Biomedical subjects
P Sleight
Publications and source records attributed to P Sleight.
Effects of physical training in chronic heart failure.
Eleven patients with chronic heart failure secondary to ischaemic heart disease (mean [SEM] age 63.0 [2.3] years; left ventricular ejection fraction 19 [8]% undertook 8 weeks of home-based bicycle exercise training and 8 weeks of activity restriction (rest) in a physician-blind, random-order, crossover trial. Training increased exercise duration from 14.2 (1.1) min to 16.8 (1.3) min and peak oxygen consumption from 14.3 (1.1) ml.min-1.kg-1 to 16.7 (1.3) ml.min-1.kg-1. Heart rates at submaximum workloads and rate-pressure products were significantly reduced by training, and there was also a significant improvement in patient-rated symptom scores. No adverse events occurred during the training phase. Thus home-based physical training programmes are feasible even in severe chronic heart failure and have a beneficial effect on exercise tolerance, peak oxygen consumption, and symptoms. The commonly held belief that rest is the mainstay of treatment of chronic heart failure should no longer be accepted.
Skeletal muscle metabolism in heart failure: a 31P nuclear magnetic resonance spectroscopy study of leg muscle.
1. The gastrocnemius muscle of seven patients with mild to moderate chronic heart failure and of five healthy control subjects was studied using 31P nuclear magnetic resonance spectroscopy. Spectra were collected at rest and during an incremental, symptom-limited, exercise protocol. Blood flow was measured in the same study during brief interruptions to exercise. 2. The phosphocreatine/(phosphocreatine plus inorganic phosphate) ratio was lower in patients with heart failure than in control subjects at an exercise rate of 1.5 W, although intracellular pH and blood flow were similar. 3. The cytosolic free adenosine 5'-diphosphate concentration was markedly increased in patients with heart failure exercising at 1.5 W compared with control subjects exercising at the same workload. 4. Although the maximum workload achieved by patients with heart failure was less than half of that reached by control subjects, the pH and the phosphocreatine/(phosphocreatine plus inorganic phosphate) ratio were lower in patients with heart failure at maximal load. Blood flow was less at maximal exercise in patients with heart failure than in control subjects in keeping with the reduced work load. 5. The phosphocreatine depletion induced in the gastrocnemius muscle by exercise was more severe than previously described in the forearm of patients with heart failure. 6. Metabolic abnormalities in skeletal muscle may contribute to exercise intolerance in heart failure, particularly during submaximal exercise.
Survival following thrombolytic therapy.
The results of the major mortality studies of thrombolytic drugs in myocardial infarction demonstrate that streptokinase, APSAC and t-PA reduce mortality significantly. Large studies (GISSI-2 comparing Genentech t-PA with streptokinase and ISIS-3 comparing streptokinase, APSAC and Wellcome t-PA) are currently under way to identify which, if any, of the above agents is the most effective. Review of the results of the reported studies has emphasized the importance of treatment being given as soon as practical after the onset of symptoms. It has also revealed that substantial benefit is achievable in patients often not considered to be candidates for thrombolytic therapy, such as those presenting for treatment between 6 and 24 h after symptom onset, and elderly patients. It is emphasized that important benefit may be missed in clinical practice in deciding who should, or should not, receive thrombolytic drug therapy by complying too rigidly to what were investigative clinical study entry criteria.
Proposals for a new training programme for cardiology. Joint Training and Manpower Group representing the Specialty Advisory Committee and the Cardiology Committee of the Royal College of Physicians of London, and the British Cardiac Society.
Explore the source record for details and available documents.
Do we need to intervene after thrombolysis in acute myocardial infarction?
Explore the source record for details and available documents.
Medical interventions in acute myocardial infarction.
