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Biomedical subjects

H Frank

Publications and source records attributed to H Frank.

At least 37 records · Page 2Linked to original sources
PubMed2000

Uptake, toxicity, and effects on detoxication enzymes of atrazine and trifluoroacetate in embryos of zebrafish.

The uptake, toxicity, and elimination of atrazine and trifluoroacetate (TFA) were studied in early life stages of the zebrafish (Danio rerio). Furthermore, the effects of these xenobiotics on soluble (s) and microsomal (m) glutathione S-transferases (GST) of zebrafish embryos were investigated using 1-chloro-2,4-dinitrobenzene (CDNB), 1,2-dichloro-4-nitrobenzene (DCNB), and [(14)C]atrazine. [(14)C]Atrazine was taken up by the embryos within seconds, unhindered by the chorions. It accumulated in the embryos by a factor of 19 after 24 h of exposure time. LC(50) (48 h) was determined at 36.8 mg/L. At a level of 5 mg/L atrazine, activities of s and m GSTs were elevated in most stages, especially in prim 6 and long pec stage (24, 48 h after fertilization, respectively). GST activity toward atrazine was detectable only in untreated D. rerio eggs, increasing with developmental time. [(14)C]Atrazine was eliminated from the embryos between 24 and 48 h, indicating a possible metabolism to a more hydrophilic GSH conjugate. [(14)C]TFA was taken up by embryos, reaching at maximum fivefold the concentration of the incubation medium after 10 h. The chorions served no physiological protection. TFA (1 g/L) caused low elevation of the GST activity. No acute toxic effects (48 h) were observed up to 4 g/L TFA.

Animals↗
PubMed2000

Right ventricle lipoma with pseudoaneurysmatic appearance.

The case of a 78-year-old female patient, with a large lipoma (13 x 17 x 10 cm) of the right ventricle, appearing pseudoaneurysmatic, is presented. Radical resection left a considerable right ventricle wall and interventricular septum defect which was reconstructed with a bovine pericardium patch.

Aged↗
PubMed2000

Congenital malformations of the right atrium and the coronary sinus: an analysis based on 103 cases reported in the literature and two additional cases.

STUDY OBJECTIVES: Congenital malformations of the right atrium (RA) and the coronary sinus (CS) are rare, and only sporadic cases have been reported. Little is known about the clinical relevance of this disorder. We report on two patients, one with a giant RA diverticulum, the other with a diverticulum of the CS, and review 103 cases of such malformations that have been reported previously. DESIGN: A MEDLINE search was performed to collect all cases of congenital malformations of the RA and the CS reported in the literature between 1955 and 1998. Cases were classified into the following categories: (1) congenital enlargement of the RA; (2) single diverticulum of the RA; (3) multiple diverticula of the RA; and (4) diverticulum of the CS. Clinical presentation and outcome of the different types of malformations were analyzed. RESULTS: The patients most frequently presenting with symptoms were those with diverticula of the CS (n = 28) followed by those with single diverticula of the RA (n = 13), multiple diverticula (n = 4), and congenital enlargements of the RA (n = 60). The percentages of symptomatic patients were 93, 84, 75, and 53%, respectively. Symptoms were frequently caused by arrhythmias. Supraventricular tachycardia (SVT) was found in 42 of the patients (40%) and was most common in patients with diverticula of the CS (24 of 28 patients) and multiple atrial diverticula (3 of 4 patients). Sudden cardiac death was reported more frequently in patients with diverticula of the CS (18%) compared to those with congenital enlargement of the RA (5%) or single or multiple diverticula of the RA (6%). All seven patients with diverticula of the CS who were not treated with catheter or surgical ablation eventually died. CONCLUSION: Congenital malformations of the RA and the CS frequently are associated with arrhythmias. SVT and sudden cardiac death have been reported in a significant percentage of patients with diverticula of the CS.

Adult↗
PubMed1999

A dual inhibitor of platelet-derived growth factor beta-receptor and Src kinase activity potently interferes with motogenic and mitogenic responses to PDGF in vascular smooth muscle cells. A novel candidate for prevention of vascular remodeling.

