Disease progression and adverse events in patients listed for elective percutaneous coronary intervention.

OBJECTIVE: To record disease progression and the timing of adverse events in patients on a waiting list for elective percutaneous coronary intervention (PCI). DESIGN: Observational prospective study. SETTINGS: A UK tertiary cardiothoracic centre, at a time when waiting lists for PCI were up to 18 months. PATIENTS: 145 patients (116 men, median age 59.5 years) placed on an elective waiting list for PCI between October 1998 and September 1999. MAIN OUTCOME MEASURES: Adverse events recorded were death, myocardial infarction, need for urgent hospital admission because of unstable angina, and need for emergency revascularisation while waiting for PCI. RESULTS: During a median follow up of 10 months (range 1-18 months), nine (6.2%) patients experienced an adverse event. Eight (5.52%) patients were admitted with unstable angina as emergencies. One was admitted with a myocardial infarction. Twenty nine (20.0%) patients had significant disease progression at the time of the repeat angiogram before PCI. In 10 (7%), disease had progressed so that PCI was no longer feasible and patients were referred for coronary artery bypass graft. Sixteen (11%) were removed from the PCI waiting list because of almost complete resolution of their anginal symptoms. CONCLUSION: Adverse coronary events and clinically significant disease progression occur commonly in patients waiting for PCI. Despite the presence of severe coronary lesions, myocardial infarction was rare and no patients died while on the waiting list. Resolution of anginal symptoms was also comparatively common. The pathophysiology of disease progression frequently necessitates a change in the treatment of patients waiting for PCI.

Effectiveness of rotational atherectomy of right coronary artery ostial stenosis.

Balloon angioplasty and stenting of right coronary ostial stenosis may frequently be impeded by lesion calcification, whereas rotational atherectomy, which ablates calcified plaque, should treat these lesions effectively. Accordingly, we evaluated procedural success and longterm clinical outcome of rotational atherectomy of right coronary ostial stenosis. Procedural data were obtained from a comprehensive interventional registry and follow-up information was obtained by chart review and patient enquiry. All patients who developed recurrent angina underwent angiographic restudy. During a 5-year interval, 119 patients underwent rotational atherectomy of right coronary ostial stenosis. Multilesion interventions were performed in 55% of patients. Ostial lesions were 3.73+/-3.69 mm in length (mean +/- SD), and 57.1% were significantly calcified. Reference vessel diameter was 3.42+/-0.56 mm. Maximum burr:artery ratio was 0.64+/-0.1 with adjunct balloon angioplasty in 89.1% and adjunct stenting in 9.2%. Procedural success (<50% residual stenosis without major complication) was 97.5%, with 1.7% uncomplicated failure and 0.8% Q-wave infarction. Maximum residual stenosis was 15+/-17%. During 6-month follow-up, available in 94% of patients, 82.7% remained angina-free, 10.9% developed recurrent angina due to right coronary ostial restenosis, and 6.4% developed recurrent angina due to another lesion. Two years after intervention, target lesion revascularization rate was 16%. Predictors of symptomatic angiographic restenosis were dissection >10 mm, final minimal luminal diameter <2.5 mm, lesion length >10 mm, restenotic lesion, and diabetes. We conclude that rotational atherectomy of right coronary ostial stenosis results in excellent acute procedural success and in low incidence of clinical recurrence, with a high proportion of patients remaining angina-free 2 years after intervention.

Aortocoronary saphenous vein graft disease: pathogenesis, predisposition, and prevention.

Aortocoronary saphenous vein graft disease, with its increasing clinical sequelae, presents an important and unresolved dilemma in cardiological practice. During the 1st month after bypass surgery, vein graft attrition results from thrombotic occlusion, while later the dominant process is atherosclerotic obstruction occurring on a foundation of neointimal hyperplasia. Although the risk factors predisposing to vein graft atherosclerosis are broadly similar to those recognized for native coronary disease, the pathogenic effects of these risk factors are amplified by inherent deficiencies of the vein as a conduit when transposed into the coronary arterial circulation. A multifaceted strategy aimed at prevention of vein graft disease is emerging, elements of which include: continued improvements in surgical technique; more effective antiplatelet drugs; increasingly intensive risk factor modification, in particular early and aggressive lipid-lowering drug therapy; and a number of evolving therapies, such as gene transfer and nitric oxide donor administration, which target vein graft disease at an early and fundamental level. At present, a key measure is to circumvent the problem of vein graft disease by preferential selection of arterial conduits, in particular the internal mammary arteries, for coronary bypass surgery whenever possible.

