Search PubMed⌕ Search

Biomedical subjects

A Lerman

Publications and source records attributed to A Lerman.

At least 91 records · Page 5Linked to original sources
PubMed1997

Arterial remodeling after experimental percutaneous injury is highly dependent on adventitial injury and histopathology.

BACKGROUND: The extent and nature of unfavorable geometric remodeling, especially related to the adventitia, has not been studied previously. The purpose of this study was to examine two methods of experimental arterial injury, characterize the extent of remodeling, and determine if remodeling is injury-specific. METHODS: Two methods for producing coronary stenoses in pigs were used: heat injury using thermal balloon angioplasty (resulting in adventitial fibrosis), and copper stent implantation (resulting in intense inflammation). Histomorphometric parameters included changes in neointimal thickness (delta neointima) from uninjured to injured sections, and differences in area circumscribed by the internal and external elastic laminas (delta internal elastic lamina area and delta external elastic lamina area, respectively). Remodeling was calculated for each lesion as the enlargement of the external elastic lamina area or internal elastic lamina area for incremental neointimal thickening, expressed as the slopes delta external elastic area/delta neointima and delta internal elastic lamina area/delta neointima. RESULTS: Remodeling indices for the heat lesions for the heat lesions were negative (delta internal elastic lamina area/delta neointima = 0.15, delta external elastic lamina area/delta neointima = 0.64) and indicated little remodeling in contrast to copper stent injury (delta internal elastic lamina area/delta neointima = 0.95, delta external elastic lamina area/delta neointima = 1.20). CONCLUSIONS: Remodeling in fibrotic compared to inflammatory lesions differs markedly, and may explain increased restenosis rates observed in thermal balloon angioplasty in patients. This formulation may be useful to study remodeling and restenosis following interventional technologies.

Angioplasty, Balloon, Coronary↗
PubMed1997

Short wave ultraviolet laser energy in porcine coronary arteries: medial cell death and neointimal formation.

BACKGROUND AND OBJECTIVE: Smooth muscle cell migration and proliferation from arterial media into the neointima are major factors in the restenosis process following coronary angioplasty. Because short wave ultraviolet (UV) radiation is cytotoxic for rat carotid artery smooth muscle cells, the aims of this study were to determine the effects of short wave UV irradiation on normal pig coronary arteries and to evaluate the efficacy of UV laser energy for reducing neointimal hyperplasia (NI). STUDY DESIGN/MATERIALS AND METHODS: In 13 pigs fed a normal diet, 37 coronary arteries were studied. UV laser light (275 nm) was applied in escalating doses from 0-16,353 mJ/cm2 via fiberoptic through a 20 mm PTCA balloon catheter. The pigs were euthanized at 21 days and histologic analysis performed. Arterial media was rendered acellular (ACM) in 20 of 33 irradiated coronary arteries (61%). The minimum UV energy density inducing ACM was 1348 mJ/cm2. The fraction of acellular media to internal elastic lamina length (ACM/IEL) was 0.79 +/- 0.29. RESULTS: No statistically significant difference was found between NI thickness at normal media sites (NM) vs. ACM sites (0.17 +/- 0.14 mm vs. 0.16 +/- 0.17 mm). No correlation was found between UV dose and NI formation (r = 0.307, P = 0.08). CONCLUSION: Short wave UV irradiation induces ACM in normal porcine coronary arteries. Induction of acellular media is not associated with a reduction of NI formation in this porcine coronary model.

Angioplasty, Balloon, Coronary↗
PubMed1997

Clinical outcome of patients undergoing endoluminal coronary artery reconstruction with three or more stents.

