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Biomedical subjects

S M Cobbe

Publications and source records attributed to S M Cobbe.

At least 127 records · Page 7Linked to original sources
PubMed1992

Coronary venous lipid peroxide concentrations after coronary angioplasty: correlation with biochemical and electrocardiographic evidence of myocardial ischaemia.

BACKGROUND: Raised lipid peroxide concentrations in coronary venous plasma have been reported after coronary angioplasty in humans. This may reflect increased free radical activity after myocardial ischaemia and reperfusion. If so, it may be possible to correlate lipid peroxide concentrations with the degree of myocardial ischaemia produced during angioplasty. METHODS: 15 patients (age range 42-70; 12 men) with stable angina pectoris undergoing angioplasty of a proximal left anterior descending coronary artery stenosis were studied. Plasma lipid peroxide and lactate concentrations were measured in sequential blood samples taken from the great cardiac vein before and immediately after one to five serial 60 second balloon inflations. The maximum ST segment shift during each balloon inflation was also measured. RESULTS: Lipid peroxide concentrations in coronary venous plasma were raised from pre-angioplasty values by more than 2 SDs of the relevant measurement error after 27 out of 46 (59%) balloon inflations. Lactate concentrations were raised after 43 out of 46 (93%) balloon inflations. No significant difference was found between the peak percentage change of either lipid peroxide or lactate concentrations after any of the first three serial inflations. The maximum ST segment shift after each of the first three serial inflations was also similar. Coronary venous lactate concentrations after balloon inflation correlated positively with the maximum ST segment shift, but did not correlate with lipid peroxide concentrations. CONCLUSIONS: Raised lipid peroxide concentrations in coronary venous plasma can be detected in humans after balloon angioplasty. There is no positive correlation between lipid peroxide concentrations in coronary venous plasma after angioplasty and the degree of preceding myocardial ischaemia as assessed by either ST segment shift or lactate production. These indices showed that one to three serial 60 second balloon inflations each produce a similar degree of myocardial ischaemia. The origin of the raised lipid peroxide concentrations in coronary venous plasma after angioplasty remains unknown.

Adult↗
PubMed1991

Effects of early captopril administration on infarct expansion, left ventricular remodeling and exercise capacity after acute myocardial infarction.

In a double-blind study, 99 patients (82 men, age range 40 to 75 years) with acute myocardial infarction (AMI) were randomly assigned to receive captopril or placebo. Treatment began within 24 hours of admission. Serial echocardiographic measurements of endocardial segment lengths and left ventricular (LV) volumes, and ejection fractions were obtained. The 2 groups were matched at baseline except for an excess of previous AMI in the placebo group (13 of 50 vs 2 of 49 patients, p = 0.002). The increase in anterior segment length, from baseline to 2 months, was significantly less in the captopril than in the placebo group (2.8 +/- 1.6 vs 10.4 +/- 2.4mm, 95% confidence interval [CI] -13.5 to -1.7, p = 0.01). The increase in posterior segment length was also less in the captopril group, but the difference was not significant (3.2 +/- 1.2 vs 7.0 +/- 1.8mm, 95% CI -8.0 to 0.5, p = 0.08). Fewer patients in the captopril group demonstrated increases in segment length greater than 2 standard deviations of the measurement error (14 of 70 [20%] vs 29 of 72 [40%] patients, p = 0.009). In patients with anterior AMI, the infarct-containing anterior segment length increased by 4.5 +/- 2.3 mm in the captopril versus 12.4 +/- 3.1 mm in the placebo group (95% CI -15.7 to -0.2, p = 0.046), and fewer patients in the captopril group demonstrated infarct expansion (6 of 20 [30%] vs 13 of 21 [62%] patients, p = 0.04).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

"Heartstart Scotland"--initial experience of a national scheme for out of hospital defibrillation.