PP1 has previously been described as an inhibitor of the Src-family kinases p56(Lck) and FynT. We have therefore decided to use PP1 to determine the functional role of Src in platelet-derived growth factor (PDGF)-induced proliferation and migration of human coronary artery smooth muscle cells (HCASMCs). A synthetic protocol for PP1/AGL1872 has been developed, and the inhibitory activity of PP1/AGL1872 against Src was examined. PP1/AGL1872 potently inhibited recombinant p60(c-src) in vitro and Src-dependent tyrosine phosphorylation in p60(c-srcF572)-transformed NIH3T3 cells. PP1/AGL1872 also potently inhibited PDGF-stimulated migration of HCASMCs, as determined in the modified Boyden chamber, as well as PDGF-stimulated proliferation of HCASMCs. Surprisingly, in addition to inhibition of Src kinase, PP1/AGL1872 was found to inhibit PDGF receptor kinase in cell-free assays and in various types of intact cells, including HCASMCs. PP1/AGL1872 did not inhibit phosphorylation of the vascular endothelial growth factor receptor KDR (VEGF receptor-2; kinase-insert domain containing receptor) in cell-free assays as well as in intact human coronary artery endothelial cells. In line with the insensitivity of KDR, PP1/AGL1872 had only a weak effect on vascular endothelial growth factor-stimulated migration of human coronary artery endothelial cells. On treatment of cells expressing different receptor tyrosine kinases, the activities of the epidermal growth factor receptor, fibroblast growth factor receptor-1, and insulin-like growth factor-1 receptor were resistant to PP1/AGL1872, whereas PDGF alpha-receptor was susceptible, albeit to a lesser extent than PDGF beta-receptor. These data suggest that the previously described tyrosine kinase inhibitor PP1/AGL1872 is not selective for the Src family of tyrosine kinases. It is also a potent inhibitor of the PDGF beta-receptor kinase but is not a ubiquitous tyrosine kinase inhibitor. PP1/AGL1872 inhibits migration and proliferation of HCASMCs probably by interference with 2 distinct tyrosine phosphorylation events, creating a novel and potent inhibitory principle with possible relevance for the treatment of pathological HCASMC activity, such as vascular remodeling and restenosis.

3T3 Cells↗
PubMed1999

[An unusual cause of hepatorenal symptoms].

CASE REPORT: A 65-year-old patient with normal blood pressure had an exclusive elevation of the cholestasis enzymes (alkaline phosphatase 297 U/l, gamma-GT 315 U/l) and elevated bilirubin levels (1.4 mg/dl) since August 1994. A biopsy of the liver in March 1995 showed features of a "subacute viral hepatitis"; DD drug-induced or toxic lesions. Serological tests gave no support for an acute hepatitis. Intra- or extrahepatic cholestasis could not be proved neither by ultrasound nor by an endoscopic retrograde cholangiopancreatography. Since November 1995 serum creatinine increased up to 1.7 mg/dl (March 1995 1.1 mg/dl) and proteinuria (2.1 g/d) developed. Due to worsening of renal function (serum creatinine 2.8 mg/dl) and increasing proteinuria (3.5 g/d) without nephrotic syndrome, a kidney biopsy was performed. Histologically an amyloidosis (type A lambda) was proven, involving glomerula, kidney vessels and tubules. Further biopsies from the stomach and the duodenum showed profound infiltration of the mucosa and submucosa with amyloid. Therefore, staining of the liver biopsy of March 1995 with congo red proved the diagnosis of liver amyloidosis. By a punch biopsy of the iliac crest a low-grade non-Hodgkin's lymphoma could be identified as the cause for this generalized amyloidosis. DISCUSSION: In the present case, the reason for these unusual hepatorenal symptoms with unclear cholestasis over years as the first clinical symptom and a succeeding progressive renal insufficiency with proteinuria could be found by the use of kidney biopsy and extending the analysis of a liver sample taken by biopsy 1 year ago. Immunoglobulin light chains produced by a low-grade non-Hodgkin's lymphoma caused a generalized amyloidosis type A lambda. CONCLUSION: As a consequence, by an occurrence of unusual hepatorenal symptoms with cholestasis and progressive renal failure, amyloidosis should be considered as a pathogenetic factor.