OBJECTIVES: We sought to evaluate the outcome of patients undergoing multiple (three or more), contiguous stent implantation within a single native coronary artery. BACKGROUND: The implantation of multiple stents within a single coronary artery is increasing in frequency, although the outcome of such patients is not well described. METHODS: Forty-five patients without previous coronary artery bypass graft surgery (CABG) undergoing multiple, contiguous stent implantation in a single coronary artery were identified. Clinical and angiographic characteristics and outcomes were analyzed. RESULTS: The angiographic success rate was 97.8%. The procedural success rate was 91.1%; stent occlusion during the initial hospital period occurred in four patients (8.9%). Death, myocardial infarction (MI), CABG, repeat target vessel intervention or severe angina occurred in 10 (23.3%) of 43 hospital survivors at 6-months follow-up. The indication for stent placement was threatened or abrupt closure in 30 patients (66.7%). Of the 25 patients with abrupt or threatened closure whose clinical and angiographic data would have indicated emergent CABG had stents not been available, the frequency of in-hospital death and Q wave MI was similar to that of a matched consecutive series of patients at our institution who underwent emergent CABG after failed angioplasty. At 1 year, the frequency of death, Q wave MI, CABG and severe angina at 1 year was similar in the two groups; the need for repeat percutaneous intervention was more common in the stent group (25% vs. 0%, p = 0.01). CONCLUSIONS: Implantation of multiple, contiguous intracoronary stents was associated with a high initial success rate, although the incidence of early stent closure was relatively high. Adverse events at 6 months of follow-up were more frequent than previously reported for elective single-stent implantation; however, adverse angiographic characteristics such as dissection and thrombus were frequent in this group. In addition, the strategy of multiple stent implantation in the setting of failed angioplasty is a reasonable alternative to emergent CABG, although the need for further percutaneous intervention must be anticipated.

Angioplasty, Balloon, Coronary↗
PubMed1997

The effect of basic fibroblast growth factor on coronary vascular tone in experimental hypercholesterolemia in vivo and in vitro.

OBJECTIVE: To determine whether bFGF causes coronary vasoconstriction in experimental hypercholesterolemia in association with endothelial dysfunction. METHODS: We infused 0.02 microgram/kg per min bFGF into the left anterior descending artery of anesthetized pigs (n = 5) before and after 10 weeks of a high-cholesterol diet. The coronary artery diameter (CAD) was measured by quantitative angiography and the coronary blood flow (CBF) was calculated using coronary-flow Doppler measurements. In additional in-vitro studies, epicardial arteries from normal and hypercholesterolemic pigs were exposed to cumulative concentrations of bradykinin (10(-11)-10(-6) mol/l) after precontraction with 10(-6) mol/l endothelin-1. Cumulative concentrations of bFGF (10(-13)-10(-8) mol/l) were added to other vessels with and without prior contraction with 10(-5) mol/l PGF2 alpha. Similar in-vitro studies were performed using rings from which the endothelium had been removed. RESULTS: In vivo, intracoronary administration of bFGF increased the CBF by 33 +/- 33% and the CAD by 12 +/- 5% at baseline, but reduced the CBF by 45 +/- 8% and the CAD by 14 +/- 6% after 10 weeks of a high-cholesterol diet. In vitro, the endothelium-dependent vasorelaxation in response to bradykinin was attenuated significantly in coronary arteries from hypercholesterolemic pigs (P < 0.05). Cumulative concentrations of bFGF exerted no effect on the coronary epicardial tone both in normal (with and without endothelium) and in hypercholesterolemic pigs. CONCLUSIONS: Acute administration of intracoronary bFGF caused coronary vasodilatation under steady-state conditions and vasoconstriction under diet-induced hypercholesterolemia. In vitro, bFGF did not affect the coronary epicardial tone. These findings suggest that the coronary vasoactive properties of bFGF may be exerted indirectly and are affected by the functional integrity of the endothelium.

Animals↗
PubMed1997

Enhanced endothelin-B-receptor-mediated vasoconstriction of small porcine coronary arteries in diet-induced hypercholesterolemia.

