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Biomedical subjects

S Pugh

Publications and source records attributed to S Pugh.

At least 55 records · Page 3Linked to original sources
PubMed1990

Responses to changes in filling and contractility of indices of human left ventricular mechanical performance.

1. Beat-by-beat indices of contractility for assessment of inotropic effects in a given subject were studied using pacing with beta-adrenergic blockade, in eight patients undergoing routine left heart catheterization. A catheter-tip manometer was sited in the left ventricle and an electromagnetic velocity transducer was mounted further back on the same catheter so that it was sited in the ascending aorta. 2. The maximum rate of rise of left ventricular pressure (dPLV/dtmax), and of aortic velocity (maximum acceleration, MA) and stroke volume (SV) were all obtained with this catheter. Filling effects were assessed by head-up to head-down tilt, inotropic effects by paced post-extrasystolic potentiation. 3. Tilt produced a mean increase in left ventricular end-diastolic pressure (PLVED) of 8.1 mmHg (P less than 0.05), dPLV/dtmax decreased 4.3% (n.s.), peak velocity (PV) increased 23% (P less than 0.05), MA increased 5.4% (n.s.), and SV increased 17.5% (P less than 0.05). Post-extrasystolic potentiation produced a mean decrease in PLVED of 2.8 mmHg (n.s.), dPLV/dtmax increased 35% (P less than 0.05), PV increased 14% (P less than 0.05), MA increased 55% (P less than 0.05), and SV increased 8.7% (n.s.). 4. There was no difference in response between patients with normal and patients with impaired left ventricular ejection fraction. 5. It is concluded that increased left ventricular filling increases stroke volume greatly (Starling effect) but does not affect dPLV/dtmax, which (together with MA) nevertheless responds markedly to increased contractility. dPLV/dtmax appears to be a volume-insensitive index of contractility in the intact human, whether ejection fraction is normal or impaired.

Adrenergic beta-Antagonists↗
PubMed1990

Specialized gastrointestinal units for the management of upper gastrointestinal haemorrhage.

In 1986, 292 patients were admitted to a joint medical-surgical gastrointestinal unit with upper gastrointestinal haemorrhage. Fourteen patients died (4.8%) a mortality considerably lower than recorded in most series. The low mortality may result from the use of a specialized gastrointestinal unit to which all patients with upper gastrointestinal haemorrhage are admitted and managed with strict protocols for resuscitation, transfusion and surgery.

Aged↗
PubMed1989

Duodenal and antral mucosal prostaglandin E2 synthesis in a study of normal subjects and all stages of duodenal ulcer disease treated by H2 receptor antagonists.

We tested the hypothesis that the production of prostaglandin E2 (PGE2) is impaired in duodenal ulcer disease and affected by treatment and healing. This was investigated by a study of maximal PGE2 synthesis rates in duodenal and antral mucosal biopsies obtained at endoscopy. The patients were divided into three groups. Group (a): endoscopically normal controls (n = 56); group (b): treatment controls (non-DU disease: gastric ulcer or oesophagitis treated by histamine H2 receptor antagonists) (n = 41); and group (c): patients with DU disease (n = 183) further subdivided into group (c1) active ulcer not on treatment (n = 47), (c2) treated active ulcer (n = 35), (c3) healed ulcer on treatment (n = 86), and (c4) healed ulcer not on treatment (n = 15). Group (a) synthesised (mean (SD] 106.6 (39.0) pg PGE2/mg wt of tissue from the duodenal bulb and 129.9 (56.9) from the second part of the duodenum. No difference was found between group (a) and (b) at either site. Group (c1) ulcer rim made 49.8 (22.7) and at all stages ulcer rim and scar made less than the control duodenal bulb (p less than 0.02). Uninvolved duodenal bulb form groups (c1) (63.4 (31.0], (c2) (83.6 (38.5], and (c3) (81.5 (31.1], however, also made significantly less than controls (p less than 0.02) and a similar though non-significant trend was seen in group (c4). Biopsies from the second part of the duodenum did not synthesise significantly less than the control group but a similar trend was noticed at each stage of ulcer treatment. Biopsies of control antrum synthesised 124.5 (32.2) but only 93.7 (44.2) in group (cl) (p < 0.005). All stages of duodenal ulcer healing were associated with a decreased capacity to synthesise the major prostaglandin PGE2 at the ulcer site and the uninvolved duodenal bulb and, in acute untreated duodenal ulcer, the uninvolved antrum. This decreased capacity may be the consequence of the disease process itself and not secondary to the treatment, indicating a basic pathophysiological abnormality which may explain the characteristic tendency of the disease to relapse.

