Algorithm to detect left ventricular dysfunction after myocardial infarction. Low specificity of algorithm would lead to extensive overtreatment.
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Algorithms↗
Biomedical subjects
A D Struthers
Publications and source records attributed to A D Struthers.
C-type natriuretic peptide.
C-type natriuretic peptide is a 22-amino acid peptide that was initially identified in the central nervous system. The distribution of C-type natriuretic peptide, which has structural homology with atrial and brain natriuretic peptides, is wide and includes the endothelium, myocardium, gastrointestinal, and genitourinary tracts. The biological effects of this peptide are being elucidated in a number of sites in a number of species; however, the novel endothelial site of production of C-type natriuretic peptide and the proximal situation of its receptor in vascular smooth muscle suggest that this vascular natriuretic peptide system may play a role in concert with other local systems in the control of vascular tone.
Animals↗
Aldosterone escape during angiotensin-converting enzyme inhibitor therapy in chronic heart failure.
In chronic heart failure, angiotensin-converting enzyme inhibitors produce an acute decrease in aldosterone levels. Long-term angiotensin-converting enzyme inhibition is, however, associated with aldosterone suppression that is weak, variable, and unsustained (ie, aldosterone escapes). The possible harmful effects of this residual aldosterone are multiple Magnesium loss caused by aldosterone and by diuretics could contribute to coronary artery spasm and arrhythmias. Aldosterone blocks norepinephrine uptake by the myocardium; extracellular catecholamines may, therefore, lead to arrhythmias and ischemia. Aldosterone has been shown to have an acute arrhythmogenic effect as well as a detrimental effect on parasympathetic and baroreflex function. Both angiotensin II and aldosterone stimulate myocardial fibrosis, which may lead to a higher incidence of malignant ventricular arrhythmias. Spironolactone therapy added to the regimen of an angiotensin-converting enzyme inhibitor and diuretic has been shown to cause natriuresis, magnesium retention, increased myocardial norepinephrine uptake, and reduced incidence of ventricular arrhythmias. It may well be that residual aldosterone mediates many harmful effects in chronic heart failure and that to optimize the benefit of blocking the renin-angiotensin-aldosterone system may require specific blockade of residual aldosterone as well as traditional angiotensin-converting enzyme inhibition.
Aldosterone↗
Arginine, lysine and ornithine as vasodilators in the forearm of man.
Nitric oxide is an endogenous vasodilator produced from L-arginine and oxygen by stereospecific enzymes. L-arginine itself can act as a vasodilator when administered at high doses to humans. This effect has been attributed by some to provision of extra substrate for production of nitric oxide. This work compares L-arginine-induced vasodilation with that caused by D-arginine, hyperosmolar sodium chloride and by other cationic amino acids in the resting forearm vasculature of normal subjects. By these means we identify whether L-arginine-induced vasodilation has a component related to stereospecific provision of substrate for nitric oxide production, or whether it can be accounted for by other phenomena. Effects of hyperosmolar sodium chloride and both L and D isomers of arginine, lysine and ornithine on forearm blood flow in eight normal male subjects were compared by bilateral forearm venous occlusion plethysmography. Vasodilator responses to saline and each amino acid were compared as the area under dose-response curves with single-factor analysis of variance (ANOVA). The magnitude of vasodilation obtained with the D isomers of each amino acid was compared with the L counterpart by application of single-factor ANOVA to the appropriate areas under dose-response curves. All three cationic amino acids increased forearm blood flow. Part of the increase could be related to the high osmolality of infusates-comparison with equiosmolar sodium chloride solutions shows that ornithine does not differ significantly as a vasodilator (P > 0.4), but that arginine and lysine have greater vasodilator effects than can be accounted for by osmolality alone (P < 0.001). The D isomers of arginine and lysine were more potent dilators than their L counterparts (arginine P < 0.03, lysine P < 0.02). The vasodilator effects of arginine in the forearm vascular bed at rest are not stereospecific, they are common to other cationic amino acids, greater for D isomers and occur only when normal plasma concentrations are raised far above the physiological range. These features suggest that the vasodilator effect of arginine is in part physical and related to the presence of the molecule in the vessel lumen. They do not suggest that increased provision of substrate, with a consequence of increased nitric oxide production, is the principal basis of L-arginine-induced vasodilation in normal humans.
Adolescent↗
Diastolic dysfunction and ANP/BNP levels.
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Atrial Natriuretic Factor↗
Identification, diagnosis and treatment of heart failure: could we do better?