The coronary vasoconstrictor effects of endothelins, mediated by both endothelin ETA and ETB receptors, may be differentially altered in pathophysiological states associated with endothelial dysfunction and elevated endothelin levels. Experimental hypercholesterolemia is associated with coronary endothelial dysfunction and increased circulating endothelin concentrations. These studies were designed to test the hypothesis that experimental hypercholesterolemia is characterized by a differentially altered coronary contractile response to ETA- and ETB-receptor stimulation, in vitro. Pigs were fed either a normal or a high-cholesterol diet for 10 to 13 weeks. Changes in the intraluminal diameter of pressurized small coronary arteries (< 481 +/- 25 microns in diameter) to cumulative concentrations (10(-10) to 10(-6) mol/L) of endothelin-1 (ET-1), and sarafotoxin 6c (S6c), a specific ETB-receptor agonist, were measured using a video dimension analyzer. The maximal contraction attained with ET-1 was greater than with S6c in both normal (86 +/- 7% versus 47 +/- 7%, P = .001) and hypercholesterolemic (77 +/- 6% versus 37 +/- 7%, P < .001) pigs. At 10(-10) mol/L, vessels from hypercholesterolemic pigs manifested greater contraction to both ET-1 (23 +/- 6% versus 8 +/- 3%, P = .02) and S6c (17 +/- 5% versus 4 +/- 2%, P = .02). Incubation of arteries from hypercholesterolemic pigs with BQ-788 (ETB-receptor antagonist), but not FR-139317 (ETA-receptor antagonist), altered the contractile response to ET-1 at 10(-10) mol/L. Removal of the endothelium abolished the difference in response to S6c between normal and hypercholesterolemic pigs. These studies demonstrate that experimental hypercholesterolemia is characterized by enhanced coronary vasoconstriction to endothelins in vitro, the mechanism of which is mediated mainly through the ETB receptor. Thus, the ETB receptor has a role in regulation of coronary artery tone in both the steady-state and pathophysiological states.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1996

Enhanced coronary vasoconstriction to endothelin-B-receptor activation in experimental congestive heart failure.

BACKGROUND: Endothelin (ET), a coronary vasoconstrictor, mediates its activity through the specific receptors ET-A and ET-B, which may demonstrate different activity under pathophysiological conditions. Thoracic inferior vena cava constriction (TIVCC) is an experimental model of congestive heart failure that is characterized by a decrease in cardiac output and an increase in circulating ET concentrations. The present study was designed to test the hypothesis that experimental heart failure altered coronary vascular responsiveness to ET-A- and ET-B-receptor stimulation in vivo. METHODS AND RESULTS: ET-1 was infused at a rate of 2 ng/kg per minute into the left circumflex coronary artery in normal dogs (n = 5) and in dogs subjected to TIVCC (TIVCC dogs, n = 6). Similarly, sarafotoxin, an ET-B-receptor agonist, was infused at the same dosage in normal (n = 5) and TIVCC (n = 6) dogs. Intracoronary infusion of ET-1 significantly decreased coronary blood flow and increased coronary vascular resistance in normal dogs; this effect was significantly attenuated in TIVCC compared with normal dogs. The percent changes in coronary blood flow and coronary vascular resistance in the TIVCC compared with the normal dogs was -11 +/- 8% versus -48 +/- 7% (P < .01) and 29 +/- 10% versus 105 +/- 23% (P < .01), respectively. There was no significant effect on coronary blood flow, coronary vascular resistance, or coronary artery diameter in normal dogs that received an intracoronary infusion of sarafotoxin. In contrast, the administration of intracoronary sarafotoxin in TIVCC compared with normal dogs resulted in significant percent changes in coronary blood flow and coronary vascular resistance (-31 +/- 4% versus -7 +/- 3% [P < .001] and 53 +/- 12% versus 12 +/- 8% [P < .02], respectively). CONCLUSIONS: The present study demonstrates an attenuated coronary vasoconstrictor response to ET-1 with an enhanced vasoconstrictor response to sarafotoxin and suggests an alteration in coronary ET receptor sensitivity in experimental heart failure.

