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Biomedical subjects

P Sleight

Publications and source records attributed to P Sleight.

At least 163 records · Page 9Linked to original sources
PubMed1988

Effects of acute and chronic beta-adrenoceptor blockade on baroreflex sensitivity in humans.

To determine whether beta-adrenoceptor blockade lowers blood pressure by potentiating arterial baroreflex sensitivity (BRS), we compared the effect of acute i.v. and chronic oral beta-blockade on the BRS (phenylephrine technique) of 51 subjects with essential hypertension. Subjects were randomly assigned in a double-blind protocol to one of atenolol, metoprolol, pindolol or propranolol. There was an increase in BRS, unrelated to changes in heart rate, after both acute and chronic beta-blockade. This effect was most evident in younger and less hypertensive subjects. Decreases in blood pressure after 5-months' treatment were unrelated to increases in BRS, indicating that the hypotensive action of these drugs is not dependent upon augmented baroreflex control of heart rate. Only propranolol, of the 4 beta-blockers, increased BRS significantly after acute and chronic treatment. The acute effect of propranolol was significantly different from that of i.v. metoprolol (P less than 0.008) but the effect of long-term treatment with propanolol was not significantly different from that of the other 3 beta-blockers. We conclude that the impaired reflex regulation of heart rate can be improved in younger and mild-to-moderate hypertensive patients by beta-adrenoceptor blockade. Further studies, involving larger numbers and perhaps fewer drugs are needed to determine the relative importance of lipophilicity and beta 1- or beta 2-receptor selectivity in mediating the increase in baroreflex sensitivity seen with treatment.

Adolescent↗
PubMed1988

Supraventricular tachycardia after heterotopic heart transplantation.

Heterotopic cardiac transplantation where the recipient heart remains in tandem with the donor heart has a one-year survival of approximately 80%. Rhythm disturbances after heterotopic cardiac transplantation have rarely been described and their potential influence on the patients symptoms and prognosis is unclear. We report a case of supraventricular tachycardia of the recipient heart in a patient following heterotopic heart transplantation recorded during ambulatory electrocardiographic monitoring.

Electrocardiography↗
PubMed1988

Consequences of impaired arterial baroreflexes in essential hypertension: effects on pressor responses, plasma noradrenaline and blood pressure variability.

In 62 untreated patients with essential hypertension, arterial baroreflex sensitivity (BRS) for heart rate, i.e. the change in pulse interval in response to a phenylephrine-induced increase in blood pressure, was compared with (1) haemodynamic changes during mental arithmetic, a reaction time test, isometric and bicycle exercise; (2) plasma noradrenaline (PNA) concentrations at rest, and during bicycle exercise and; (3) the variability of ambulatory intra-arterial blood pressure. Subjects with diminished BRS showed the following responses: (1) higher mean arterial blood pressure (MAP) during all four stimuli; (2) a greater pressor response to cycling; (3) tended to have higher PNA concentrations during bicycle exercise and; (4) greater variation in ambulatory blood pressure. Furthermore, an increased pressor response to the reaction time test and increased ambulatory blood pressure variability was seen in younger subjects with reduced BRS. When subjects were subgrouped according to their WHO stage of hypertension, there were significant inverse relationships between BRS and the pressor responses to mental arithmetic, the reaction time test and cycling, and with ambulatory blood pressure variability only in those subjects without ECG or radiographic evidence of left ventricular enlargement (WHO stage I hypertension; n = 42). None of these correlations were present in subjects with one or both of these clinical findings (WHO stage II; n = 20). Pressor responses to the four laboratory stimuli and ambulatory blood pressure variability were similar in both groups, despite significantly higher arterial pressure and significantly lower BRS in WHO stage II subjects. These results suggest that differing mechanisms may be responsible for the regulation of blood pressure variation in these two groups. The arterial baroreflex can buffer acute changes in blood pressure in subjects with WHO stage I hypertension, but this ability is attenuated with progressive reduction of BRS. With the development of clinically evident cardiac adaptation to hypertension (WHO stage II), the contribution of the arterial baroreflex to the regulation of blood pressure is no longer detectable and the influence of cardiac and somatic afferents to reflex circulatory adjustments to activity may predominate.

