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P Sleight

Publications and source records attributed to P Sleight.

At least 19 recordsLinked to original sources
PubMed1999

Baroreflex sensitivity and the blood pressure response to beta-blockade.

The objective of this analysis was to determine whether changes in baroreflex sensitivity (BRS) within 35 hypertensive patients (25 M, 10 F, mean age 47 years) treated with beta-blockade as monotherapy relate to reductions in ambulatory blood pressure (BP) or its variability. BP was recorded intra-arterially directly from the brachial artery before and during submaximal exercise. BRS was determined by the phenylephrine injection technique. MAP and its variability were determined for the awake period of 24-h BP monitoring. Subjects were randomised to one of atenolol, metoprolol, pindolol, or propranolol, and restudied after a mean of 5 months. Beta-blockade increased BRS in 24 patients and decreased BRS in 11. BRS increased from 6.53+/-4.94 to 9.40+/-8.62 ms/mm Hg (mean +/- s.d.) (P<0.01). Waking ambulatory MAP decreased from 125.8+/-15.8 to 106.4+/-16.2 mm Hg (P<0.0001), but its variability did not change. Higher BRS after chronic beta-blockade was associated with a decrease in waking ambulatory MAP (r = -0.55, P<0.001), but not with its variability (r = -0.08). Beta-blockade attenuated the pressor response to exercise, but there was a positive relationship between the effect of beta-blockade on BRS, and on the rise in systolic BP during bicycling (r = 0.63; P<0.001). Any dampening effect of beta-blockade on BP variability at rest in hypertensive patients with the greatest increase in BRS may be offset by increased pressor responses to physical activity such as exercise. Consequently, BP variability is unaffected, even though reductions in ambulatory BP during chronic beta-blockade are inversely related to changes in BRS. BP responses to beta-blockade may be a function of the action of this class of drugs on BRS. However, there is considerable variation, between subjects, in their effect on BRS. This may have implications for other conditions, such as dilated cardiomyopathy, or following myocardial infarction, in which improvement in BRS is one mechanism by which beta-adrenoceptor blockade could improve survival.

Adolescent↗
PubMed1998

James conway

Explore the source record for details and available documents.

Journal Article↗
PubMed1998

ISIS-2: 10 year survival among patients with suspected acute myocardial infarction in randomised comparison of intravenous streptokinase, oral aspirin, both, or neither. The ISIS-2 (Second International Study of Infarct Survival) Collaborative Group.

OBJECTIVE: To assess effects of intravenous streptokinase, one month of oral aspirin, or both, on long term survival after suspected acute myocardial infarction. DESIGN: Randomised, "2 x 2 factorial," placebo controlled trial. SETTING: 417 hospitals in 16 countries. SUBJECTS: 17 187 patients with suspected acute myocardial infarction randomised between March 1985 and December 1987. Follow up of vital status complete to at least 1 January 1990 for 95% of all patients and to mid-1997 for the 6213 patients in United Kingdom. INTERVENTIONS: Intravenous streptokinase (1.5 MU in 1 hour) and oral aspirin (162 mg daily for 1 month) versus matching placebos. MAIN OUTCOME MEASURES: Mortality from all causes during up to 10 years' follow up, with subgroup analyses based on 4 year follow up. RESULTS: After randomisation, 1841 deaths were recorded in days 0-35, 991 from day 36 to end of year 1, 1478 in years 2-4, and 1230 in years 5-10. Allocation to streptokinase was associated with 29 (95% confidence interval 20 to 38) fewer deaths per 1000 patients during days 0-35. This early benefit persisted (death rate ratio 0.98 (0.92 to 1.04) for additional deaths between day 36 and end of year 10), so that there were 28 (14 to 42) and 23 (2 to 44) fewer deaths per 1000 patients treated with streptokinase after 4 years and 10 years respectively. There was no evidence that absolute survival benefit increased with prolonged follow up among any category of patient, including those presenting early after symptoms started or with anterior ST elevation. Nor did the early benefits seem to be lost in any category (including those aged over 70). Allocation to one month of aspirin was associated with 26 (16 to 35) fewer deaths per 1000 during first 35 days, with little further benefit or loss during subsequent years (death rate ratio 0.99 (0.93 to 1.06) between day 36 and end of year 10). The early benefit obtained with combination of streptokinase and one month of aspirin also seemed to persist long term. CONCLUSIONS: The early survival advantages produced by fibrinolytic therapy and one month of aspirin started in acute myocardial infarction seem to be maintained for at least 10 years.

