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Biomedical subjects

H Ikram

Publications and source records attributed to H Ikram.

At least 73 records · Page 4Linked to original sources
PubMed1991

The early diagnosis of acute myocardial infarction.

Latex agglutination for serum myoglobin (Rapitex) was compared with the initial ECG for the early diagnosis of acute myocardial infarction. Forty patients suspected of myocardial infarction were prospectively evaluated by initial electrocardiogram and Rapitex serum myoglobin. The initial ECG was categorised into one of three groups: Group 1 had ST segment elevation of at least 1 mm in a limb lead or 2 mm in a precordial lead (with or without Q waves); Group 2 had abnormalities other than those seen in Group 1; and Group 3 had no particular abnormalities present that is, a normal ECG. Myocardial infarction was confirmed by a rise in creatine kinase to greater than or equal to twice the upper limit of normal for our laboratory range and with a CKMB fraction of greater than 6%. Nineteen of 40 patients sustained myocardial infarction; nine ECG group 1, six ECG group 2, and four ECG group 3. Eleven of the 19 patients with myocardial infarction had positive serum myoglobin agglutination. The initial ECG was the most predictive of a subsequent rise in CK (p = 0.003), while Rapitex serum myoglobin determination was the least predictive (p = 0.8517). We conclude that the Rapitex serum myoglobin test offers little diagnostic or economic advantage over the initial electrocardiogram.

Biomarkers↗
PubMed1991

EC 24.11 inhibition in man alters clearance of atrial natriuretic peptide.

Metabolic clearance and the biological effects of exogenous human atrial natriuretic factor (ANF) were assessed in two groups each of eight normal volunteers receiving 2-h iv infusions of ANF (2.5 pmol/kg.min) on the fifth day of dosing with the orally active inhibitor of endopeptidase 24.11, candoxatril (25 mg every 12 h in group 1 and 100 mg every 12 h in group 2), and placebo in balanced randomized, double blind, placebo-controlled, cross-over experiments. Although 4 days of pretreatment with the endopeptidase inhibitor did not affect basal plasma ANF, candoxatril enhanced mean ANF-induced increases in plasma ANF by 27 pmol/L (P = NS) and 42 pmol/L (P less than 0.002) in groups 1 and 2, respectively. Calculated MCRs for ANF were significantly reduced by both doses of candoxatril [group 1, 2.5 +/- 0.4 vs. 4.3 +/- 0.6 L/min (P less than 0.01); group 2, 2.3 +/- 0.4 vs. 5.6 +/- 0.8 L/min (P less than 0.001)]. ANF significantly enhanced urinary sodium excretion above preinfusion values in both study phases in both groups. Candoxatril significantly further augmented natriuresis in group 2 (P less than 0.01), but not group 1. Inulin clearance was minimally enhanced, and para-aminohippuran clearance was slightly decreased by candoxatril in both groups. Neither effect alone was statistically significant, but derived renal filtration fractions were significantly enhanced in both groups [group 1, 15.5 +/- 0.5% vs. 13.9 +/- 0.6% (P less than 0.01); group 2, 19.3 +/- 1.9% vs. 18.0 +/- 2.7% (P less than 0.01)]. Basal and stimulated cGMP concentrations in both plasma and urine were significantly enhanced by candoxatril in the two groups (P less than 0.001 and P less than 0.01, respectively, for combined data). Urinary ANF immunoreactivity was significantly enhanced by candoxatril in both groups (P less than 0.05 and P less than 0.01 in groups 1 and 2, respectively), with a more pronounced effect evident at the higher dose (P less than 0.01). These results show that chronic pretreatment with an endopeptidase inhibitor in normal man causes a dose-related reduction in the metabolic clearance of exogenous ANF, amplifies cGMP, and increases renal filtration and the natriuretic responses to infused ANF.

Adult↗
PubMed1991

Prolonged inhibition of endopeptidase 24.11 in normal man: renal, endocrine and haemodynamic effects.

The renal, hormonal and haemodynamic effects of chronic (4 days) dosing with an inhibitor of endopeptidase EC 3.4.24.11 (UK 79300) were assessed in two groups, each of eight normal volunteers, receiving 25 mg every 12 h (group 1) or 100 mg every 12 h (group 2) of UK 79300 in double-blind, balanced-randomized, placebo-controlled, crossover studies. Group 2 (but not group 1) exhibited a significant transient natriuresis (P less than 0.01) and a consequent sustained negative cumulative sodium balance (70 +/- 21 mmol) which was established within 48 h and remained for the duration of dosing with UK 79300. Urine and plasma cyclic guanosine monophosphate (cGMP) levels rose significantly above placebo values (P less than 0.01 and P less than 0.001, respectively) in both groups and the effect was sustained throughout the dosing period. Plasma atrial natriuretic factor (ANF) was slightly enhanced by UK 79300 in group 1 (P less than 0.05) but not significantly increased in group 2. Despite a significant increase in heart rate in both groups (P less than 0.001) and of natriuresis in group 2, there was minimal evidence of renin-aldosterone activation in either group. Trends towards lower systolic pressures, observed in both groups, did not attain statistical significance. These findings suggest chronic treatment with UK 79300 induces an increase in tissue ANF levels, with sustained enhancement of plasma and urine concentrations of ANF second messenger (cGMP) and increased heart rate.