Adult↗
PubMed1988

Prevention of coronary heart disease and hypertension.

This review will concentrate on more recent evidence on the prevention of coronary heart disease and hypertension. With the evidence from lipid-lowering regimes using cholestyramine or gemfibrozil, it is clear that cardiovascular mortality can be reduced by relatively short interventions (years rather than decades). This is surprising in a disease with a long incubation period. We are also on the threshold of much more powerful intervention with the 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors. Follow-up of the very large number of subjects screened for the Multiple Risk Factor Intervention Trial study showed that the relation between serum cholesterol and risk is linear, with no hint of a "safe" level or threshold. This is borne out with the data from rural Chinese, who show the same trend, albeit at levels of risk that are 4% of those of Western populations. The suggestion that low cholesterol levels increase cancer risk appears to result from an artifact. The best dietary interventions for cholesterol lowering are still unresolved, with recent interest in fish oil and olive oil. On the background of raised cholesterol (most Western levels could be regarded as biologically abnormal), cigarette smoking assumes very great importance. Recent evidence from the U.S. Nurses survey points out a two- or threefold increase in risk from as few as four cigarettes per day. With other risk factors the relative risk increases 20-fold. These data are particularly important given that young girls in the United Kingdom and United States currently smoke more than boys.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1988

Ventricular arrhythmias in long term survivors of orthotopic and heterotopic cardiac transplantation.

Fourteen long term survivors with orthotopic (recipient heart replaced by donor heart) and nine with heterotopic cardiac transplants (recipient heart retained) had 24 hour ambulatory electrocardiographic monitoring to detect ventricular arrhythmias. Arrhythmia was uncommon in the patients with orthotopic transplants; none of them had more than one extrasystole per hour. In the patients with heterotopic cardiac transplants the recipient's own heart showed significantly more frequent ventricular arrhythmias than the corresponding donor heart: abnormal complexes (mean/24 h) 4583 vs 42.7; extrasystoles 1772 vs 17.8; pairs 121 vs 0.8. There was no relation between the abnormal ventricular activity of the two hearts in the patients with heterotopic transplants on a beat by beat, hourly, or 24 hour basis. There was no consistent diurnal variation in the frequency of the abnormal ventricular beats after cardiac transplantation. The occurrence of ventricular arrhythmia was unrelated to the interval from operation to the study. In long term survivors of cardiac transplantation the denervated heart shows a little ventricular ectopic activity even when compared with normal hearts. In patients with heterotopic transplants ventricular arrhythmias commonly occur in the recipient's own heart; these are probably related to the underlying severity of the original disease.

Adult↗
PubMed1988

Skeletal muscle metabolism during exercise under ischemic conditions in congestive heart failure. Evidence for abnormalities unrelated to blood flow.

Previous studies with 31P nuclear magnetic resonance have demonstrated that patients with chronic congestive heart failure often exhibit increased glycolytic metabolism and impaired oxidative phosphorylation in exercising skeletal muscle, but the mechanism for these changes remains unresolved. This study was conducted to determine whether these abnormalities result from impaired blood flow or oxygen delivery. Nine patients with mild-to-moderate congestive heart failure and nine age- and size-matched, healthy control volunteers were studied during repetitive submaximal finger flexion exercise under aerobic and ischemic conditions. Skeletal muscle metabolism was assessed by 31P nuclear magnetic resonance of the flexor digitorum superficialis muscle. During steady-state aerobic exercise at 33% of each subject's predetermined maximum workload, the patients with congestive heart failure exhibited significantly lower pH values (6.65 +/- 0.22 vs. 6.97 +/- 0.09, p less than 0.002) and phosphocreatine concentrations, expressed as [phosphocreatine]/([phosphocreatine] + [inorganic phosphate]) (0.59 +/- 0.14 vs. 0.79 +/- 0.08, p less than 0.002). Similar differences were also present throughout ischemic exercise at the same workload. Based upon these measurements, calculated lactate production and adenosine 5'-triphosphate consumption rates were significantly higher in the patients with congestive heart failure. These results indicate that in many patients with congestive heart failure exercising muscle exhibits increased glycolytic metabolism and appears to be metabolically less efficient in relation to external work performed. These changes cannot be explained by impaired blood flow or oxygen delivery alone.

