RESUMO
INTRODUCTION: Peer review is frequently incorporated within radiographer reporting services. The aim of this study is to establish peer review systems used for radiograph reports provided by reporting radiographers in London. METHODS: An online cross-sectional survey of NHS diagnostic imaging departments was performed. Reporting radiographer demographics (number, frequency of reporting, scope of practice) and systems used to provide peer review of radiograph reports (review frequency, case selection, volume, outcome measure, practitioner performing the review) were collected. RESULTS: Thirteen eligible responses were received (61.9% response rate). Variability was found between Trusts in the number of reporting radiographers, frequency of reporting sessions and scope of practice. Most Trusts (9 of 13, 69.2%) have active peer review systems for radiographer reporting. All peer review systems use random case selection, most often performed on a monthly basis. Both a fixed number or a percentage of cases reported were used, with true positive, true negative, false positive, false negative the most frequent outcome measure. Of the 12 Trusts that have or are planning a peer system, all currently or plan to use reporting radiographers to conduct the review, with five (41.2%) also using consultant radiologists. CONCLUSION: Peer review of radiographer reporting is common in London NHS Trusts although there is variation in the methods used. IMPLICATIONS FOR PRACTICE: Radiographer reports frequently undergo peer review. Standardisation of reporting radiographer peer review systems should be considered, and a standardised systematic peer review system has been proposed.
Assuntos
Competência Clínica , Medicina Estatal , Estudos Transversais , Humanos , Londres , Revisão por Pares , RadiografiaRESUMO
Saphenous vein graft aneurysm (SVG) formation after coronary artery bypass grafting is a rare complication of the surgery. We present a case of a 68-year-old man with an unusual presentation of such an aneurysm. Thirty-four years after his initial bypass surgery, the patient presented with a fistula formation into his right atrium from a vein graft aneurysm. Late aneurysm formation is thought to occur secondary to atherosclerotic degeneration of the SVG with background hypertension and dyslipidaemia accelerating the process. Diagnostic modalities used to investigate SVG aneurysms include computed tomography, transthoracic echocardiogram, magnetic resonance imaging and cardiac catheterisation. Aneurysms with fistula formation historically require aggressive surgical intervention. Resection of the aneurysm with subsequent revascularisation if required is the surgical norm. SVG aneurysm with fistula formation into a cardiac chamber is a rare complication of coronary artery bypass grafting (CABG), which can occur with atypical presenting symptoms. Physicians should keep in mind the possibility of this occurring in post-CABG patients presenting with heart failure and a new murmur.
Assuntos
Aneurisma/diagnóstico , Ponte de Artéria Coronária/efeitos adversos , Insuficiência Cardíaca/diagnóstico , Complicações Pós-Operatórias/diagnóstico , Veia Safena/patologia , Idoso , Aneurisma/complicações , Fístula/complicações , Fístula/diagnóstico , Insuficiência Cardíaca/etiologia , Humanos , Masculino , Complicações Pós-Operatórias/etiologiaRESUMO
Myocardial metastasis from a cutaneous squamous cell carcinoma (SCC) is rare. Herein we have presented a case of metastasis from cutaneous SCC to the myocardium in a renal transplant recipient, which was confirmed by a cardiac fine-needle biopsy. Postmortem examination revealed disseminated metastatic disease involving myocardium, lungs, thyroid, skin, and peritoneum secondary to cutaneous SCC likely related to immunosuppression. At 46 years of age, he received a renal transplant for chronic renal failure caused by chronic glomerulonephritis. He started to develop multiple nonmelanoma skin cancers 4 years later. At least 23 invasive SCCs and 14 basal cell carcinomas were excised. His immunosuppressive regimen consisted of cyclosporine (150 mg), azathioprine (75 mg), and prednisone (10 mg daily), which was not modified despite multiple nonmelanoma skin cancers. Our case report further illustrates the potentially aggressive and fatal nature of cutaneous SCCs that can develop in organ transplant recipients. It argues for modification of the immunosuppressive regimen in such patients. The management of renal transplant patients with nonmelanoma skin cancers remains difficult and complex.
