Biomedical subjects
Publications and source records attributed to P Sleight.
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OBJECTIVES: The aim of this study was to study the hemodynamic effects of orally administered captopril and isosorbide mononitrate in suspected acute myocardial infarction. BACKGROUND: Early treatment with converting enzyme inhibitors and nitrates in acute myocardial infarction may limit infarct expansion and prevent left ventricular dilation. METHODS: In a double-blind study, 81 patients were randomized within 36 h of the onset of symptoms of suspected acute myocardial infarction to 1 month of oral captopril (6.25 mg initial dose, followed 2 h later by 12.5 mg and continuing with 12.5 mg three times daily), isosorbide mononitrate (initial dose 20 mg followed by 20 mg three times daily) or matching placebo. The effects of treatment on changes from baseline in mean arterial blood pressure, heart rate, stroke volume, cardiac output and systemic vascular resistance were assessed noninvasively using Doppler echocardiography 1 h after the first dose, 1 week after infarction and at 6 weeks (that is, 2 weeks after the scheduled end of trial treatment). RESULTS: One hour after the start of treatment, blood pressure was reduced by approximately 10% with both captopril and isosorbide mononitrate, but this difference did not persist at 1 week. Captopril was associated with a significant increase in cardiac output compared with placebo of 13 +/- 3% at 1 h (p < 0.01), 23 +/- 5% at 1 week (p < 0.001) and 22 +/- 6% (p < 0.05) at 6 weeks (2 weeks after the end of trial treatment). This increase in cardiac output with captopril was mainly due to a substantial and sustained increase in stroke volume, although there was also a small increase in heart rate at 1 week. Both captopril and isosorbide mononitrate reduced systemic vascular resistance within 1 h of the start of treatment, but only the effect of captopril was sustained (perhaps because the three-times daily nitrate regimen induced tolerance). Study treatment was well tolerated, and the incidence of withdrawal of study treatment for hypotension was not significantly different from that with placebo. CONCLUSIONS: This study indicates that the hemodynamic effects of both captopril and isosorbide mononitrate are well tolerated in the acute phase of myocardial infarction and that captopril favorably influences cardiac function.
Thrombolytic treatment and aspirin will save about 50 in 1000 patients treated for acute myocardial infarction, but with a risk of cerebral or other serious bleeding in two to three in every 1000. Early treatment (< 4 h) about halves mortality; the benefits decline with time but are clearly proven up to 12 h from onset. Benefit is best and risk least when there is ST elevation and bundle branch (BB) block on the initial ECG. Hypotension is not a contraindication. There is no clear benefit from treatment of patients with ST depression, T wave change or a normal ECG. Streptokinase (SK), tissue plasminogen activator (tPA) or APSAC are equally effective with no mortality benefit for any of the drugs. SK is safer, particularly in older or more hypertensive patients. tPA is reserved for patients who have received SK during the previous year, when high antibody titres may neutralize its effect on a second myocardial infarction (MI). Heparin (either i.v. or high dose S/Q) added to aspirin may confer some small additional benefit, but at the cost of significantly increased risk of bleeding. It should be reserved for high risk patients. Routine angioplasty is unhelpful. Investigation should be reserved for patients with continuing symptoms or ECG evidence of ischaemia, at rest or after stress testing. The benefits of thrombolysis are seen at all ages, in both sexes, and whatever the site of the MI. Aspirin 75-100 mg daily should be continued long-term.
INTRODUCTION: This document is the result of discussions held during a Scientific Workshop in Brescia, Italy, where the numerous methods, old and new, for evaluation of organ damage in hypertension were considered. Not all of the methods can be recommended as routine diagnostic procedures for every hypertensive subject. Current routine diagnosis of organ damage by clinic blood pressure, retinal appearances, the electrocardiogram, serum creatinine estimation and urinary analysis will probably suffice; of the more refined methods, only the echocardiogram is likely to be often included in the examination of hypertensive patients. All of the other techniques will be useful in the diagnostic approach to patients with particular problems, or for the purposes of special investigation. RECOMMENDATIONS: It is recommended that the validity of the methods, the clinical relevance of the abnormalities (including left ventricular hypertrophy, reduced coronary reserve, arterial changes in the eye grounds, reduced large artery compliance and microalbuminuria) and the potential benefits of therapeutically reverting these alterations should be assessed by including organ damage evaluation in future epidemiological and interventional trials in hypertension.