Adult↗
PubMed1988

Factors influencing blood pressure and heart rate variability in hypertensive humans.

We examined the influence of baroreceptor reflex sensitivity (the increase in pulse interval in response to a phenylephrine-induced increase in blood pressure), age, blood pressure, and beta-adrenergic receptor blockade on the variability of blood pressure and heart rate in essential hypertension. Fifty-six subjects were studied before treatment; intra-arterial blood pressure was recorded outside the hospital for 24 hours. Variability was defined (from all beats occurring while subjects were awake) as the standard deviation about the average waking value for mean arterial pressure (MAP) or pulse interval. The correlation (r) between baroreceptor reflex sensitivity and blood pressure variability was -0.47 (p less than 0.0002). Baroreceptor reflex sensitivity was the only independent determinant of blood pressure variability on multiple regression analysis. Thirty subjects were restudied after 5 months of beta-adrenergic receptor blockade. Ambulatory blood pressure was lower during treatment, whereas pulse interval, its variability, and baroreceptor reflex sensitivity were higher. Blood pressure variability was unchanged. The variability of MAP was inversely correlated with baroreceptor reflex sensitivity before (r = -0.42, p less than 0.02) and during (r = -0.45, p less than 0.02) treatment, but it was unrelated to the average ambulatory MAP or to the variability of pulse interval either before or during beta-blockade. Sixteen subjects whose average waking ambulatory blood pressure was 140/90 mm Hg or less were not treated. This group of borderline hypertensive subjects had less variable MAP than did the remaining 40 subjects (12.4 +/- 2.3 [SD] vs 14.5 +/- 2.5 mm Hg; p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic beta-Antagonists↗
PubMed1988

Changes in autonomic regulation induced by physical training in mild hypertension.

The adaptive effects of physical training on cardiovascular control mechanisms were studied in 11 subjects with mild hypertension. In these subjects we assessed the gain of the heart period-systolic arterial pressure relationship in the unfit and the fit state by using 1) an open loop approach, whereby the gain is expressed by the slope of the regression of heart period as a function of systolic arterial pressure, during a phenylephrine-induced pressure rise and 2) a closed loop approach with proper simplification, whereby the gain is expressed by the index alpha, obtained through simultaneous spectral analysis of the spontaneous variabilities of heart period and systolic arterial pressure. Both methods indicated that training significantly increased the gain of the relationship between heart period and systolic arterial pressure at rest and reduced arterial pressure and increased heart period significantly. This gain was drastically reduced during bicycle exercise both in the unfit and fit state. In a second group of normotensive (n = 7; systolic pressure, 133 +/- 3 mm Hg) and hypertensive (n = 7; systolic pressure, 180 +/- 10 mm Hg) subjects undergoing 24-hour diagnostic continuous electrocardiographic and high fidelity arterial pressure monitoring, the index alpha was significantly reduced in the hypertensive group at rest. Furthermore, when analyzed continuously over the entire 24-hour period, this index underwent minute-to-minute changes with lower values during the day and higher values during the night. We propose the index alpha as a quantitative indicator of the changes in the gain of baroreceptor mechanisms occurring with physical training in mild hypertension and during a 24-hour period in ambulatory subjects.

Adult↗
PubMed1988

The use of ambulatory blood pressure monitoring to improve the accuracy and reduce the numbers of subjects in clinical trials of antihypertensive agents.

