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1.
Z Kardiol ; 94(12): 824-8, 2005 Dec.
Article in English | MEDLINE | ID: mdl-16382384

ABSTRACT

Angiosarcoma of the heart, the most common primary malignant cardiac tumor in adults is known to carry a dismal prognosis. The diagnosis is often delayed because of the nonspecific clinical presentation. Symptoms are determined by the size and location of the tumor. Echocardiography has become the primary diagnostic technique because of its high degree of accuracy, noninvasiveness, and cost effectiveness. Complete surgical resection is required for improved survival. Conventional postoperative chemotherapy does not appear to modify the clinical course. We report a case of cardiac angiosarcoma with a large mural mass infiltrating the right atrial and ventricular walls and critically review the pertinent literature.


Subject(s)
Heart Atria/diagnostic imaging , Heart Atria/surgery , Heart Neoplasms/diagnostic imaging , Heart Ventricles/diagnostic imaging , Heart Ventricles/surgery , Female , Heart Neoplasms/surgery , Humans , Middle Aged , Treatment Outcome , Ultrasonography
2.
Z Kardiol ; 94 Suppl 4: IV/43-48, 2005.
Article in German | MEDLINE | ID: mdl-16416064

ABSTRACT

Echocardiography is the preferred method for assessment of aortic and mitral valvular lesions. The pressure gradient in aortic stenosis may be misleading in patients with poor left ventricular function. Aortic valve area planimetry by transesophageal echocardiography results in a flow independent anatomic measurement. Low-dose dobutamine stress echocardiography provides important prognostic information. Quantitative Doppler echocardiography allows accurate assessment of mitral regurgitation severity. However, the definition of what is severe mitral regurgitation is different in patients with left ventricular dysfunction.


Subject(s)
Aortic Valve Stenosis/diagnostic imaging , Echocardiography, Transesophageal , Hemodynamics/physiology , Mitral Valve Insufficiency/diagnostic imaging , Ultrasonography, Doppler , Ventricular Dysfunction, Left/diagnostic imaging , Aortic Valve/diagnostic imaging , Aortic Valve/physiopathology , Aortic Valve Stenosis/physiopathology , Blood Flow Velocity/physiology , Blood Pressure/physiology , Echocardiography, Stress , Heart Failure/diagnostic imaging , Heart Failure/physiopathology , Humans , Mitral Valve/diagnostic imaging , Mitral Valve/physiopathology , Mitral Valve Insufficiency/physiopathology , Prognosis , Sensitivity and Specificity , Ventricular Dysfunction, Left/physiopathology
3.
Thorac Cardiovasc Surg ; 52(5): 274-9, 2004 Oct.
Article in English | MEDLINE | ID: mdl-15470608

ABSTRACT

BACKGROUND: Left ventricular (LV) aneurysms may complicate myocardial infarctions. Reliable quantification of LV functional parameters is mandatory to predict clinical outcome in patients undergoing LV aneurysmectomy. We compared global LV function measured by magnetic resonance (MR) and 2-D-echocardiography in patients before and after aneurysmectomy. METHODS: 31 patients (23 male), mean age 64 (range 35 - 85) years with an LV aneurysm (25/31 anterior MI, 5/31 inferior MI, 1/31 both) were enrolled. MR and echocardiography were performed directly before and 3 - 65 (median 8) days after surgery. MR studies were performed on a 1.5 Tesla scanner. End-diastolic and end-systolic volumes and diameters (EDV/ESV, EDD/ESD), ejection fraction (EF) and stroke volume (SV) were determined. Echocardiography was performed to determine EF, EDD and ESD. NYHA class was assessed before and 3 months after surgery. RESULTS: After aneurysmectomy MR analysis showed a decrease in EDV (255 +/- 68 ml to 202 +/- 59 ml) ( p < 0.001) and ESV (186 +/- 71 ml to 134 +/- 53 ml; p < 0.001); EF increased (28 +/- 10 % to 35 +/- 12 %; p < 0.001); EDD/ESD decreased ( p < 0.01). Compared to echocardiography, a low correlation was found in EF before/after surgery r = 0.76/r = 0.69 and ESD r = 0.43/r = 0.60, respectively. In EDD a good correlation was found before surgery (r = 0.81), and a lower correlation after surgery (r = 0.72). NYHA class improved from 3.0 +/- 0.5 before to 1.8 +/- 0.8 after operation ( p < 0.001). CONCLUSION: Resection of an LV aneurysm results in a mean improvement of 25 % in LV function, and improved clinical outcome. In asymmetric ventricles with aneurysms MR proved to be superior as a sensitive and non-invasive tool compared to conventional 2-D-echocardiography.