Numerous studies have shown that it is very difficult to diagnose mild heart failure accurately on clinical grounds alone. Routine echocardiography would help to solve this problem but studies have shown that this technique is greatly underused. Providing open access echocardiography, and/or targeting this resource to the most deserving cases by measuring plasma natriuretic peptides may help to optimize the use of this technique while improving the diagnosis of heart failure patients. Studies have also demonstrated the value, but apparent underuse, of angiotensin-converting enzyme (ACE) inhibitor therapy. Further questions for the management of heart failure patients have been presented by these investigations. Uncertainty remains over the appropriate timing of ACE inhibitor therapy and whether low or high doses are more effective. The ongoing ATLAS study aims to answer these questions and promotes an improvement in the treatment of heart failure patients.
Angiotensin-Converting Enzyme Inhibitors↗
The impact of angiotensin converting enzyme inhibitors on the arterial wall.
There is recent interest in the possibility that angiotensin converting enzyme inhibitors (ACE inhibitors) may reduce the damage inflicted on the arterial wall by common cardiovascular risk factors such as hypertension, hyperlipidaemia and ageing. The efficacy of these drugs in blood pressure reduction is accepted, but whether there is an excess benefit on arterial structure and function, conferred by use of ACE inhibitors over more traditional antihypertensives, is still under debate. There is also evidence in animal models to suggest that ACE inhibition is effective in reduction of arterial damage due to experimental hyperlipidaemia. ACE inhibitors not only reduce the conversion of angiotensin I and angiotensin II, which can interact with the sympathetic nervous system, but also prevent the degradation of bradykinin. This means that ACE inhibitors have several potential mechanisms through which they could suppress intimal hypertrophy and prevent endothelial dysfunction, which is believed to precede arteriosclerosis in man. Although much further work is needed to clarify the mechanism underlying the beneficial effects on the arterial wall of this group of drugs, they do appear to have significant potential in the effort to reduce cardiovascular mortality and morbidity, especially in high risk groups.
Angiotensin II↗
Hormonal and renal differences between low dose and high dose angiotensin converting enzyme inhibitor treatment in patients with chronic heart failure.
OBJECTIVE: To assess the differential effects of low dose (5 mg) and high dose (20 mg) lisinopril treatment on cardiovascular hormones, renal function, and blood pressure over 24 hours in patients with heart failure. DESIGN: Double-blind crossover study. SETTING: Department of Clinical Pharmacology, Ninewells Hospital and Medical School, Dundee. PATIENTS: 19 patients with chronic heart failure and left ventricular ejection fraction < or = 45%. RESULTS: Plasma concentrations of aldosterone and endothelin were lower on the 20 mg dose (plasma aldosterone mean at peak drug effect: 90.7 v 152.0 pg/ml, P < 0.001; mean at trough effect: 124.7 v 174.4 pg/ml, P < 0.01; plasma endothelin at trough effect 4.70 v 6.04 pmol/l, P = 0.03). Creatinine clearance was lower on 20 mg lisinopril (68.7 v 82.1 ml/min, P < 0.05). The area under the curve for diastolic blood pressure over 24 hours was significantly lower on 20 mg (mean difference 3.0 mm Hg, P = 0.04); for systolic blood pressure there was a similar trend (mean difference 5.7 mmHg, P = 0.05). Plasma concentrations of atrial natriuretic peptide (ANP) and B-type natriuretic peptide were similar for both doses; urinary excretion of ANP was lower on 20 mg (12.2 v 13.6 pmol, P < 0.05). CONCLUSIONS: These results indicate that within the usual therapeutic range, high doses of lisinopril cause greater suppression of selected cardiovascular hormones than low doses in heart failure, but are associated with lower creatinine clearance in some patients.
Aldosterone↗
Changing echocardiography request patterns between 1988 and 1993.
There is little published data on the demand for echocardiography services in the U.K. This retrospective survey of echocardiography request forms and reports was performed to assess potential changes in echocardiography request patterns between 1988 and 1993. These years were chosen as they were likely to reflect changes in clinical practice as a result of trials involving Angiotensin Converting Enzyme (ACE) inhibitors. A total of 400 consecutive request forms and reports were analysed. There was a 2.46 fold increase in the total number of echocardiograms performed between 1988 and 1993 with a disproportionate 12.5 fold increase in the relative number of requests for assessments of left ventricular function. This large increase is likely to be a result of recent major clinical trials which show morbidity and mortality benefits when patients with left ventricular systolic dysfunction (including those who are asymptomatic) are treated with ACE inhibitors. Future planning of the echocardiographic services should include provision for the increasing numbers of patients requiring assessment of left ventricular function.
