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Biomedical subjects

A L Clark

Publications and source records attributed to A L Clark.

At least 37 records · Page 2Linked to original sources
PubMed2003

The effects of alpha and beta blockade on ventilatory responses to exercise in chronic heart failure.

OBJECTIVE: To assess the influence of acute alpha and beta blockade on ventilation and symptoms of breathlessness during exercise in patients with chronic heart failure and in controls. METHODS: 11 patients with chronic heart failure and 11 control subjects underwent repeated exercise testing with metabolic gas exchange after random, double blind administration of either an alpha blocker and placebo, a beta blocker and a placebo, both an alpha blocker and a beta blocker, or double placebo. RESULTS: Patients had a lower peak oxygen consumption (mean (SD) 20.7 (4.9) v 37.6 (9.6) ml/kg/min, p < 0.0001) and a steeper slope relating ventilation to carbon dioxide production (VE/CO2 slope) (26.5 (4.1) v 37.1 (8.2), p = 0.0011), than controls. Blood pressure was lower following alpha and beta blockade (p < 0.05) and the gradients of the slopes relating heart rate to oxygen consumption following the beta blocker were reduced (p < 0.05). Exercise time and peak ventilatory variables following beta or alpha blockers were unchanged. Ventilation was reduced during submaximal exercise following the active medications. Combined alpha and beta blockade produced the greatest difference (p < 0.005), but the alpha and beta blockers alone also reduced ventilation (p < 0.05). There was no difference in perceived exertion during exercise with any of the treatments. CONCLUSION: Acute sympathetic inhibition can reduce submaximal ventilation during exercise in patients with heart failure and control subjects, suggesting that autonomic nervous system activation has an important role in the abnormal ventilatory response to exercise in chronic heart failure.

Adrenergic alpha-Antagonists↗
PubMed2003

Pattern of ventilation during exercise in chronic heart failure.

OBJECTIVE: To determine the pattern of the abnormal ventilatory response in heart failure and how it relates to symptoms by looking at tidal volume (VT) and frequency (f) during exercise. METHODS: 45 patients with heart failure and 21 controls underwent maximal treadmill based exercise testing with metabolic gas exchange analysis. The relation of ventilation (VE) to VT was plotted to look for an inflection point where VT failed to increase further. The slope of the relation before this inflection point was documented. Time to the inflection point, VT, and f at the inflection point were recorded. The relation of symptom scores to f and E was also examined. RESULTS: Peak oxygen consumption (PVO2) (mean (SD)) was lower (19.7 (4.5) v 37.9 (8.6) ml/kg/min; p < 0001) and the ventilation to carbon dioxide production (VE/VCO2) slope was steeper (40.0 (6.5) v 26.0 (1.6); p < 0.0001) in patients with heart failure than in the control group. The patients reached the inflection point of the VE/VT slope sooner during exercise than the controls (271 (110) v 502 (196) seconds; p < 0.0001). Patients had a higher f and a smaller VT at that point and throughout exercise until the peak where f was the same for patients and controls. VT at the inflection point correlated with PVO2 (r = 0.67; p < 0.0001). Despite having an increased sensation of breathlessness for a given E, patients were less symptomatic of f than controls. CONCLUSIONS: Patients with heart failure breathe at a higher f throughout exercise, reaching an apparent maximal VT earlier. The VT at an inflection point on the VE/VT slope predicts PVO2.

Aged↗
PubMed2002

Contact area and pressure distribution in the feline patellofemoral joint under physiologically meaningful loading conditions.

The purpose of this study was to determine contact area and mean and peak pressures in the healthy feline patellofemoral joint over the complete range of possible applied force. Furthermore, we wanted to improve upon the repeatability of previous measurements while maximizing the physiological relevance of the results obtained. The patellae and femora were secured in a loading frame approximating an in situ loading configuration. Low- and medium-grade Fuji film was used to assess patellofemoral contact area and pressure distribution, respectively. Constant force was applied to the patellofemoral joints for 2s (short duration trials) or 5min (long duration trials). For the short duration trials, contact area was shown to increase logarithmically with the force applied. In contrast, mean and peak pressures increased linearly with force. Furthermore, the rate of increase of peak pressure with force was approximately three times greater than that of mean pressure. For the long duration trials, contact area increased up to 33% compared to the short duration trials. This effect could no longer be detected with our approach after an unloading period of 5-10s. Increasing contact area is one mechanism that the feline patellofemoral joint may use to regulate the pressures experienced by the cartilage as the force applied to the joint increases. The attenuation of external forces inside a joint is achieved by the specific geometry of the articulating surfaces and the viscoelastic properties of the articular cartilage. It likely represents a natural protection of joints to high external load magnitudes.