Administration, Oral↗
PubMed1998

Rationale and design for the Controlled ONset Verapamil INvestigation of Cardiovascular Endpoints (CONVINCE) Trial.

The Controlled ONset Verapamil INvestigation of Cardiovascular Endpoints (CONVINCE) Trial is a randomized, prospective, double-blind, parallel-group, two-arm, actively controlled, multicenter, international 5-year clinical trial involving 15,000 patients. CONVINCE will compare the incidence of fatal or nonfatal myocardial infarction (MI), fatal or nonfatal stroke, or cardiovascular-disease-related death in two antihypertensive treatment regimens. One treatment arm begins with controlled onset-extended release (COER)-verapamil, which has its major antihypertensive effect 6-12 hours after administration. The other arm (standard of care (SOC)) begins with either hydrochlorothiazide (HCTZ) or atenolol, one of which is preselected by the investigator for an individual patient prior to randomization. Secondary objectives include comparisons of the regimens for each of the components of the primary endpoint (separately), death or hospitalization related to cardiovascular disease, efficacy in lowering blood pressure to goal, primary events occurring between 6 am and noon, all-cause mortality, withdrawals from blinded therapy, cancer, and hospitalizations due to bleeding. Patients may be enrolled if they are hypertensive and at least 55 years of age and have an established second risk factor for cardiovascular disease. Initial medications include COER-verapamil (180 mg/d), HCTZ (12.5 mg/d), or atenolol (50 mg/d). Initial doses are doubled if blood pressure (BP) does not reach goal (systolic BP < 140 mm and diastolic BP < 90 mm Hg). If BP is not controlled by the higher dose of the initial medication, HCTZ is added to COER-verapamil, or the SOC choice not initially selected is added in the SOC arm. An ACE-inhibitor is recommended (although nearly any open-label medication is allowed) as the third step for patients whose BP is not adequately controlled or who have a contraindication to one of the two SOC medications. Patients take two sets of tablets daily, one in the morning and one in the evening. Although most patients switch from an established antihypertensive medication to randomized treatment, untreated patients with stages I-III hypertension (SBP between 140 and 190 or DBP between 90 and 110 mm Hg) are eligible. Outcomes are monitored by an independent Data and Safety Monitoring Board. Enrollment began during the third quarter of 1996, and follow-up is to be completed in the third quarter of 2002.

Aged↗
PubMed1998

Lipophilic versus hydrophilic beta(1) blockers and the cardiac sympatho-vagal balance during stress and daily activity in patients after acute myocardial infarction.

OBJECTIVE: To compare the effects of a lipophilic and a hydrophilic beta(1) blocker on cardiac sympatho-vagal balance during daytime activity and stress in patients four to six weeks after myocardial infarction. DESIGN: Randomised, double blind, crossover study comparing the effect of atenolol (50 mg once daily) with metoprolol CR (100 mg once daily) with treatment periods of four weeks. SETTING: Large teaching hospital. PATIENTS: 50 patients (45 male, 5 female, age range 40 to 75 years), four to six weeks after an acute myocardial infarction. METHODS: At the end of each treatment period the 24 hour heart rate variability, heart rate variability power spectra during head up tilt and mental stress, baroreflex sensitivity, and exercise performance were evaluated. RESULTS: During daytime activity and during orthostatic and mental stress, both heart rate and the ratio between the low and high frequency spectral components of the heart rate variability were significantly lower with atenolol. Conversely, there was no difference between treatments in baroreflex sensitivity and resting plasma catecholamines. Exercise duration and peak oxygen consumption did not differ between treatments, but the heart rate during submaximal and peak exercise was significantly lower with atenolol. CONCLUSIONS: At the doses used in this study, atenolol achieved greater beta(1) adrenergic blockade than metoprolol CR and this was associated with significant inhibition of vagal withdrawal during stress. This suggests that peripheral blockade of beta(1) adrenergic receptors may be more important than central blockade in preventing stress induced vagal withdrawal in patients after myocardial infarction.