Streptokinase, APSAC, and rtPA clearly reduce mortality in acute myocardial infarction. rtPA is definitely superior at recanalization; it does it faster and more effectively in the first 1-2 h after infusion. There is no evidence that it causes less bleeding, but rather that the proneness to bleeding might be a little higher. rtPA is expensive. Therefore, on the whole, physicians in the United Kingdom mainly use streptokinase and some APSAC. rtPA is probably the best agent for second-time use within 6-12 months of the first use of streptokinase or APSAC, when antibodies may limit the effectiveness of these agents. Aspirin is clearly useful, and one should remember to use it long term in any patient who has had a vascular event. It should not be used for primary prevention except where there is a clear vascular risk. For secondary prevention, it is very effective. Intravenous beta-blockers should be considered for less ill patients, who amount to about 50% of all patients admitted. Beta-blocker treatment reduces cardiac rupture and should be used in conjunction with thrombolysis and continued long term in patients without contraindications. It also has proven antiarrhythmic benefit (sudden death). Anticoagulants are promising but yet to be proven. Nitrates may have a place in the acute therapy of myocardial infarction, but calcium blockers and lidocaine are definitely not suited for routine use. Lidocaine should generally be used only in patients who already have ventricular fibrillation or severe or symptomatic ventricular arrhythmia. Finally, before getting too enthusiastic, one should remember that this overview deals only with those people who reach the hospital alive. There is a huge number of patients at least equal to those admitted who die before reaching medical help. They have to be prevented from getting a myocardial infarction. Therefore, along with better treatment, we need to focus on prevention, with arguments against smoking, excess weight, and in favor of more exercise. These arguments are still very important.
Routine medical management of acute myocardial infarction. Lessons from overviews of recent randomized controlled trials.
In recent years, several large randomized trials have clarified the role of various interventions in acute myocardial infarction. There is clear evidence that thrombolytic therapy, aspirin, and beta-blockers reduce mortality. Both aspirin and beta-blockers also reduce reinfarction and stroke. Of the thrombolytic agents, comparative trials have established that tissue plasminogen activator and streptokinase have similar effects on mortality, morbidity, and left ventricular function. There appears to be an increased risk of cerebral hemorrhage with tissue plasminogen activator. The benefits of heparin in conjunction with aspirin and a thrombolytic agent are unclear and, at best, are likely to be modest. Heparin increases the risk of hemorrhagic complications twofold. Although trials of vasodilators conducted before the widespread use of thrombolytic therapy and aspirin have been promising, newer trials are needed to evaluate their effects among patients receiving these agents. The aggregate of all trials of the routine use of calcium antagonists or antiarrhythmic agents indicates that these agents do not improve survival.
Wider inclusion criteria needed for thrombolytic therapy.
Explore the source record for details and available documents.
Ambulatory pressure monitoring in the assessment of antihypertensive therapy.
A low-cost, ambulatory blood-pressure monitor has been calibrated and validated against a random zero sphygmomanometer. The repeatability of ambulatory pressure recordings after a placebo month in 44 mild to moderate untreated hypertensives was assessed. Systolic blood pressure showed a mean difference over 1 month of 2.0 mmHg, with a standard deviation of differences of 9.3 mmHg. The diastolic blood pressure mean difference was 0.1 mmHg (SD = 6.3 mmHg). This variability was much less than for clinic readings (SD = 17.3 mmHg) or for single home pressure readings (SD = 19.7 mmHg). Using ambulatory monitoring to detect a drop in pressure of 8/5 mmHg with a power of 0.9, the number of subjects needed in a parallel group trial is reduced from 360 to 68, and in a crossover study from 88 to 16 subjects. The usefulness of ambulatory pressure monitoring is demonstrated in a placebo-controlled comparison of atenolol, nifedipine retard, or their combination in random order. Eleven subjects, 21-60 years, with initial average blood pressures of 166.5/104.7 mmHg, showed a reduction in pressure with atenolol 50 mg a day of 15.1/10.0 mmHg, with nifedipine retard 20 mg b.i.d. of 21.0/11.6 mmHg, and with atenolol 50 mg and nifedipine retard 20 mg once a day of 26.2/16.8 mmHg. Ambulatory monitoring of pressure improved the accuracy of the trial and demonstrated a reduction in the alerting response with atenolol.