Subject(s)
Heart Aneurysm/surgery , Ventricular Function, Left , Adult , Aged , Aged, 80 and over , Female , Heart Aneurysm/physiopathology , Heart Ventricles/diagnostic imaging , Humans , Magnetic Resonance Imaging , Male , Middle Aged , Ultrasonography
4.
Ann Thorac Surg ; 72(4): 1251-4; discussion 1255, 2001 Oct.
Article in English | MEDLINE | ID: mdl-11603445

ABSTRACT

BACKGROUND: Restoration of atrial transport function (ATF) is a major goal of the maze procedure. This prospective study was undertaken to evaluate predictors of left atrial transport function in patients undergoing a mini-variant of the maze III procedure 3 and 12 months postoperatively. METHODS: Mini-maze operation was performed in 72 patients with a mean age of 64 +/- 8.7 years during a 5-year period. Seventy of 72 (97%) had combined procedures. Clinical and electrophysiologic examination was carried out before surgery, and 3 and 12 months postoperatively. RESULTS: Early mortality was 1.4% (1 of 72 patients) and late death occurred in 5.6% (4 of 71 patients). After 3 months, 54 of 68 (80%) patients showed sinus rhythm, and 48 of 60 (80%) after 12 months. ATF was restored in 87% (echocardiography) and 82% (magnetic resonance imaging) after 3 months, and in 86% (echocardiography) and 78% (magnetic resonance imaging) after 12 months. Independent predictors for ATF restoration after 12 months were better preoperative left ventricular function (p = 0.02), and smaller preoperative left atrial diameter (p = 0.005). Correlation between echocardiography and magnetic resonance imaging was 80% after 12 months. CONCLUSIONS: Restoration of ATF after mini-maze procedure is achieved in over 80%. Independent predictors for ATF restoration are smaller preoperative left atrial diameter and better preoperative left ventricular ejection fraction.


Subject(s)
Atrial Fibrillation/surgery , Atrial Function, Left/physiology , Minimally Invasive Surgical Procedures , Postoperative Complications/physiopathology , Adult , Aged , Atrial Fibrillation/mortality , Atrial Fibrillation/physiopathology , Echocardiography , Female , Follow-Up Studies , Hospital Mortality , Humans , Magnetic Resonance Imaging , Male , Middle Aged , Postoperative Complications/diagnosis , Postoperative Complications/mortality , Survival Rate
5.
Z Kardiol ; 90(5): 359-61, 2001 May.
Article in German | MEDLINE | ID: mdl-11452898

ABSTRACT

We report a female patient with mitral valve replacement and preservation of subvalvular apparatus in which parts of the papillary muscle ruptured postoperatively. During systole the ruptured papillary muscle prolapsed through the native aortic valve. Echocardiographic documentation and operative procedure were demonstrated.


Subject(s)
Echocardiography, Transesophageal , Heart Valve Prosthesis Implantation , Mitral Valve Insufficiency/surgery , Papillary Muscles/diagnostic imaging , Postoperative Complications/diagnostic imaging , Adult , Aortic Valve/diagnostic imaging , Endoscopy , Female , Humans , Mitral Valve Insufficiency/diagnostic imaging , Papillary Muscles/surgery , Postoperative Complications/surgery , Prolapse , Reoperation , Rupture, Spontaneous
6.
Thorac Cardiovasc Surg ; 49(2): 122-4, 2001 Apr.
Article in English | MEDLINE | ID: mdl-11339450

ABSTRACT

A 45-year-old man experienced arterial thromboembolism to the right leg requiring surgical restoration of blood flow. Transesophageal echocardiography (TEE) was performed to determine the source of embolism and identified a localized atherosclerotic lesion in the distal ascending aorta with an adherent, highly mobile thrombus. The patient underwent surgery with removal of the atherosclerotic plaque and attached thrombus, and resection of the adjacent aortic wall. This case illustrates an unusual location for a complex atherosclerotic lesion in the ascending aorta, and points out the opportunity for remedial surgery once a symptomatic embolus has occurred.


