonstrated mean plasma ANP concentration of 21+/-5.4 pg/mL. Of the 36 horses with HVR, 17 horses possessed normal echocardiographic heart size (group 1), 10 horses had a left atrial dilatation (group 2) and 9 horses had both left atrial and ventricular dilatation (group 3). Mean plasma ANP concentration of groups 1, 2 and 3 was 20.1+/-5.6 pg/mL, 22.9+/-11.0 pg/mL and 27.6+/-17.4 pg/mL, respectively. The plasma ANP concentrations of HVR and control horses were not significantly different. The highest ANP concentrations were observed in horses with atrial and ventricular dilatation. No correlation between left atrial or ventricular size, weight, or sex and the plasma ANP concentration was found.. No significant differences in plasma ANP concentration was observed between groups. Further study, especially in horses with clinical signs of heart failure is needed.

Topics: Animals; Aortic Valve Insufficiency; Atrial Natriuretic Factor; Case-Control Studies; Echocardiography; Electrocardiography; Female; Horse Diseases; Horses; Male; Mitral Valve Insufficiency; Severity of Illness Index

In 40 patients with chronic moderate to severe aortic regurgitation, brain natriuretic peptide, N-brain natriuretic peptide, and atrial natriuretic peptide were higher in symptomatic patients compared with asymptomatic patients after adjustment for age, gender, and ejection fraction, but each natriuretic peptide correlated weakly with echocardiographic measures of left ventricular size and function. In patients with chronic aortic regurgitation, measurement of natriuretic peptide levels may provide information on left ventricular function in addition to echocardiography.

Topics: Adult; Aortic Valve Insufficiency; Atrial Natriuretic Factor; Chronic Disease; Echocardiography; Female; Humans; Male; Natriuretic Peptide, Brain; Predictive Value of Tests; Sensitivity and Specificity; Severity of Illness Index; Stroke Volume; Ventricular Dysfunction, Left

Uncoupling proteins, inner mitochondrial membrane proton transporters, are important for regulating myocardial energy efficiency. We investigated the effects of the ACE inhibitor perindopril on cardiac performance, myocardial energy efficiency, and uncoupling protein expression in an aortic regurgitation rat model. Twenty male Sprague-Dawley rats, in which aortic regurgitation was produced, were divided into untreated and perindopril-treated (5 mg x kg(-1) x d(-1)) rats. The treatments were initiated 3 days after operation. Ten control rats were sham-operated. Measurements of blood pressure and echocardiography were repeated before and 100 days after operation (endpoint). Left ventricular uncoupling protein-2 expression, creatine phosphate, and adenosine triphosphate were measured at endpoint. In perindopril-treated rats, systolic and diastolic blood pressure decreased after treatment (92+/-4/65+/-2 mm Hg). At endpoint, left ventricular end-diastolic dimension in untreated (10.7+/-0.2 mm) and treated rats (9.2+/-0.2 mm) was increased, and fractional shortening was reduced in untreated rats (28+/-1%) but did not change in treated rats (36+/-2%). Uncoupling protein-2 mRNA expression increased in untreated rats (3.7-fold) and was suppressed by perindopril (1.5-fold). The creatine phosphate was reduced in untreated rats (10.6+/-0.7 micro mol/g) but not in treated rats (15.9+/-2.0 micro mol/g). In the chronic stage of aortic regurgitation, perindopril improved cardiac performance and myocardial energy efficiency, in which the suppression of uncoupling protein-2 may play an important role.

Topics: Adenosine Triphosphate; Angiotensin-Converting Enzyme Inhibitors; Animals; Aortic Valve Insufficiency; Atrial Natriuretic Factor; Blood Pressure; Echocardiography, Doppler; Energy Metabolism; Heart; Heart Failure; Heart Rate; Ion Channels; Male; Membrane Transport Proteins; Mitochondrial Proteins; Myocardium; Organ Size; Perindopril; Phosphocreatine; Protein Biosynthesis; Proteins; Rats; Rats, Sprague-Dawley; RNA, Messenger; Uncoupling Protein 2

Topics: Adenosine Triphosphate; Animals; Aortic Valve Insufficiency; Atrial Natriuretic Factor; Blotting, Northern; Cardiac Output, Low; Disease Models, Animal; Humans; Ion Channels; Male; Membrane Transport Proteins; Mitochondria, Heart; Mitochondrial Proteins; Muscle, Skeletal; Myocardium; Phosphocreatine; Proteins; Rats; Rats, Sprague-Dawley; RNA, Messenger; Tumor Necrosis Factor-alpha; Uncoupling Agents; Uncoupling Protein 2

Alpha-human atrial natriuretic peptide (alpha-hANP) has a vasodilating and diuretic action. Intravenous continuous administration of alpha hANP (0.05 microgram/kg/min) was attempted for two patients with low urine output despite good hemodynamics following open-heart surgery. Following the administration of alpha-hANP, urine volume increased markedly, and central venous and pulmonary capillary wedge pressures immediately decreased. Intravenous continuous administration of alpha-hANP is useful for the management of patients associated with the volume overload following open-heart surgery.