Animals↗
PubMed1996

Altered coronary endothelial function in a patient with asymptomatic left ventricular dysfunction.

Coronary endothelial dysfunction has been demonstrated in patients with symptomatic heart failure. Furthermore the endothelium has been implicated in the pathogensis of cardiomyopathy in patients with normal coronary angiograms and no other known causes of heart failure. Herein we describe an asymptomatic patient with an early cardiomyopathy and abnormal coronary endothelial function. There was no evidence for coronary disease by both angiography and intravascular ultrasound. Epicardial coronary artery vasoconstriction and a decrease in coronary blood flow was noted during the intracoronary infusion of graded concentrations of acetylcholine. This case demonstrates that endothelial dysfunction occurs in the setting of asymptomatic left ventricular dysfunction and highlights the potential importance of the endothelium in the early development of heart failure.

Acetylcholine↗
PubMed1996

Evaluation of patients with minimally obstructive coronary artery disease and angina.

Atherosclerotic coronary artery disease is a progressive process adversely affecting the integrity of the coronary vasculature. In past years, most studies have focused on the morphological changes leading to compromised coronary blood flow in atherosclerosis. However, in recent years it has become apparent that abnormal coronary vasomotor regulation may precede or accompany gross morphological changes in coronary atherosclerotic disease. In fact, the pathophysiology of angina pectoris in many patients with risk factors for atherosclerosis and minimally obstructive disease may involve abnormal coronary vasomotor tone regulation. The aim of the present article is to describe a clinical approach to patients with angina pectoris and minimally obstructive coronary artery disease based on current knowledge of coronary vasomotor regulation.

Acetylcholine↗
PubMed1996

The role of endothelin in coronary atherosclerosis.

During the evolution of coronary atherosclerosis, growth factors, cytokines, and other molecules are involved in cell recruitment, migration, and proliferation. Endothelin is an endothelial-derived vasoconstrictor peptide that possesses mitogenic properties. In this review, current evidence is provided that suggests that endothelin fulfills proposed criteria to be considered an atherogenic peptide because of its mitogenic and proliferative properties, as well as its inter-actions with known atherogenic factors. In addition, a proposed role of endothelin in the evolution of atherosclerosis is outlined.

Angioplasty, Balloon, Coronary↗
PubMed1996

Coronary hemodynamics before and after rotational atherectomy with adjunctive balloon angioplasty.

The phenomenon of "no-reflow" has been described frequently after rotational atherectomy. The aim of this study was to determine the coronary hemodynamic changes by Doppler flow wire before and after rotational atherectomy and adjunctive balloon angioplasty in 10 patients. All patients had TIMI-III flow at baseline. After rotational atherectomy alone, two patients had TIMI-I, four patients had TIMI-II, and four patients had TIMI-III flow. In addition, the number of Cineframes to Opacification of a preselected distal landmark increased twofold (from 49 +/- 12 to 118 +/- 27 frames; P < 0.05). Intracoronary nitroglycerin and verapamil was associated with return to baseline of both measurements. Following adjunctive balloon angioplasty, there was an increase in lumen diameter (1.29 +/- 0.1 vs. 2.6 +/- 0.1 mm; P < 0.05), coronary flow (81 +/- 14 to 154 +/- 18 ml/min; P < 0.05), maximal absolute velocity (23 +/- 4 to 52 +/- 4 cm/sec; P < 0.05), and vascular resistance decreased (1.74 +/- 0.4 to 0.74 +/- 0.4 mm Hg/ml/min; P < 0.05). However, no change in coronary flow reserve was noted (1.24 +/- 0.1 vs. 1.5 +/- 0.3). Immediately after rotational atherectomy alone, there is a reduction in angiographically determined coronary flow, suggesting either distal microvascular spasm or distal microvascular obstruction. Regardless of the mechanism, the transient reduction of coronary flow was rapidly reversed by coronary vasodilators. Despite the significant improvement of coronary hemodynamics noted immediately after combined rotational atherectomy and balloon angioplasty, coronary flow reserve remained abnormal. Similarly, no change in coronary flow reserve has been reported immediately after balloon angioplasty alone. The lack of improvement in flow reserve after both balloon angioplasty and rotational atherectomy suggests that the mechanisms of improved flow reserve may be device independent, and remain unexplained.

