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PubMed1998

Atrial natriuretic peptide in patients with heart failure and chronic atrial fibrillation: role of duration of atrial fibrillation.

The purpose of this study was to analyze the determinants of atrial natriuretic peptide level in patients with congestive heart failure and atrial fibrillation. In particular, the duration of atrial fibrillation was analyzed because atrial fibrillation per se might have a specific effect on atrial natriuretic peptide level. The study group consisted of 26 patients with mild to moderate stable congestive heart failure and chronic atrial fibrillation. Plasma samples of atrial natriuretic peptide were obtained at rest and were analyzed with radioimmunoassay. Median atrial natriuretic peptide level was 213 (range 42 to 438) ng/L. Multivariate determinants of atrial natriuretic peptide level were use of calcium antagonists and the duration of atrial fibrillation; both factors showed an inverse relation with atrial natriuretic peptide level. The finding that atrial natriuretic peptide level was lower among patients with atrial fibrillation of longer duration suggests a form of insufficiency of the atria to produce atrial natriuretic peptide because of degenerative changes in the atria inherent to chronic atrial fibrillation.

Aged↗
PubMed1998

Atrial natriuretic peptide release is more dependent on atrial filling volume than on filling pressure in chronic congestive heart failure.

BACKGROUND: The mechanism of atrial natriuretic peptide (ANP) release has been difficult to demonstrate in patient studies because of inaccuracies in measuring atrial volumes using conventional techniques. METHODS: Magnetic resonance imaging was performed in 28 clinically stable patients (New York Heart Association class 3) with chronic heart failure to determine right atrial (RA), left atrial (LA), and ventricular volumes. In addition, right heart catheterization was serially performed and plasma ANP levels (in picograms per milliliter) were drawn from the right atrium. RESULTS: Five patients had to be excluded from data analysis for technical reasons. The remaining 23 patients had the following hemodynamic measurements (mean +/- SD): RA mean pressure 7+/-5 mm Hg, pulmonary artery mean pressure 28+/-10, pulmonary capillary wedge pressure 21+/-8 mm Hg, and cardiac index 2.9+/-1.4 (L/min/m2), respectively. Plasma ANP levels were significantly elevated at 162+/-117 (normal range 20 to 65 pg/ml, p < 0.05), as were LA and RA volumes compared with healthy controls (RA volume 128+/-64 ml vs 82+/-25 ml, p < 0.05; LA volume 157+/-54 ml vs 71+/-24 ml, p < 0.01, respectively). ANP showed a stronger relation with atrial volumes (RA volume, r = 0.91, p = 0.0001; LA volume, r = 0.80, p = 0.001) than with atrial pressures (RA mean pressure, r = 0.45, p = 0.03; pulmonary capillary wedge pressure, r = 0.67, p = 0.001). A subgroup analysis of patients with increased RA or LA volumes (>1 SD of mean of controls) revealed a stronger relation between ANP and RA volumes than between ANP and LA volumes. CONCLUSIONS: These data suggest that increased right heart volume with subsequent increased atrial stretch is the major determinant for ANP release in patients with stable CHF.

Adult↗
PubMed2001

A new procedure for chronic atrial fibrillation: bilateral appendage-preserving maze procedure.

BACKGROUND: Atrial transport and atrial natriuretic peptide secretion is severely reduced from normal after the maze III procedure. To improve these factors, we developed a bilateral appendage-preserving maze procedure (BAP-maze). METHODS: Forty-six patients with chronic atrial fibrillation who underwent the BAP-maze procedure were compared with 40 patients who underwent the maze III procedure. The ratio of the peak velocity of the A and E waves of transmitral flow (transthoracic pulsed Doppler echocardiography), the left atrial appendage ejection fraction (transesophageal echocardiography), and the atrial natriuretic peptide secretory reserve during treadmill exercise test were measured at 6 months postoperatively. RESULTS: Sinus rhythm was restored in 44 patients (95.7%) by the BAP-maze procedure and in 39 patients (97.5%) by the maze III procedure. The ratio of the peak velocity of the A and E waves was 0.52 +/- 0.22 in the BAP-maze group and 0.25 +/- 0.19 in the maze III group (p < 0.0001). The left atrial appendage ejection fraction was 44.7% +/- 11.5%, and the atrial natriuretic peptide secretory reserve was greater in the BAP maze group (p = 0.037). CONCLUSIONS: The BAP-maze procedure improved atrial transport and atrial natriuretic peptide secretion as well as simplifying the maze operation, without decreasing its effectiveness against atrial fibrillation.