Adult↗
PubMed1988

Effect of intravenous ketanserin on the human action potential duration at fixed heart rate.

In this study any changes in action potential duration or Q-T interval due to acute doses of ketanserin were monitored. The effect of a bolus dose (10 or 20 mg) followed by an infusion (10 or 20 mg over 20 minutes) of ketanserin on the Q-T interval and action potential duration was studied in six patients undergoing routine cardiac catheterization. Action potential duration was measured with a silver-silver chloride electrode catheter while heart rate was kept constant by atrial pacing and reflex effects avoided by beta-adrenergic blockade. There were some prolongations of the action potential duration but they were not in excess of 40 msec and did not reach statistical significance (control 263 +/- 46.0 msec; bolus 269 +/- 52.1 msec; infusion 262 +/- 53.6 msec; nor were there any significant changes in Q-T interval. Thus acute intravenous doses of ketanserin, in the absence of hypokalaemia or other Q-T interval-prolonging drugs, have no consistent effect on Q-T interval or action potential duration; prolongation of the action potential, when it occurs, is small.

Action Potentials↗
PubMed1988

Hemodynamic response to treadmill exercise in normal volunteers: an assessment by Doppler ultrasonic measurement of ascending aortic blood velocity and acceleration.

Accurate assessment of ascending aortic blood velocity indices and reproducibility of a Doppler ultrasonic system during exercise were determined; the Doppler technique was then used to assess the effects of age, sex, and beta blockade on exercise hemodynamics. Doppler-determined velocity correlated well with an invasive electromagnetic system. Reproducibility of Doppler variables during three exercise tests was high (coefficient of variation less than 10%) and did not deteriorate appreciably with exercise. Peak velocity (PV) and maximum acceleration (MA) were inversely related to age, the relationship being more significant during exercise, whereas the systolic velocity integral showed no such relationship either at rest or during exercise. Doppler variables showed no difference between sexes, except at high levels of exercise. Beta blockade markedly attenuated the exercise response as shown by significant decreases in both MA and PV during exercise. The Doppler velocity data presented in this study provide a reference against which previously documented changes in exercising ischemic patients can be better related.

Adult↗
PubMed1988

Which peptic ulcer patients bleed?

In order to identify factors associated with peptic ulcers which present with bleeding rather than with pain, we have prospectively evaluated patient and endoscopic features in 139 consecutive patients presenting with acute bleeding and 74 presenting with pain found to have peptic ulceration at endoscopy. Patients with bleeding were more likely to have taken non-steroidal anti-inflammatory drugs within the preceding four weeks (58% v 18%, p less than 0.001). They were older (66 v 51 years, p less than 0.001), more likely to have had a previous ulcer complication (21% v 1%, p less than 0.001), and to have an ulcer diameter greater than 20 mm (27% v 6%, p less than 0.05). The presence of one or more of these features in a patient who develops a peptic ulcer appears to be associated with a greater likelihood of presentation with a gastrointestinal haemorrhage.

Adult↗
PubMed1988

Endogenous prostaglandin E2 synthesis preserved following cytoprotection by Roter (bismuth subnitrate) in the rat alcohol model of gastric ulceration.