Implementation of ISO 9000 in the healthcare sector: a case study.

In order to compete at the international level, companies are beginning to recognize ISO 9000 registration as a virtual necessity. As a result, the number of ISO certifications issued in the U.S. and Canada tripled between 1992 and 1994. By means of a case study, this paper describes how a large healthcare manufacturing organization recently achieved its ISO 9001 certification. Specifically, the strategies and the process used by the organization in obtaining the registration is explained.

Natriuretic response to neutral endopeptidase inhibition is blunted by enalapril in healthy men.

We studied six healthy male subjects in a randomized, placebo-controlled, single-blind fashion to determine the comparative effects on renal hemodynamics and natriuresis of the angiotensin-converting enzyme inhibitor enalapril (5 mg on each of 5 days preceding the study), the neutral endopeptidase inhibitor candoxatrilat (200 mg IV), and the combination of enalapril and candoxatrilat. Enalapril pretreatment alone, compared with placebo, produced slight nonsignificant increments in absolute and fractional sodium excretions and a marked increase in effective renal plasma flow but no change in glomerular filtration rate. Candoxatrilat alone produced marked augmentation of both absolute and fractional sodium excretions. The candoxatrilat-mediated increment in absolute sodium excretion was significantly correlated with increases in urinary cGMP and plasma atrial natriuretic peptide in response to this drug, but neither effective renal plasma flow nor glomerular filtration rate was altered compared with placebo. Combining enalapril pretreatment with candoxatrilat significantly attenuated the increments in absolute and fractional sodium excretions in response to the neutral endopeptidase inhibitor. Blood pressure was reduced by enalapril alone compared with placebo, whereas candoxatrilat treatment alone led to a marginal but significant enhancement of blood pressure. The combination of enalapril and candoxatrilat abolished any significant blood pressure change compared with placebo. Thus, candoxatrilat-mediated natriuresis occurs via a renal tubular rather than glomerular mechanism and is blunted by enalapril. This attenuation by enalapril may occur by interference with angiotensin II-dependent effects on the renal tubule or on systemic blood pressure.

The need for implementing TQM in the health care industry: an empirical investigation.

The U.S. health care industry is facing an era of increased competition, declining profits, decreed hospital utilization, and consolidation. By reviewing existing literature on the application of total quality management in the health care industry, and by surveying a hospital in which this technique has been recently applied, this paper shows that service providing organization can indeed use the same methods used by manufacturing organizations to increase quality.

Determinants of the initial effects of captopril on blood pressure, glomerular filtration rate, and natriuresis in mild-to-moderate chronic congestive heart failure secondary to coronary artery disease.

Whereas angiotensin-converting enzyme inhibitors are now indicated for all grades of chronic heart failure, the 2 adverse effects that limit use of these drugs are systemic hypotension and renal dysfunction. The recognized clinical correlates such as hyponatremia and high diuretic dose, which predict occurrence of these adverse effects in severe chronic congestive heart failure (CHF), are rarely evident in patients with mild-to-moderate CHF. Accordingly, we studied 36 patients with stable, moderate CHF in a double-blind, placebo-controlled, crossover fashion to evaluate by multiple discriminate regression analysis the pathophysiologic determinants of changes in blood pressure, glomerular filtration rate, and urinary sodium excretion after initial converting enzyme inhibition with captopril 25 mg. A captopril-mediated decrease in mean arterial pressure was predicted by 3 factors (r2 = 0.74): the decrease in serum angiotensin II (F ratio = 10.3, p < 0.01), the decrease in plasma norepinephrine (F = 8, p = 0.02), and, inversely by pretreatment mean arterial pressure (F = 5.6, p = 0.04), patients with higher initial values exhibiting greater decreases in response to captopril. A captopril-mediated decline in glomerular filtration rate, determined by radioisotope elimination, was also predicted by 3 factors (r2 = 0.67): a decrease in renal plasma flow (F = 48.6, p < 0.01), low pretreatment glomerular filtration rate (F = 11.1, p < 0.01), and low absolute post-treatment serum angiotensin II (F = 5, p = 0.04).(ABSTRACT TRUNCATED AT 250 WORDS)

Interactive effects of indomethacin, angiotensin II and frusemide on renal haemodynamics and natriuresis in man.