Topics: Aged; Aortic Valve Insufficiency; Atrial Natriuretic Factor; Cardiac Surgical Procedures; Diuretics; Heart Valve Prosthesis; Hemodynamics; Humans; Male; Middle Aged; Mitral Valve Insufficiency; Peptide Fragments; Postoperative Care

The aim of this study was to assess the blood pressure profile and vasoactive hormones in valvular aortic disease. Thirteen aortic stenosis and/or aortic regurgitation patients were matched with 13 control subjects. Ambulatory blood pressure monitoring was performed for 24 h. Arterial and venous plasma concentrations of renin, angiotensin II, aldosterone, arginine vasopressin, atrial natriuretic peptide, immunoreactive endothelin and cyclic-GMP were measured. The mean 24-h blood pressure was higher in the patient group (94.9 mmHg) compared with control subjects (88.2 mmHg) (p < 0.0001), despite no differences in daytime blood pressures. The nocturnal blood pressure fall was attenuated in the patients (systolic/diastolic blood pressure -8.5/-3.5; -20.3/-14.3 mmHg (p < 0.001/p < 0.01)); in heart rate too the nightly fall was blunted in the patients (-4.8/ -13.4/min (p < 0.0013)). PRA, Ang II, AVP, ANP, ir-ET and cGMP were significantly increased in the patients compared to the controls. Nightly systolic blood pressure fall was inversely related to arterial (r = -0.75, p < 0.003) and venous (r = -0.65, p < 0.04) plasma renin activity and arterial aldosterone (r = -0.64, p < 0.05) in valvular aortic disease patients. In conclusion, valvular aortic disease patients have attenuated falls in blood pressure and heart rate during the night. Increased activity in the renin aldosterone system may be involved in this abnormal blood pressure regulation.

Topics: Adult; Aged; Aldosterone; Angiotensin II; Aortic Valve Insufficiency; Aortic Valve Stenosis; Arginine Vasopressin; Atrial Natriuretic Factor; Blood Pressure; Blood Pressure Monitoring, Ambulatory; Circadian Rhythm; Cyclic GMP; Endothelins; Female; Heart Rate; Hormones; Humans; Male; Middle Aged; Renin

The hypothesis that in normal pituitary patients (pts) with heart failure the heart is a target-organ of the hypophysis has not be held in due consideration. Aim of the study was: 1) to determine Growth Hormone (GH) plasma levels in pts with various degree of heart failure; 2) to evaluate the relationship between GH, left ventricular mass and some haemodynamic and endocrine parameters of ventricular dysfunction.. Blood samples for determination of GH and Atrial Natriuretic Factor (ANF) were collected 24 hours before haemodynamic study. Plasma concentrations of GH and ANF were determined by radio-immuno-assay in 20 normotensive pts (age ranging 31 to 54) without mellitus diabetes in IV (10 pts) and III (10 pts) NYHA FC: Echocardiographic determination of left atrial diameter, end-diastolic and end-systolic left ventricular diameters, index of left ventricular mass (ILVM), were performed. All pts underwent right and left cardiac catheterization and coronary angiography.. The pts in IV NYHA FC, Group A, had lower cardiac index (IC) (1.8 +/- 0.4 vs 2.9 +/- 0.1, p < 0.0001) and higher GH and ANF plasma levels than those in III NYHA FC, Group B (4.9 +/- 4.5 vs 0.12 +/- 0.04, p < 0.01; 157.9 +/- 43.9 vs 65.6 +/- 14.6, p < 0.0001). No significant difference was found by comparing in both groups ILVM (212.6 +/- 64.7 vs 192.9 +/- 71.9, NS). GH and ANF plasma levels were 4.1 +/- 5.0 and 113.8 +/- 59.6 in pts with ILVM > or = 200 g/mq and 0.9 +/- 2.7 and 109.7 +/- 57.3 in pts with ILVM < 200 g/mq (no significant statistical difference). We found an high correlation by comparing GH and ANF in group with ILVM > or = 200 g/mq (r = 0.82, p < 0.005) and in group with ILVM < 200 g/mq (r = 0.68, p < 0.05).. Our study demonstrated: 1) increased GH plasma levels in pts with severe heart failure; 2) an high correlation between GH and ANF plasma levels in pts with ILVM > or = 200 g/mq.

