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Biomedical subjects

D R Holdright

Publications and source records attributed to D R Holdright.

At least 19 recordsLinked to original sources
PubMed1998

Long-term prognosis in unstable angina. The importance of early risk stratification using continuous ST segment monitoring.

AIMS: To assess the ability of clinical characteristics, admission ECG and continuous ST segment monitoring in determining long-term prognosis in unstable angina. METHODS: Two hundred and twelve patients with unstable angina (mean age 59 years), presenting within 24 h of an acute episode of angina were recruited at three hospitals and treated with standardized medical therapy. All patients kept chest pain charts and underwent ST segment monitoring for 48 h. The occurrence of death, myocardial infarction, and need for revascularization was assessed over a median follow-up of 2.6 years. RESULTS: The risk of death of myocardial infarction was greatest in the first 6-8 weeks after admission. Admission ECG ST depression and the presence of transient ischaemia predicted increased risk of subsequent death or myocardial infarction, whereas a normal ECG predicted a good prognosis. In 14 patients, ST segment monitoring provided the only evidence of recurrent ischaemia, and 72% of this group suffered an adverse event. Transient ischaemia and a history of hypertension were the most powerful independent predictors of death or myocardial infarction. CONCLUSIONS: Adverse events in unstable angina occur early after admission and can be predicted by clinical and ECG characteristics, and by the presence of transient ischaemia during ST segment monitoring. Risk stratification by these simple assessments can identify patients with unstable angina at high risk.

Adult↗
PubMed1997

Pathophysiology of transient myocardial ischemia in acute coronary syndromes. Characterization by continuous ST-segment monitoring.

BACKGROUND: Transient ischemia in stable coronary disease peaks in the morning, reflecting increased myocardial oxygen demand and coronary vasomotor tone after walking. In acute coronary syndromes, however, ischemia may result from transient thrombus formation or coronary spasm at the site of a ruptured plaque. We report on the pathophysiological mechanisms underlying transient ischemia in acute coronary syndromes despite optimal therapy, on the basis of analysis of heart rate changes preceding ischemia and its circadian variation. METHODS AND RESULTS: Two hundred fifty-six patients with unstable angina or non-Q-wave myocardial infarction underwent continuous ST-segment monitoring for 48 hours while receiving maximal medical therapy. All ischemic episodes were characterized by their timing, duration, association with pain, and heart rate changes before the onset of ischemia. During 10,629 hours of monitoring, 44 patients (17.2%) had 176 episodes of transient ischemia. The mean heart rate at onset of ischemia was 68 +/- 12.8 bpm, and > 55% of ischemic episodes were not preceded by a significant increase in heart rate. Ischemic activity had a single nocturnal peak, with 64% of all episodes occurring between 10 PM and 8 AM, this nocturnal preponderance being evident for episodes with or without a preceding increase in heart rate. The characteristics and timing of transient ischemia were similar in unstable angina and non-Q-wave myocardial infarction, but transient ischemia was more frequent (27.3% versus 15.1%; P < .05) and prolonged (median, 20 versus 13.5 minutes; P < .01) in non-Q-wave myocardial infarction. CONCLUSIONS: In acute coronary syndromes, transient ischemia has a low threshold, occurs predominantly without an increase in myocardial oxygen demand, and is present mainly at night rather than in the morning. These findings in patients receiving maximal medical therapy suggest significant pathophysiological differences underlying transient ischemia compared with stable coronary disease.

Acute Disease↗
PubMed1996

Early continuous ST segment monitoring in unstable angina: prognostic value additional to the clinical characteristics and the admission electrocardiogram.