Animals↗
PubMed2002

Clinical trials update: RENEWAL (RENAISSANCE and RECOVER) and ATTACH.

This article continues a series of reports on recent research developments in the field of heart failure. Reports of two key presentations made at the European Society of Cardiology Heart Failure Update meeting held in Oslo, Norway from 8 to 11 June 2002, are included in this article. Summaries of the results of the RENEWAL (RENAISSANCE and RECOVER) and ATTACH studies, presented at the Hot Line sessions held during the meeting are reported.

Antibodies, Monoclonal↗
PubMed2002

Clinical trials update from the European Society of Cardiology: CARMEN, EARTH, OPTIMAAL, ACE, TEN-HMS, MAGIC, SOLVD-X and PATH-CHF II.

This article continues a series of reports on research developments related to the field of heart failure. Reports of presentations made at the Hot Line sessions of the European Society of Cardiology XXIV Congress held in Berlin, Germany, between 31 August and 4 September 2002 are included. Summaries of the results of the following trials are presented: CARMEN, EARTH, OPTIMAAL, ACE, TEN-HMS, MAGIC, SOLVD-X and PATH-CHF II.

Cardiology↗
PubMed2002

Does cardiologist- or radiographer-operated fluoroscopy and image acquisition influence optimization of patient radiation exposure during routine coronary angiography?

The operator of radiation exposure during coronary angiography varies between different centres. The purpose of this study was to explore whether radiation dose was lower during cardiologist- or radiographer-controlled radiation exposure and to determine if the grade of cardiologist performing angiography influenced radiation dose. Patients were randomly allocated either to cardiologist- or radiographer-controlled radiation exposure during coronary angiography. Screening time and radiation dose during fluoroscopy and image acquisition, measured by dose-area product meter, were recorded. Mean radiation dose during cardiologist-controlled radiation exposure (n=176) of 15.6 Gy cm(2) (95% confidence interval (CI), 14.4-16.8) was significantly lower than that produced by the radiographer-controlled group (n=192) of 17.3 Gy cm(2) (95% CI, 16.2-18.6) (p<0.044). There was no significant difference in screening times produced by the two groups of radiation exposure operators. The difference in radiation dose produced by the two operator groups was principally owing to exposure produced at image acquisition. Irrespective of radiation exposure operator, consultant cardiologists produced significantly lower screening times and radiation doses compared with registrars. During routine coronary angiography, radiographer-controlled radiation exposure does not reduce screening time or radiation dose. Senior cardiologists produce the lowest radiation doses during coronary angiography when they are responsible for radiation exposure.

Body Height↗
PubMed2001

Chronic heart failure and micronutrients.

Heart failure (HF) is associated with weight loss, and cachexia is a well-recognized complication. Patients have an increased risk of osteoporosis and lose muscle bulk early in the course of the disease. Basal metabolic rate is increased in HF, but general malnutrition may play a part in the development of cachexia, particularly in an elderly population. There is evidence for a possible role for micronutrient deficiency in HF. Selective deficiency of selenium, calcium and thiamine can directly lead to the HF syndrome. Other nutrients, particularly vitamins C and E and beta-carotene, are antioxidants and may have a protective effect on the vasculature. Vitamins B6, B12 and folate all tend to reduce levels of homocysteine, which is associated with increased oxidative stress. Carnitine, co-enzyme Q10 and creatine supplementation have resulted in improved exercise capacity in patients with HF in some studies. In this article, we review the relation between micronutrients and HF. Chronic HF is characterized by high mortality and morbidity, and research effort has centered on pharmacological management, with the successful introduction of angiotensin-converting enzyme inhibitors and beta-adrenergic antagonists into routine practice. There is sufficient evidence to support a large-scale trial of dietary micronutrient supplementation in HF.