Aged↗
PubMed1995

Endothelin at pathophysiological concentrations mediates coronary vasoconstriction via the endothelin-A receptor.

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.

Animals↗
PubMed1995

Endothelin in coronary endothelial dysfunction and early atherosclerosis in humans.

BACKGROUND: The endothelium modulates vascular tone through release of vasodilating substances, such as endothelium-derived relaxing factors, and vasoconstricting substances, such as endothelin. Endothelin concentrations are elevated in humans with atherosclerosis and in hypercholesterolemic pigs. Furthermore, the endothelium-dependent vasodilator acetylcholine increases endothelin in hypercholesterolemia in association with coronary vasoconstriction. The present study was designed to test the hypotheses that coronary endothelial dysfunction in humans is characterized by enhanced coronary and circulating endothelin and that the vasoconstriction associated with acetylcholine results in further release of coronary endothelin. METHODS AND RESULTS: Coronary and circulating endothelin concentrations were measured at baseline and during intracoronary acetylcholine administration in 20 patients undergoing diagnostic coronary angiography. Patients were divided into two groups on the basis of their response to intracoronary acetylcholine. Group 1 (n = 7) demonstrated a normal vasodilatory response, but group 2 (n = 13) demonstrated coronary vasoconstriction. Baseline coronary and circulating endothelin concentrations (as determined by coronary sinus and femoral artery measurements, respectively) were higher in patients who responded to acetylcholine with coronary vasoconstriction (group 2) than in group 1 patients (coronary sinus, 15.9 +/- 1.0 pg/mL versus 7.1 +/- 1.0 pg/mL; femoral, 14.1 +/- 0.9 pg/mL versus 6.8 +/- 1.0 pg/mL, respectively; P < .01). In response to intracoronary acetylcholine, a further increase in coronary endothelin was observed only in group 2; this increase correlated with changes in coronary artery diameter. CONCLUSIONS: This study demonstrates that endothelin immunoreactivity is enhanced in the coronary and systemic circulation in humans with coronary endothelial dysfunction. Moreover, acetylcholine further increased coronary endothelin concentration in patients with coronary endothelial dysfunction and was associated with coronary vasoconstriction. These observations strongly support a role for endothelin as an early participant in and marker for coronary endothelial dysfunction in humans.

Acetylcholine↗
PubMed1995

Epicardial vasomotor responses to acetylcholine are not predicted by coronary atherosclerosis as assessed by intracoronary ultrasound.

OBJECTIVES: The purpose of this study was to use intravascular ultrasound to determine the morphologic appearance of the coronary arteries, relating the absence, presence and extent of atherosclerosis to the response of the coronary arteries to acetylcholine infusion. BACKGROUND: Endothelial function plays a major role in the pathophysiology of myocardial ischemia and angina pectoris. The response of the coronary arteries to selective infusion of acetylcholine has been used to examine endothelial function, with vasoconstriction occurring in the absence of intact endothelial function. Vasoconstriction to acetylcholine infusion in humans without overt coronary artery disease has been attributed to early atherosclerosis not detected by coronary angiography. METHODS: Twenty-nine patients without overt coronary artery disease underwent selective coronary angiography and selective intracoronary infusion of increasing concentrations of acetylcholine (10(-6), 10(-5) and 10(-4) mol/liter), followed by intravascular ultrasound imaging. RESULTS: The response of the coronary arteries to acetylcholine infusion was not dependent on the absence or presence of atherosclerotic plaque, as detected by intravascular ultrasound. The percent change in epicardial coronary artery diameter during acetylcholine infusion versus baseline was -14 +/- 28% (mean +/- SD) in the seven patients with no visible atherosclerosis on intravascular ultrasound versus -9 +/- 20% in the 22 patients with visible atherosclerosis on intravascular ultrasound (p = NS, confidence interval -14% to 25%). There was a greater vasoconstrictive response to acetylcholine infusion in patients with risk factors for coronary artery disease than in those without risk factors (p = 0.003). CONCLUSIONS: The vasoreactive response to acetylcholine is not necessarily dependent on ultrasound detection of the presence or absence of atherosclerosis.