Aldosterone↗
PubMed1991

Fourier coefficient description of left ventricular shape.

A method of quantifying the shape of the left ventricle of the heart as seen in 2D echocardiograms was developed. It is based on describing the shape in terms of the coefficients a fifth-order trigonometric Fourier series. Such a series has eleven Fourier coefficients which is too large a number for clinical application so pairs of coefficients are combined to give six coefficients (alpha 0, alpha 1, ... , alpha 5). A trial was conducted to test the ability of the coefficient description to classify subjects as having normal right ventricles or ventricles with an apical abnormality. The tests showed that one of the coefficients (alpha 2) was higher for the subjects with an apical abnormality and that this difference increased with exercise. This is as was expected. However, it was found to be difficult to get a reliable estimate of alpha 2 from a single scan of a patient and that it is therefore probably necessary to average data from several scans to obtain a reliable alpha 2 value for a single patient.

Coronary Angiography↗
PubMed1990

Antianginal, hemodynamic and coronary vascular effects of captopril in stable angina pectoris.

A pilot study was performed to assess the short-term effects of intravenous captopril on anginal threshold and systemic and coronary hemodynamics in patients with stable angina pectoris. Twelve patients with documented coronary artery disease, stable angina pectoris and normal left ventricular function were studied by an incremental atrial pacing stress test before and after intravenous captopril (n = 8) or placebo (n = 4). There were no significant differences in the extent of coronary disease or left ventricular function between the 2 groups and resting plasma-renin levels were normal. Captopril increased the time to angina (14 +/- 4 to 9 +/- 5 minutes, p less than 0.05), increased heart rate at development of angina (126 +/- 7 to 142 +/- 7 beats/min, p less than 0.05) and tended to increase coronary blood flow (229 +/- 154 to 296 +/- 259 ml/min, p = 0.11) and decrease coronary vascular resistance (53 +/- 10 to 47 +/- 3 dynes s cm-5/1,000, p = 0.11) at peak stress without alteration in systemic hemodynamics. No significant changes were seen after placebo administration. Therefore, intravenous captopril appears to cause a short-term increase of coronary vascular reserve, and anginal threshold in patients with chronic stable angina. This effect appears to be independent of inhibition of the systemic renin-angiotensin system or systemic hemodynamic changes.

Angina Pectoris↗
PubMed1990

Twenty-four hour profile of the hypotensive action of felodipine in essential hypertension.

Felodipine, 10 mg twice daily, and placebo were administered for 5 weeks to ten untreated essential hypertensives in a double-blind, random-order, crossover study. At the end of each phase patients were assessed by 36 hours of continuous intraarterial blood pressure recordings, both during normal activities and specified activities. Patients were also assessed by 36-hour Holter analysis, maximal exercise testing, radionuclide cardiac scan, and measurement of endogenous creatinine clearance and 2-hourly vasoactive hormones. Arterial pressure was significantly reduced by felodipine, with mean falls in blood pressure of 25.1 mmHg and 12.5 mmHg (systolic and diastolic, respectively) over 24 hours. Blood pressure was reduced by felodipine during moderate and maximal exercise and mental stress. There were no significant changes in heart rate, exercise capacity, ventricular ectopy, endogenous creatinine clearance, or vasoactive hormones.

Adult↗
PubMed1990

ANP infusion in the treatment of heart failure and comparison with ACE inhibition.