Assuntos
Carcinoma de Células Escamosas/patologia , Neoplasias Cardíacas/secundário , Transplante de Rim/patologia , Metástase Neoplásica/patologia , Complicações Pós-Operatórias/patologia , Neoplasias Cutâneas/patologia , Carcinoma de Células Escamosas/cirurgia , Ecocardiografia , Neoplasias de Cabeça e Pescoço/patologia , Neoplasias de Cabeça e Pescoço/cirurgia , Neoplasias Cardíacas/diagnóstico por imagem , Neoplasias Cardíacas/patologia , Neoplasias Cardíacas/cirurgia , Humanos , Imunossupressores/uso terapêutico , Masculino , Pessoa de Meia-Idade , Resultado do TratamentoRESUMO
The aims of this study were to examine the relationships between CYP2D6 genotype and metoprolol dose, S- and R-metoprolol concentrations and clinical effects in patients with systolic heart failure. Data were obtained for 52 subjects, of which 27 had 2 functional alleles (24/27, CYP2D6*1/*1), 22 had 1 functional allele (18/22, CYP2D6*1/*4) and 3 had no functional alleles (CYP2D6*4/*4). Median dose-adjusted concentrations of S-metoprolol (active) were 6.3- and 3.2-fold higher in subjects with zero or one functional allele (P=0.016 and P=0.006), respectively, compared with subjects with two functional alleles. For the R-enantiomer (inactive), these concentrations were 10.7- and 3.7-fold higher (P=0.013 and P=0.003), respectively. Despite clear gene-concentration differences, no relationships between CYP2D6 genotype and dose or clinical effects could be shown. Although the number with no functional alleles was too small (n=3) to show effects, in patients with 1 functional allele other sources of variance are likely to be obscuring differences in clinical effects.
Assuntos
Antagonistas Adrenérgicos beta/uso terapêutico , Citocromo P-450 CYP2D6/genética , Insuficiência Cardíaca/tratamento farmacológico , Metoprolol/farmacologia , Sístole , Antagonistas Adrenérgicos beta/administração & dosagem , Alelos , Relação Dose-Resposta a Droga , Genótipo , Humanos , EstereoisomerismoRESUMO
BACKGROUND: Natriuretic peptides have actions likely to ameliorate cardiac dysfunction. B-type natriuretic peptide (BNP) is indicated as treatment for decompensated cardiac failure. OBJECTIVE: To determine the utility of BNP in acute myocardial infarction (MI). DESIGN: Double-blind randomised placebo-controlled trial. SETTING: Tertiary hospital coronary care unit. PATIENTS: 28 patients with acute MI with delayed or failed reperfusion and moderate left ventricular dysfunction. INTERVENTIONS: Infusion of BNP or placebo for 60 hours after MI. MAIN OUTCOME MEASURES: Neurohormonal activation and renal function in response to BNP infusion, secondary end points of echocardiographic measures of left ventricular function and dimension. RESULTS: BNP infusion resulted in a significant rise in BNP (276 pg/l vs 86 pg/l, p = 0.001). NT-proBNP levels were suppressed by BNP infusion (p = 0.002). Atrial natriuretic peptide (ANP) and NT-proANP levels fell with a significant difference in the pattern between BNP infusion and placebo during the first 5 days (p<0.005). C-type natriuretic peptide (CNP) and NT-proCNP levels rose during the infusion with higher levels than placebo at all measurements during the first 3 days (p<0.01). Cyclic guanosine monophosphate (cGMP) was raised during the infusion period showing a peak of 23 pmol/l on day 2 (placebo 8.9 pmol/l, p = 0.002), with a correlation between BNP and cGMP levels (p<0.001). Glomerular filtration rate (GFR) fell with BNP infusion but was not significantly lower than with placebo (71.0 (5.6) vs 75.8 (5.4) ml/min/1.73 m2, p = 0.62). Patients receiving nesiritide exhibited favourable trends in left ventricular remodelling. CONCLUSIONS: Nesiritide, given soon after MI, induced increments in plasma cGMP and CNP and decrements in other endogenous cardiac peptides with a neutral effect on renal function and a trend towards favourable ventricular remodelling.