A low-cost ambulatory blood pressure measuring device has been developed from a commercially available stationary apparatus. The device, which has been compared for accuracy with a mercury manometer, has functioned satisfactorily as an ambulatory monitor for 4 years. To minimize errors, blood pressure readings were made in the sitting position at half-hourly intervals over the waking day. The utility of the device in clinical trials has been investigated. On repeated readings no placebo effect on blood pressure was detectable and the mean difference between two readings in 42 subjects was 1.9/-0.33 mmHg. The standard deviation of the difference were 8.1/5.6 mmHg. This should make it possible to detect differences of 8/5 mmHg between two treatments in about 16 subjects. There was no detectable tendency for blood pressure to change during the day but the variability between readings was substantially increased if the observation periods were reduced to 4 h.

Adult↗
PubMed1987

31P nuclear magnetic resonance evidence of abnormal skeletal muscle metabolism in patients with congestive heart failure.

In patients with congestive heart failure (CHF), exercise limitation correlates poorly with central hemodynamic abnormalities, suggesting that additional abnormalities in skeletal muscle blood flow or metabolism play an important pathophysiologic role. Therefore, muscle metabolism was examined by 31P nuclear magnetic resonance (NMR) at rest and during repetitive bulb squeeze exercise in 11 patients with New York Heart Association class II to IV CHF and 7 age-matched control subjects. Serial spectra were obtained at rest, at 2 levels of exercise and during recovery. At rest, the only abnormal finding was an elevated inorganic phosphate (Pi) concentration (5.0 +/- 1.5 vs 3.6 +/- 0.4 mM, p less than 0.01). At the lower exercise level, phosphocreatine (PCr) utilization, which was followed as the ratio of [PCr]/[( PCr] + [Pi]), was greater (0.36 +/- 0.16 vs 0.53 +/- 0.10, p less than 0.02), and pH fell more rapidly and to a lower value (6.38 +/- 0.25 vs 6.85 +/- 0.17, p less than 0.001). At the higher level of exercise, the patients could not work effectively and the group differences narrowed. Compared with control subjects, acidification was disproportionately greater in relation to PCr depletion in patients, further suggesting excessive dependence on glycolytic metabolism. The Pi peak was prominently double in 5 patients, indicating presence of a population of muscle fibers undergoing unusually active glycolysis. PCr resynthesis, a reflection of oxidative phosphorylation, was delayed in 4 patients. These findings indicate that in many patients with CHF, exercising muscle has marked metabolic changes consistent with impaired substrate availability and altered biochemistry.

Adenosine Triphosphate↗
PubMed1987

Beta blockade early in acute myocardial infarction.

Intravenous beta blockers given early in acute myocardial infarction have been shown to reduce chest pain, enzyme release and incidence of arrhythmias. Data published before the first report of the ISIS-1 group (International Studies of Infarct Survival) showed a 12% decrease in the probability of death using intravenous beta blockade but with large confidence limits. This study assessed and compared the effects of early intravenous atenolol and control treatment in the first week and first year after acute myocardial infarction in 16,027 patients. The principal endpoint was vascular death; most of the 15% decrease in mortality occurred in the first 24 to 36 hours with a significant difference at 1 week (313 vs 365 deaths in the atenolol and control groups, respectively). There was no rebound effect after stopping treatment after 7 days. Mortality at 1 year also showed a significant difference in favor of the atenolol group. Subgroup analysis found no significant difference in mortality by age, sex, initial heart rate, diabetes or entry electrocardiogram but data-derived analysis revealed a highly significant decrease in mortality if treatment began within 2 hours of the onset of pain. There was a significant 1% to 2% excess in inotrope use in the atenolol group in the first 36 hours, and first-degree heart block and bundle branch block emerged as relative contraindications to this treatment. The results suggest that early intravenous beta blockade in acute myocardial infarction is safe and effective and also cost effective in comparison with postdischarge oral beta blockade therapy.

Adrenergic beta-Antagonists↗
PubMed1987

Significance of elevated MB isoenzyme with normal creatine kinase in acute myocardial infarction.