Subject(s)
Aorta , Embolism/etiology , Peripheral Vascular Diseases/etiology , Thromboembolism/complications , Thromboembolism/surgery , Arterial Occlusive Diseases/diagnostic imaging , Arterial Occlusive Diseases/etiology , Echocardiography, Transesophageal , Embolism/diagnostic imaging , Follow-Up Studies , Humans , Male , Middle Aged , Peripheral Vascular Diseases/diagnostic imaging , Thrombectomy/methods , Thromboembolism/diagnostic imaging , Treatment Outcome
8.
J Am Soc Echocardiogr ; 11(10): 972-7, 1998 Oct.
Article in English | MEDLINE | ID: mdl-9804103

ABSTRACT

Transesophageal echocardiography (TEE) has a definitive role in the diagnosis and management of critically ill patients with cardiovascular disease and patients undergoing cardiac operations. The diagnostic role of emergency intraoperative TEE and the impact on clinical outcome have not been evaluated. We reviewed the indications, findings, and impact of emergency intraoperative TEE in 66 patients over a 4-year period. The indications for emergency TEE were unexplained hemodynamic instability (36 patients), preoperative evaluation of patients having emergency surgery (19 patients), cardiac evaluation of trauma cases (6 patients), and unexplained intraoperative hypoxemia (5 patients). New findings were disclosed in 53 (80%) patients, with an alteration of the planned surgical procedure in 15 (23%). Despite the therapeutic impact, 24 patients (36%) did not survive to hospital dismissal. We recommend that TEE be considered as the diagnostic tool of choice when surgical patients have unexplained hemodynamic instability, when time does not permit complete preoperative evaluation, when cardiovascular injury is suspected in a trauma patient, and to evaluate unexplained hypoxemia.


Subject(s)
Cardiovascular Diseases/surgery , Echocardiography, Transesophageal , Adolescent , Adult , Aged , Aged, 80 and over , Cardiovascular Diseases/diagnostic imaging , Emergencies , Female , Heart Valve Diseases/diagnostic imaging , Heart Valve Diseases/surgery , Humans , Intraoperative Period , Male , Middle Aged
10.
Hypertension ; 30(2 Pt 1): 184-90, 1997 Aug.
Article in English | MEDLINE | ID: mdl-9260978

ABSTRACT

C-type natriuretic peptide (CNP) is a newly described 22-amino acid peptide of endothelial and renal cell origin with selective cardiovascular actions. Recent in vitro studies have reported that CNP is the most susceptible of all natriuretic peptides to enzymatic degradation by neutral endopeptidase 24.11 (NEP). The present study was undertaken to define the role of NEP in total and regional CNP metabolism and the modulatory actions of NEP inhibition on the biological actions of CNP. CNP (10 ng x kg(-1) x min(-1)) followed by candoxatrilat (240 microg x kg(-1) bolus and 8 microg x kg(-1) x min(-1)), a potent and selective NEP inhibitor, was administered intravenously to a group of anesthetized mongrel dogs (group 1) to permit calculation of total metabolic clearance rate (MCR); results were compared with those in a group receiving vehicle infusion followed by candoxatrilat (group 2; both groups, n=7). NEP inhibition increased circulating CNP achieved by exogenous infusion and reduced total MCR in group 1. The regional CNP MCRs increased after CNP administration. While the pulmonary MCR did not change during concomitant candoxatrilat infusion, renal MCR was suppressed. Hemodynamic changes were not different between groups. A mild natriuretic and diuretic effect in association with an increase in circulating and urinary ANP levels was not different between groups. Urinary CNP excretion did not change with CNP infusion but markedly increased after NEP inhibition. We conclude that (1) circulating CNP achieved by exogenous CNP infusion is regulated by NEP in vivo, (2) regional MCRs are heterogeneous with NEP inhibition, (3) NEP inhibition does not potentiate acute cardiovascular actions of CNP, and (4) a mild natriuretic and diuretic effect observed with CNP and NEP inhibition may be ANP dependent.