Assuntos
Doença da Artéria Coronariana/tratamento farmacológico , GMP Cíclico/metabolismo , Infarto do Miocárdio/tratamento farmacológico , Natriuréticos/administração & dosagem , Peptídeo Natriurético Encefálico/administração & dosagem , Receptores do Fator Natriurético Atrial/administração & dosagem , Idoso , Fator Natriurético Atrial/sangue , Doença da Artéria Coronariana/sangue , Relação Dose-Resposta a Droga , Método Duplo-Cego , Ecocardiografia Doppler de Pulso/métodos , Feminino , Seguimentos , Humanos , Rim/efeitos dos fármacos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/sangue , Peptídeo Natriurético Encefálico/sangue , Fragmentos de Peptídeos/sangue , Receptores do Fator Natriurético Atrial/sangueRESUMO
BACKGROUND: Risk stratification for patients with acute dyspnoea is a challenging task. No quantitative tool for mortality prediction among patients with acute dyspnoea is available. METHODS: 595 dyspnoeic subjects were enrolled in an emergency department. Clinical and biochemical factors independently predictive of death by 1 year were used to develop a mortality risk prediction tool. RESULTS: Seven factors comprised the final tool: age (x0.3), heart rate (x0.2), blood urea nitrogen (x0.3), New York Heart Association class (x5), amino-terminal pro-B-type natriuretic peptide (NT-proBNP) >or=986 pg/ml (18 points), systolic blood pressure <100 mm Hg (11 points) and presence of a murmur (11 points). A continuous rise in mortality was seen from 1.7% in the lowest score quintile (n = 118; score
Assuntos
Diagnóstico por Computador/métodos , Dispneia/etiologia , Doença Aguda , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Serviço Hospitalar de Emergência , Métodos Epidemiológicos , Feminino , Insuficiência Cardíaca/complicações , Insuficiência Cardíaca/diagnóstico , Humanos , Masculino , Pessoa de Meia-Idade , Peptídeo Natriurético Encefálico/sangue , Fragmentos de Peptídeos/sangue , Sistemas Automatizados de Assistência Junto ao Leito , PrognósticoRESUMO
OBJECTIVES: To investigate the effect of short-term statin treatment on impaired endothelium-dependent vasodilatation and haemodynamic abnormalities typically occurring in chronic heart failure (CHF). METHODS: In a double-blind, crossover study endothelium-dependent vasodilatation was measured in conduit and resistance vessels of 23 patients with non-ischaemic CHF after 6 weeks of placebo and 40 mg atorvastatin. The haemodynamic impact was assessed by cardioendocrine hormones, echocardiography and clinical indicators of CHF. RESULTS: Cholesterol concentrations were population average (low density lipoprotein 3.56 (SEM 0.16) mmol/l, triglycerides 1.70 (0.20) mmol/l and high density lipoprotein 1.17 (0.07) mmol/l). In resistance vessels, the area under the curve ratio during acetylcholine infusion increased from 9.2 (1.9) with placebo to 12.2 (2.1) with statin (p < 0.01). This improvement was reversed during co-infusion with the nitric oxide antagonist N(G)-monomethyl-L-arginine. In conduit arteries, flow-mediated dilatation increased from 5.64 (SEM 0.88)% with placebo to 6.83 (0.97)% with statin (p < 0.05). Endothelium-independent vasodilatation did not change (p = 0.68 for conduit and p = 0.45 for resistance vessels). Endothelin 1 and atrial natriuretic peptide (ANP) decreased from 1.57 (0.08) and 51.3 (1.0) with placebo to 1.42 (0.09) pg/ml (p < 0.05) and 42.1 (7.5) pmol/l (p < 0.05), respectively, with statin. CONCLUSIONS: In patients with non-ischaemic CHF and population-average cholesterol concentrations, short-term statin treatment improves endothelial function in conduit and resistance vessels and lowers plasma endothelin 1 and ANP concentrations.