The responses of renal haemodynamic and natriuretic indices to the oral prostaglandin synthetase inhibitor indomethacin (200 mg), to infused angiotensin II (1 ng min-1 kg-1) and to the combination of the two were studies in placebo-controlled fashion in eight normal male subjects both prior to and following administration of intravenous frusemide (20 mg). As compared with placebo, angiotensin II infusion alone caused significant reductions in absolute rate of sodium excretion, fractional sodium excretion, urine flow rate and effective renal plasma flow (all P < 0.001 vs placebo) but had no effect on glomerular filtration rate. The only change observed in these parameters with indomethacin alone was a small but significant reduction in urine flow rate (P < 0.005 vs placebo). As compared with the effects of angiotensin II alone, indomethacin pre-treatment followed by angiotensin II infusion led to much greater falls in absolute rate of sodium excretion, fractional sodium excretion, urine flow rate and effective renal plasma flow (all P < 0.0001 vs placebo) associated with a significant reduction in glomerular filtration rate (P < 0.0001) not observed with angiotensin II alone. Frusemide administration at the midpoint of each study limb resulted in each case in a prompt 15 to 20 fold increase in natriuresis. The renal haemodynamic and natriuretic effects of angiotensin II, indomethacin and their combination were not qualitatively different from those observed in the pre-frusemide phase. Our findings provide a clear demonstration in man of the important homeostatic role of renal prostaglandins in preserving renal function, particularly glomerular filtration, under conditions of elevated circulating angiotensin II.

Comparison of two methods of determining renal perfusion with and without captopril pretreatment in groups of patients with left ventricular dysfunction.

Methods of effective renal plasma flow measurement by 125I-orthoiodohippurate elimination and para-aminohippurate clearance were compared with and without captopril pretreatment in 10 chronic heart failure patients and in 20 patients after transmural myocardial infarction. In the chronic heart failure group measurements of effective renal plasma flow by the two techniques were strongly correlated (r = 0.92, P < 0.00001), as was the captopril-mediated change in effective renal plasma flow by the two methods (r = 0.85, P = 0.002). However, in absolute terms para-aminohippurate clearance significantly exceeded 125I-orthoiodohippurate clearance by a mean (+/- SD) of 24.8 +/- 43.7 ml.min-1 (P < 0.05) so that only using the former technique was a significant increment in renal perfusion observed in response to converting enzyme inhibition. In the post-myocardial infarction group, correlations between the two methods were variable and much poorer than in the chronic heart failure group (r = 0.54, P = 0.01 and r = 0.74, P = 0.002 on consecutive days). Furthermore, captopril-mediated increments in effective renal plasma flow by the two techniques were unrelated (r = -0.19, P = 0.59). In this group 125I-orthoiodohippurate elimination significantly exceeded para-aminohippurate clearance (P < 0.05). This reversed association and the weaker relationships between methods in post-infarction as compared to chronic heart failure patients may be related to interference by thrombolytic or aspirin treatments.

Dose-ranging effects of candoxatril on elimination of exogenous atrial natriuretic peptide in chronic heart failure.

