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H J Dargie

Publications and source records attributed to H J Dargie.

At least 19 recordsLinked to original sources
PubMed1992

Pulmonary extraction and left atrial secretion of atrial natriuretic factor during cardiopulmonary bypass surgery.

We have investigated the role of the lungs in the extraction of atrial natriuretic factor (ANF) by measuring plasma levels in samples taken from the central circulation in 12 patients (mean age 59 years; range 43 to 68) undergoing cardiac surgery. We also investigated the effects of cardiopulmonary bypass on ANF levels. ANF levels (mean +/- SD) were lower in pulmonary venous samples (41 +/- 20 pg/ml) than in pulmonary arterial samples (54 +/- 18 pg/ml; p less than 0.001), demonstrating 24% extraction of ANF by the lungs. Both left atrial (47 +/- 23 pg/ml) and systemic arterial levels (52 +/- 22 pg/ml) were higher than pulmonary venous levels (both p less than 0.05), indicating secretion of ANF into the left side of the heart. During cardiopulmonary bypass, plasma ANF concentration fell from 68 +/- 23 pg/ml before aortic cross-clamping to 35 +/- 13 pg/ml 10 minutes after and 28 +/- 9 40 minutes after the application of clamps (both p less than 0.001). A rebound rise to 122 +/- 33 pg/ml followed the release of the clamp (p less than 0.001). This study demonstrates that ANF is extracted by the lungs and secreted directly into the left side of the heart. The considerable fall in plasma levels that was observed during aortic cross-clamping might contribute to the neurohumoral activation and increased peripheral resistance observed after prolonged cardiopulmonary bypass and to the risk of renal ischemic injury.

Atrial Function, Left↗
PubMed1992

Late results following coronary artery bypass grafting.

Coronary bypass surgery is well into its third decade. The randomized trials of saphenous vein grafting together with the various registries[57-60] have provided us with a wealth of information not only on the effects of surgery but also on the natural history of coronary heart disease itself. Numerous improvements have been introduced, the most notable being the use of the IMA as an arterial conduit. Thus the results of the randomized trials which significantly influence our clinical decisions may not accurately reflect what modern surgery can now offer, especially to the type of patient being operated upon in the 1970s. Nevertheless the decision about whom to operate on probably will not change, at least in terms of clinical variables affected by the coronary anatomy and left ventricular function. But there is every expectation that the long-term clinical results of surgery will be better since graft patency has already been shown to have improved as a result of anti-platelet therapy and, most of all, by the IMA. We will never have a randomized trial to prove this, but experience to date justifies this conclusion. The other great change that has occurred during the last decade is angioplasty and hopefully the randomized trials will put this technique in perspective. But practice has already changed and surgery for single vessel disease is now much less commonly performed given the greater appreciation of the good prognosis with which this lesion is associated and the ease with which angioplasty can alleviate the symptoms it causes.(ABSTRACT TRUNCATED AT 250 WORDS)

Aerospace Medicine↗
PubMed1992

The use of an exponential protocol for bicycle and treadmill exercise testing in patients with chronic cardiac failure.

We have studied a standardized exercise protocol suitable for use with a treadmill or bicycle (STEEP protocol) and compared it with a modified Bruce treadmill protocol in a group of patients with chronic cardiac failure. The STEEP protocol has been previously validated in normal subjects. Exercise time (6.79 +/- 2.42 vs 5.34 +/- 1.95 min, P < 0.05) and peak VO2 (16.66 +/- 4.09 vs 15.01 +/- 3.72 ml.min-1.kg-1, P < 0.05) were greater with the STEEP treadmill compared with the bicycle protocol, but VO2 was very similar at equal exercise stages in both modalities. Heart rate and respiratory exchange ratio tended to be greater during bicycle exercise at equal stages. Exercise time was greater with the modified Bruce protocol (9.00 +/- 3.02 min, P < 0.05) than with either STEEP protocol, but peak VO2 (17.13 +/- 4.52 ml.min-1.kg-1) was similar to that obtained with the STEEP treadmill test. We conclude that the STEEP protocol may be used to test patients with chronic cardiac failure, and that exercise times relate well in both treadmill and bicycle. The protocol should prove useful in studies involving a wide range of exercise capacities or both bicycle and treadmill exercise.