Aged↗
PubMed1984

Rat atrial natriuretic factor: complete amino acid sequence and disulfide linkage essential for biological activity.

The complete amino acid sequence of an atrial natriuretic peptide from rat possessing both natriuretic and smooth muscle relaxant activity has been determined. The peptide has the structure (sequence in text) and a calculated molecular weight of 2,706. The ring structure formed by the disulfide linkage between the two half-cystine residues was found essential for both the natriuretic activity and smooth muscle relaxant activity. The purified peptide caused 50% relaxation of norepinephrine (5 X 10(-8)M) induced contraction of rabbit thoracic aorta at the concentration of 2 X 10(-9)M and complete relaxation at 6 X 10(-9)M.

Amino Acid Sequence↗
PubMed1989

Brain natriuretic peptide is a novel cardiac hormone.

Using a radioimmunoassay for brain natriuretic peptide (BNP), we have measured levels of BNP-like immunoreactivity (-LI) in extract of the porcine heart, in perfusate from the isolated porcine heart and in porcine plasma. BNP-LI was detected in the extract of the atrium, though no detectable amount of BNP-LI (more than 1 ng/g) was present in the ventricle. The BNP-LI level in the porcine atrium was 148.7 +/- 23.3 ng/g. BNP-LI was also detected in the perfusate from the heart. Basal secretory rate of BNP was 3.18 +/- 0.76 ng/min. Moreover, BNP-LI was detected in porcine plasma at the concentration of 4.2 +/- 1.3 pg/ml. Gel filtration studies showed that BNP is present in the atrium as a large molecule and is secreted into the circulation as a small molecule. The percentage of BNP-LI to atrial natriuretic peptide (ANP)-LI was almost the same among the extract, the perfusate and the plasma (2-3 percent). These results indicate that BNP is synthesized in and is secreted into the circulation from the heat in a similar fashion as ANP.

Animals↗
PubMed1975

P wave abnormalities in the orthogonal electrocardiogram: Correlation with ventricular overload in pulmonic and aortic valvular heart disease.

The correlation between several P wave measurements form the orthogonal electrocardiogram (SVEC III lead system) extracted by computer analysis and simple hemodynamic parameters related to ventricular dysfunction was studied in two groups of patients. Group I consisted of 32 patients with pulmonic valvular stenosis and intact interventricular septum. There was a significant correlation between electrocardiographic criteria of right atrial overload and the two hemodynamic parameters studied: peak pulmonic systolic pressure gradient and right ventricular end diastolic pressure (r = 0.502, p smaller than 0.005 and r = 0.661, p smaller than 0.001 respectively). Group II consisted of 49 patients with aortic valve disease. In this group, a significant correlation between the electrocardiographic parameters of left atrial overload and the left ventricular end diastolic pressure could be demonstrated only be a multivariate regression analysis (r = 0.630, p smaller than 0.005). The P wave measurements that are well correlated with the ventricular end diastolic pressure can be considered as valuable criteria for atrial enlargement secondary to a decrease of ventricular compliance, such as seen in ventricular hypertrophy, failure or in ventricular constrictive or restrictive diseases. The pathophysiologic mechanisms of the influence of the ventricular overload (dysfunction) on the atrial function and the resulting P wave changes are discussed.

Adolescent↗
PubMed1995

Analysis of alternans in late potentials. Correlations between epicardial and body surface recordings.