BACKGROUND AND OBJECTIVE: In unstable angina, clinical characteristics, resting electrocardiography, and early continuous ST segment monitoring have been individually reported to identify subgroups at increased risk of adverse outcome. It is not known, however, whether continuous ST monitoring provides additional prognostic information in such a setting. DESIGN: Observational study of 212 patients with unstable angina without evidence of acute myocardial infarction admitted to district general hospitals, who had participated in a randomised study comparing heparin and aspirin treatment versus aspirin alone. METHODS: Clinical variables and a 12 lead electrocardiogram (ECG) were recorded at admission, and treatment was standardised to include aspirin, atenolol, diltiazem, and intravenous glyceryl trinitrate, in addition to intravenous heparin (randomised treatment). Continuous ST segment monitoring was performed for 48 h and all inhospital adverse events were recorded. RESULTS: The admission ECG was normal in 61 patients (29%), showed ST depression in 59 (28%) (17 > or = 0.1 mV), and T wave changes in a further 69 (33%). The remaining 23 had Q waves (18), right bundle branch block (four), or ST elevation (one). During 8963 h of continuous ST segment monitoring (mean 42.3 h/patient), 132 episodes of transient myocardial ischaemia (104 silent) were recorded in 32 patients (15%). Forty patients (19%) had an adverse event (cardiac deaths (n = 3), non-fatal myocardial infarction (n = 6) and, emergency revascularisation (n = 31)). Both admission ECG ST depression (P = 0.02), and transient ischaemia (P < 0.001) predicted an increased risk of non-fatal myocardial infarction or death, while no patients with a normal ECG died or had a myocardial infarction. Adverse outcome was predicted by admission ECG ST depression (regardless of severity) (odds ratio (OR) 3.41) (P < 0.001), and maintenance beta blocker treatment (OR 2.95) (P < 0.01). A normal ECG predicted a favourable outcome (OR 0.38) (P = 0.04), while T wave or other ECG changes were not predictive of outcome. Transient ischaemia was the strongest predictor of adverse prognosis (OR 4.61) (P < 0.001), retaining independent predictive value in multivariate analysis (OR 2.94) (P = 0.03), as did maintenance beta blocker treatment (OR 2.85) (P = 0.01) and admission ECG ST depression, which showed a trend towards independent predictive value (OR 2.11) (P = 0.076). CONCLUSIONS: Patients with unstable angina and a normal admission ECG have a good prognosis, while ST segment depression predicts an adverse outcome. Transient myocardial ischaemia detected by continuous ST segment monitoring in such patients receiving optimal medical treatment provides prognostic information additional to that gleaned from the clinical characteristics or the admission ECG.

Adrenergic beta-Antagonists↗
PubMed1996

Endothelial control of lower limb blood flow in chronic heart failure.

BACKGROUND: Limitation of the blood supply to skeletal muscle in chronic heart failure may contribute to the symptoms of fatigue and diminished exercise capacity. The pathophysiology underlying this abnormality is not known. The purpose of this study was to assess the effect of endothelium dependent and independent vasodilator agents on blood flow in the leg of patients with heart failure. METHODS AND RESULTS: Blood flow in the leg was measured in patients with heart failure (n = 20) and compared with that in patients with ischaemic heart disease and normal left ventricular function (n = 16) and patients with chest pain and normal coronary arteries (n = 8). External iliac artery blood flow was measured using intravascular Doppler ultrasound and quantitative angiography. Flow was recorded at rest and in response to bolus doses of the endothelium independent vasodilator, papaverine. Endothelium dependent responses were measured by infusion of acetylcholine and substance P. Mean (SEM) baseline blood flow was reduced at rest (2.9 (0.4) v 4.5 (0.3) ml/s, P < 0.001) and vascular resistance was raised (37.4 (3.6) v 27.1 (3.0) units, P < 0.05) in patients with heart failure compared with that in controls. The peak blood flow response to papaverine (8 mg), acetylcholine (10(-7)-10(-5) mol/l), and substance P (5 pmol/min) was reduced in heart failure, with greater impairment of the response to acetylcholine than substance P. There was a correlation between baseline blood flow in the heart failure group and diuretic dose (r = -0.62, P = 0.003), New York Heart Association classification (r = -0.65, P = 0.002), and left ventricular ejection fraction (r = 0.80, P = 0.0004). CONCLUSIONS: There is reduced blood flow and raised vascular resistance at rest in the legs of patients with heart failure. The degree of impaired blood flow in the leg correlates with the severity of heart failure. There is impairment of the response to both endothelium dependent and independent vasodilators. Abnormal function of the vascular myocyte in heart failure may explain these results as would structural abnormalities of the resistance vessels.

Acetylcholine↗
PubMed1995

The effects of cardiopulmonary bypass on systemic and coronary levels of von Willebrand factor.

Von Willebrand factor antigen (vWF Ag) is a marker of endothelial injury which has been shown to rise during surgical procedures, including cardiopulmonary bypass (CPB). The aim of this study was to determine whether intermittent aortic cross-clamping during CPB causes the release of vWF Ag from the coronary vascular bed, which would suggest coronary vascular endothelial cell perturbation. Fifteen consecutive patients undergoing CPB with aortic cross-clamping during coronary artery bypass surgery and/or valve replacement by the same surgeon were studied. Paired venous and coronary sinus samples were taken pre- and post-thoracotomy, prior to cross-clamping on CPB, and 1, 5 and 10 minutes after release of the aortic cross-clamp. Plasma vWF Ag (IU/ml) was measured by ELISA. Venous vWF Ag measured prior to skin incision was 0.75 +/- 0.11 IU/ml (mean +/- SEM) and fell to 0.53 +/- 0.07 IU/ml after institution of CPB but prior to aortic cross-clamping (P < 0.01 vs pre-incision sample). Coronary sinus vWF Ag measured prior to aortic cross-clamping was 0.54 +/- 0.06 IU/ml (P = NS vs paired venous sample). At 1, 5 and 10 min after release of the aortic cross-clamp there was a progressive rise in vWF Ag in both venous and coronary sinus samples (1 min: 0.67 +/- 0.05 IU/ml vs 0.75 +/- 0.10 IU/ml, 5 min: 0.73 +/- 0.07 IU/ml vs 0.76 +/- 0.09 IU/ml, 10 min: 0.74 +/- 0.08 IU/ml vs 0.79 +/- 0.09 IU/ml; P = NS venous vs coronary sinus, respectively). Levels of vWF Ag were highest immediately prior to the termination of CPB (venous: 0.95 +/- 0.12 IU/ml; coronary sinus: 0.91 +/- 0.14 IU/ml). We conclude that cardiac surgery using CPB with aortic cross-clamping is associated with a progressive rise in coronary sinus and venous levels of vWF Ag.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Acute effect of oestrogen replacement therapy on treadmill performance in postmenopausal women with coronary artery disease.