Aged↗
PubMed1992

Antioxidant effects of angiotensin-converting enzyme (ACE) inhibitors: free radical and oxidant scavenging are sulfhydryl dependent, but lipid peroxidation is inhibited by both sulfhydryl- and nonsulfhydryl-containing ACE inhibitors.

With an assay that generates free radicals (FR) through photooxidation of dianisidine sensitized by riboflavin, 4 x 10(-5) M captopril, epicaptopril (SQ 14,534, captopril's stereoisomer), zofenopril, and fentiapril [all sulfhydryl (-SH)-containing angiotensin-converting enzyme (ACE) inhibitors] were shown effective scavengers of nonsuperoxide free radicals whereas non-SH ACE inhibitors were not. Captopril was a more effective FR scavenger at pH 5.0 than at pH 7.5. Captopril (2 x 10(-5) M) also scavenged the other toxic oxygen species hydrogen peroxide and singlet oxygen and inhibited microsomal lipid peroxidation. Finally, captopril reduced the amount of superoxide anion-radical detected after neutrophils in whole blood were activated with zymosan, probably by inhibiting leukocyte superoxide production.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1992

Twenty-four-hour beta-blockade in stable angina pectoris: a study of atenolol and betaxolol.

We examined the importance of a long plasma half-life (t1/2) on the antianginal effects of beta-blockade by comparing equivalent doses of once-daily atenolol 100 mg (t1/2 6-8 h) and betaxolol 20 mg (t1/2 20-22 h) in a double-blind placebo-controlled cross-over study of 20 patients with stable angina pectoris. At 20 h postdose, heart rate (HR) was lower with betaxolol than with atenolol whereas blood pressure (BP) was equally reduced by both drugs. Twenty-four-hour ambulatory HR recording demonstrated that this difference existed for the last 6 h of the dosage cycle. During treadmill exercise, HR remained lower with betaxolol than with atenolol and exercise time was significantly prolonged only by betaxolol. With placebo, radionuclide ventriculography demonstrated that left ventricular ejection fraction (LVEF) decreased during exercise. Betaxolol, but not atenolol, significantly attenuated the exercise-induced decrease in EF. Thus, the long plasma t1/2 of betaxolol is associated with a reduction in exercise-induced ischemia when tested toward the end of the 24-h dosage cycle. Plasma t1/2 therefore is of clinical relevance to the antianginal, but not antihypertensive, actions of beta-blockers.

Administration, Oral↗
PubMed1992

Circulating endothelin in acute ischaemic syndromes.

BACKGROUND: Endothelin is an extremely potent vasoconstrictor that may have a role in the pathogenesis of acute myocardial ischaemia. Atrial natriuretic factor is an endogenous antagonist of endothelin. To find the pattern and possible importance of circulating endothelin in ischaemic heart disease, concentrations in normal controls and those in patients with stable and unstable angina, acute myocardial infarction, and chronic cardiac failure were compared. The relation between circulating concentrations of endothelin and atrial natriuretic factor in the aftermath of myocardial infarction was also examined. METHODS: Eighteen patients with acute myocardial infarction, 10 with unstable angina, 10 with stable angina, 12 with chronic cardiac failure, and 10 normal controls were studied. Endothelin concentration was measured in venous plasma by radioimmunoassay. In patients with acute myocardial infarction simultaneous concentrations of endothelin and atrial natriuretic factor were measured on admission and at one, four, and 24 hours. RESULTS: Mean concentrations (SEM) of endothelin were 5.72 (0.19) fmol/ml in controls, 6.56 (0.48) fmol/ml in stable angina, 6.41 (0.48) fmol/ml in unstable angina, and 13.83 (0.95) fmol/ml in chronic cardiac failure. In acute myocardial infarction concentrations were 8.81 (0.69) fmol/ml on admission, 11.85 (1.02) fmol/ml at one hour, 11.88 (1.10) fmol/ml at four hours, and 7.30 (0.49) fmol/ml at 24 hours. Concentrations of atrial natriuretic factor at the same times were 68.1 (13.1) pg/ml, 8.4 (1.5) pg/ml, 24.4 (4.1) pg/ml, and 42.0 (6.9) pg/ml. CONCLUSIONS: Plasma endothelin is raised in chronic heart failure and in the aftermath of acute myocardial infarction but not in stable or unstable angina. After myocardial infarction endothelin concentrations are raised whereas concentrations of atrial natriuretic factor are relatively low. The role of endothelin in the pathogenesis of acute myocardial infarction and its interactions with other humoral factors require further investigation.