OBJECTIVE: To determine the outcome of out of hospital defibrillation in Scotland during the year after the introduction of automated external defibrillators in October 1988. DESIGN: Retrospective analysis of ambulance service reports and hospital records. SETTING: Scottish Ambulance Service and acute receiving hospitals throughout Scotland. MAIN OUTCOME MEASURES: Delay from cardiac arrest to first defibrillator shock; vital state on arrival at hospital accident and emergency department; survival to hospital discharge. RESULTS: During the study period 268 defibrillators were purchased by public subscription and 96% of the 2000 ambulance crew underwent an eight hour training programme in cardiopulmonary resuscitation and defibrillation. A total of 1111 cardiac arrests were recorded, and defibrillation was indicated and undertaken in 602 (54%) patients, mean age 63 (range 14-92) years. A spontaneous pulse was present on arrival at hospital in 180 (30%) of the defibrillated patients, and 75 (12.5%) were subsequently discharged alive. As expected, the likelihood of survival was inversely related to the delay from the onset of cardiac arrest to the time of the first shock and was greater in the case of witnessed arrest. If ventricular fibrillation occurred after the arrival of the ambulance, survival to discharge was 33%. CONCLUSIONS: An effective scheme for out of hospital defibrillation can be introduced rapidly, and with limited training implications and costs, by the use of automated external defibrillators in ambulances.

Adolescent↗
PubMed1991

Reference values and reproducibility of Doppler echocardiography in the assessment of the tricuspid valve and right ventricular diastolic function in normal subjects.

The Doppler echocardiographic indexes of the tricuspid and mitral valves were assessed in 74 normal subjects (35 women and 39 men, mean age 45 years). A reproducibility study was also performed to examine the various sources of technical and biological variability. There were significantly higher peak early and late flow velocities across the mitral valve than across the tricuspid valve (0.67 +/- 0.13 and 0.47 +/- 0.12 vs 0.51 +/- 0.08 and 0.35 +/- 0.09 m.s-1, respectively; all p less than 0.0001). There was no significant difference between the early:late (E:A) velocity ratios of the 2 valves (1.65 +/- 0.73 vs 1.75 +/- 0.67, p less than 0.01). There was a steeper mitral early deceleration slope (-3.59 +/- 1.07 vs -2.95 +/- 0.91 m.s-2) but no significant difference in pressure half-times across the 2 valves (47 +/- 7 vs 51 +/- 12 ms, p less than 0.1). No influence of gender or body surface area could be demonstrated. There was a weak but significant relation between mitral peak early, peak atrial velocity and E:A ratio and age (r = -0.39, p less than 0.001, r = 0.23, p less than 0.01, and r = -0.245, p less than 0.01, respectively). There was no significant correlation between any of the tricuspid flow parameters and age. Respiration caused pronounced variability in the tricuspid Doppler indexes and all tricuspid flows were sampled and analyzed only during inspiration. The intra- and interobserver variabilities were small for all of the Doppler indexes measured, but the day-to-day variability was quite significant especially for the pressure half-time, deceleration and acceleration slope values.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

Effect of glibenclamide on extracellular potassium accumulation and the electrophysiological changes during myocardial ischaemia in the arterially perfused interventricular septum of rabbit.