Adrenergic beta-Antagonists↗
PubMed1998

Coronary event and case fatality rates in an English population: results of the Oxford myocardial infarction incidence study. The Oxford Myocardial Infarction Incidence Study Group.

OBJECTIVES: To determine coronary event and case fatality rates in an English population aged less than 80 years in Oxfordshire, and to compare these rates with those reported by the UK monitoring trends and determinants of cardiovascular disease (MONICA) centres in Scotland and Northern Ireland and those ascertained in Oxfordshire in 1966-67. DESIGN: A population wide surveillance study conducted in 1994-95 using prospective and retrospective case ascertainment. SETTING: A resident population in Oxfordshire of 568,800. SUBJECTS: Patients with suspected myocardial infarction or coronary death. OUTCOME MEASURES: A diagnosis of definite or possible myocardial infarction or coronary death using WHO MONICA diagnostic criteria based on symptoms, electrocardiograms, cardiac enzymes, necropsy findings, and past medical history. RESULTS: The annual rate for a first or recurrent coronary event per 100,000 population aged less than 65 years in 1994-95 was 273 for men and 66 for women after age adjustment to a standard world population. Rates in the age group 65-79 years were 1350 for men and 677 for women. Between 1966-67 and 1994-95, the age standardised event rate in the age group 30-69 years decreased significantly by 33% (95% confidence interval (CI) 44 to 21) in men, and there was a non-significant reduction of 8% (95% CI -33 to 17) in women. The age standardised 28 day case fatality rates also decreased significantly by 28% (95% CI 41 to 15) in men and by 32% (95% CI 55 to 9) in women. CONCLUSIONS: The coronary event rate in Oxfordshire was much lower than rates reported by MONICA centres in Glasgow and Belfast, and similar to rates reported by MONICA centres in France and northern Italy. The substantially lower event rate accounts for lower coronary heart disease mortality in Oxfordshire than in Scotland and Northern Ireland. The reduced coronary mortality in this region is attributable to declines in coronary event and case fatality rates.

Adult↗
PubMed1997

Abnormal awake respiratory patterns are common in chronic heart failure and may prevent evaluation of autonomic tone by measures of heart rate variability.

BACKGROUND: Reduced heart rate variability, particularly in the Very-low-frequency (VLF) spectral band, has been found to be a marker for poor prognosis in patients after myocardial infarction, but the origin of the VLF oscillations is unclear. In this study, we demonstrate that the power of cardiovascular oscillations in the VLF band in awake patients with mild to severe chronic heart failure is greatly increased by the common occurrence of unrecognized irregularity of breathing, which may confound the use of heart rate variability measures as indexes of autonomic tone or prognosis. METHODS AND RESULTS: Among 110 consecutive patients referred for consideration of transplantation, 90 were in sinus rhythm, of whom 10 were excluded as unstable. The remaining 80 patients underwent recordings of ECG, beat-to-beat arterial oxygen saturation (SaO2), and respiration during both spontaneous and controlled breathing. During spontaneous awake breathing, 64% showed periodic breathing or Cheyne-Stokes respiration (CSR), which was associated with dominant power in the VLF band of all signals. This VLF power accounted for 55%, 77%, and 87% of heart rate variability, respectively, in patients with normal breathing, periodic breathing, and CSR. It was reduced by 48% and 62%, respectively, during controlled breathing in patients with periodic breathing or CSR. Controlled ventilation also improved oxygen saturation and markedly reduced its variability. CONCLUSIONS: Breathing disorders are surprisingly common in awake patients with poor left ventricular function and produce large VLF oscillations in heart rate variability. If measures of heart rate variability are used for prognostic purposes during both short-term and long-term recordings, the confounding effects of variable respiratory patterns should be excluded. Respiratory rehabilitation might help control potentially hazardous surges in sympathetic tone.