Angina Pectoris↗
PubMed1992

Increased circulating atrial natriuretic factor concentrations in patients with chronic heart failure after inhibition of neutral endopeptidase: effects on diastolic function.

OBJECTIVE: +/- Candoxatrilat was used to raise atrial natriuretic factor (ANF) concentrations in patients with heart failure, and the effects on left ventricular systolic and diastolic function were studied to determine the contribution of peripheral and central mechanisms to the haemodynamic effects. DESIGN: This was a single blind, randomised comparison of +/- candoxatrilat and placebo in patients with mild heart failure. All patients received two intravenous doses of +/- candoxatrilat and two placebo doses on four consecutive days. SETTING: A teaching hospital department of cardiology. PATIENTS: Six men (mean age 52 years) with mild heart failure (New York Heart Association class II) due to ischaemic heart disease (four patients) or dilated cardiomyopathy (two patients) were included. Mean ejection fraction was 37.5% and mean peak oxygen consumption was 20.4 ml/min/kg. MAIN OUTCOME MEASURES: Plasma ANF concentrations, haemodynamic indices and left ventricular diastolic function measured by early to atrial filling rate (E:A ratio) with Doppler echocardiography were determined before and after +/- candoxatrilat and placebo. RESULTS: +/- Candoxatrilat caused a threefold rise of plasma ANF compared with placebo (p < 0.005), but there was no significant change in heart rate, blood pressure, or cardiac output. Mean right atrial pressure fell from 6.7 to 4.7 mmHg (NS) and pulmonary artery wedge pressure fell from 9.2 to 6.7 mmHg (p < 0.05). Doppler echocardiographic measurements of transmitral blood flow showed a significant fall in peak early left ventricular filling velocity from 39.5 to 34.2 cm/s (p < 0.05), along with a non-significant rise in peak atrial filling velocity from 39.7-41.6 cm/s after +/- candoxatrilat. The E:A ratio, a Doppler index of left ventricular diastolic function, fell from a mean of 1.04 to 0.87 (p < 0.05). CONCLUSIONS: +/- Candoxatrilat increased plasma ANF concentrations and reduced right atrial and pulmonary artery wedge pressures. No evidence of an improvement in left ventricular systolic or diastolic function was found, so the fall in preload was due to peripheral effects, either an increase in venous capacitance or a fall in circulating blood volume.

Atrial Natriuretic Factor↗
PubMed1992

Evidence for oxidative stress in unstable angina.

OBJECTIVE: To determine whether unstable angina, which is characterised by recurring episodes of myocardial ischaemia and reperfusion, is associated with oxidative stress (that is, where there is an imbalance between oxidants, such as free radicals, which are in excess and antioxidants). DESIGN: Between group comparison of patients with unstable angina, stable angina, and healthy controls. SETTING: The coronary care unit and cardiac investigation ward of a regional cardiology centre. PATIENTS: Twenty five consecutive patients admitted to the coronary care unit with unstable angina. Twenty five consecutive patients admitted to the cardiac investigation ward (patients with stable angina undergoing coronary angiography) were used as controls for the presence of atherosclerosis, drug treatment, and smoking habit. Thirty eight healthy controls (hospital staff and patients admitted for minor surgical procedures who were otherwise healthy) were also studied. MAIN OUTCOME MEASURES: Thiobarbituric acid related substances (TBARS) in plasma and plasma reduced thiol (PSH) as indicators of oxidative damage to lipids and proteins respectively were measured. Coronary angiography was performed in all patients with stable angina and roughly half of those with unstable angina. RESULTS: Mean (SEM) plasma TBARS in unstable angina and stable angina were 9.95 (0.36) nmol/ml and 9.14 (0.28) nmol/ml respectively (p = 0.08). Mean plasma TBARS in healthy controls were 8.09 (0.21) nmol/ml (p < 0.05 compared with both angina groups). Mean (SEM) PSH concentration in unstable angina was 4.21 (9) nmol/ml and in stable angina was 4.85 (9) nmol/ml (p < 0.05). Mean PSH in healthy controls was 5.64 (8) nmol/ml (p < 0.001 compared with both angina groups). The extent of coronary artery disease, use of medication, and smoking habit were not significantly different between the angina groups. CONCLUSIONS: Biochemical indicators of oxidative stress are more abnormal in unstable than stable angina. This is in keeping with experimental evidence that episodes of ischaemia and reperfusion lead to generation of free radicals and toxic oxygen species and depression of endogenous antioxidant activity. The clinical significance of this finding remains to be determined, although, experimentally, free radicals and toxic oxygen species have adverse effects on myocardial contractile function, myocardial electrical stability, endothelial mediated vasodilatation, and coagulation.