Seven patients with chronic heart failure were treated in single-blind crossover fashion with placebo and 10 mg, 50 mg, and 200 mg doses of the neutral endopeptidase inhibitor candoxatril to determine the effects of candoxatril on the elimination kinetics of exogenously infused atrial natriuretic peptide (ANP). An incremental dose-response effect was observed on the mean maximum observed plasma concentration (Cmax) of the active metabolite candoxatrilat (107.4, 453.5, and 1584 ng/ml in response to 10, 50, and 200 mg candoxatril, respectively). Pooled active versus placebo comparisons showed that candoxatril reduced the clearance (p = 0.021) and elimination rate constant (p = 0.006) and increased Cmax (p = 0.002) and time to reach Cmax (p = 0.01) of exogenous ANP. Individually, both 50 mg and 200 mg but not 10 mg candoxatril significantly altered the elimination kinetics of ANP. The most favorable effects were observed in response to 200 mg candoxatril, although even this dose may not have achieved the maximal modulating effect on elimination of circulating ANP.

Circulating angiotensin II and renal sodium handling in man: a dose-response study.

1. Animal studies have shown that angiotensin II has a biphasic effect on urinary sodium excretion. To examine whether this is also true in man, we studied seven salt-replete male subjects in a single-blind placebo-controlled manner. 2. While undergoing maximum diuresis, subjects were infused with 0, 1, 2, 5 or 10 ng of angiotensin II min-1 kg-1 over 80 min. Subjects were studied while seated, and stood every 20 min for urine collection. 3. Angiotensin II produced a dose-dependent antidiuretic effect. The urine flow rate, in ml/min expressed as the change from baseline with increasing dose of angiotensin, was: +3.4 +/- 1.77, -1.26 +/- 0.49 (P < 0.05), -2.75 +/- 1.23 (P < 0.05), -4.21 +/- 0.82 (P < 0.05) and -6.51 +/- 1.07 (P < 0.01). 4. In contrast, the effect of angiotensin II on sodium excretion showed a flat dose-response curve beyond 5 ng min-1 kg-1. The urinary sodium excretion, in mumol/min expressed as the change from baseline with increasing dose of angiotensin, was: 9.5 +/- 21.2, -18.9 +/- 29.6, -37.0 +/- 11.6 (P < 0.05), -67.7 +/- 19.6 (P < 0.01) and -63.8 +/- 14.3 (P < 0.01). 5. The fractional distal reabsorption of sodium, determined by using the lithium clearance technique, showed a rise with all doses of angiotensin II used and reached statistical significance with the top two doses. 6. Unlike antidiuresis, antinatriuresis after graded doses of angiotensin II in human subjects showed a flat dose-response curve beyond 5 ng min-1 kg-1. Pressor doses of angiotensin II also have a significant effect on the distal tubule in promoting sodium reabsorption.

Plasma brain natriuretic peptide as an indicator for angiotensin-converting-enzyme inhibition after myocardial infarction.

Brain natriuretic peptide (BNP) is a cardiac ventricular hormone that may be a sensitive and specific marker of changes in ventricular function. In a prospective, randomised open trial with 16 patients followed for 6 months after first Q wave anterior myocardial infarction we set out to determine: whether BNP concentrations are raised acutely, the effect on circulating BNP of angiotensin-converting enzyme (ACE) inhibition, how BNP and atrial natriuretic peptide (ANP) concentrations compared as correlates of left-ventricular ejection fraction, and whether plasma BNP concentrations could distinguish patients with low (< 40%) and relatively preserved (> 40%) ejection fractions. Plasma concentrations of BNP measured on days 2, 7, 8, 42, and 180 postinfarction were significantly raised in patients compared with normal controls and to a proportionately greater degree than ANP concentrations. Treatment with placebo (n = 8) or oral captopril (n = 8) from day 8 resulted in significantly lower BNP concentrations at days 42 (p = 0.05) and 180 (p < 0.05) in the captopril-treated group. Compared with ANP, BNP concentrations were much more strongly correlated with radionuclide-measured left-ventricular ejection fraction at days 2, 42, and 180. All 8 patients with baseline (day 2) ejection fractions of 40% or above had plasma BNP concentrations less than 10 pmol/L, whereas the 8 patients with ejection fractions less than 40% had BNP concentrations greater than 10 pmol/L. Our findings suggest that measurements of circulating BNP may identify those patients with significant left-ventricular dysfunction who have been highlighted by the Survival and Ventricular Enlargement study as likely to benefit from long-term ACE inhibition after myocardial infarction.