The significant reduction in cardiovascular morbidity and mortality following oestrogen replacement therapy in postmenopausal women is only partly explained by an improved lipid profile. Given acutely, oestradiol causes vasodilatation and increases coronary blood flow and, in large doses, improves treadmill performance in postmenopausal women with coronary artery disease. However, the significance of oestrogen-mediated vasodilatation is unknown since the acute effects of oestradiol in doses and preparations commonly used clinically have not been tested. The aim of this study was to evaluate the acute effects of conventional replacement therapy with 17 beta-oestradiol on treadmill performance in 16 postmenopausal women with angina in a randomized, double-blind, placebo-controlled cross-over trial. Following baseline treadmill testing a transdermal oestrogen patch releasing 50 micrograms oestradiol. 24 h-1 or matching placebo was applied and the exercise test repeated 24 h later. The patch was then removed. Seven to 14 days later the sequence was repeated using the alternative patch. The changes in time to angina, time to 1 mm ST segment depression and total exercise time for each treatment compared with the corresponding baseline test were calculated. Plasma 17 beta-oestradiol increased with active therapy from 56 +/- 30 pmol.l-1 to 204 +/- 90 pmol.l-1, indicating adequate replacement. Compared with their respective baseline exercise tests there were no differences between active and placebo patches for time to angina (active: 13 +/- 55 s vs placebo: 10 +/- 47 s), time to 1 mm ST segment depression (active: -30 +/- 52 s vs placebo: 24 +/- 71 s) or total exercise time (active: 14 +/- 45 s vs placebo: 13 +/- 35 s). Despite the recognized acute vasodilator action of larger doses of oestrogen, doses conventionally used in hormone replacement therapy had no acute effect on treadmill performance in this group of postmenopausal women with coronary artery disease.

Administration, Cutaneous↗
PubMed1995

Significant differences between side-mounted and end-mounted intracoronary Doppler flow probes for the measurement of blood flow velocity.

Use of the intracoronary Doppler flow probe is an established method for the assessment of coronary blood flow velocity. The aim of this study was to perform an in vitro comparison of two commonly used Doppler probes, which differ in the location of the piezoelectric crystal (end-mounted vs side-mounted). Blood flow velocity was measured over a wide range of flow rates in a flow simulator using heparinized whole blood. Measurements were made with both Doppler probes assessed in two positions (supported and unsupported) within the tubing. The results were compared with estimated true velocities. Further measurements were made with six side-mounted probes, correcting for the assumed crystal mounting angle and for the angle calculated from magnified images of the individual crystals. Mean velocities for end- and side-mounted probes correlated highly with predicted velocities (all r > or = 0.99), but the side-mounted probes significantly overestimated velocity by > 100%. Estimation of the true crystal mounting angle of the side-mounted probe revealed considerable variability (range 30-42 degrees) and was lower than the recommended angle correction factor of 60 degrees. Velocities corrected for the individual crystal mounting angles agreed more closely with predicted mean velocities. Although both probes are adequate for the assessment of relative changes in flow, the side-mounted probe considerably overestimates mean velocity, which is partly explained by the variable mounting angle of the crystal. The demonstrated limitations of the side-mounted Doppler flow probe in vitro should be considered in undertaking measurement of intracoronary blood flow velocity.

Analysis of Variance↗
PubMed1994

Chest pain in women: clinical, investigative, and prognostic features.