The therapeutic potential of atrial natriuretic peptide (ANP) was assessed in an ovine model of heart failure induced by rapid left ventricular (LV) pacing and compared with the effects of angiotensin converting enzyme (ACE) inhibition. Hemodynamic, hormonal, and metabolic measurements were studied during three 5-day periods of LV pacing. No treatment (control) or a continuous ANP infusion (25 ng/kg/min) was given in random order during the first two periods, while ACE inhibitor was always given during the third period. Baseline measurements immediately prior to the start of each pacing phase showed no significant variation. Significant neurohumoral activation and hemodynamic responses were observed in each pacing phase. During ANP infusion, plasma ANP levels were 3-5-fold higher than those observed in the control or ACE inhibition treatment phases. Compared with control, a natriuresis was observed on the first day, whereas glomerular filtration rate (GFR) tended to be maintained during ANP infusion. The rise in left atrial pressure and plasma aldosterone tended to be blunted. When the two treatment phases were compared, the rise in left atrial pressure during LV pacing was less with ACE inhibition, whereas there was a similar reduction in sodium retention after the initial natriuresis with ANP. By contrast, GFR tended to be maintained better during ANP infusion compared to ACE inhibition. These results suggest that ANP, or a similar "enhancing" analogue, may be useful in the treatment of heart failure, especially if administered early in the development of the disorder.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1990

Renal effects of ACE inhibition in ovine heart failure: a comparison of intermittent and continuous ACE inhibition.

Results of uncontrolled studies suggest that the duration of action of an ACE inhibitor may be an important determinant of renal impairment when using these agents to treat patients with heart failure. To determine whether there is experimental evidence for this hypothesis, we compared the effects of intermittent (captopril, 25 mg i.v. bolus twice daily) and continuous (captopril. 25 mg bolus, then 50 mg/day by constant infusion) ACE inhibition in an ovine model where heart failure was induced by rapid left ventricular pacing (LVP). Six sheep underwent three 4-day periods of LVP with intermittent, continuous, or no treatment (control) given in random order from the onset of LVP. Despite evidence that intermittent captopril administration allowed significant recovery of serum ACE activity (4.6 +/- 1.2 vs. 1.1 +/- 0.5 pmol/L before and after captopril bolus on day 4, p less than 0.001) and restitution of arterial pressure between successive boluses (48 +/- 7 vs. 41 +/- 4 mm Hg, p less than 0.01), there was no difference in the renal effects of intermittent and continuous ACE inhibition (creatinine clearance was 44 +/- 14 and 47 +/- 8 ml/min on day 4 of the intermittent and continuous phase, respectively). Nevertheless, there was a significant correlation between the decline in arterial pressure and fall in creatinine clearance induced by ACE inhibition (r = 0.65, p less than 0.05), with evidence that drug accumulation may potentiate hypotension and renal impairment should arterial pressure be reduced below the threshold for renal autoregulation.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗
PubMed1990

Ambulatory pulmonary arterial pressure in primary pulmonary hypertension: variability, relation to systemic arterial pressure, and plasma catecholamines.

The variability of pulmonary arterial pressure, the relation of pulmonary pressure to systemic pressure, pulmonary pressure responses to stimuli (exercise, hypoxia, smoking, free ambulation), and plasma catecholamine responses were assessed in five patients with primary pulmonary hypertension. Ambulatory monitoring techniques provided data for the computerised analysis of continuous, beat-to-beat, direct recordings of both pulmonary and systemic arterial pressures for 8 to 10 hours. The absolute variability of pulmonary arterial pressure and the magnitude of absolute changes in this variable in response to stimuli were increased in primary pulmonary hypertension. The variability of systemic pressure was similar to that in healthy volunteers. Basal and stimulated plasma catecholamine values were normal, suggesting preservation of normal sympathetic nervous system activity in primary pulmonary hypertension.

Adult↗
PubMed1990

Hemodynamic and hormonal effects of renin inhibition in ovine heart failure.

The effects of renin inhibition have not previously been documented in established heart failure (HF). Accordingly, we investigated the acute hemodynamic and hormonal effects of a renin inhibitor (EMD 52297) in an ovine model of HF induced by rapid ventricular pacing (LVP). In seven sheep, recordings were made for 1 h before, during a 2-h infusion of renin inhibitor (RI) or vehicle, and after each infusion on the 5th and 6th day after commencing LVP. The RI (20 micrograms.kg-1.min-1) or vehicle was given in random order. RI infusion induced a rapid fall in plasma renin activity (PRA) and angiotensin II, reaching a nadir at 20 min. The vasodilator response was characterized by a 16% fall in mean arterial pressure (MAP), which was related to the fall in PRA (r = 0.78, P less than 0.05). MAP and PRA remained suppressed throughout the infusion period, and both returned to preinfusion levels within 10 min of terminating infusions. Left atrial pressure and plasma aldosterone were not significantly altered, while renal function was preserved despite the fall in perfusion pressure. RI has significant hemodynamic actions in a model of established HF.

Animals↗
PubMed1990

Inhibition of endopeptidase EC 24.11 in humans. Renal and endocrine effects.