Chronic Disease↗
PubMed2001

Clinical trials update: highlights of the scientific sessions of the American Heart Association year 2000: Val HeFT, COPERNICUS, MERIT, CIBIS-II, BEST, AMIOVIRT, V-MAC, BREATHE, HEAT, MIRACL, FLORIDA, VIVA and the first human cardiac skeletal muscle myoblast transfer for heart failure.

This article continues a series of reports summarising recent research developments pertinent to the topic of heart failure. This is a summary of presentations made at scientific sessions of the American Heart Association in November 2000. Clinical studies of particular interest to people caring for patients with heart failure include Val-HeFT, AMIOVIRT and V-MAC. New data from beta-blockers trials are reviewed, highlights from some important developments in post-infarction care, including MIRACL and FLORIDA, discussed and results of some early studies of gene therapy reported.

Animals↗
PubMed2001

Clinical trials update: Highlights of the Scientific Sessions of Heart Failure 2001, a meeting of the Working Group on Heart Failure of the European Society of Cardiology. CONTAK-CD, CHRISTMAS, OPTIME-CHF.

This article continues a series of reports summarising recent research developments pertinent to the topic of heart failure. This is a summary of presentations made at Scientific Sessions of Heart Failure 2001, a meeting of the Working Group on Heart Failure of the European Society of Cardiology. Clinical studies of particular interest to people caring for patients with heart failure include CONTAK-CD, CHRISTMAS and further updates on OPTIME-CHF. A brief review of the current status of cardiac resynchronisation therapy is included.

Cardiology↗
PubMed2001

Ventricular assist device in severe heart failure: effects on cytokines, complement and body weight.

AIMS: Inflammatory and immune activation and body wasting are important features of end-stage chronic heart failure. It is not known whether restoration of cardiac output by assist device implantation can improve these abnormalities. METHODS: We studied 48 patients (39 males; age 45+/-2 years) with NYHA class IV heart failure. All patients underwent ventricular assist device implantation for end-stage heart failure as a bridge to cardiac transplantation. Plasma levels of tumour necrosis factor alpha, and its receptors, interleukin-6, elastase, activated complement, and soluble CD14 receptors were measured at the time of operation and in survivors at 1 week (n=46), 40 days (n=35) and 90 days (n=26). Follow-up was for a minimum of 1 year. RESULTS: One-year survival was 35% (95% CI: 22-49%). Body mass index was the only predictor of survival (body mass index >25 (n=16); survival 63 (39-86) %; body mass index <25 (n=32); survival 22 (7.5-36) %: P=0.003). Tumour necrosis factor alpha fell from 9.66+/-1.33 pg x ml(-1) to 4.2+/-1.0 at 1 week (P=0.008), but returned to pre-operative levels at 90 days. Interleukin-6, activated complement and elastase fell progressively to 40 days, but were rising at 90 days. There was no change in tumour necrosis factor receptor. There was a gradual rise in CD14 (3.99+/-0.15 microg x ml(-1) at baseline, 5.02+/-0.39 at 90 days, P=0.006). After surgery, body weight fell from 80+/-2 to 73+/-2 kg by 1 month (P<0.001) and to 72+/-2 kg at 90 days. CONCLUSIONS: Ventricular assist device implantation results in a short-term fall in tumour necrosis factor alpha and interleukin-6, but no change in CD14 or tumour necrosis factor receptor, suggesting that the pathophysiological process resulting in inflammation was not altered by left ventricular assist device implantation. Low body mass index is related to poor outcome after assist device implantation, and no weight gain.

Body Weight↗
PubMed2000

Exercise endpoints in patients with chronic heart failure.