The protective effect of the compound preparation Roter, principally bismuth subnitrate and the other base constituents of these tablets, magnesium carbonate and sodium bicarbonate, were assessed using the standard alcohol model of gastric ulceration in the rat. Groups of ten rats were studied with Group A as controls, Group B alcohol alone, Group C pretreatment with base components followed by alcohol, Group D pretreatment with bismuth subnitrate followed by alcohol and Group E pretreatment with full formulation Roter followed by alcohol. The study was assessed by measurement of areas of gastric ulceration and tissue prostaglandin E2 (PGE2) levels. Alcohol alone caused gross ulceration and reduction in PGE2 synthesis compared to controls (P less than 0.001). Pretreatment with tablet base gave only marginal protection whilst bismuth subnitrate gave marked protection against ulceration compared to alcohol alone (P less than 0.001). Full formulation Roter also gave marked protection against ulceration compared to alcohol alone (P less than 0.001) and this was associated with PGE2 synthesis indistinguishable from controls but significantly greater than in the alcohol alone group (P less than 0.001). It was not possible to determine whether the normal PGE2 synthesis was the cause or the result of protective effect of Roter and the accompanying reduction in ulceration. It was possible however to conclude that using this model of experimental ulceration. Roter and bismuth subnitrate are 'cytoprotective' and this was associated with the preservation of normal prostaglandin synthesis.

Animals↗
PubMed1987

Aortic and mitral valve calcification in patients with end-stage renal disease.

The frequency and aetiology of aortic valve and mitral annular calcification was studied by echocardiography in 87 patients aged 35-70 on maintenance haemodialysis for a mean of 7.5 years (range 0.5-19). Aortic valve calcification (AVC) was found in 24 patients (28%) and mitral annular calcification (MAC) was found in 31 (36%). AVC was severe and produced aortic stenosis in 5 patients with a tricuspid aortic valve (mean age 51.6 years), which confirms that calcific aortic stenosis is a complication of chronic uraemia. MAC was associated with functional mitral stenosis in 1 patient. Premature AVC and MAC were associated with an increased calcium X phosphate product and long-term haemodialysis. There were no significant differences between those patients with aortic stenosis and those with AVC but no stenosis. Patients with AVC had an increased incidence of MAC and vascular calcification. Premature AVC and MAC is frequent in dialysis patients and appears to be related to abnormal calcium and phosphate metabolism and to increased mechanical stress on the valve cusps. In a small but important group of patients on long-term dialysis, premature valve calcification is severe and produces aortic stenosis, or less frequently, mitral stenosis.

Adult↗
PubMed1987

Validation of beat by beat pulsed Doppler measurements of ascending aortic blood velocity in man.

The volume, velocity, and acceleration of ascending aortic blood were measured in man using a pulsed Doppler ultrasound instrument, with online spectral analysis and offline computer processing of velocity data. This system was firstly validated in a test rig capable of generating pulsatile flow of talc particles in water at physiological velocities and accelerations in a model aorta. Doppler measurements correlated well (r greater than or equal to 0.90) with simultaneous electromagnetic measurements of stroke volume, peak ejection velocity, and maximum acceleration in this rig. In vivo validation was performed firstly by comparing simultaneous Doppler and thermodilution cardiac output (Q) measurements; this yielded the following regression equation: Doppler Q = 0.90 X thermodilution Q + 0.03 litre.min-1, r = 0.92; n = 38. Beat by beat measurements were then validated against simultaneous invasive aortic blood velocity measurements made using a Mills electromagnetic cathetertip probe. When paced single beats of different size were compared within subjects the correlation coefficients between Doppler and electromagnetic measurements averaged 0.89 for stroke volume, 0.91 for peak ejection velocity, and 0.79 for maximum acceleration in five subjects. The absolute values for velocity and acceleration from the Doppler system differed significantly from the absolute values given by the electromagnetic system and this difference was not consistent between subjects. It is concluded that the Doppler system can non-invasively record relative changes in left ventricular ejection in man.