Subject(s)
Neprilysin/physiology , Proteins/metabolism , Animals , Diuresis , Dogs , Hemodynamics , Hormones/blood , Male , Natriuresis , Natriuretic Peptide, C-Type , Proteins/antagonists & inhibitors , Renal Circulation
11.
Circulation ; 92(11): 3312-7, 1995 Dec 01.
Article in English | MEDLINE | ID: mdl-7586319

ABSTRACT

BACKGROUND: Endothelin-1 (ET-1) is an endothelium-derived vasoconstrictor peptide. Controversy persists regarding the predominant ET receptor that mediates coronary vasoconstriction at pathophysiological concentrations. The aim of the present study was to test the hypothesis that ET mediates local coronary vasoconstriction via the ET-A receptor at low concentrations of exogenous ET-1 designed to mimic pathophysiological states compared with pharmacological concentrations. METHODS AND RESULTS: ET-1 (group 1, n = 5) or sarafotoxin, a specific ET-B receptor agonist (group 3, n = 6) (each at 2 ng/kg per minute), was infused into the left circumflex coronary artery in the anesthetized dog. In group 2 dogs (n = 5), the same dose of ET-1 was infused with 4 micrograms/kg per minute of the specific ET-A receptor antagonist FR-139317. In group 4 (n = 5), the same dose of sarafotoxin was infused with 50 micrograms/kg per minute of the specific inhibitor of nitric oxide formation, NG-monomethyl-L-arginine (L-NMMA). No difference in hemodynamics, coronary blood flow (CBF), coronary vascular resistance (CVR), or coronary artery diameter (CAD) was observed at baseline between the groups. In group 1, intracoronary ET-1 significantly decreased CBF and CAD in association with an increase in CVR. The percentage decrease in CBF and CAD in the group that received ET-1 and the ET-A receptor antagonist (group 2) was significantly less than that in the group that received ET-1 alone (group 1) (-12 +/- 3% versus -48 +/- 6% [P < .001] and -4.6 +/- 0.8 versus 1.0 +/- 0.3 [P < .05], respectively). The administration of the ET-A receptor antagonist (group 2) abolished the ET-mediated increase in CVR (7 +/- 5% versus 105 +/- 21%, P < .005). There was no significant effect on CBF, CVR, or CAD in the group receiving sarafotoxin alone (group 3). The administration of L-NMMA and sarafotoxin (group 3). The administration of L-NMMA and sarafotoxin (group 4) resulted in a significant percentage decrease in CBF compared with the group that received sarafotoxin alone (-28 +/- 7% versus -8 +/- 2% [P < .05]). CONCLUSIONS: The present study demonstrates that low concentrations of exogenous ET-1, which may mimic pathophysiological concentrations, result in coronary vasoconstriction mediated predominantly via the ET-A receptor because such vasoconstriction is significantly attenuated by blockade with FR-139317. The ET-B receptor may have a dual vasoconstrictive and vasodilatory effect.


Subject(s)
Coronary Vessels/physiology , Endothelins/physiology , Receptors, Endothelin/physiology , Vasoconstriction/physiology , Animals , Arginine/analogs & derivatives , Arginine/pharmacology , Azepines/pharmacology , Coronary Vessels/drug effects , Dogs , Endothelin Receptor Antagonists , Endothelins/pharmacology , Enzyme Inhibitors/pharmacology , Indoles/pharmacology , Nitric Oxide Synthase/antagonists & inhibitors , Receptor, Endothelin A , Receptor, Endothelin B , Receptors, Endothelin/agonists , Receptors, Endothelin/drug effects , Vasoconstriction/drug effects , Viper Venoms/pharmacology , omega-N-Methylarginine
12.
J Am Soc Echocardiogr ; 8(6): 930-3, 1995.
Article in English | MEDLINE | ID: mdl-8611295

ABSTRACT

A patient with the diagnosis of small cell lung cancer had syncopal episodes. The tumor was found to invade the right upper pulmonary vein with extension into the left atrium. The mass was protruding across the mitral valve producing ball-valve blockade. In this report the echocardiographic signs of a primary lung tumor with intraatrial extension causing left ventricular inflow tract obstruction are described.