The methodical performance of the signal-averaged electrocardiogram is strongly influenced by the beat-to-beat reproducibility of late potentials (LPs). Especially at higher heart rates, epicardial recordings from infarct regions show progressive beat-to-beat prolongations with alternating conduction block. To analyze the influence of beat-to-beat-alternans of LPs on the signal-averaging process, epicardial and body surface recordings were studied at different heart rates and extrastimulation. Epicardial and body surface recordings were obtained from dogs with 4-day postligation of the left anterior descending coronary artery (Harris model). Body surface potentials were averaged in different modes to a final noise level of 0.3 microV (rms) and digitally bandpass filtered (40-250 Hz). Modulation of the heart rate was performed by atrial or His-bundle pacing and by atrial premature extrastimulation. Pacing up to heart rates close to 180 beats/min produced no significant changes in the duration of LPs in epicardial and averaged body surface recordings; however, at higher pacing rates, considerable prolongation of LPs with different patterns in the epicardial leads was observed. In these cases, averaging of all beats revealed only a slight prolongation of LPs, as seen from the body surface. Selective averaging of beats with prolonged epicardial LPs showed the prolongation or absence of LPs, as seen in the epicardial recordings. Similar observations were made using an atrial extrastimulation technique, whereby the average of the premature beats was compared to the average of all normal sinus beats. Selective beat averaging of body surface potentials can unmask the prolongation of LPs due to atrial pacing or extrastimulation, as seen in recordings from the infarcted epicardium. The evidence of this modulation of LPs may improve the positive predictive value of the signal-averaged electrocardiogram.

Action Potentials↗
PubMed1998

Effect of the Cox maze procedure on the secretion of atrial natriuretic peptide.

OBJECTIVES: The Cox maze procedure has been confirmed to be effective in curing atrial fibrillation. Some authors have reported severe fluid retention after the Cox maze procedure and have suggested decreased secretion of atrial natriuretic peptide as a possible mechanism. This study was designed (1) to examine the serial changes in atrial natriuretic peptide after the Cox maze procedure as compared with changes occurring after coronary artery bypass grafting and (2) to elucidate any differences in atrial natriuretic peptide levels between patients with transient recurrence of atrial fibrillation after the Cox maze procedure and those without recurrence of atrial fibrillation. METHODS: Blood samples were drawn from the right and left atria in patients undergoing the Cox maze procedure (n = 19) and from the right atrium in patients undergoing coronary artery bypass grafting (n = 6) before and 1, 2, and 3 days after the operation. In six patients undergoing the Cox maze procedure, samples were also drawn from the radial artery before and 1, 2, 3, 5, and 7 days after the operation. The plasma samples were prepared by refrigerated centrifugation and stored until radioimmunoassay. In the Cox maze procedure group, atrial natriuretic peptide levels in the right atrium were 629 +/- 366, 154 +/- 112, 162 +/- 112, and 183 +/- 97 pg/ml and those in the left atrium were 276 +/- 168, 152 +/- 91, 162 +/- 111, and 145 +/- 80 pg/ml before and 1, 2, and 3 days after the operation, respectively. A marked decrease in atrial natriuretic peptide levels was evident after the Cox maze procedure (p < 0.001). There was no significant correlation between atrial natriuretic peptide levels and atrial pressures after the Cox maze procedure, which suggests that secretion of atrial natriuretic peptide by the atria was impaired. There was a significant correlation between the atrial natriuretic peptide levels in the left atrium and those in the peripheral radial artery, and the decreased levels of atrial natriuretic peptide in the radial artery continued for 7 days after the Cox maze procedure. There were no differences in the atrial natriuretic peptide levels between the patients with transient recurrence of atrial fibrillation (n = 6) and those without recurrence (n = 13) after the Cox maze procedure. In the coronary artery bypass grafting group, the atrial natriuretic peptide levels in the right atrium were 115 +/- 37, 124 +/- 48, 154 +/- 54, and 156 +/- 36 pg/ml before and 1, 2, and 3 days after the operation, respectively. No change was seen after the operation. CONCLUSIONS: We observed a significant decrease in atrial natriuretic peptide levels after the Cox maze procedure. This may be one of the possible causes of fluid retention after this procedure. These decreased atrial natriuretic peptide levels after the Cox maze procedure may result from the multiple atriotomy incisions and excision of both atrial auricles performed during the procedure, rather than from the conversion of atrial fibrillation to normal sinus rhythm.

Atrial Fibrillation↗
PubMed1995

Pathophysiology of hydrops fetalis.