Aorta↗
PubMed1987

Problem of measuring the positive inotropic property of a vasodilating drug: an illustration using felodipine.

A study was undertaken to determine the presence or absence in patients of positive inotropic activity in a vasodilator drug that improves cardiac output by virtue of that vasodilatation. Felodipine is a dihydropyridine calcium antagonist that has a positive inotropic effect at low concentration in the dog in vivo. In nine patients undergoing coronary angiography in whom heart rate was kept constant by atrial pacing the solvent for the intravenous administration of the drug was infused followed by the active solution. Haemodynamic variables were measured with the Mills combined left ventricular cathetertip manometer and aortic electromagnetic blood velocity transducer. Reflex positive inotropic effects were blocked with the beta adrenergic blocking drug atenolol. An index of contractility was used to assess inotropic effects--the maximum rate of rise of left ventricular pressure measured by cathetertip micromanometry; this was an isovolumic event and therefore not sensitive to arterial pressure change, and it was unaffected by changes in left ventricular end diastolic pressure. In all patients peripheral vasodilatation was observed in the plasma felodipine concentration range of 2-40 nmol.litre-1. In eight patients this was accompanied by an 11-36% increase in maximum rate of rise of left ventricular pressure, indicating a small positive inotropic effect. Felodipine appears to show both agonist and antagonist properties in man as well as in the dog.

Adult↗
PubMed1987

Relation of human cardiac action potential duration to the interval between beats: implications for the validity of rate corrected QT interval (QTc).

Fourteen patients undergoing routine cardiac catheterisation were paced at a steady frequency; after this test, stimuli were introduced with a variable preceding interval (test pulse interval). The QT interval of the electrocardiogram and the duration of the monophasic action potential of the right ventricle were measured. QT interval is a function of action potential duration; the two variables were very closely correlated in this study. Both these variables increased in duration with increasing test pulse interval. A biphasic response, as previously reported, was not seen. An increase in steady state pacing frequency caused QT interval and action potential duration to decrease for any given R-R interval. When frequency of stimulation was suddenly increased and then maintained, there was an immediate action potential shortening followed by a further more gradual shortening occurring over several minutes. These results imply that a simple correction of QT interval for heart rate (QTc) is inadequate. It is concluded that the relation between action potential duration (or QT interval) and heart rate depends on both the instantaneous interval between beats and the duration of the prevailing heart rate.

Action Potentials↗
PubMed1987

The effects of felodipine on left ventricular function in beta-blocked patients.

Felodipine is a dihydropyridine calcium antagonist which has a positive inotropic effect in the dog in vivo. However to date, no inotropic effects have been described in man. Thus, the solvent for the intravenous administration of the drug was infused, followed by the active solution, in 9 beta-blocked patients undergoing coronary angiography; heart rate was held constant by atrial pacing. Haemodynamic variables were measured with the Mills combined left ventricular catheter-tip manometer and aortic electromagnetic blood velocity transducer. In all patients, peripheral vasodilatation was observed. In 8 patients, this was accompanied by a 9 to 50% increase in maximum rate of rise of left ventricular pressure indicating a small positive inotropic effect.

Adrenergic beta-Antagonists↗
PubMed1986

Retarded habituation and lateral asymmetries in electrodermal activity in cardiovascular disorders.

Electrodermal activity was recorded bilaterally during a sequence of moderate-intensity tones in 40 cardiac patients who exhibited clinical signs of exhaustion and in 40 controls. Responsive patients were slower to habituate than responsive controls. The groups did not differ in non-specific responses. Patients also showed lateral asymmetries in amplitudes and latencies indicative of abnormalities in right hand activity. Levels of skin conductance were higher in patients largely because of an abnormal elevation of right hand levels in both responders and non-responders. The results were consistent with limbic dysfunction together with a loss of left hemispheric contralateral inhibition. The deficit in habituation and the laterality effect may relate to the role of effort and exhaustion in cardiovascular disorders.

Adult↗