The effects of an orally active inhibitor (UK 79300) of the neutral metalloendopeptidase EC 3.4.24.11 were investigated in six healthy male volunteers maintained on a constant diet (150 mmol sodium/day and 80 mmol potassium/day). Subjects were studied in a random order, single-blind study on two occasions, each 48 hours in length, when they were given UK 79300 (25 or 50 mg p.o.) or placebo at 12-hour intervals (each agent for 24 hours). The endopeptidase inhibitor enhanced plasma concentrations of atrial natriuretic factor in association with suppression of both plasma renin activity and aldosterone concentrations. Twenty-four-hour urinary excretion of sodium was doubled by UK 79300, and the urinary excretion rates of phosphorus, atrial natriuretic factor immunoreactivity, and cyclic guanosine monophosphate were also significantly enhanced, whereas urinary aldosterone excretion was halved. The profile of biological effects closely paralleled those previously reported with low dose infusions of atrial natriuretic factor in humans and animals. Therapeutic trials of such inhibitors are now indicated for hypertension or heart failure together with further studies to clarify the underlying mechanisms of action.

Adult↗
PubMed1990

Brain natriuretic peptide administered to man: actions and metabolism.

To investigate the effects and metabolism of brain natriuretic peptide (BNP) in man, eight normal subjects received 3-h infusions of synthetic porcine BNP (2 pmol/kg.min) in a placebo-controlled study. The MCR and plasma half-life of BNP were 2.69 L/min and 3.1 min, respectively. BNP clearly suppressed PRA to less than 50% of placebo values (P less than 0.001). Plasma aldosterone concentrations were also significantly reduced by 30% (P less than 0.05). Urinary sodium excretion tended to rise (P = 0.054), and urinary cGMP excretion was clearly enhanced (P less than 0.01). Systemic and renal hemodynamics, hematocrit, plasma protein concentrations, plasma ACTH, arginine vasopressin, PRL, and catecholamines were unchanged. Porcine BNP has a similar range of effects and is similarly metabolized in man as human ANP. Further elucidation of the possible role of BNP as a circulating hormone in man awaits measurement of tissue and plasma concentrations of human BNP in health and disease and provision of fuller dose-response data for human as well as porcine BNP.

Adult↗
PubMed1990

Relationship between plasma atrial natriuretic peptide concentration and atrial pressure in acute and chronic heart failure.

Several reports have demonstrated a close correlation between plasma atrial natriuretic peptide (ANP) concentration and atrial pressure in stable heart diseases. However, few studies have investigated whether plasma ANP concentration is a noninvasive indicator of hemodynamic parameters during the treatment of heart failure. Thus, we have studied the relationship between peripheral plasma ANP concentration and concurrent hemodynamic variables during the treatment of heart failure, and, in order to determine whether secretion of ANP is stimulated in this disease condition, we compared the plasma ANP concentration in the pulmonary artery with that in the peripheral veins. Studies were performed in each of 9 patients with acute heart failure due to myocardial infarction (Group A) or chronic heart failure (Group B), who were matched as closely as possible for treatment, age, sex and cardiac output. In group A, no significant correlation was found between plasma ANP levels and any measured hemodynamic variables. In group B, peripheral plasma ANP concentrations were significantly correlated with left atrial pressure (r = 0.82, p less than 0.01), but not with right atrial pressure (r = 0.56, p greater than 0.05). Furthermore, in group B ANP levels in pulmonary arterial plasma were consistently higher than those in peripheral venous plasma, whereas in group A the opposite was observed in expired cases. These results suggest that measurement of peripheral plasma ANP is a useful noninvasive method for estimating left atrial pressure during the treatment of chronic heart failure. However, plasma ANP concentration may not be a valid means of estimating hemodynamic parameters in acute heart failure due to myocardial infarction. In such cases, the increased secretion of ANP was not obvious, and there may be other factors, in addition to atrial pressure, that regulate cardiac secretion of ANP.

Aged↗
PubMed1989

Competitive peptide antagonists of ANF-induced cyclic guanosine monophosphate production.

Atrial natriuretic factor (isoleucine ANF 101-126), cleaved ANF (isoleucine ANF 101-105/106-126) and des (Gln 18, Ser 19, Gly 20, Leu 21, Gly 22) ANF 4-23-NH2 (C-ANF 4-23) stimulated cyclic guanosine monophosphate production (cGMP) by rat aortic vascular smooth muscle cells (VSMC) in culture. Cleaved ANF and ANF C4-23 also antagonised or diminished the response to ANF 101-126. Agonist and antagonist actions of both peptides were dose-related. In contrast, prepro ANF (104-123), an ANF precursor fragment, exhibited no agonist or antagonist effect on cGMP production.

Animals↗