Assuntos
Insuficiência Cardíaca/tratamento farmacológico , Ácidos Heptanoicos/uso terapêutico , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Pirróis/uso terapêutico , Atorvastatina , Biomarcadores/sangue , Colesterol/sangue , Estudos Cross-Over , Método Duplo-Cego , Ecocardiografia , Endotélio Vascular , Feminino , Insuficiência Cardíaca/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Peptídeos Natriuréticos/sangue , Resistência Vascular/efeitos dos fármacos , Vasodilatação/efeitos dos fármacosRESUMO
OBJECTIVES: To determine levels of natriuretic peptides (NPs) in patients with end-stage renal disease (ESRD) and to examine the relationship of these cardiovascular peptides to left ventricular hypertrophy (LVH) and to cardiac mortality. PATIENTS AND METHODS: One hundred twelve dialysis patients without clinical evidence of congestive heart failure underwent plasma measurement of NP concentrations and echocardiographic investigation for left ventricular mass index (LVMI). RESULTS: Plasma atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) concentrations correlated positively with LVMI and inversely with left ventricular ejection fraction, whereas C-type NP and Dendroaspis NP levels did not correlate with LVMI. In dialysis patients with LVH (LVMI >125 g/m2), plasma ANP and BNP concentrations were increased compared with those in dialysis patients without LVH (both P<001). In a subset of 15 dialysis patients without LVH or other concomitant diseases, plasma BNP concentrations were not significantly increased compared with those in 35 controls (mean +/- SD, 20.1+/-13.4 vs 13.5+/-9.6 pg/mL; P=.06), demonstrating that the BNP concentration was not increased by renal dysfunction alone. Furthermore, the BNP level was significantly higher in the 16 patients who died from cardiovascular causes compared with survivors (mean +/- SD, 129+/-13 vs 57+/-7 pg/mL; P<.003) and was significantly associated with greater risk of cardiovascular death in Cox regression analysis (P<.001), as was the ANP level (P=.002). CONCLUSIONS: Elevation of the plasma BNP concentration is more specifically related to LVH compared with the other NP levels in patients with ESRD independent of congestive heart failure. Thus, BNP serves as an important plasma biomarker for ventricular hypertrophy in dialysis patients with ESRD.
Assuntos
Fator Natriurético Atrial/sangue , Hipertrofia Ventricular Esquerda/sangue , Falência Renal Crônica/sangue , Peptídeo Natriurético Encefálico/fisiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores , Estudos de Casos e Controles , Comorbidade , Feminino , Hemodinâmica , Humanos , Falência Renal Crônica/etiologia , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Peptídeo Natriurético Encefálico/sangue , Curva ROC , Diálise Renal , Fatores de RiscoRESUMO
The drug treatment of heart failure, once simple, has become complex. Apart from a loop diuretic and digoxin, most patients should now be receiving an angiotensin-converting enzyme inhibitor (or angiotensin II receptor blocker), a beta-blocker and spironolactone. Newer drugs, such as endothelin-receptor antagonists and combined blockers of converting-enzyme and neutral endopeptidase, might soon become available. When to introduce these drugs and what dose is optimal for any individual, are questions that currently vex clinicians. We proposed that plasma levels of the cardiac hormone brain natriuretic peptide (BNP, or better, its 1-76 amino-acid N-terminal fragment, N-BNP), would provide an objective index for guiding drug treatment in patients with established, stable cardiac failure. In a pilot study, 69 patients were randomized to drug treatment based on clinical criteria, or based on plasma levels of N-BNP. After a median follow-up of 9.6 months, those in the N-BNP group had fewer clinical end-points than those in the group managed by clinical criteria alone (19 vs 54; P= 0.02). These preliminary data encourage the concept that the increasingly complex pharmacotherapy for heart failure, both chronic (as in this trial) and acute, might best be guided by an objective measure such as plasma levels of BNP or N-BNP.