Effectiveness of captopril in reversing renal vasoconstriction after Q-wave acute myocardial infarction.

The purpose of this investigation was to study whether favorable renal effects might contribute to the influence of captopril in offsetting ventricular dilatation after infarction. Effective renal plasma flow and glomerular filtration rate were estimated by isotope injection methods in 20 patients on days 2, 7, 8, 42 and 180 after a first transmural anterior myocardial infarction. After measurements on day 7, patients were randomized to receive either captopril 25 mg 3 times daily (n = 10) or placebo (n = 10) for the remainder of the study. At baseline (day 7) there were no differences between the 2 treatment groups in radionuclide left ventricular ejection fraction, effective renal plasma flow, glomerular filtration rate or neurohormones. Left ventricular ejection fractions (40 +/- 4% [mean +/- 2 SD] at baseline) were higher in the captopril- than the placebo-treated patients on days 42 (p < 0.05) and 180 (p < 0.01) after infarction. Effective renal plasma flow became significantly higher at all time points after randomization in the captopril-treated group than in the placebo group (p < 0.001). A similar but lesser trend was observed for glomerular filtration rate. Plasma atrial natriuretic factor and aldosterone were significantly higher in the placebo group (p < 0.05). Renal hemodynamic indexes were directly correlated with and neurohumoral indexes inversely correlated with ejection fractions. In a second group of 12 patients with higher baseline ejection fractions (48 +/- 4%) after an inferior infarction, none of these beneficial effects of captopril were demonstrable. It is proposed that in the setting of left ventricular dysfunction after infarction, a prompt and sustained improvement in renal hemodynamics, by reducing inappropriate fluid retention and thus ventricular preload, may be one contributory mechanism by which captopril prevents progression of left ventricular dilatation.

Comparison of three methods of glomerular filtration rate measurement with and without captopril pretreatment in groups of patients with left ventricular dysfunction.

Methods of glomerular filtration rate measurement by 51Cr EDTA elimination, inulin clearance and creatinine clearance were compared with and without captopril pretreatment in 10 chronic heart failure patients and in 20 patients after transmural myocardial infarction. Strong intermethod correlations were found in chronic heart failure patients (EDTA: inulin r = 0.87; EDTA: creatinine r = 0.84; inulin: creatinine r = 0.9; all P less than 0.00001). Despite this, substantial absolute differences were observed in results obtained by different techniques. In particular, creatinine clearance significantly overestimated both 51Cr EDTA (18.0 +/- 18.4 ml.min-1, mean difference +/- SD, P less than 0.001) and inulin clearance (26.8 +/- 17.0 ml.min-1, P less than 0.001). The slight reduction in 51Cr EDTA elimination on captopril versus placebo (-8.3 +/- 9.2 ml.min-1, P less than 0.05) was related to a similar treatment difference in inulin clearance (r = 0.67, p = 0.03), but changes observed by either method were unrelated to captopril-induced changes in creatinine clearance. Thus, creatinine clearance is an unsatisfactory means of assessing the effect of angiotensin converting enzyme inhibition on glomerular filtration rate in chronic heart failure. In the post-myocardial infarction group, correlations between methods were poorer (EDTA: inulin r = 0.79; EDTA: creatinine r = 0.76; inulin: creatinine r = 0.67). In this group no significant effect of captopril on glomerular filtration rate was detected by any technique. As compared to the chronic heart failure patients, the weaker relationship between techniques post-myocardial infarction may be related to interference by thrombolytic or aspirin treatment.

Effect of angiotensin-converting enzyme inhibition on plasma brain natriuretic peptide levels in patients with heart failure.