OBJECTIVE: To assess the effects of oral vasodilator treatment on ventricular arrhythmias in acute myocardial infarction. SETTING: Coronary care units at the John Radcliffe Hospital, Oxford, and the Royal Infirmary, Edinburgh. PATIENTS: 100 patients with suspected acute myocardial infarction entered the study at a mean of 13 hours from symptom onset. DESIGN OF INTERVENTION: Double blind randomisation to 4 weeks treatment with captopril (12.5 mg three times a day after a 6.25 mg test dose (n = 32)) or isosorbide mononitrate (20 mg three times a day (n = 31)) or placebo control (n = 37). OUTCOME MEASURES: Ventricular arrhythmic events assessed by 48 hours of Holter monitoring starting at the time of randomisation. RESULTS: The number of ventricular extrasystoles/hour for captopril, mononitrate, and placebo was respectively (median and range) 6 (0-162), 4 (0-38), and 10 (0-932) (2p < 0.02 mononitrate v placebo). The number of episodes of multiple extrasystoles/hour was 0.2 (0-22), 0.3 (0-4), and 0.5 (0-19); (2p < 0.02 mononitrate v placebo). Episodes of ventricular tachycardia showed a non-significant decrease in the captopril and mononitrate groups (mean (SEM) 3.2 (0.8), 2.4 (0.7), and 4.7 (1.3) for the 48 hour period). The incidence of idioventricular rhythm was also reduced in both active treatment groups (28%, 19%, and 46% (2p < 0.05 mononitrate v placebo)). CONCLUSIONS: Oral mononitrate (and perhaps also captopril) seems to reduce the incidence of ventricular arrhythmias in the early phase of acute myocardial infarction. The effects on life-threatening arrhythmias, such as ventricular fibrillation, and on death can only be assessed in a much larger trial.
Hemodynamics (by aortic Doppler), autonomic factors (power spectrum analysis of heart rate and blood pressure variabilities and baroreceptor sensitivity), and plasma renin activity during the hypotension after maximal exercise were studied in 10 normal subjects on two separate days: a nonexercise (control) day (30 min of upright rest followed by 60 min of supine rest) and an exercise day (maximal upright bicycle exercise followed by 60 min supine) in random order. After exercise, diastolic pressure was reduced for the entire hour, cardiac output increased (+33.8%, P < 0.05), stroke volume was unchanged, and systemic vascular resistance fell (-28.6%, P < 0.01). Indexes of vagal activity were reduced for 60 min, whereas the sympathetic indexes were elevated. Baroreflex sensitivity was also reduced for the first 10 min after exercise. Renin activity increased threefold after exercise. The postexercise hypotension results from a persisting peripheral vasodilation despite an increase in renin activity: the persistent sympathetic activity and reduced vagal tone are probably reflex responses to this vasodilatation.