Assuntos
Insuficiência Cardíaca/sangue , Insuficiência Cardíaca/tratamento farmacológico , Peptídeo Natriurético Encefálico/sangue , Insuficiência Cardíaca/mortalidade , Humanos , Projetos Piloto , Sistemas Automatizados de Assistência Junto ao Leito , Resultado do TratamentoRESUMO
Mild heart failure is characterized by increases in atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) in the absence of activation of the renin-angiotensin-aldosterone system (RAAS). Vasopeptidase (VP) inhibitors are novel molecules that coinhibit neutral endopeptidase 24.11, which degrades the natriuretic peptides (NPs) and ACE. In a well-characterized canine model of mild heart failure produced by ventricular pacing at 180 bpm for 10 days, we defined the renal and humoral actions of acute VP inhibition with omapatrilat (OMA, n=6) and acute ACE inhibition (n=5) alone with fosinoprilat. We also sought to determine whether the NPs participate in the renal actions of acute VP inhibition by the administration of OMA together with an intrarenal administration of the NP receptor antagonist HS-142-1 (n=5). OMA resulted in a greater natriuretic response than did ACE inhibition in association with increases in plasma cGMP, ANP, BNP, urinary cGMP, urinary ANP excretion, and glomerular filtration rate (P<0.05 for OMA versus ACE inhibition). Plasma renin activity was increased only in the group subjected to ACE inhibition. Administration of intrarenal HS-142-1 attenuated the renal properties of OMA in association with a decrease in urinary cGMP excretion despite similar increases in plasma ANP and BNP. This study provides new insight into a unique new pharmacological agent that has beneficial renal actions in experimental mild heart failure beyond the actions that are observed with ACE inhibition alone and that are linked to the NP system.
Assuntos
Fator Natriurético Atrial/fisiologia , Insuficiência Cardíaca/sangue , Insuficiência Cardíaca/urina , Neprilisina/antagonistas & inibidores , Inibidores de Proteases/farmacologia , Piridinas/farmacologia , Tiazepinas/farmacologia , Inibidores da Enzima Conversora de Angiotensina/farmacologia , Animais , Pressão Sanguínea/efeitos dos fármacos , GMP Cíclico/sangue , GMP Cíclico/urina , Cães , Fosinopril/análogos & derivados , Fosinopril/farmacologia , Taxa de Filtração Glomerular/efeitos dos fármacos , Insuficiência Cardíaca/fisiopatologia , Masculino , Polissacarídeos/farmacologia , Receptores do Fator Natriurético Atrial/antagonistas & inibidores , Sódio/urinaAssuntos
Comparação Transcultural , Infarto do Miocárdio/diagnóstico , Creatina Quinase/sangue , Creatina Quinase Forma MB , Eletrocardiografia , Humanos , Isoenzimas/sangue , Infarto do Miocárdio/classificação , Infarto do Miocárdio/epidemiologia , Valor Preditivo dos Testes , Troponina/sangue , Organização Mundial da SaúdeRESUMO
Adrenomedullin is a 52-amino acid peptide that circulates in human plasma. The plasma concentrations of the peptide are increased in cardiovascular disease in proportion to the degree of hemodynamic impairment. Plasma adrenomedullin levels in heart failure, and in subjects with acute myocardial infarction, have been shown to convey independent prognostic information. Adrenomedullin has multiple biologic effects, but characteristically causes vasodilatation. The actions of adrenomedullin and the activation of this peptide in cardiovascular disease suggest it may have an important pathophysiologic role in heart failure. Manipulation of adrenomedullin or its receptor may have therapeutic potential.