BACKGROUND: Peak oxygen consumption (V(O(2))) is a powerful predictor of outcome in patients with chronic heart failure. This is not a test that is readily clinically available. We therefore sought to establish a method of assessing peak V(O(2)) from non-invasively acquired data. METHODS: We analysed the results from incremental treadmill exercise tests in 60 patients [aged 59.0 (S.D. 12.4) years] with chronic heart failure or left ventricular dysfunction [left ventricular ejection fraction (29.6 (15.2)%)] and 52 control subjects [aged 36.7 (12.3)]. Metabolic gas exchange during exercise was measured with a respiratory mass spectrometer. Heart rate and blood pressure were measured. RESULTS: Peak V(O(2)) was lower in patients than controls [19.9 (7.7) ml/kg/min vs. 38.3 (9.0), P<0. 001]. Exercise time (r=0.84, P<0.001), heart rate at peak exercise (r=0.63, P<0.0001), change in heart rate (r=0.72, P<0.0001), rate pressure product at peak exercise (r=0.64, P<0.0001) and change in systolic blood pressure (r=0.31, P=0.002) all correlated with peak V(O(2)). In a stepwise regression model, exercise time was the most powerful predictor of peak V(O(2)) (r(2)=0.79). The only additional independent variable was change in heart rate from rest to peak exercise, which increased r(2) to 0.80. In a survival analysis, measured peak V(O(2)) and the peak V(O(2)) estimated from exercise time and change in heart rate had similar predictive power. CONCLUSIONS: In this preliminary study, peak V(O(2)) can be estimated from non-invasively acquired parameters. Estimated peak V(O(2)) and measured peak V(O(2)) have similar predictive power for outcome. Further work is necessary to see if estimated peak V(O(2)) is widely applicable in a clinical setting.

Adolescent↗
PubMed2000

Update of ELITE-II, BEST, CHAMP, and IMPRESS clinical trials in heart failure.

The ELITE-II, BEST and CHAMP Trials were reported for the first time at the American Heart Association in November 1999. These trials provide valuable new information to guide clinical practice in the management of heart failure and of myocardial infarction, although none mandate a major change from current clinical practice. The IMPRESS trial of the vasopeptidase inhibitor, omapatrilat, indicated a promising new treatment for the management of heart failure.

Adrenergic beta-Antagonists↗
PubMed2000

Clinical trials update: OPTIME-CHF, PRAISE-2, ALL-HAT.

This is a summary of reports of presentation made at the American College of Cardiology 49th Scientific Sessions, Anaheim, 12-15 March 2000. Studies with a particular interest for heart failure physicians have been reviewed. OPTIME-CHF: Outcomes of a Prospective Trial of Intravenous Milrinone for Exacerbations of Chronic Heart Failure. OPTIME-CHF was a randomised-controlled trial comparing a 48-h infusion of Milrinone or standard therapy in 951 patients recruited over a 2-year period. Patients were excluded if the investigator believed their clinical condition mandated inotropic therapy. Patients were randomised within 48 h of admission for an acute exacerbation of chronic heart failure to receive Milrinone or placebo infision for 48 h. Of the patients 43% were diabetics, 70% were receiving an angiotensin converting enzyme inhibitor, 25% were already on a beta-Blocker, and 34% had atrial fibrillation. There was no significant difference between the two groups in length of hospital stay during the index admission, subsequent readmissions and days in hospital over the following 60 days. Subjective clinical assessment scores were also no different. There was an average admission rate over the next year of one per patient in both groups. However, there was a significant increase in the incidence of sustained hypotension in the Milrinone group, which accounted for all of the increased adverse event rates for the active therapy. The 60-day mortality was 10% in both groups. This and previous trials of the oral formulation of Milrinone have now clearly demonstrated a lack of benefit with Milrinone in either during acute exacerbations of or in stable severe chronic heart failure [Packer M, Carver JR, Rodeheffer RJ et al. Effect of oral Milrinone on mortality in severe chronic heart failure. N Engl J Med 1991;325:1468-1475.]. Medium sized studies of Milrinone in patients with milder severities of heart failure also suggested an adverse impact on prognosis in the presence or absence of digoxin [DiBianco R, Shabetai R, Kostuk W, Moran J, Schlant RC, Wright R. A comparison of oral Milrinone, digoxin, and their combination in the treatment of patients with chronic heart failure. N Engl J Med 1989;320:677-683.]. Whether Milrinone even has a role for the management of a haemodyamic crisis requiring inotropic therapy must also be questioned.

Adrenergic alpha-Antagonists↗