How much should blood pressure be lowered? The problem of the J-shaped curve.
Explore the source record for details and available documents.
The relevance of baroreflex mechanisms to the control of ambulatory and exercise blood pressure in humans.
1. The article reviews the phenylephrine 'ramp' method for studying the baroreceptor-heart rate reflex and the method of power spectral analysis for studying variability of blood pressure and of the R-R interval. 2. These methods have been used to study changes in reflex properties during arousal from sleep, changes which occur acutely after physical exercise and with training, changes in hypertension, and after myocardial infarction. 3. Several of the above changes are attributable to altered properties of the arterial baroreceptors, but some involve changes in central nervous information processing.
Systemic and forearm vascular resistance changes after upright bicycle exercise in man.
1. Blood pressure, cardiac function and forearm blood flow following voluntary maximal upright bicycle exercise were studied in thirteen normal volunteers in a cross-over design against a control day. 2. After exercise there was a short-lived (5-10 min) increase in systolic blood pressure, peak aortic blood velocity and aortic acceleration suggesting a persistence of the positive inotropic influence of exercise. 3. Systemic vasodilation, which was seen immediately exercise stopped, lasted at least 60 min. This was associated with a reduction in diastolic blood pressure for the whole hour. After 30 min systolic blood pressure was also reduced. Heart rate and cardiac output were still significantly elevated and systemic vascular resistance still reduced at 60 min post-exercise. 4. A non-exercising limb vascular bed (forearm) showed a marked vasodilation for 1 h after predominately leg exercise indicating the presence of a vasodilatory influence affecting vascular beds other than the exercising muscle groups.
Significant reduction in mortality with streptokinase given 7-24 hours after pain onset.
Explore the source record for details and available documents.
The 24-hour heart rate behavior in long-term survivors of cardiac transplantation.
A detailed computerized analysis of heart rate (HR) behavior during ambulatory monitoring was performed in 19 long-term survivors of cardiac transplantation (12 orthotopic, 7 heterotopic) and in 10 normal volunteers. Compared with normal hearts, the transplanted denervated and the recipient innervated hearts in the heterotopic group showed higher average HRs over the whole 24 hours, the waking and sleeping periods. The rates of the denervated and the recipient hearts did not differ significantly. The maximal HR was similar in all 3 groups, but the minimal HR was lower in the normal hearts than in denervated and recipient hearts. The 24-hour RR interval variability was greatly reduced in the denervated hearts (60 +/- 22 ms) compared with the recipient (89 +/- 26 ms) and normal (151 +/- 38 ms) hearts. During arousal from sleep, the magnitude, time and rate of the HR change were significantly reduced in the denervated hearts compared with the innervated hearts and in the recipient compared with the normal hearts. These findings demonstrate that denervated hearts can show significant variations in HR during the 24-hour period, but to a lesser extent than normal hearts. The widest deviation from normal occurs during sleep, when the denervated heart shows minimal slowing probably due to lack of parasympathetic innervation. In heterotopic transplant recipients, the patients' own HR responses also are significantly blunted.
Importance of cardiovascular reflexes in disease.
Circulatory reflexes are important in effecting rapid distribution of blood flow and an adequate driving pressure during adjustment to the stress of exercise, posture change, and other environmental challenges. Their primary evolutionary role may be a response to the extreme stress of hemorrhage. Derangements of reflex control may lead to adverse effects on organ blood flow, particularly renal blood flow; adjustments appropriate for support of the circulation during hemorrhage may be inappropriate in congestive heart failure. The balance between one control system and another may be altered by disease. Arterial baroreflex control of the circulation is impaired in hypertension, but may be partially compensated by increased gain in cardiopulmonary reflexes. Changes in autonomic balance in acute myocardial ischemia may be important in the mechanism of sudden death. Physical training can favorably modify arterial baroreflex function and adds to the evidence in favor of active rehabilitation after infarction.
Diurnal variations of QT interval after cardiac transplantation.
Explore the source record for details and available documents.
Blood pressures, hearts, and U-shaped curves.
Explore the source record for details and available documents.