Aged↗
PubMed1999

Formation of N-methylnicotinamide in the brain from a dihydropyridine-type prodrug: effect on brain choline.

The enhancement of brain choline levels is a possible therapeutic option in neurodegenerative diseases; however, brain choline levels are held within narrow limits by homeostatic mechanisms including the rapid clearance of excess choline from the brain. The present study tests whether N-methylnicotinamide (NMN), an inhibitor of the outward transport of choline from the brain, can elevate brain choline levels in vivo. As NMN does not cross the blood-brain barrier, we synthesized and administered the brain-permeable prodrug, 1,4-dihydro-N-methyl-nicotinamide (DNMN), and tested its effect on the levels of NMN and choline in brain extracellular fluid, using the microdialysis procedure. Administration of DNMN (1 mmol/kg s.c.) caused a 4- and 9-fold increase in plasma and liver NMN levels, respectively, as determined by HPLC. Concomitantly, the brain tissue levels of NMN were increased by a factor of twenty. In brain extracellular fluid, the injection of DNMN (1-3 mmol/kg s.c.) elevated NMN levels by 3- to 10-fold to maximum levels of >10 microM. In spite of these enhanced NMN levels, the choline concentrations in the brain extracellular fluid and in the cerebrospinal fluid (4.7 microM) remained unchanged or were even slightly decreased. Microsomal incubations of DNMN indicated that cytochrome P-450 3A isoforms may be involved in NMN formation in the liver, but not in the brain. We conclude that DNMN, a brain-permeable prodrug of NMN, is efficiently oxidized to NMN in the brain, but a 10-fold increase in extracellular NMN levels is not sufficient to reduce the clearance of choline from the brain.

Animals↗
PubMed1999

Magnetic resonance imaging evaluation of myocardial and pericardial disease.

Magnetic resonance imaging (MRI) has been shown to be an ideal noninvasive tool for imaging and diagnosing myocardial and pericardial diseases. In dilated and hypertrophic cardiomyopathy, MRI is suitable for the diagnosis and quantification of ventricular volume, stroke volume, and myocardial mass. Recent developments in the area of fast imaging techniques and MR contrast agents rapidly are increasing the utility of MRI for studying and assessing myocardial diseases. MRI may become a helpful technique with which to diagnose myocarditis and myocardial involvement in amyloidosis and sarcoidosis. Contrast-enhanced MRI also can be used for patients who have undergone heart transplantation to assess early signs of transplant rejection by improved contrast between normal and pathologic myocardium. For pericardial diseases, MRI provides an exact evaluation of the pericardial thickness, and it is a very sensitive technique for identifying pericardial effusions. Differentiation between hemorrhagic, serous, or chylous pericardial effusions usually can be made by using the typical signal behavior on T1-weighted and T2-weighted sequences. Due to its greater field of view and its ability to evaluate functionally the regional ventricular and atrial motion abnormalities in the typical tissue pattern, MRI has a significant potential in the evaluation of pericardial inflammation and constrictive pericarditis. J. Magn. Reson. Imaging 1999;10:617-626.

Cardiomyopathies↗
PubMed1999

Epitope mapping of cytochrome P4502D6 autoantigen in patients with chronic hepatitis C during alpha-interferon treatment.