Adult↗
PubMed1992

Plasma endothelin in chronic heart failure.

BACKGROUND: Endothelins are recently characterized vasoconstrictor peptides. As chronic heart failure (CHF) is characterized by peripheral arteriolar and renal vasoconstriction, we have measured venous plasma endothelin-like immunoreactivity ("endothelin") in patients with this syndrome. METHODS AND RESULTS: Compared with age- and sex-matched healthy volunteers (mean +/- SEM plasma endothelin concentration 6.4 +/- 0.3 pmol/l, n = 16), patients with severe CHF had elevated peripheral venous endothelin concentrations (12.4 +/- 0.6 pmol/l, n = 47, p less than 0.01). Plasma endothelin did not increase with exercise in normal subjects or in patients. Plasma endothelin concentration (mean, 13.4 +/- 0.9 pmol/l) did not correlate with plasma atrial natriuretic factor concentration (mean, 88.9 +/- 11.9 pg/ml) in patients with CHF (n = 21). There was also no correlation between plasma endothelin and serum urea or between endothelin and serum creatinine in patients with CHF (n = 34). There was, however, significant renal extraction of endothelin (aorta, 11.1 +/- 0.8 pmol/l; renal vein, 8.8 +/- 0.6 pmol/ml; p = 0.02) in patients with CHF (n = 13). CONCLUSIONS: Evidence suggests that circulatory endothelin concentrations in the range 5-40 pmol/l are vasoactive. Consequently, the endothelin concentrations found in patients with CHF may be of pathophysiological significance.

Aged↗
PubMed1992

Circulating endothelin is not extracted by the pulmonary circulation in man.

To determine whether endothelin is extracted from plasma during passage through the pulmonary circulation, we measured its concentration at several points, including the pulmonary artery and the left superior pulmonary vein in seven patients undergoing cardiac surgery. Endothelin concentrations were very similar at all sites sampled. In patients undergoing coronary artery bypass grafting, there is no net pulmonary clearance of endothelin.

Adult↗
PubMed1991

Exercise.

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Coronary Disease↗
PubMed1991

Effects of early captopril administration on infarct expansion, left ventricular remodeling and exercise capacity after acute myocardial infarction.

In a double-blind study, 99 patients (82 men, age range 40 to 75 years) with acute myocardial infarction (AMI) were randomly assigned to receive captopril or placebo. Treatment began within 24 hours of admission. Serial echocardiographic measurements of endocardial segment lengths and left ventricular (LV) volumes, and ejection fractions were obtained. The 2 groups were matched at baseline except for an excess of previous AMI in the placebo group (13 of 50 vs 2 of 49 patients, p = 0.002). The increase in anterior segment length, from baseline to 2 months, was significantly less in the captopril than in the placebo group (2.8 +/- 1.6 vs 10.4 +/- 2.4mm, 95% confidence interval [CI] -13.5 to -1.7, p = 0.01). The increase in posterior segment length was also less in the captopril group, but the difference was not significant (3.2 +/- 1.2 vs 7.0 +/- 1.8mm, 95% CI -8.0 to 0.5, p = 0.08). Fewer patients in the captopril group demonstrated increases in segment length greater than 2 standard deviations of the measurement error (14 of 70 [20%] vs 29 of 72 [40%] patients, p = 0.009). In patients with anterior AMI, the infarct-containing anterior segment length increased by 4.5 +/- 2.3 mm in the captopril versus 12.4 +/- 3.1 mm in the placebo group (95% CI -15.7 to -0.2, p = 0.046), and fewer patients in the captopril group demonstrated infarct expansion (6 of 20 [30%] vs 13 of 21 [62%] patients, p = 0.04).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

Effect of captopril, an angiotensin-converting enzyme inhibitor, in patients with angina pectoris and heart failure.