Topics: Adult; Aortic Valve Insufficiency; Atrial Natriuretic Factor; Cardiac Catheterization; Cardiomyopathy, Dilated; Female; Growth Hormone; Hemodynamics; Humans; Male; Middle Aged; Radioimmunoassay

The correlations between the plasma concentration of atrial natriuretic factor and right atrial or left atrial pressure were studied in experimentally induced aortic regurgitation and mitral regurgitation in dogs.. Aortic regurgitation was created by opening the tip of a basket wire catheter placed at the aortic annulus via the left ventricular wall, and terminated by pulling back the catheter. To create mitral regurgitation a basket catheter was inserted into the mitral annular position via a pulmonary vein. Regurgitation was induced by opening the tip of the catheter, and terminated promptly by closing it.. Seven beagle dogs were prepared for the aortic regurgitation model and six for the mitral regurgitation model (weights 11.5 to 14.5 kg).. The plasma concentration of atrial natriuretic factor was highly correlated with right atrial pressure (r = 0.78, SD = 0.07, n = 7) and left atrial pressure (r = 0.82, SD = 0.05, n = 7) in aortic regurgitation; and with right atrial pressure (r = 0.82, SD = 0.05, n = 6) and left atrial pressure (r = 0.84, SD = 0.05, n = 6) in mitral regurgitation. Further evaluation of the molecular forms of plasma atrial natriuretic factor revealed the alpha form in all 13 dogs and the gamma form in two (one with aortic and the other with mitral regurgitation); no evidence of the beta form was seen.. Atrial natriuretic factor secretion responds rapidly to the circulatory changes caused by valvular incompetence.

Topics: Animals; Aorta; Aortic Valve Insufficiency; Atrial Natriuretic Factor; Blood Pressure; Disease Models, Animal; Dogs; Female; Heart Atria; Heart Ventricles; Hemodynamics; Male; Mitral Valve Insufficiency; Pulmonary Artery

We investigated whether or not the extent of secretion of atrial natriuretic peptide (ANP) was altered during the chronic course of aortic regurgitation (AR) in rabbits. AR was induced by aortic valve perforation in 20 rabbits. Left ventricular end-diastolic pressure (LVEDP) was used as an index of the severity of heart failure. LVEDP and plasma immunoreactive(IR)-ANP were measured before and at 15 min, 1 week, and 4 weeks after induction of AR. In each period a correlation between LVEDP and plasma IR-ANP was observed, and the coefficients and covariances did not vary throughout the experiment. We conclude, therefore, that a chronic change in ANP secretion does not develop during the first 4 weeks after induction of AR in rabbits.

Topics: Animals; Aortic Valve Insufficiency; Atrial Natriuretic Factor; Blood Pressure; Female; Heart Atria; Heart Rate; Heart Ventricles; Organ Size; Rabbits

We have established an easily reversible acute heart failure model in beagle canines by reversible aortic or mitral regurgitation (AR or MR). To cause reversible AR, a basket catheter was inserted into the left ventricle from the apex and fixed at the aortic valve in 10 canines. To cause MR, a basket catheter was inserted into the left atrium via the pulmonary vein and fixed at the mitral valve in 10 canines. The regurgitation by AR or MR was caused by extending the tip basket wire, and the recovery from the regurgitation was immediately possible by closing it. Left atrial pressure (LAP), right atrial pressure (RAP) and pulmonary artery pressure (PAP) were increased significantly during AR or MR, and decreased to the normal level after the release of AR or MR. Using these reversible acute heart failure models, the effects of both advancing and restoring acute heart failure by the secretion of ANP were examined by observing the changes of ANP concentration and its molecular forms in the plasma and left atrial tissue in the same canine. Plasma ANP concentration showed a reversible change. In group analysis, plasma ANP concentration did not correlate with LAP or RAP, but in each canine it showed high correlations with LAP (r = 0.70 approximately 0.94, 0.82 +/- 0.07) and RAP (r = 0.60 approximately 0.93, 0.79 +/- 0.08), having a different slope in each regression line. The ANP concentration in the atrial tissue was decreased during AR or MR, but the low level was maintained after AR or MR. The main molecular form of ANP in the plasma was alpha-ANP and that in the tissue was gamma-ANP. In summary, the tissue storage of ANP was decreased because the ANP secretion caused by stimulation of acute heart failure exceeded its production. The ANP secretion was decreased by the subsequent elimination of heart failure, but the production was not stimulated rapidly, because the tissue content remained unchanged.