BACKGROUND: Reduced cardiac vagal tone in patients with myocardial infarction (MI) is associated with a high risk of sudden death. Muscarinic blocking agents in small doses induce a paradoxical increase in cardiac vagal activity in normal subjects. We tested whether low doses of scopolamine delivered transdermally enhance tonic and reflex cardiac vagal activity in patients in the acute phase of MI. METHODS AND RESULTS: Patients were randomized to a scopolamine (n = 17) or a placebo patch (n = 19) in a double-blind fashion 4.20 +/- 0.18 days after acute MI. Cardiac vagal activity was assessed by testing the arterial baroreflex sensitivity (BRS) using the phenylephrine method and by power spectral analysis of the RR interval variability. Twenty-four hours after scopolamine, we found a significant increase in BRS (from 7.05 +/- 1.21 to 13.99 +/- 2.33 ms/mm Hg, P < .05) and in RR variability, expressed as the mean standard deviation of 512 normal consecutive RR intervals (from 18.09 +/- 2.64 to 31.16 +/- 4.16 milliseconds, P < .05). The amplitude of respiratory sinus arrhythmia, measured by the absolute power of the high-frequency spectral component, was also enhanced (from 62.55 +/- 21.49 to 305.33 +/- 95.68 milliseconds squared, P < .05), whereas the power in the low-frequency spectral component of the RR variability, which results from the interaction between cardiac sympathetic and vagal activity, did not change significantly (from 73.12 +/- 24.44 to 126.46 +/- 44.29 milliseconds squared, P = .93). CONCLUSIONS: In patients in the acute phase of MI, low doses of scopolamine cause a sustained increase in cardiac vagal tone and improve the autonomic indices associated with mortality.
The significance of angina pectoris in patients with aortic valve disease (AVD) and the need for coronary arteriography before valve replacement are controversial. The history of chest pain and coronary arteriographic findings were reviewed in 333 patients > or = forty years old, with AVD: 142 with aortic stenosis, 87 with mixed AVD and 104 with aortic regurgitation. The prevalence of coronary artery disease (CAD) was similar among different types of AVD. Angina pectoris was more frequent in patients with aortic stenosis (56%) and mixed AVD (53%) than in patients with aortic regurgitation (24%) (p < 0.0001). Similar results were found in patients with and without CAD. Twenty-six of 95 (27%) patients with CAD had no chest pain at all. The absence of any chest pain in CAD patients was more frequent in those > or = sixty years old than in those < sixty (p < 0.05). Thus, since a significant number of patients had CAD in the absence of any chest pain, the authors recommend coronary arteriography for all patients > or = forty years of age before aortic valve replacement.
Patients who survive a myocardial infarction are at high risk of future recurrent infarction, sudden death and other vascular events. While it is possible to predict many risks, it is not possible to predict reinfarction. Since reinfarction carries a poor prognosis we should attempt to reduce this risk in all patients who survive an acute myocardial infarction. This paper reviews the wide range of lifestyle modifications and pharmacological interventions aimed at improving the long term prognosis of patients who have suffered an acute myocardial infarction.
Coronary heart disease is the most common cause of death in hypertensives--about twice as common as stroke. Smoking increases this raised risk of hypertension by some 2 to 3 times. Surprisingly perhaps, this increased risk from smoking declines rapidly on quitting--within 2-3 years. Smoking increases the risks of vascular damage by increasing sympathetic tone, platelet stickiness and reactivity, free radical production, damage to endothelium, and by surges in arterial pressure. The latter may interfere with the action of some hypotensive agents. Persuading hypertensive patients not to smoke is the single most effective measure we can take to reduce their risk.
BACKGROUND: The results of many studies designed to assess the effect of antihypertensive treatment have been, at first sight, disappointing with regard to expectations of a reduction in mortality due to coronary events. However, meta-analysis shows that there is a significant benefit, which is about two-thirds of that expected from the epidemiological data. EFFECTS OF THIAZIDE DIURETICS: Older antihypertensive agents like thiazide diuretics have been shown to confer a degree of cardioprotection, although the mechanism of this effect is still unknown. Since these drugs have adverse effects on lipid and glucose metabolism, they are not (in theory) ideal agents, especially in younger patients. However, recent evidence suggests that these adverse effects may have been overemphasized. EFFECTS OF NEWER ANTIHYPERTENSIVE AGENTS: Newer agents, such as angiotensin converting enzyme inhibitors and vasodilating beta-blockers, may have experimental and theoretical advantages over older agents but there are insufficient mortality data to allow firm conclusions. CONCLUSIONS: While it is clear that hypertension is a risk factor for cardiovascular mortality, the effect of specific antihypertensive treatments on coronary heart disease mortality is still unresolved. There is a critical need for data on mortality, comparing the newer agents with thiazide diuretics, now increasingly well proven.