Assuntos
Insuficiência Cardíaca/genética , Insuficiência Cardíaca/fisiopatologia , Adrenomedulina , Humanos , Peptídeos/genética , Peptídeos/metabolismo , Vasodilatadores/sangueRESUMO
Dendroaspis natriuretic peptide (DNP), a recently discovered peptide, shares structural similarity to the other known natriuretic peptides, ANP, BNP, and CNP. Studies have reported that DNP is present in human and canine plasma and atrial myocardium and increased in plasma of humans with congestive heart failure (CHF). In addition, synthetic DNP is markedly natriuretic and diuretic and is a potent activator of cGMP in normal animals. To date, the ability of synthetic DNP to improve cardiorenal function in experimental CHF is unknown. Synthetic DNP was administered intravenously at 10 and 50 ng. kg(-1). min(-1) in dogs (n=7) with severe CHF induced by rapid ventricular pacing for 10 days at 245 bpm. In addition, we determined endogenous DNP in normal (n=4) and failing (n=4) canine atrial and ventricular myocardium. We report that administration of synthetic DNP in experimental severe CHF has beneficial cardiovascular, renal, and humoral properties. First, DNP in CHF decreased cardiac filling pressures, specifically right atrial pressure and pulmonary capillary wedge pressure. Second, DNP increased glomerular filtration rate in association with natriuresis and diuresis despite a reduction in mean arterial pressure. Third, DNP increased plasma and urinary cGMP and suppressed plasma renin activity. Fourth and finally, we report that DNP immunoreactivity is present in canine atrial and ventricular myocardium and increased in CHF. These studies report the acute intravenous actions of synthetic DNP in experimental severe CHF and suggest that on the basis of its beneficial properties, DNP may have potential as a new intravenous agent for the treatment of decompensated CHF.
Assuntos
Fármacos Cardiovasculares/uso terapêutico , Venenos Elapídicos/uso terapêutico , Insuficiência Cardíaca/tratamento farmacológico , Peptídeos/uso terapêutico , Análise de Variância , Animais , Pressão Sanguínea/fisiologia , Fármacos Cardiovasculares/metabolismo , GMP Cíclico/sangue , Cães , Venenos Elapídicos/metabolismo , Taxa de Filtração Glomerular/efeitos dos fármacos , Insuficiência Cardíaca/metabolismo , Insuficiência Cardíaca/fisiopatologia , Hemodinâmica , Peptídeos e Proteínas de Sinalização Intercelular , Túbulos Renais/fisiologia , Masculino , Miocárdio/metabolismo , Peptídeos/metabolismo , Pressão Propulsora Pulmonar/fisiologia , Radioimunoensaio , Renina/sangueRESUMO
Although the biological effects of adrenomedullin (AM) and PAMP have been reported extensively in animal studies and from in-vitro experiments, relatively little information is available on responses to the hormone administered to man. This review summarizes data from the few studies carried out in man. In healthy volunteers, i.v. infusion of AM reduces arterial pressure, probably at a lower rate of administration than is required to elicit other responses. AM stimulates heart rate, cardiac output, plasma levels of cAMP, prolactin, norepinephrine and renin whilst inhibiting any concomitant response in plasma aldosterone. Little or no increase in urine volume or sodium excretion has been observed. Patients with essential hypertension differ only in showing a greater fall in arterial pressure and in the development of facial flushing and headache. In patients with heart failure or chronic renal failure, i.v. AM has similar effects to those seen in normal subjects but also induces a diuresis and natriuresis, depending on the dose administered. Infusion of AM into the brachial artery results in a dose-related increase in forearm and skin blood flow, more prominent and more dependent on endogenous nitric oxide in healthy volunteers than in patients with cardiac failure. When infused into a dorsal hand vein, AM partially reversed the venoconstrictor action of norepinephrine. Although much more information is required to clarify the role of AM under physiological and pathophysiological circumstances, it is clear that it has prominent hemodynamic and neurohormonal effects, though generally lesser urinary effects when administered short-term in doses sufficient to raise its levels in plasma to those seen in a number of clinical disorders. The only study of PAMP in man showed that its skeletal muscle vasodilator potency, when infused into the brachial artery of healthy volunteers, was less than one hundredth that of AM, and it was without effect on skin blood flow.