Subject(s)
Carcinoma, Small Cell/complications , Heart Neoplasms/complications , Lung Neoplasms/complications , Ventricular Outflow Obstruction/etiology , Aged , Carcinoma, Small Cell/pathology , Echocardiography , Echocardiography, Transesophageal , Heart Atria , Heart Neoplasms/pathology , Humans , Lung Neoplasms/pathology , Male , Neoplasm Invasiveness , Ventricular Outflow Obstruction/diagnostic imaging
13.
J Cardiovasc Electrophysiol ; 6(8): 630-3, 1995 Aug.
Article in English | MEDLINE | ID: mdl-8535561

ABSTRACT

In a patient with severe left ventricular dysfunction resulting from chronic nonparoxysmal sinus tachycardia, rate control and improvement in left ventricular function were achieved with atrioventricular junction ablation and ventricular pacemaker implantation. Within 12 hours after the ablation procedure, several episodes of polymorphic ventricular tachycardia that may have been triggered by the abruptly decreased heart rate occurred. Recurrence of polymorphic ventricular tachycardia was prevented by an increase in pacing rate.


Subject(s)
Bradycardia/etiology , Catheter Ablation/adverse effects , Tachycardia, Ventricular/complications , Bradycardia/physiopathology , Cardiomyopathy, Dilated/etiology , Cardiomyopathy, Dilated/physiopathology , Electrocardiography , Female , Humans , Middle Aged , Tachycardia, Ventricular/physiopathology
14.
Am J Physiol ; 269(1 Pt 2): H326-31, 1995 Jul.
Article in English | MEDLINE | ID: mdl-7631865

ABSTRACT

C-type natriuretic peptide (CNP) is a newly described 22-amino acid peptide of endothelial cell origin, which has selective cardiovascular actions and is structurally related to atrial natriuretic peptide (ANP). Recent in vitro studies have demonstrated that an important regulatory pathway for the clearance of natriuretic peptides involves binding to a common clearance receptor [natriuretic peptide C receptor (NPR-C)]. Although CNP has also been identified as a ligand for NPR-C in binding assays, no studies have defined the in vivo interaction of CNP with NPR-C. CNP (10 ng.kg-1.min-1) followed by C-ANP-(4-23), a specific ligand for NPR-C blockade, was infused intravenously in two groups (both n = 7) of anesthetized dogs at two different doses (0.1 or 1.0 micrograms.kg-1.min-1) to permit calculation of total metabolic clearance rate (TMCR). C-ANP-(4-23) increased circulating CNP and reduced TMCR in both groups. Pulmonary metabolic clearance rate was negative at baseline, suggesting a net secretion of CNP across the lung, which was increased during CNP infusion and was abolished with NPR-C blockade. Renal and femoral metabolic clearance rates were positive at baseline and increased with CNP infusion. A decrease in cardiac output and cardiac filling pressures in response to CNP administration was potentiated by NPR-C blockade. We conclude that 1) circulating CNP achieved by CNP infusion is regulated by NPR-C in vivo, 2) the pulmonary circulation is a possible site of CNP secretion, 3) the renal and peripheral circulations are sites of CNP clearance, and 4) NPR-C blockade potentiates the selective cardiovascular actions of CNP.