Hydrops fetalis occurs when the rate of interstitial fluid production by capillary ultrafiltration exceeds the rate of interstitial fluid return to the circulation via lymphatic vessels. Developmental differences in the microcirculation and lymphatic system of the fetus, as compared with mature subjects, renders the fetus susceptible to interstitial fluid accumulation. These differences include greater capillary permeability, more compliant interstitial compartment, and greater influence of venous pressures on lymphatic return. The balance between interstitial fluid production and removal is most commonly disrupted as a consequence of homeostatic mechanisms serving to preserve adequate systemic delivery of metabolic substrate when cardiocirculatory function is impaired. The pathophysiology of two conditions of impaired cardiocirculatory function, atrial tachycardia and severe anemia, serve as examples of the mechanisms by which these homeostatic mechanisms perturb the balance of interstitial fluid movement.

Capillary Permeability↗
PubMed2002

Electrophysiologic cardiac effects of the new local anesthetic IQB-9302 and of bupivacaine in the anesthetised dog.

BACKGROUND: Local anesthetics are not free from potentially fatal complications. Therefore every new local anesthetic should be tested to demonstrate a lower, or at least similar, degree of toxicity over clinically used analogs. Most toxic effects from local anesthetics affect the cardiac electrophysiologic function, so the aim of this study was to characterize the electrophysiologic effects of a new long-acting local anesthetic (IQB-9302, Ciprocaine), and compare them with those of bupivacaine in the anesthetized dog. METHODS: Eight Beagle dogs received three increasing infusion doses of either IQB-9302 or bupivacaine. Under isoflurane anesthesia, dogs were instrumented to monitor cardiovascular (cardiac output, arterial and venous blood pressures) and cardiac electrophysiologic data (sinus and atrioventricular (AV) node function, atrial, nodal and ventricular conduction times, and refractoriness). RESULTS: Only the highest dose of both drugs induced hemodynamic or electrophysiologic alterations: cardiac output and heart rate were reduced while blood pressures remained unchanged. Atrial and intranodal conduction times and atrial refractoriness increased similarly with both anesthetics, but to a slightly lesser extent with IQB-9302. Significant increases in His-Purkinje and intraventricular conduction times were the most severe noxious effects and occurred only with large doses of either drug. IQB-9302 was slightly less toxic than bupivacaine and, unlike this latter drug, potentially fatal arrhythmias were not induced. CONCLUSION: IQB-9302 has hemodynamic and cardiac electrophysiologic effects similar to those caused by bupivacaine. Nevertheless, slightly less toxic effects were derived from IQB-9302 administration than with bupivacaine, and, unlike the latter, the former might be less proarrhytmogenic. The new long-acting local anesthetic IQB-9302 may offer clinical advantages compared with bupivacaine.

Anesthetics, Inhalation↗
PubMedDate not supplied

Purification, sequencing and synthesis of natriuretic and vasoactive rat atrial peptide.

Mammalian atria contain potent natriuretic and diuretic substances which exist in high- and low-molecular-weight forms and which appear to be associated with atrium-specific granules. The natriuretic effect of atrial extract is largely accountable for by its renal haemodynamic effects; atrial extracts also antagonize hormone- and non-hormone-induced contraction of the isolated rabbit aorta and isolated rat kidney vasculature. We have completely purified a low-molecular-weight natriuretic and vasoactive substance from rat atria and characterized it as a 24-amino acid peptide. Synthetic peptide, produced by solid-phase synthesis, mimics biological effects of crude atrial extract and purified peptide; its activity is enhanced by slow oxidation, suggesting a disulphide (Cys 4-Cys 20) configuration for the native peptide. If secreted into blood, this atrial natriuretic peptide (' auriculin B') could be a novel peptide hormone of considerable importance to renal and cardiovascular homeostasis.

Amino Acid Sequence↗
PubMedDate not supplied

Cloning and sequence analysis of the cDNA for the rat atrial natriuretic factor precursor.