The significance of elevated levels of the MB isomer of creatine kinase (CK-MB) when creatine kinase (CK) level is normal was studied in 400 patients with suspected acute myocardial infarction (AMI). In 350 patients both CK and CK-MB were elevated (group 1), in 21 only CK-MB was elevated (group 2), in 24 neither enzyme was elevated (group 3) and in 5 only CK was elevated (group 4). In 57% of patients in group 2 the CK level was doubled, with a characteristic enzyme curve, within the normal range, suggesting that an increase in CK had been missed because arbitrary definitions of "normal" were used. The median CK increase (60 IU/liter) in group 2 was greater than that in group 3 (23 IU/liter) (p less than 0.001). Patients in group 1 with small AMIs had a relative increase in CK similar to that in group 2. However, patients in group 2 had a lower baseline CK level so that peak CK did not become abnormally high despite a 5-fold increase in some patients. In patients in group 1 with small AMIs, CK was elevated in fewer samples than CK-MB. If only 2 samples were obtained in all patients, elevation of CK levels would have been missed in 63 group 1 patients, erroneously increasing the number of patients in group 2 fourfold (to 84 of 400, or 21%, instead of 21 of 400, or only 5%). Conversely, if patients in group 2 with a doubling of CK are excluded, the prevalence of elevated CK-MB with normal CK would be only 9 of 400 (2%).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1987

Pressor responses to laboratory stresses and daytime blood pressure variability.

We studied 56 patients with essential hypertension to determine whether responses to standardized laboratory mental and physical challenges accurately reflect blood pressure variability during routine daily activities. Four activities were performed in the laboratory: mental arithmetic, a reaction time test, isometric exercise, and submaximal bicycle exercise. Blood pressure was measured directly from a brachial artery catheter. We then recorded intra-arterial ambulatory blood pressure away from hospital over 24 h. A frequency histogram was constructed from all cardiac cycles when subjects were awake. Variability of ambulatory blood pressure was defined as the standard deviation about the mean waking value. The increase in mean arterial pressure (MAP) during each of these four challenges correlated significantly with the variability of mean arterial pressure (highest correlation: reaction time test, r = 0.53, P less than 0.00001; lowest correlation: mental arithmetic, r = 0.26, P less than 0.03), and five subjects who were highly reactive to all four challenges also demonstrated increased blood pressure variability. We therefore conclude that these commonly used laboratory tests can give some information about the behaviour of blood pressure in daily life in some subjects, but overall the variance in blood pressure variability that can be accounted for by the pressor response to these standardized challenges is low.

Activities of Daily Living↗
PubMed1987

Skeletal muscle metabolism in patients with congestive heart failure: relation to clinical severity and blood flow.

We and others have previously demonstrated excessive phosphocreatine (PCr) depletion and acidosis in skeletal muscle during exercise in patients with congestive heart failure (CHF). In the present study, we performed serial measurements of PCr and pH during gradually incremental flexor digitorum superficialis exercise in 22 patients with CHF and 11 age-matched controls to determine: (1) whether abnormalities were present at the same relative workloads (a comparison that would at least partially compensate for differences in muscle mass), (2) the temporable course of the metabolic changes, (3) the relationship of the metabolic findings to clinical variables, and (4) the relationship of the metabolic abnormalities to forearm blood flow. The patients with CHF had significantly lower [PCr] and pH at all submaximal levels of exercise, and these abnormalities were apparent from the onset of low-level exercise. There was considerable heterogeneity among the patients with CHF with respect to the metabolic findings, with 14 of 22 exhibiting either PCr or pH values more than 2 SDs below normal. Patients whose capacity was more limited during the protocol had lower [PCr], and especially pH, at low loads than did other patients with CHF or the control subjects. The more symptomatic patients and those with more limited bicycle exercise tolerance also had lower pH values. In contrast, there were no significant differences in forearm blood flow between the patients and controls and no relationship between forearm blood and either clinical variables or the metabolic findings. These results indicate that skeletal muscle metabolic abnormalities are present in many patients with CHF and that they are not primarily due to either muscle atrophy or impaired blood flow. These changes may explain in part the marked heterogeneity of symptom status and exercise capacity of patients with similar degrees of cardiac dysfunction.

Blood Flow Velocity↗