Subject(s)
Guanylate Cyclase/physiology , Proteins/pharmacokinetics , Receptors, Atrial Natriuretic Factor/physiology , Animals , Atrial Natriuretic Factor/pharmacology , Dogs , Guanylate Cyclase/antagonists & inhibitors , Hemodynamics/drug effects , Kidney/metabolism , Lung/metabolism , Male , Metabolic Clearance Rate , Natriuretic Peptide, C-Type , Peptide Fragments/pharmacology , Proteins/pharmacology , Receptors, Atrial Natriuretic Factor/antagonists & inhibitors
15.
Am J Physiol ; 268(3 Pt 2): F455-60, 1995 Mar.
Article in English | MEDLINE | ID: mdl-7900845

ABSTRACT

Endothelin (ET) is a potent vasoconstrictor peptide of endothelial origin, which at low doses results in renal vasoconstriction and diuresis with variable actions on sodium excretion. The current study conducted in four groups of anesthetized dogs was designed to define the role of the ETA and ETB receptor subtypes in the renal actions of low-dose exogenous ET. Group 1 (n = 4) animals served as time controls. In group 2 (n = 6) a systemic ET-1 (5 ng.kg-1.min-1) infusion mediated renal vasoconstriction, antinatriuresis with increases in proximal fractional reabsorption of sodium, and diuresis with a decrease in urine osmolality. In group 3 (n = 6) intrarenal BQ-123 (4 micrograms.kg-1.min-1), a selective ETA antagonist, abolished the systemic ET-1-mediated changes in renal hemodynamics and unmasked a natriuretic action at the level of the proximal tubule. In contrast, the diuretic response of ET was not altered by BQ-123. In group 4 (n = 6) intrarenal sarafotoxin 6-c, a selective ETB receptor agonist, resulted in a diuretic response without a change in sodium excretion. These studies suggest that the ETA receptor contributes to the renal vasoconstriction, whereas the ETB receptor is largely responsible for the diuretic response during exogenous ET. This study also suggests that at low doses ET is natriuretic in vivo by decreasing proximal tubular reabsorption of sodium independent of ETA or ETB receptor activation.


Subject(s)
Kidney/physiology , Receptors, Endothelin/classification , Receptors, Endothelin/physiology , Animals , Cardiovascular Physiological Phenomena , Cardiovascular System/drug effects , Diuresis/drug effects , Diuresis/physiology , Dogs , Endothelins/pharmacology , Kidney/drug effects , Male , Natriuresis/drug effects , Natriuresis/physiology , Peptides, Cyclic/pharmacology , Receptors, Endothelin/drug effects , Renal Circulation/drug effects , Renal Circulation/physiology , Vasoconstriction/drug effects , Vasoconstriction/physiology , Viper Venoms/pharmacology
16.
Am J Physiol ; 268(2 Pt 2): H921-5, 1995 Feb.
Article in English | MEDLINE | ID: mdl-7864220

ABSTRACT

The endothelium is the production site of several potent vasoactive substances that modulate vascular tone and growth. The present study was undertaken to investigate the presence and secretion of atrial natriuretic peptide (ANP) immunoreactivity from vascular endothelial cells. ANP immunoreactivity was present in cultured human aortic endothelial cells by both immunohistochemical staining and radioimmunoassay. ANP immunoreactivity was also detectable in culture medium from human aortic endothelial cells in low picogram concentrations. These findings suggest that vascular endothelium is a site of ANP production and secretion of ANP. There was a differential distribution of ANP and endothelin-1 (ET-1), with a higher ANP concentration in cell extracts and a higher ET-1 concentration in cell culture media. Although ANP has been conceived as a circulating endocrine hormone, these findings are consistent with ANP functioning also as an autocrine and paracrine modulator in the regulation of vascular tone and growth.


Subject(s)
Aorta/metabolism , Atrial Natriuretic Factor/metabolism , Endothelium, Vascular/metabolism , Aorta/cytology , Cells, Cultured , Endothelins/metabolism , Endothelium, Vascular/cytology , Humans , Immunohistochemistry , Osmolar Concentration , Radioimmunoassay
17.
Kidney Int ; 46(3): 744-7, 1994 Sep.
Article in English | MEDLINE | ID: mdl-7996796