The effects of captopril and placebo were compared in 18 patients with chronic heart failure and angina pectoris with use of a double-blind crossover trial design. Symptoms were assessed by patient treatment preference, visual analogue scores and nitroglycerin consumption. Exercise performance was assessed using two different treadmill protocols of different work intensity with simultaneous measurement of oxygen consumption and by supine bicycle exercise and simultaneous radionuclide ventriculography. Arrhythmias were assessed by 48 h ambulatory electrocardiographic monitoring. Patients generally preferred placebo to captopril, and this appeared to be due to an increase in symptoms of angina with captopril. Treadmill exercise time on a high intensity protocol was shorter with captopril than with placebo; on a low intensity protocol, angina became a more frequent limiting symptom even though overall exercise performance was not changed. The heart rate-blood pressure product was reduced, but largely because of a reduction in blood pressure rather than in heart rate. During supine bicycle exercise, no differences in symptoms, exercise performance, ejection fraction or changes in blood pressure were noted and ventricular arrhythmias were reduced. Captopril does not appear to be clinically useful in alleviating angina pectoris in patients with heart failure, and this effect may be related to a decrease in coronary perfusion pressure. Nonetheless, desirable metabolic effects, a reduction in arrhythmias and potential effects on survival require further study of captopril in patients with both angina and heart failure.

Aged↗
PubMed1991

Submaximal, but not maximal, exercise testing detects differences in the effects of beta-blockers during treadmill exercise: a study of celiprolol and atenolol. II.

Celiprolol is a new-generation beta-blocker with ancillary properties that include partial beta 2-agonism and direct vasodilating activity. The effects of atenolol and celiprolol on maximal exercise capacity and on both respiratory variables and subjective indices of breathlessness and fatigue during submaximal exercise were compared in a placebo-controlled crossover study of 12 trained volunteers. Both atenolol and celiprolol equally and significantly reduced exercise capacity and maximal oxygen consumption. During constant submaximal exercise at 70% maximal oxygen uptake, however, differences emerged between the two beta-blockers. Atenolol was associated with a significantly higher minute ventilation than placebo. In contrast, values for minute ventilation and respiratory exchange ratio with celiprolol were similar to values with placebo. During the early stages of exercise, treatment with atenolol was also associated with higher scores for the subjective indices of breathlessness and fatigue. Thus submaximal exercise, which may be physiologically more relevant to the everyday activities of patients, may demonstrate potentially useful differences between drugs that are not seen during maximal exercise testing.

Adrenergic beta-Antagonists↗
PubMed1991

Angina, ischemia, and effort tolerance with vasodilating beta-blockers.

beta-Blockers are known to suppress exercise-induced ischemia but give rise to such problems as fatigue or dyspnea on effort and also bradycardia. In a series of double-blind, placebo-controlled studies of celiprolol (a cardioselective beta 1-blocker with beta 2-agonist and vasodilatory properties) in patients with hypertension and angina and in normal volunteers, it was found that celiprolol did not produce bradycardia when given in combination with verapamil. Celiprolol did reduce exercise-induced ischemia, but there was no reduction in cardiac output at rest or on exercise compared with placebo. Compared with atenolol, celiprolol produced less dyspnea and fatigue at submaximal levels of exercise. It is concluded that celiprolol possesses certain differences, compared with conventional beta-blockers, that may be of direct clinical benefit.

Adrenergic beta-Antagonists↗
PubMed1991

Synergism of histidyl dipeptides as antioxidants.

Histidyl dipeptides such as carnosine (beta-alanyl-L-histidine) and homocarnosine (gamma-amino-butyryl-L-histidine) are reported at millimolar concentrations in several mammalian tissues (O'Dowd et al., 1988; House et al., 1989), but their precise physiological function, or functions, is uncertain. These compounds are known to be potent buffers at physiological pH (Davey, 1960). They are also able to restore functional capacity to fatigued muscle preparations, stimulate some glycolytic enzymes and maintain coupling between mitochondrial oxidation and phosphorylation (Severin, 1964). Histidyl dipeptides may also have antioxidant activity, though this finding is controversial. For example, Aruoma et al. have argued that these compounds, individually, are unable to scavenge superoxide (O2-.), hydrogen peroxide (H2O2) or hypochlorous acid (HOCl) at rates which could offer antioxidant protection in vivo. Since there is a range of these histidyl dipeptides within mammalian tissue we have investigated possible synergism between them in respect of antioxidant activity. Our results show that combining histidine-containing compounds at near physiological concentrations results in synergistic antioxidant activity.

Anserine↗