BACKGROUND/AIMS: Cytochrome P450 2D6 (CYP2D6) has been documented as the major target antigen of liver kidney microsomal autoantibodies type-1 (anti-LKM-1) in both autoimmune hepatitis type-2 (AIH-2) and hepatitis C (HCV). In HCV/anti-LKM-1-positive patients, the choice between alpha-interferon (alpha-IFN) or immunosuppression may be difficult. This study was conducted to evaluate the course and outcome of alpha-IFN therapy in HCV/anti-LKM-1-positive and -negative patients and the alterations in these autoantibody titers by the indirect immunofluorescence and a novel radioligand assay. Epitope mapping was also performed to screen for a potential shift in anti-LKM-1 binding towards small linear epitopes, which are more often detected in AIH-2 patients. METHODS: Twenty-one patients with HCV infection received alpha-IFN. Seven patients were anti-LKM-1 positive (study group) and 14 patients were anti-LKM-1 negative (disease control group). Anti-CYP2D6 detection was based on immunoprecipitation of [35S]-methionine-labeled CYP2D6 recombinant protein (rCYP2D6) produced by in vitro transcription/translation. RESULTS: Four out of seven (57%) patients in the study group and 5/14 (36%) in the disease control group initially responded, but subsequently relapsed. During follow-up, alanine aminotransferase significantly increased in the study group compared to the disease control group (p<0.01). A slight increase, followed by a plateau of autoantibody titers was recorded by the radioligand assay and by indirect immunofluorescence during therapy and follow-up in most cases. In one patient, however, gamma-globulins and anti-LKM-1 titers increased, reaching very high levels (1:40 960). alpha-IFN was interrupted and immunosuppression was started. HCV/anti-CYP2D6 positive sera recognized CYP2D6 expressed in E. coli and two truncated proteins (aa 250-494 and 321-494). Two out of seven sera, in addition reacted with a small linear epitope of aa 257-269 (one of which also reacted with a C-terminal domain of aa 350-494). CONCLUSIONS: A rather mild deterioration in liver disease was observed in only 1/7 HCV/anti-LKM-1-positive patients during alpha-IFN treatment. This patient showed high anti-CYP2D6 titers before the initiation of therapy, a sharp increase in anti-LKM-1 titers during treatment, and reactivities to a small linear epitope and an infrequently recognized C-terminal domain of CYP2D6. After switching to immunosuppressive treatment, a complete and sustained response was recorded. Further prospective studies from many centers are needed to define whether these features have general, clinical significance or not.

Adolescent↗
PubMed1999

Inhibition of the hydrolytic and transpeptidase activities of rat kidney gamma-glutamyl transpeptidase by specific monoclonal antibodies.

Monoclonal antibodies (mAb) against the native form of rat kidney gamma-glutamyl transpeptidase (GGT) were isolated by screening hybridomas with rat kidney brush-border membrane vesicles. They were directed against protein rather than sugar epitopes in that each recognized all GGT isoforms. All of them inhibited partially the enzyme activity of GGT. They were specific in that they inhibited the rat enzyme, but not the mouse or human enzyme. Kinetic analyses were carried out with free GGT and GGT-mAb complexes with d-gamma-glutamyl-p-nitroanilide in the presence or absence of maleate, or in the presence or absence of alanine, cysteine, cystine or glycylglycine as gamma-glutamyl acceptors. mAbs 2A10 and 2E9 inhibited the hydrolytic and glutaminase activities of GGT and had little effect on the transpeptidation activity of the enzyme, whereas mAbs 4D7 and 5F10 inhibited transpeptidation, but not hydrolytic or glutaminase activities. mAb 5F10 mimicked the effect of maleate on GGT, in that it inhibited transpeptidation, enhanced the glutaminase activity and increased the affinity of the donor site of GGT for acivicin. Such mAbs may be useful for long-term studies in tissue cultures and in vivo, and for the identification of GGT epitopes that are important for the hydrolytic and transpeptidase activities.

Animals↗
PubMed1999

The coronary endothelium: a target for vascular endothelial growth factor. Human coronary artery endothelial cells express functional receptors for vascular endothelial growth factor in vitro and in vivo.

Vascular endothelial growth factor (VEGF) is an angiogenic peptide that can stimulate endothelial cell proliferation and migration in vitro and collateral development in ischemic organs in vivo. Although postulated, the expression of functional VEGF receptors in the heart has not been demonstrated yet. To prove this hypothesis and to extend the molecular basis of myocardial angiogenesis, we have characterized the expression and function of VEGF receptors in human coronary artery endothelial cells (HCAEC) and in human heart tissue. VEGF strongly induces proliferation and migration of HCAEC. These cells express transcripts of the two VEGF receptors KDR and Flt-1. Their expression levels are higher in HCAEC as compared with human umbilical vein endothelial cells. In HCAEC, VEGF stimulates phosphorylation of KDR in a concentration-dependent manner proving that KDDR is a functional receptor tyrosine kinase. Scatchard analysis demonstrated the presence of the high affinity receptor Flt-1 in HCAEC with a kd of 8 pM. Flt-1 protein could be visualized as a single band corresponding to a size of 210 kd. In addition mature KDR protein could be detected in adult human heart. Taken together, HCAEC and human heart tissue express high levels of functional VEGF receptors. These results broaden the molecular basis for understanding and manipulating VEGF-induced endothelial function and angiogenesis in the coronary circulation.