Echocardiography↗
Effects of adding spironolactone to an angiotensin-converting enzyme inhibitor in chronic congestive heart failure secondary to coronary artery disease.
In chronic heart failure, a diuretic plus an angiotensin-converting enzyme (ACE) inhibitor only partially suppresses aldosterone despite the fact that aldosterone has many harmful effects independent of angiotensin II. These possible harmful effects of aldosterone are magnesium loss, increased cardiac sympathetic activity, and increased ventricular arrhythmias. We have therefore assessed whether adding the aldosterone antagonist, spironolactone, to a loop diuretic and ACE inhibitor reverses any of these potentially harmful effects of residual aldosterone. In a preliminary animal study, we found that exogenous aldosterone reduced myocardial norepinephrine uptake by 24% in anesthetized rats in vivo. In our main study, 42 patients with New York Heart Association II to III congestive heart failure were randomized to spironolactone (50 to 100 mg/day, titrated to blood pressure and plasma potassium) or placebo in a double-blind fashion. Our principal finding is that cardiac norepinephrine uptake as assessed by 123I-metaiodobenzylguanidine scintigraphy increased with spironolactone (p < 0.01). Spironolactone also elevated plasma magnesium (p < 0.05), reduced urinary magnesium excretion (p < 0.05), and caused a reduction in ventricular arrhythmias on 24-hour ambulatory electrocardiography (p < 0.05). Spironolactone increased plasma renin activity, plasma aldosterone (p < 0.01), 24-hour urinary sodium excretion (p < 0.05), and urinary sodium/potassium ratio (p < 0.01). Echocardiographic-determined measurements of left ventricular systolic and diastolic function were unaltered by spironolactone.(ABSTRACT TRUNCATED AT 250 WORDS)
Aged↗
Predicting ejection fraction after myocardial infarction.
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Humans↗
The L-arginine:nitric oxide pathway is the major source of plasma nitrite in fasted humans.
15N guanidino-labelled L-arginine was infused into fasted human volunteers giving, at equilibrium, a stable 1:10 ratio of 15N to 14N arginine in the plasma. Separate GC-MS assays were used to compare the degree of enrichment of plasma arginine, nitrite and nitrate and thus define the quantitative relationship between the L-arginine:nitric oxide (NO) pathway and the formation of these oxides of nitrogen. 15N nitrite enrichments rose to 8.3% (SD 0.5), five hours after the start of the infusion. In contrast, 15N nitrate enrichments apparently rose to only 1.6% (SD 0.4) at this time. This discrepancy could be explained by our finding that the commonly used Tesch GC-MS nitrate assay is subject to considerable interference from non-nitrate sources in plasma. Taking this into account, nitrate enrichments were similar to those observed for plasma nitrite. These results therefore indicate that the measurement of these compounds in plasma is a valid indicator of NO generation in fasted humans.
Adult↗
N-terminal proatrial natriuretic peptide and brain natriuretic peptide are stable for up to 6 hours in whole blood in vitro.
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Atrial Natriuretic Factor↗
Effects of lisinopril on congestive heart failure in normotensive patients with diastolic dysfunction but intact systolic function.
This study examined the effects of lisinopril on diastolic function in 12 normotensive patients (mean age 72 years) with symptomatic congestive heart failure, intact left ventricular systolic function and abnormal diastolic function secondary to ischaemic heart disease in a placebo-controlled double blind crossover study, with each treatment dosed orally for 5 continuous weeks. Compared to placebo, lisinopril significantly decreased blood pressure, increased plasma renin activity without altering heart rate or plasma norepinephrine. There was no statistically significant improvement with lisinopril in radionuclide derived peak filling rate and time to peak filling rate, in Doppler echocardiographic measurements of the ratio of peak flow velocity in early diastole to the peak flow velocity of atrial contraction (E:A ratio) and in visual analogue scales of symptoms. Thus, although angiotension converting enzyme inhibitors may have an established role in the treatment of heart failure secondary to left ventricular systolic dysfunction, its use in patients with isolated diastolic dysfunction remains unclear.
Aged↗
Raised plasma levels of atrial natriuretic factor in cardiac allograft recipients: evidence of increased cardiac secretion and decreased renal clearance.