1. The aim of this study was to examine the effect of captopril, an angiotensin-converting enzyme inhibitor, on plasma levels of human brain natriuretic peptide-like immunoreactivity (hBNP-li) in patients with congestive heart failure. 2. Six male patients (aged 52-74 years) with mild to moderate congestive heart failure were studied on two occasions in the semi-recumbent position. After a 30 min rest, patients were randomized to receive oral tablets of either captopril (6.25 mg followed by 25 mg 2 h later) or placebo in a single-blind manner. Plasma hBNP-li, atrial natriuretic peptide-like immunoreactivity (ANP-li) and angiotensin II-like immunoreactivity (ANG II-li) levels and blood pressure were measured. 3. Baseline plasma hBNP-li and ANP-li levels in these patients with mild to moderate congestive heart failure were 13.5 +/- 3.2 pmol/l and 50.9 +/- 11.8 pmol/l, respectively. In 11 healthy male subjects aged 20-23 years, the peripheral plasma hBNP-li and ANP-li levels were 1.3 +/- 0.2 pmol/l and 5.6 +/- 1.7 pmol/l, respectively. In all patients, captopril decreased the plasma ANG II-li level (from 24.3 +/- 8.1 to 6.6 +/- 3.2 pmol/l, P < 0.05) and mean arterial blood pressure (from 92 +/- 3 to 80 +/- 3 mmHg, P < 0.05). Compared with placebo, captopril treatment was associated with significant reductions in plasma hBNP-li (from 14.3 +/- 3.0 to 12.8 +/- 2.1 pmol/l, P < 0.05) and in plasma ANP-li (from 53.9 +/- 1.11 to 36.8 +/- 7.6 pmol/l, P < 0.05) levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Furosemide-induced natriuresis is augmented by ultra-low-dose captopril but not by standard doses of captopril in chronic heart failure.

BACKGROUND: Ten chronic heart failure patients were studied on three occasions in randomized double-blind fashion to compare the acute hemodynamic, neurohormonal, and renal sodium-handling responses to 1 mg captopril versus 25 mg captopril, both in the absence of loop diuretic therapy and during furosemide-stimulated natriuresis. METHODS AND RESULTS: Compared with placebo, 1 mg captopril caused nonsignificant decreases in mean arterial pressure and circulating angiotensin II level and had no effect on glomerular filtration rate as determined by 51Cr-EDTA elimination. Captopril (25 mg) produced marked suppression of serum angiotensin II with or without oral furosemide (both p less than 0.002), a marked decrease in mean arterial pressure (p less than 0.001) that was accentuated by furosemide (p less than 0.00001), and a decrease in glomerular filtration rate (p = 0.0007). No difference from placebo in renal sodium excretion was noted with either 1 or 25 mg captopril in the absence of furosemide. In contrast, while 25 mg captopril caused slight attenuation of the natriuretic response to furosemide, 1 mg captopril significantly enhanced furosemide-induced natriuresis (p less than 0.05). No correlation was found in our patients between the natriuretic effect of furosemide and either absolute mean arterial pressure or change in mean arterial pressure during the furosemide phase of each study session. This suggests that blood pressure is not the important factor mediating the divergent renal responses to furosemide of the two captopril dosage regimens. CONCLUSIONS: We propose that in the face of furosemide-induced postglomerular vasodilatation in chronic heart failure, captopril at a starting dose of 1 mg (but not 25 mg) preserves enough circulating angiotensin II to maintain efferent arteriolar tone and thus glomerular filtration, while offsetting the antinatriuretic renal tubular effects of angiotensin II.

Captopril augments both basal and frusemide-induced natriuresis in normal man by suppression of circulating angiotensin II.

1. We studied the renal effects of reinfusing low dose angiotensin II (1 ng kg-1 min-1) into seven salt-replete healthy volunteers after pretreatment with the angiotensin converting enzyme (ACE) inhibitor captopril (25 mg) to establish whether the natriuretic and renal haemodynamic responses to ACE inhibition in normal man result from suppression of circulating angiotensin II. In the same subjects we also studied the effect of captopril (25 mg) with and without exogenous angiotensin II (1 ng kg-1 min-1) on the natriuretic response to intravenous frusemide (20 mg). 2. In the pre-frusemide study captopril increased absolute and fractional excretion of sodium and paraaminohippurate clearance but had no effect on inulin clearance. 3. Reinfusion of angiotensin II after captopril pretreatment completely suppressed the renal effects of ACE inhibition, yielding renal vasoconstrictor and antinatriuretic effects equivalent to those produced by infused angiotensin II in the absence of captopril. 4. Frusemide increased renal sodium excretion without affecting paraaminohippurate or inulin clearance. Captopril augmented frusemide-induced natriuresis and again this effect was reversed by angiotensin II reinfusion. 5. We conclude that captopril augments both basal and frusemide-induced renal sodium excretion in normal man. Our findings suggest that these renal responses to ACE inhibition may be mediated by inhibition of circulating angiotensin II, specifically its renal tubular salt-retaining actions, rather than via effects on other neurohumoral systems.