OBJECTIVE: To characterise clinical, investigative, and prognostic features of women referred with chest pain who subsequently underwent coronary angiography. DESIGN: Analysis of all women with angina referred to one consultant during 1987-91 who subsequently underwent coronary angiography, with follow up to present day. SETTING: Cardiothoracic centre. SUBJECTS: Women with normal coronary arteries; women with coronary artery disease shown on angiography; men with coronary artery disease matched for age; men referred with chest pain during the same period subsequently found to have normal coronary arteries. MAIN OUTCOME MEASURES: Risk factor analysis; results of exercise testing and coronary angiography; intervention; morbidity and mortality. RESULTS: Women comprised 23% (202/886) of patients referred with chest pain who subsequently underwent angiography. 83/202 women had normal coronary angiograms compared with 55/684 men (41% v 8%, P < 0.01). Diabetes mellitus was the only risk factor more frequently encountered in women with coronary artery disease (P = 0.001). The specificity and positive predictive value of exercise testing before angiography were significantly lower in women than men (71% v 93%, P < 0.001 and 76% v 95%, P < 0.001, respectively). Revascularisation procedures were as common in women with coronary artery disease as in men (81 (68%) v 70 (59%)), and there was no difference in event rate during follow up. Many patients with normal coronary arteries, irrespective of sex, had symptoms during follow up (61 (73%) women, 36 (65%) men) and continued to take antianginal drugs (27 (33%) women, 14 (28%) men); 14 (17%) women and six (11%) men required hospital readmission for severe symptoms. CONCLUSIONS: In this series, although women comprised the minority of patients referred with chest pain, a diagnosis of normal coronary arteries was five times more common in women than men. Risk factor analysis and exercise testing were of limited value in predicting coronary artery disease in women. There was no sex bias regarding revascularisation procedures, and outcome was similar. A diagnosis of non-cardiac chest pain in patients with normal coronary arteries was of little benefit to the patient with regard to morbidity.

Angina Pectoris↗
PubMed1994

Effect of acadesine, a new metabolic agent, on exercise-induced myocardial ischemia in chronic stable angina.

Acadesine, the first of a class of adenosine-regulating agents, has been shown to possess antiischemic properties in animal models. The aim of the study was to assess the effect of acadesine on exercise-induced myocardial ischemia in patients with chronic stable angina pectoris. Twelve patients with stable angina entered a five-way, randomized double-blind study comparing the effects of four doses of acadesine with placebo on time to 1 mm ST-segment depression and other parameters of exercise tolerance. At each study period patients underwent baseline exercise testing, followed by drug or placebo infusion after a 60 minute rest period. The exercise test was repeated after 30 minutes infusion, which continued throughout recovery. Time to angina, time to 1 mm ST depression, and total exercise time during the placebo infusion were 301.1 +/- 45.3, 314.8 +/- 50.9, and 399.4 +/- 47.6 seconds. The placebo-adjusted percentage change in time to 1-mm ST segment with acadesine 6, 12, 24, and 48 mg/kg was -0.1 +/- 6.2%, 11.1 +/- 13.8%, 12.9 +/- 8.6%, and -3.2 +/- 6.8%, respectively (p = NS vs. baseline). Time to angina, total exercise time, and recovery time of the ST segment were not consistently altered by acadesine. The lack of effect across all acadesine doses is consistent with animal data from ischemia-reperfusion injury studies, where a clear dose dependency was present with a loss of effect at higher doses. Alternatively, the extent of ischemia induced by treadmill exercise may have been insufficient for the antiischemic activity of acadesine to be evident.

Aged↗
PubMed1994

The effects of intracoronary substance P and acetylcholine on coronary blood flow in patients with idiopathic dilated cardiomyopathy.

Attenuation of the increase in blood flow caused by acetylcholine in the peripheral vasculature and coronary circulation of patients with heart failure has been interpreted as an impairment of endothelium-dependent vasodilation. The aim of this study was to compare in man the effects of acetylcholine, which also has endothelium-independent actions, with substance P, which appears to be a pure endothelium-dependent vasodilator, on epicardial and resistance coronary arteries in patients with idiopathic dilated cardiomyopathy. The effects of intracoronary acetylcholine (10(-7) M and 10(-6) M) and substance P (5, 10 and 25 pmol.min-1) on epicardial coronary artery diameter and coronary blood flow velocity were measured with an intracoronary Doppler flow probe and quantitative coronary angiography in 11 patients with idiopathic dilated cardiomyopathy and 10 control subjects. Epicardial coronary artery diameter did not change with acetylcholine but increased significantly with substance P in both groups (cardiomyopathy patients: 3.3 +/- 0.2 mm (mean +/- SEM) at baseline vs 3.9 +/- 0.2 mm with substance P25 pmol.min-1, P < 0.01; controls: 3.1 +/- 0.2 mm at baseline vs 3.9 +/- 0.3 mm with substance P25 pmol.min-1, P < 0.05). Coronary flow ratios with acetylcholine were lower in cardiomyopathy patients (10(-7) M: 1.4 +/- 0.1 vs 2.3 +/- 0.4, P = 0.05; 10(-6) M: 1.8 +/- 0.2 vs 3.2 +/- 0.5, P = 0.05 vs controls).(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