Animals↗
PubMed1998

Differential enantioselectivity of murine glutathione S-transferase isoenzymes in the glutathione conjugation of trans-3,4-dihydroxy-1, 2-oxy-1,2,3,4-tetrahydrobenzo[c]phenanthrene stereoisomers.

The kinetics of the glutathione (GSH) conjugation of (+)- and (-)-enantiomers of anti- as well as syn-3,4-dihydroxy-1,2-oxy-1,2,3, 4-tetrahydrobenzo[c]phenanthrene (B[c]PDE) catalyzed by murine GSH S-transferase (GST) isoenzymes has been investigated. Murine GSTs exhibited significant differences in their enantioselectivity toward B[c]PDE stereoisomers. For example, while pi class isoenzyme mGSTP1-1 was virtually inactive toward stereoisomers with 1S configuration [(-)-syn-and (+)-anti-B[c]PDE], these stereoisomers were good substrates for alpha class isoenzyme mGSTA1-2. When GST activity was measured as a function of varying B[c]PDE concentration (10-320 microM) at a fixed saturating concentration of GSH (2 mM), each isoenzyme examined obeyed Michaelis-Menten kinetics with all four B[c]PDE stereoisomers. Alpha class isoenzyme mGSTA4-4 exhibited negligible activity toward all four stereoisomers of B[c]PDE. The catalytic efficiency of mGSTA1-2 was approximately 1.5- to 15-fold higher than other murine GSTs in the GSH conjugation of (-)-anti-B[c]PDE, which among the four B[c]PDE stereoisomers is the most potent pulmonary carcinogen in the newborn mouse model and a potent skin tumor-initiator. While alpha class isoenzymes mGSTA3-3 and mGSTA1-2 were equally efficient in the GSH conjugation of (+)-anti-B[c]PDE, their catalytic efficiencies toward this stereoisomer were significantly higher than those of mGSTP1-1 and mGSTM1-1. Likewise, mGSTA1-2 was relatively more efficient than other GSTs in the GSH conjugation of both enantiomers of syn-B[c]PDE. In summary, our results indicate that (a) murine GSTs significantly differ in their enantioselectivity in the GSH conjugation of B[c]PDE stereoisomers, which may partially account for the observed differences in the carcinogenic potency of B[c]PDE stereoisomers, and (b) mGSTA1-2 and mGSTA3-3 play a major role in the detoxification of B[c]PDE.

Animals↗
PubMed1998

Decrease of blood pressure by ventrolateral medullary decompression in essential hypertension.

BACKGROUND: About 20% of adults worldwide will develop hypertension. Studies and clinical observations suggest an association between hypertension and pulsatile compression of the ventrolateral medulla oblongata by a looping artery. We investigated whether neurosurgical microvascular decompression substantially decreases blood pressure long-term in patients with severe essential hypertension. METHODS: We included eight patients who had received three or more antihypertensive drugs without adequate control of blood pressure, intolerable side-effects, or both. All patients underwent microvascular decompression at the root-entry zone of cranial nerves IX and X after neurovascular compression of the ventrolateral medulla oblongata was seen on magnetic-resonance angiography. FINDINGS: 3 months after surgery, blood pressure and antihypertensive regimens had decreased substantially in three patients. Four patients who were followed up for more than 1 year became normotensive, but their antihypertensive regimens remained the same as those at 3 months. One patient did not improve. No complications associated with decompression occurred. One patient experienced a transient vocal-cord paresis after the laryngeal part of the vagus nerve was manoeuvered during surgery. INTERPRETATION: We showed a direct causal relation between raised blood pressure and irritation of cranial nerves IX and X. A subgroup of patients with essential hypertension may exist who have secondary forms of hypertension related to neurovascular compression at the ventrolateral medulla and who may be successfully treated with decompression.