Atrial extracts contain factors which induce potent natriuresis changes in renal haemodynamics, and relax pre-contracted vascular smooth muscle. Low-molecular-weight peptides which mimic these actions have now been purified by several groups, including ours (see accompanying paper), and higher-molecular-weight proteins with similar but less potent biological activities have also been identified and are presumed to be precursors. If released into the circulation, these peptides, collectively called atrial natriuretic factor (ANF), may play a significant part in blood-pressure homeostasis, regulation of extracellular fluid volume and as antagonists to the hypertensive effects of the renin-angiotensin system and other hormonal and neurotransmitter systems. We describe here the isolation and characterization of rat atrial cDNA clones which encode ANF. Nucleotide sequence analysis shows that auriculin corresponds to the 25 amino acids located close to the C-terminus of a 152-amino acid ANF precursor. Analysis of the in vitro translation products of precursor ANF mRNA suggests that multiple forms of the precursor may exist.

Amino Acid Sequence↗
PubMedDate not supplied

Cloning and sequence analysis of cDNA encoding a precursor for human atrial natriuretic polypeptide.

Recent identification of natriuretic-diuretic activity in peptides isolated from human and rat atrial tissue implicates them in the control of extracellular fluid volume and electrolytic homeostasis. The presence of multiple forms of the peptides ranging from 3,000 to 13,000 molecular weight (MW) suggests they may all derive from the same precursor. The established amino acid sequence of alpha-human atrial natriuretic polypeptide (alpha- hANP ), a 28-residue peptide with potent natriuretic activity, provided the means to elucidate the structure of the precursor for alpha- hANP and the gene encoding it. Here we report the cloning and sequence analysis of the cDNA of human atrial mRNA encoding a precursor of alpha- hANP . The cDNA encodes gamma-human atrial natriuretic polypeptide (gamma- hANP ) of 13,000 MW, whose C-terminal 28 amino acid residues may be processed as alpha- hANP .

Amino Acid Sequence↗
PubMedDate not supplied

Nucleotide sequence of the gene encoding human atrial natriuretic factor precursor.

The mammalian atrium is an endocrine organ that may be involved in the control of blood pressure and extracellular fluid volume. A series of peptides, which seem to be associated with atrium-specific secretory granules, have potent natriuretic, diuretic and smooth muscle relaxant activities. Sequence determination of several of these peptides, which range from 21 to 126 amino acids long, shows that they form a family, derived from a common precursor. Rat and human complementary DNAs that encode the precursor to the various peptides, collectively called atrial natriuretic factors (ANFs), have been cloned. Nucleotide sequencing showed that the ANFs are located at the C-terminus of a polypeptide of relative molecular mass 13,000. We describe here the isolation and characterization of the corresponding human gene. Two introns interrupt the gene; one is located in the region coding for the N-terminus of the precursor and the other separates the codon for the C-terminal tyrosine from the rest of the peptide.

Amino Acid Sequence↗
PubMed1990

Response to dynamic exercise in cardiac transplant recipients: implications for control of the sodium regulatory hormone atrial natriuretic peptide.

1. To study the importance of cardiac innervation in the regulation of atrial natriuretic peptide, plasma atrial natriuretic peptide levels were measured during symptom-limited, graded exercise on a cycle ergometer in seven male orthotopic cardiac transplant recipients. 2. Resting plasma atrial natriuretic peptide was significantly higher in the transplant recipients than in two control groups, one matched to the transplant recipients (group I) and the other to the age of the donor heart (group II). 3. The response to exercise of the cardiac transplant recipients was compared with the response of control group II. Mean maximal work load achieved with exercise was around 40% lower in the cardiac transplant recipients. During exercise, plasma atrial natriuretic peptide levels increased in both the cardiac transplant recipients and the control subjects. The increase in plasma atrial natriuretic peptide with exercise was greater in absolute, but less in percentage, terms in transplant recipients than in the control subjects. 4. The increase in mean arterial pressure with exercise was similar in patients and in control subjects; however, heart rate increased in the patients by only 33% compared with a rise of 151% in the control group. 5. These results provide insight into the control of the sodium regulatory hormone atrial natriuretic peptide. First, factors other than a change in heart rate appear of importance in the regulation of atrial natriuretic peptide. Secondly, these findings suggest that cardiac innervation is not of dominant importance in the modulation of atrial natriuretic peptide secretion.

Atrial Function↗