Assuntos
Doenças Cardiovasculares/prevenção & controle , Fragmentos de Peptídeos/uso terapêutico , Peptídeos/uso terapêutico , Proteínas/uso terapêutico , Adrenomedulina , Ensaios Clínicos como Assunto , Insuficiência Cardíaca/prevenção & controle , Humanos , Hipertensão/prevenção & controle , Hipertensão Pulmonar/prevenção & controle , Falência Renal Crônica/prevenção & controle , Fragmentos de Peptídeos/farmacologia , Peptídeos/farmacologia , Proteínas/farmacologia , Veias/efeitos dos fármacosRESUMO
Myocardial actions of the vasodilator peptide adrenomedullin (ADM) in the intact animal are unknown. Negative and positive inotropic actions have been reported in ex vivo experiments. Myocardial and load-altering actions of ADM in dogs before and after development of heart failure were studied. With controlled heart rate (atrial pacing) and after beta-blockade, ADM was administered to five normal dogs in doses of 20 ng. kg(-1). min(-1) iv, 100 ng. kg(-1). min(-1) iv, and 200 ng. kg(-1). min(-1) into the left ventricle (LV). LV peak systolic pressure and end-systolic volume decreased with each dose of ADM. End-systolic pressure decreased with the two higher doses. At the highest dose, arterial elastance and the time constant of LV isovolumic relaxation (tau) decreased, and LV end-systolic elastance (E(es)) increased. LV end-diastolic pressure and volume were unchanged. In five additional normal dogs receiving only the highest dose of ADM (200 ng. kg(-1). min(-1) intra-LV), to control for increased heart rate and sympathetic activation observed with the cumulative infusion, ADM produced arterial vasodilation but no change in E(es) or tau. In four dogs with pacing-induced heart failure, ADM (200 ng. kg(-1). min(-1) intra-LV) was without effect on tau, E(es), and systolic or diastolic pressure and volume. In vivo, ADM appears to be a selective arterial dilator without inotropic or lusitropic effects. The vasodilatory actions are attenuated in heart failure.
Assuntos
Insuficiência Cardíaca/metabolismo , Coração/efeitos dos fármacos , Contração Miocárdica/efeitos dos fármacos , Peptídeos/administração & dosagem , Vasodilatadores/administração & dosagem , Adrenomedulina , Animais , Pressão Sanguínea/efeitos dos fármacos , Estimulação Cardíaca Artificial , AMP Cíclico/sangue , Modelos Animais de Doenças , Cães , Relação Dose-Resposta a Droga , Epinefrina/sangue , Coração/fisiopatologia , Insuficiência Cardíaca/fisiopatologia , Frequência Cardíaca/efeitos dos fármacos , Infusões Intravenosas , Masculino , Contração Miocárdica/fisiologia , Norepinefrina/sangue , Peptídeos/sangue , Vasodilatação/efeitos dos fármacos , Vasodilatadores/sangue , Função Ventricular Esquerda/efeitos dos fármacosRESUMO
The actions of adrenomedullin (ADM), a 52-amino acid peptide, are not well defined in man. We, therefore, studied eight normal volunteers aged 1832 yr in a placebo-controlled crossover study. On the 2 study days, subjects received, in random order, ADM in "low" and "high" dose (2.9 pmol/kg x min and 5.8 pmol/kg x min for 2 h each) or vehicle (hemaccel) infusion on day 4 of a metabolic diet (Na+ 80 mmol/day, K+ 100 mmol/day). Achieved plasma ADM levels were in the pathophysiological range, and plasma cAMP values rose 5 pmol/L during the higher dose. Compared with time-matched vehicle infusion, high-dose ADM increased peak heart rate by 10 beats per minute (P < 0.05) and lowered diastolic (by 5 mm Hg, P < 0.01) blood pressure. Cardiac output increased in both phases of ADM (low dose, 7.6 L/min; high dose, 10.2 L/min; vehicle, 6 L/min; P < 0.05 for both). Despite a 2-fold rise in PRA during high-dose ADM (P < 0.01), aldosterone levels were unaltered. Norepinephrine levels increased by 50% during high-dose ADM (P < 0.001), but epinephrine levels were unchanged. Plasma PRL levels increased during high-dose ADM (P = 0.014). ADM had no significant effect on urine volume and sodium excretion. Infusion of ADM to achieve pathophysiological plasma levels produced significant hemodynamic effects, stimulated renin but inhibited the aldosterone response to endogenous angiotensin II, and activated the sympathetic system and PRL without altering urine sodium excretion in normal subjects.