Acetylcholine↗
PubMed1994

Endothelin in human congestive heart failure.

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.

Chromatography, Gel↗
PubMed1993

Circulating N-terminal atrial natriuretic peptide as a marker for symptomless left-ventricular dysfunction.

Early identification of patients with symptomless left-ventricular dysfunction and early pharmacologic intervention may have an impact on the outlook of patients with heart failure. Atrial natriuretic peptide (ANP) is a cardiac hormone that is released as a C-terminal (C-ANP) and an N-terminal peptide (N-ANP). Since N-ANP has reduced clearance rates compared with C-ANP, N-ANP circulates at higher concentrations. Based on the known increased concentration of C-ANP in symptomatic congestive heart failure, our study was designed to evaluate prospectively N-ANP profile and left-ventricular function in subjects with symptomless and symptomatic heart failure, and the role of plasma N-ANP as a marker for early identification of patients with heart failure. 180 patients who were referred for rest and exercise radionuclide angiography for evaluation of left-ventricular function were studied. Blood was taken for measurement of C-ANP and N-ANP before angiography. Patients were grouped according to New York Heart Association (NYHA) heart failure classification and left-ventricular function. Mean (SD) plasma N-ANP concentration in patients with symptomless left-ventricular dysfunction (NYHA class I, n = 70) was 243 (256) pmol/L (range 27-922 pmol/L), and was higher (p < 0.001) than in 25 control subjects (28 pmol/L). A plasma N-ANP concentration above 54 pmol/L (mean +/- 1.96SD of the control group) had a sensitivity of 90% and a specificity of 92% for detection of patients with symptomless left-ventricular dysfunction. We have shown that plasma N-ANP concentrations are significantly increased in patients with symptomless left-ventricular dysfunction and that this peptide can serve as a marker for diagnosis of such patients.

Adult↗
PubMed1993

Natriuretic peptide system in human heart failure.

BACKGROUND: Atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and C-type natriuretic peptide (CNP) are a family of structurally related peptides that participate in the integrated control of renal and cardiovascular function. Previous studies suggest a functional role for these hormonal peptides in cardiorenal regulation in congestive heart failure (CHF). METHODS AND RESULTS: The present studies were performed in normal subjects (n = 6) and in patients with mild (New York Heart Association [NYHA] class I to II, n = 20) and severe (NYHA class III to IV, n = 20) CHF by use of radioimmunoassay and immunohistochemical staining (IHCS). Plasma ANP was significantly increased in both mild and severe CHF compared with normal subjects. In contrast, plasma BNP was only moderately increased in the severe CHF group, and plasma CNP concentration was unchanged in CHF compared with normal subjects. Atrial tissue concentrations of the natriuretic peptides did not parallel circulating concentrations. ANP predominated in normal atrial tissue, but BNP predominated in CHF. In ventricular tissue, IHCS staining was present for all three peptides in normal ventricular myocardium and was markedly enhanced in CHF. CONCLUSIONS: These studies support a differential regulation of ANP, BNP, and CNP circulating concentrations and tissue activity in human CHF.

Atrial Natriuretic Factor↗