ABSTRACT

The current study was undertaken to investigate the presence of CNP immunoreactivity in both human kidney and urine. Immunohistochemical staining with an indirect immunoperoxidase method utilizing an antibody which is 100% cross-reactive to both CNP-53 and CNP-22 was performed on five human kidney specimens (three biopsies of normal cadaveric donor kidneys and two of normal autopsy specimens). CNP immunoreactivity was positive in proximal, distal and medullary collecting duct tubular cells in a cytoplasmic and granular staining pattern. CNP immunoreactivity was also determined in the urine of five healthy volunteers utilizing a sensitive and specific double-antibody radioimmunoassay with a mean concentration of 10.8 +/- 1.0 pg/ml. With the utilization of high pressure liquid chromatography, this immunoreactivity proved to be consistent with both the low molecular weight form, CNP-22, as well as the high molecular weight form, CNP-53. Urinary excretion of CNP was also measured in normal subjects (N = 5) and in patients with congestive heart failure (CHF, N = 6). CHF patients excreted over three times more CNP than normals (27.2 +/- 2.8 vs. 8.7 +/- 0.81 pg/min, P < 0.004) despite no difference between the two groups in plasma CNP concentrations (6.97 +/- 0.28 vs. 8.08 +/- 1.52 pg/ml, P = NS). This study demonstrates for the first time the presence of CNP immunoreactivity in human kidney and suggests that renal tubular cells may be an additional non-vascular site of synthesis for this cardiorenal acting peptide. This study also demonstrates an increase in urinary CNP excretion in congestive heart failure.


Subject(s)
Atrial Natriuretic Factor/analysis , Kidney/chemistry , Proteins/analysis , Adult , Aged , Atrial Natriuretic Factor/urine , Chromatography, High Pressure Liquid , Female , Heart Failure/urine , Humans , Immunoenzyme Techniques , Male , Middle Aged , Natriuretic Peptide, C-Type , Radioimmunoassay
18.
Circulation ; 89(4): 1580-6, 1994 Apr.
Article in English | MEDLINE | ID: mdl-8149524

ABSTRACT

BACKGROUND: Although recent investigations report the elevation of plasma endothelin (ET) in congestive heart failure (CHF), it remains unclear if this elevation is that of the biologically active peptide ET-1 or of its precursor big-ET. Furthermore, it is unclear if such elevation is associated with increased myocardial ET and if the molecular form from cardiac tissue is altered ET. Last, it remains to be established whether circulating ET is increased at the earliest stage of CHF in patients with asymptomatic left ventricular dysfunction and correlates with the magnitude of ventricular dysfunction. METHODS AND RESULTS: The present study was designed to investigate concentrations and molecular forms of ET in plasma and cardiac tissue in healthy subjects and CHF patients with New York Heart Association (NYHA) class I through IV using cardiac radionuclide angiogram, cardiac myocardial biopsy, radioimmunoassay, gel permeation chromatography (GPC), and immunohistochemical staining (IHCS). Plasma ET was increased only in patients with moderate (NYHA class III) or severe (NYHA class IV) CHF compared with healthy subjects and individuals with asymptomatic (NYHA class I) or mild (NYHA class II) CHF. The elevation of circulating ET in CHF showed a negative correlation with left ventricular ejection fraction and cardiac index and a positive correlation with functional class and left ventricular end-diastolic volume index. GPC demonstrated that immunoreactive plasma ET was ET-1 in healthy subjects and both mature ET-1 and its precursor big-ET in severe CHF patients, with big-ET the predominant molecular form. Cardiac tissue concentrations and IHCS revealed ET presence in healthy atrial and ventricular tissue, which were not different in severe CHF. GPC revealed that the molecular form of cardiac ET was ET-1 in both healthy and CHF hearts. CONCLUSIONS: The present study establishes for the first time that the elevation of plasma ET in severe human CHF represents principally elevation of big-ET. Second, ET is present in healthy and failing myocardia, and its activity by both immunohistochemistry and radioimmunoassay is not changed in CHF. Furthermore, the elevated plasma ET is characteristic of severe CHF and not asymptomatic or mild CHF. In addition, the degree of plasma elevation of ET correlates with the magnitude of alterations in cardiac hemodynamics and functional class. The present study confirms and extends previous investigations of ET in human CHF and establishes the evolution of circulating and local cardiac ET in the spectrum of human CHF.