Adult↗
PubMed1997

Origin of respiratory sinus arrhythmia in conscious humans. An important role for arterial carotid baroreceptors.

BACKGROUND: We investigated whether respiratory sinus arrhythmia (RSA) in healthy humans originated from central neuronal oscillations or from peripheral baroreceptors responding to respiratory changes in venous return. METHODS AND RESULTS: During subjects' controlled breathing we used sinusoidal neck suction to influence RSA (spectral analysis of RR interval). In 11 subjects, 20-second apnea greatly reduced RSA, which was restored by neck suction at the frequency of respiration. Counteracting the respiration-induced cycles of carotid blood pressure decreased RSA in 13 subjects (from 2136 +/- 682 to 1372 +/- 561 ms2, P < .01). The critical phase of this neck suction was constant for each subject at around the phase shift (with regard to respiration-related fluctuations of blood pressure) best for smoothing respiratory (mechanical) changes in blood pressure. Suction of a non-baroreceptor area (the thigh) did not affect RSA. In 4 subjects, to separate the effects of peripheral baroreceptor afferents from respiration-entrained central oscillation (15 breaths/min), we cycled the neck suction at 12 cycles/min. Increasing neck suction from -7 to -30 mm Hg increased the ratio of the power of the 12 cycles compared with the 15-cycle RSA oscillation in RR interval spectral analysis from 0.26 to 2.57. A 12-cycle/min suction of an area other than the neck had little effect on the RR interval spectrum. CONCLUSIONS: RSA can be mimicked or reduced by stimulation of arterial baroreceptors with cycles of appropriately phased neck suction at the frequency of respiration. This suggests an important influence of the arterial baroreceptors in the generation of RSA in conscious humans.

Adult↗
PubMed1997

Left ventricular hypertrophy in hypertensive patients is associated with abnormal rate adaptation of QT interval.

OBJECTIVES: This study sought to examine whether the responses of the QT interval to changes in the heart rate were altered in left ventricular hypertrophy (LVH). BACKGROUND: The QT interval has been shown to have a delayed adaptation to sudden changes in heart rate in normal subjects. Abnormalities in the adaptation of the QT interval to changes in the RR interval may facilitate the development of ventricular arrhythmias. METHODS: Consecutive newly diagnosed hypertensive subjects, not taking any medications, were age and gender matched for LVH (n = 21) versus on LVH (n = 16). QT interval dynamics were analyzed under visual control using a validated algorithm with automatic QT measurements at the end of the T wave. A computerized Holter system was developed to study the QT interval response to changes in the RR interval. The adaptive response of the QT interval was measured as the ratio of the slope from 10% to 90% of the QT change relative to the RR interval change (dQT/dRR10-90). Steady state adaptation was also studied as the percent shortening and lengthening of the QT interval during acceleration and deceleration of heart rate. RESULTS: The adaptive response of the QT interval measured as dQT/dRR10-90 was increased in the LVH group compared with that in the control subjects during both acceleration (0.33 +/- 0.06 vs. 0.18 +/- 0.02, p = 0.02) and deceleration phases (0.23 +/- 0.04 vs. 0.16 +/- 0.02, p = 0.03). In the LVH group, the percent lengthening of the QT interval was greater (7.6 +/- 0.7 vs. 5.1 +/- 0.2, p = 0.03), whereas the percent shortening was not significantly different (5.71 +/- 0.5 vs. 4.6 +/- 0.3, p = 0.43), than that in control subjects. CONCLUSIONS: The QT interval response to changes in the RR interval is rapid and exaggerated in LVH. These abnormalities of the QT interval response demonstrate that there are altered repolarization dynamics in patients with LVH that may make them vulnerable to serious ventricular arrhythmias.

Adaptation, Physiological↗