Twenty-five patients (aged 62 +/- 2 years) with stable, moderate to severe ischemic congestive heart failure (CHF) (New York Heart Association class II/III: 15/10; ejection fraction 21.6 +/- 2%; and peak oxygen uptake 13.6 +/- 0.7 ml/kg/min) were studied to evaluate the ability of different methods to characterize autonomic tone in chronic CHF. Sympathovagal balance was assessed by: (1) heart rate variability in the time domain, assessed by the SD of RR intervals; (2) heart rate variability in the frequency domain, assessed by low- (0.03 to 0.14 Hz) and high- (0.18 to 0.40 Hz) frequency components of heart rate variability by autoregressive power spectral analysis; (3) 24-hour, daytime and nighttime heart rate; (4) submaximal heart rate during upright bicycle exercise, with respiratory gas analysis to obtain peak oxygen uptake; and (5) radiolabeled norepinephrine spillover. These methods did not correlate, with the exception of day and nighttime heart rate (r = 0.74; p < 0.001) and the expected inverse correlation between low and high frequency (r = -0.92; p < 0.001). No method correlated significantly with peak oxygen uptake, exercise tolerance or ejection fraction. After 8 weeks of physical training at home, all methods showed improvement in autonomic balance: increases in SD of RR intervals (+21%; p < 0.02) and high frequency (+41%; p < 0.007), and decreases in low frequency (-19%; p < 0.002), low-/high-frequency ratio (-48%; p < 0.03), norepinephrine spillover (-28.9%; p < 0.03), 24-hour heart rate (-2.7%; p < 0.005) and submaximal heart rate (-10.8%; p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
To characterize the early (1 week) and late (6 weeks) changes in left ventricular (LV) filling pattern associated with acute myocardial infarction (AMI) 45 patients (mean age 65 +/- 2 years) were studied by Doppler echocardiography. Based on clinical criteria, patients were divided into those with large (group L; n = 12) and those with small (group S; n = 33) infarcts and then compared with 16 age-matched control subjects. The following parameters were calculated from the mitral velocity waveform: (1) peak early and peak atrial velocities and their integrals; (2) peak early to atrial velocity ratio and velocity integral ratio; and (3) the pressure half-time of the early wave. One week after AMI, group L showed a decreased atrial and increased early velocity, velocity ratio and integral ratio, whereas the pressure half-time of the early wave was shorter than that in group S and in control subjects. At 6 weeks group L showed a reduction in early velocity, early to atrial velocity ratio and integral ratio, whereas pressure half-time increased. When groups S and L were combined there was a good inverse correlation between pressure half-time and infarct size as measured by peak enzyme release (r = -0.64, p < 0.001). These data suggest that, depending on infarct size, patients exhibit a "restrictive" filling pattern early after the acute event. This is manifested by the greater proportion of filling occurring in early diastole, reflecting an overall increase in chamber stiffness. At 6 weeks, this pattern is less pronounced presumably due to the remodeling process.
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In the hypertensive patient, the presence of other cardiovascular risk factors, particularly smoking, hypercholesterolemia, obesity, and diabetes, greatly influences the prognosis. In many patients, these other risk factors are linked, perhaps by adverse effects of pressure on endothelial function. The newer antihypertensive agents may have better effects on prognosis by ameliorating these other risk factors, as well as lowering pressure. We await trials to see if this promise is fulfilled.
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We describe the case history of a 32 year old male with severe paroxysmal hypertensive spikes when there was an increase in diastolic blood pressure to 150-200 mmHg. These spikes occurred during rest and especially during modest exercise. They were associated with headache and dyspnoea and were resistant to antihypertensive medication. After 5 years of observations and investigations he underwent further 24-h intra-arterial blood pressure monitoring and physiological testing. The 24-h blood pressure profile was near normal at rest. The observed hypertensive spikes seemed to be induced by involuntary Valsalva-like manoeuvres. This had not been detected previously by the investigators and the patient was unaware of inducing these manoeuvres.
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