Adult↗
PubMed1998

DNA adduct levels associated with p53 induction and delay of MCF-7 cells in S phase after exposure to benzo[g]chrysene dihydrodiol epoxide enantiomers.

Optically active isomers of a mammary carcinogen, anti-benzo[g]chrysene 11, 12-dihydrodiol 13, 14-epoxide, react to different extents with DNA and generate DNA adducts that differ in their stereochemistry. In the study reported here, the effect of these two enantiomers on the progress of human breast carcinoma MCF-7 cells through the cell cycle was investigated. Each enantiomer caused the cells to accumulate in the S phase, but a higher dose of the benzo[g]chrysene 11S, 12R-dihydrodiol 13R, 14S-epoxide than of its enantiomer was required to induce this effect. Similarly, induction of p53 also required a higher dose of benzo[g]chrysene 11S, 12R-dihydrodiol 13R, 14S-epoxide. Postlabeling studies indicated that the latter enantiomer also caused less modification of MCF-7 cell DNA for a given level of exposure than did benzo[g]chrysene 11R, 12S-dihydrodiol 13S, 14R-epoxide. These results suggest that p53 induction and delay in the S phase are similarly related to DNA binding and that a level of binding of the order of 1 adduct per 10(5) nucleotides is associated with these effects.

Chrysenes↗
PubMed1998

[Imaging and differentiation of atherosclerotic plaque with magnetic resonance tomography].

Magnetic resonance (MR) imaging studies have allowed the imaging of an atheroma, its size, shape, and lipid contents. The aim of our study was to characterize atherosclerotic lesions using a 0.5 T magnet, to delineate plaque components, and to compare MR results with histology. Thirty necropsy specimens of human iliac arteries were studied. Magnetic resonance imaging studies were carried out on a 0.5 Tesla superconducting magnet using a 5 cm surface coil. The position for the coronal MR planes was oriented by an external marker. The matrix size was 256 x 256, 4 NEX, and the FOV was 45 mm. The pulse sequences used included SE 520/29 and SE 2200/28 and 90. Signal intensity (SI) of fibrous plaques increased significantly from 28.3 +/- 3.8 to 49.1 +/- 8.2 (p < or = 0.0001) and decreased at SE 2200/90 to 24.1 +/- 6.8 (p < or = 0.0001). However, lipid plaque components showed no significant change in SI between T1-weighted pulse-sequences (28.2 +/- 5.4) and T2-weighted pulse-sequences (25.5 +/- 5.9). Only at SE 2200/90 SI of lipid plaques decreased significantly (11.8 +/- 3.9, p < or = 0.0001). As compared to histology, MR has shown a high sensitivity and specificity in the detection of fibrous and lipid plaque components. In conclusions, our study demonstrated that MR is highly effective in the characterization of atherosclerotic lesions.

Arteriosclerosis↗
PubMed1998

Expression of the gap-junction connexins 26 and 30 in the rat cochlea.

Gap junction channels which are responsible for direct intercellular communication are composed of connexin proteins. Different connexins are distributed in a tissue-specific manner. Up to now only connexin26 has been identified to be widely expressed in the inner ear. In order to investigate the role of additional gap junction proteins, the expression of connexin30 and 43 was investigated in the rat cochlea. Connexin26 and connexin30 were both expressed in the spiral limbus, the spiral ligament, the stria vascularis and between supporting cells of the organ of Corti. Double-labeling experiments suggest that both connexins are partly colocalized between cells. Weak staining of connexin43 could only be detected in the stria vascularis, the spiral ligament and between organ of Corti supporting cells. The corresponding transcripts for connexin26, 30 and 43 could be detected by Northern blot analysis. The expression of different gap junction channels in the cochlea suggests functional diversity. Gap junctions in the inner ear may control ion concentrations of cochlear fluids or act as conduits through which glucose and other metabolites diffuse.

Animals↗
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↗