Topics: Acute Disease; Animals; Aortic Valve Insufficiency; Atrial Natriuretic Factor; Blood Pressure; Cardiac Output, Low; Chromatography, High Pressure Liquid; Disease Models, Animal; Dogs; Heart Atria; Hemodynamics; Mitral Valve Insufficiency; Myocardium; Radioimmunoassay

Although atrial natriuretic factor is primarily of atrial origin, recent observations indicate that the hormone is also synthesized by hypertrophied left ventricular myocardium. To assess the separate influences of left ventricular and left atrial dilatation and left ventricular hypertrophy on human atrial natriuretic factor levels, left atrial dimension and volume and left ventricular dimension and mass were compared in 49 normal subjects, in 33 patients with chronic aortic regurgitation, and in 15 patients with chronic mitral regurgitation. When compared with normal subjects, patients with chronic aortic and mitral regurgitation had similarly dilated and hypertrophied left ventricles (p less than 0.0005), while only mitral regurgitation patients had significantly enlarged (p less than 0.0005) mean left atrial dimension and volume. Likewise, plasma atrial natriuretic factor was elevated among patients with mitral regurgitation (60.3 +/- 47.0 fmol/ml) but was normal in patients with aortic regurgitation (19.0 +/- 11.0 fmol/ml versus 12.4 +/- 5.2 fmol/ml in normals; both p less than 0.0005 versus mitral regurgitation). Among all 97 subjects, atrial natriuretic factor levels correlated more closely with left atrial dimension and volume (r = 0.62 and 0.64, p less than 0.0005) than with left ventricular dimension (r = 0.44, p less than 0.0005) or mass (r = 0.40, p less than 0.0005). In addition, multivariate analysis indicated that left atrial volume bore a stronger independent relationship to plasma atrial natriuretic factor levels than either age or left ventricular variables.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Aortic Valve Insufficiency; Atrial Natriuretic Factor; Blood Volume; Heart; Heart Atria; Heart Ventricles; Humans; Mitral Valve Insufficiency; Myocardium; Regression Analysis

The purposes of the present study are to demonstrate the presence of atrial natriuretic peptide (ANP) in canine cerebrospinal fluid (CSF) and to determine its origin as either the brain or atrium. Fifty-seven mongrel canines weighing from 7.5 to 23.0kg (male: 28, female: 29) were anesthetized with sodium pentobarbital (30mg/mg, iv) and were ventilated with a Harvard respirator. 16 canines (11.5 to 16.0kg) were used to examine the effect of endogenously increased plasma ANP level on the ANP concentration of the CSF in acute heart failure induced by experimental aortic regurgitation. Subsequently to examine the effect of exogenously increased plasma ANP level on the ANP concentration of the CSF, physiological and pharmacological doses of synthetic human alpha-ANP were continuously infused into the right ventricle (25ng/kg/min. and 250ng/kg/min., respectively) for 32 min. in 15 canines (8.0 to 23.0kg), only physiological dose (25ng/kg/min.) was infused for 180 min. in 8 canines (12.5 to 23.0kg). The concentrations of ANP in canine CSF and plasma were measured by our highly sensitive and specific radioimmunoassay (RIA). The molecular forms in the plasma, CSF and the atrium and hypothalamus tissues were determined by gel permeation chromatography (GPC). The ANP concentration in CSF was 2.8 +/- 1.2pg/ml (mean +/- SD), lower than that in the plasma which was 51.5 +/- 19.9pg/ml, and no correlation was found between them (r = 0.16, p = ns). Plasma ANP concentrations increased from 46.5 +/- 13.0pg/ml to 94.6 +/- 27.7pg/ml according to a rise of the left atrial pressure by experimental aortic regurgitation. However, no significant change was noted from 3.7 +/- 0.7pg/ml to 3.8 +/- 1.0pg/ml in CSF ANP concentrations during the aortic regurgitation. The ANP concentration in the CSF did not change significantly while the plasma ANP concentration greatly increased following each intravenous infusion of the synthetic alpha-ANP. Only a single peak corresponding to a low molecular weight form of ANP in the position of authentic alpha-ANP in the canine CSF was observed by GPC, while there were peaks for both low and high molecular forms of ANP in the canine plasma. Furthermore, both low and high molecular weight peaks were observed for the right atrium and hypothalamus tissue extracts by GPC, and those tissues of the right atrium and hypothalamus contained ANP concentrations of 1.97ng/mg wet tissue and 2.6pg/ml wet tissue, respectively. These results indicate the presence of

Topics: Animals; Aortic Valve Insufficiency; Atrial Natriuretic Factor; Blood-Brain Barrier; Brain; Chromatography, Gel; Dogs; Female; Heart Atria; Male; Molecular Weight; Radioimmunoassay