Clearance of brain natriuretic peptide in patients with chronic heart failure: indirect evidence for a neutral endopeptidase mechanism but against an atrial natriuretic peptide clearance receptor mechanism.

1. Brain natriuretic peptide is a new natriuretic hormone with striking similarity to atrial natriuretic peptide, but there are no previous data concerning its clearance in man. Two pathways of clearance for atrial natriuretic peptide are recognized: degradation by neutral endopeptidase and binding to atrial natriuretic peptide clearance receptors. We have examined the effect of candoxatril, an inhibitor of neutral endopeptidase (dose range 10-200 mg), and the effect of an infusion of a pharmacological dose [45 micrograms (90 micrograms in two patients)] of synthetic human atrial natriuretic peptide on plasma human brain natriuretic peptide-like immunoreactivity levels in seven patients with mild to moderate chronic heart failure. 2. Plasma human brain natriuretic peptide-like immunoreactivity levels were elevated in all patients (mean +/- SEM 22.0 +/- 6.2 pmol/l) compared with healthy control subjects (1.3 +/- 0.2 pmol/l, n = 11). 3. In all patients, candoxatril increased both plasma atrial natriuretic peptide (P less than 0.05) and plasma human brain natriuretic peptide-like immunoreactivity (P less than 0.05) levels. 4. By contrast, an exogenous infusion of atrial natriuretic peptide had no effect on plasma human brain natriuretic peptide-like immunoreactivity levels despite increasing the plasma atrial natriuretic peptide concentration to 424 +/- 74 pmol/l, which is a level of atrial natriuretic peptide which would have 'swamped' all atrial natriuretic peptide clearance receptors. 5. We have therefore shown that plasma human brain natriuretic peptide-like immunoreactivity levels in chronic heart failure are increased by a neutral endopeptidase inhibitor, but are unchanged by an exogenous infusion of atrial natriuretic peptide.(ABSTRACT TRUNCATED AT 250 WORDS)

Dose-response study of the redistribution of intravascular volume by angiotensin II in man.

1. The response of systemic and regional haemodynamic indices to increasing infusion rates of angiotensin II (1, 3 or 10 ng min-1 kg-1) or placebo [5% (w/v) D-glucose] was studied in eight normal male subjects. 2. As compared with placebo, angiotensin II infusion caused an incremental rise in the serum angiotensin II level [14.5 +/- 7.7 (placebo) to 187.2 +/- 36.1 (10 ng of angiotensin II min-1 kg-1) pmol/l; mean +/- 95% confidence interval] associated with a stepwise increase in total peripheral resistance [880 +/- 42 (placebo) to 1284 +/- 58 (10 ng of angiotensin II min-1 kg-1) dyn s cm-5] and a progressive reduction in cardiac output [8.3 +/- 0.4 (placebo) to 7.0 +/- 0.4 (10 ng of angiotensin II min-1 kg-1) litres/min]. 3. A stepwise fall in renal blood flow was observed with increasing angiotensin II infusion rate [1302 +/- 65 (placebo) to 913 +/- 64 (10 ng of angiotensin II min-1 kg-1) ml/min]. In contrast, calf blood flow was unaffected by 1 ng or 3 ng of angiotensin II min-1 kg-1 and was significantly increased by 10 ng of angiotensin II min-1 kg-1 (P less than 0.01). 4. Calf venous capacitance was uninfluenced by 1 ng of angiotensin II min-1 kg-1, but was significantly increased by both 3 ng (P less than 0.005) and 10 ng (P less than 0.001) of angiotensin II min-1 kg-1.(ABSTRACT TRUNCATED AT 250 WORDS)