Subject(s)
Endothelins/analysis , Heart Failure/metabolism , Myocardium/chemistry , Chromatography, Gel , Endothelin-1 , Endothelins/chemistry , Female , Heart Failure/blood , Humans , Immunohistochemistry , Male , Middle Aged , Protein Precursors/analysis , Protein Precursors/chemistry , Radioimmunoassay , Ventricular Function, Left/physiology
19.
Am J Physiol ; 266(3 Pt 2): R936-43, 1994 Mar.
Article in English | MEDLINE | ID: mdl-8160889

ABSTRACT

Circulating atrial natriuretic factor (ANF) is regulated by clearance receptors (ANFR-C). C-ANF-(4-23) is a ring-deleted analogue of ANF, which binds specifically to ANFR-C. The present studies were undertaken to determine total metabolic (TMCR), pulmonary (PCR), and renal clearance rates (RCR) of ANF in a group of seven mongrel dogs in chronic congestive heart failure (CHF) in comparison with a control group (n = 6). TMCR was not altered in CHF [1,534 +/- 319 vs. control: 1,735 +/- 208 ml/min; P = not significant (NS)] in association with an elevation of circulating endogenous ANF (206 +/- 44 vs. control: 36 +/- 10 pg/ml; P < 0.01). Infusion of C-ANF-(4-23) reduced TMCR in both groups similarly (CHF: 753 +/- 134 vs. control: 972 +/- 156 ml/min; P = NS). PCR was lower in CHF (286 +/- 431 vs. 1,672 +/- 407 ml/min; P < 0.05), whereas RCR was not different (10 +/- 24 vs. control: 15 +/- 25 ml/min; P = NS). ANFR-C blockade did not facilitate urinary sodium excretion in CHF. These studies demonstrate that 1) TMCR does not contribute to elevated endogenous ANF in CHF; 2) total functional activity of the clearance receptor pathway is preserved in CHF; and 3) renal ANF metabolism and the clearance receptor pathway are not linked to the avid sodium retention and renal ANF resistance observed in chronic CHF.


Subject(s)
Atrial Natriuretic Factor/metabolism , Heart Failure/metabolism , Receptors, Atrial Natriuretic Factor/metabolism , Animals , Diuresis , Dogs , Kidney/metabolism , Lung/metabolism , Male , Metabolic Clearance Rate , Natriuresis
20.
J Am Coll Cardiol ; 22(4 Suppl A): 86A-92A, 1993 Oct.
Article in English | MEDLINE | ID: mdl-8376700

ABSTRACT

Atrial natriuretic peptide hormone of cardiac origin, which is released in response to atrial distension and serves to maintain sodium homeostasis and inhibit activation of the renin-angiotensin-aldosterone system. Congestive heart failure is a clinical syndrome characterized by increased cardiac volume and pressure overload with an inability to excrete a sodium load, which is associated with increased activity of systemic neurohumoral and local autocrine and paracrine mechanisms. Circulating atrial natriuretic peptide is greatly increased in congestive heart failure as a result of increased synthesis and release of this hormone. Atrial natriuretic peptide has emerged as an important diagnostic and prognostic serum marker in congestive heart failure. In early heart failure, it may play a key role in preserving the compensated state of asymptomatic left ventricular dysfunction. Despite increased circulating atrial natriuretic peptide in heart failure, the kidney retains sodium and is hyporesponsive to exogenous and endogenous atrial natriuretic peptide. The mechanism for the attenuated renal response is multifactorial and includes renal hypoperfusion, activation of the renin-angiotensin-aldosterone and sympathetic nervous systems. Therapeutic strategies to potentiate the biologic actions of atrial natriuretic peptide may prolong the asymptomatic phase and delay progression to overt congestive heart failure.


Subject(s)
Atrial Natriuretic Factor/physiology , Heart Failure/physiopathology , Animals , Atrial Natriuretic Factor/biosynthesis , Atrial Natriuretic Factor/drug effects , Heart Failure/drug therapy , Heart Failure/etiology , Humans , Kidney/physiopathology , Myocardium/metabolism , Neprilysin/antagonists & inhibitors , Renin-Angiotensin System/physiology , Ventricular Function, Left/physiology
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