The mechanism(s) causing high levels of plasma atrial natriuretic factor (ANF) in cardiac allograft recipients is(are) unclear. The kidney is important for the clearance of ANF and renal function may decline with cyclosporin A therapy in these patients. The relationship between plasma ANF level and renal function and also the pharmacokinetics of a continuous infusion of ANF (15.5 ng.kg-1.min-1 for 60 min) was examined in 6 cardiac allograft recipients on cyclosporin A therapy. Resting plasma ANF levels were significantly higher in these patients than in 8 healthy subjects (71 vs. 21 ng.l-1). Both effective renal plasma flow (ERPF) and glomerular filtration rate (GFR) were significantly lower in these patients than in healthy subjects (215 vs. 617 ml.min-1 and 55 vs. 102 ml.min-1 respectively). There was a significant inverse correlation between plasma ANF and ERPF (r = -0.86) and between plasma ANF and GFR (r = -0.81). During the period of ANF infusion, steady state plasma ANF levels were significantly higher in cardiac allograft recipients. Total body clearance of ANF was marginally lower in these patients than in healthy subjects (60 vs. 10.0 l.min-1) although this difference did not reach statistical significance. Derived endogenous secretion rate of ANF was threefold higher in patients when compared to healthy subjects (633 vs. 208 ng.min-1). We have therefore shown that cardiac allograft recipients on cyclosporin A have elevated plasma ANF levels and also decreased renal function. Pharmacokinetic analysis have shown that this increase in plasma ANF levels is due more to increased ANF secretion than to decreased ANF clearance in these patients.
Adult↗
Raised plasma concentrations of brain natriuretic peptide in pulmonary arterial hypertension.
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Female↗
Comparative effects of atrial natriuretic peptide and brain natriuretic peptide on the aldosterone and pressor responses to angiotensin II in man.
1. Atrial natriuretic peptide and brain natriuretic peptide have similar vasodilator and natriuretic properties, although little information is available regarding their relative effects as antagonists of the renin-angiotensin-aldosterone system. We have therefore compared how atrial natriuretic peptide and brain natriuretic peptide affect the systemic pressor and aldosterone responses to angiotensin II in eight male subjects. 2. Each subject was studied on three separate occasions, when they received a 60-min infusion of placebo, atrial natriuretic peptide (10 pmol min-1 kg-1) or brain natriuretic peptide (10 pmol min-1 kg-1), with a concomitant infusion of angiotensin II (6 ng min-1 kg-1) given for the final 30 min of the infusion period. The change in haemodynamic parameters and plasma aldosterone induced by angiotensin II was measured. Plasma concentrations of atrial natriuretic peptide (182 +/- 23 pmol/l) and brain natriuretic peptide (193 +/- 25 pmol/l) achieved at steady-state during the infusion on each study day were not significantly different. 3. Increases in mean arterial pressure in response to angiotensin II were significantly lowered by concomitant infusion of atrial natriuretic peptide (21.0 +/- 1.7 mmHg) and brain natriuretic peptide (20.1 +/- 1.9 mmHg) compared with placebo (29.0 +/- 4.1 mmHg). There were similar effects on systolic and diastolic blood pressure. Cardiac output was decreased on each study day to the same extent y angiotensin II infusion. Total systemic vascular resistance showed a non-significant trend towards an attenuated response to angiotensin II when atrial natriuretic peptide or brain natriuretic peptide was infused concomitantly in comparison with placebo.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Aldosterone escape during ACE inhibitor therapy in chronic heart failure.
In the setting of chronic heart failure (CHF), therapy with angiotensin converting enzyme (ACE) inhibitors generally reduces serum aldosterone levels acutely. However, long-term ACE inhibition is associated with aldosterone suppression that is weak, variable, and unsustained, i.e. aldosterone 'escape'. Magnesium loss caused by aldosterone and by diuretics can contribute to coronary artery spasm and arrhythmias. Aldosterone can block noradrenaline uptake by the myocardium; extracellular catecholamines may lead to arrhythmias and ischaemia. Aldosterone has been shown to have an acute arrhythmogenic effect as well as a potential detrimental effect on baroreflex function, a marker of prognosis in CHF. Both angiotensin II and aldosterone may stimulate myocardial fibrosis, which is associated with a higher incidence of malignant ventricular arrhythmias. ACE inhibition initiated early in the progression of CHF may prevent development of patchy myocardial fibrosis and its inherent arrhythmias and thus reduce the incidence of sudden death. Spironolactone therapy added to the regimen of an ACE inhibitor and diuretic can induce natriuresis and magnesium retention, increase myocardial noradrenaline uptake, and reduce the incidence of arrhythmias.
Aldosterone↗