STUDY OBJECTIVE: The aim was to study the effects of glibenclamide on the rate of rise of extracellular potassium concentration ([K+]o) and the electrophysiological changes that occur during myocardial ischaemia. DESIGN: The study was performed in isolated, arterially perfused interventricular septa from the rabbit. Six septa were treated with glibenclamide 10(-6) mol.litre-1 and there were six untreated controls (vehicle only). [K+]o and electrophysiological variables were compared before and during a 30 min period of global zero flow ischaemia. MEASUREMENTS AND MAIN RESULTS: Prior to ischaemia, the extracellular potassium concentrations measured using potassium sensitive valinomycin electrodes were similar in the control and glibenclamide groups being 4.0 (SEM 0.1) and 4.0 (0.1) mmol.litre-1 respectively. [K+]o rose during ischaemia in both groups, and at 30 min was 13.3 (0.7) mmol.litre-1 in the control group. The increase in the glibenclamide group was less marked, reaching 9.2 (0.5) mmol.litre-1 (p less than 0.0005; unpaired t test). Glibenclamide had no electrophysiological effects prior to ischaemia. However, during ischaemia the decrease in action potential amplitude, action potential duration (APD), maximum upstroke velocity of the action potentials (dV/dtmax), and the extent of resting membrane potential (Em) depolarisation were less in the glibenclamide group than in the controls. The effective refractory period (ERP) progressively shortened over the 30 min of ischaemia in both groups, to a similar extent. When taken in conjunction with the relative changes in action potential duration the degree of post-repolarisation refractoriness (ERP-APD) that developed was less in the glibenclamide group than in the controls. CONCLUSIONS: Glibenclamide attenuated the ischaemic rise in [K+]o, with preservation of both membrane potential and action potential amplitude, duration, and upstroke velocity together with less post-repolarisation refractoriness. These effects could be potentially antiarrhythmic in acute myocardial ischaemia.

Action Potentials↗
PubMed1991

Metoprolol and ventricular repolarisation and refractoriness: lack of chronic adaptational class III effects in rabbit.

STUDY OBJECTIVE: The aim was to examine the right ventricular electrophysiological changes during metoprolol treatment and in conditions of stress in the adult rabbit. DESIGN: Metoprolol (6 mg.kg-1) was given twice daily for four weeks. Stress was induced by constant infusion of adrenaline (15.2 micrograms.kg-1.h-1) via osmotic pumps implanted in the left femoral vein. Control rabbits were treated with saline. Electrophysiological recordings were made weekly in conscious animals using bipolar pacing electrodes implanted in the right ventricular apex. SUBJECTS: Adult male New Zealand white rabbits, 2.8-3.3 kg, were used (n = 7 adrenaline/metoprolol treated, n = 7 adrenaline/saline treated, n = 7 saline/metoprolol treated, and n = 7 saline/saline treated). MEASUREMENTS AND MAIN RESULTS: Recordings were made of the effective refractory period and of the stimulus-T interval of the paced evoked response. Stimulus-T is used as an index of ventricular repolarisation time. No significant electrophysiological changes in these variables were observed throughout the study. CONCLUSIONS: These results indicate that chronic metoprolol therapy does not result in a class III antiarrhythmic effect in this in vivo rabbit model.

Animals↗
PubMed1991

Pharmacokinetic and pharmacodynamic effects of UK-68,798, a new potential class III antiarrhythmic drug.

1. The pharmacokinetic and pharmacodynamic properties of UK-68,798, a novel selective potential class III antiarrhythmic agent, were studied in 18 patients with coronary artery disease. Three groups of four patients received intravenous doses of 1.5, 3.0 and 4.5 micrograms kg-1 respectively over 10 min. 2. UK-68,798 caused a mean increase in electrocardiographic QTc interval of 41, 40 and 81 ms, and in uncorrected QT interval of 36, 52 and 83 ms at the three dose levels. There were no significant effects on heart rate, blood pressure, PR interval and QRS duration. UK-68,798 was well tolerated with no significant adverse effects. 3. A dosing regimen using a loading infusion of two thirds of the total dose over 15 min with the remainder given over the following 45 min in six patients produced stable plasma concentrations and lengthening in QTc during the maintenance infusion. 4. There was a linear correlation between plasma concentration and change in QTc. The drug exhibited first-order kinetics with a mean clearance of 4.7 +/- 1.2 ml min-1 kg-1 and a mean terminal plasma half-life of 9.7 h. 5. UK-68,798 warrants further study as a selective potential Class III antiarrhythmic agent.

Adult↗
PubMed1991

Double blind crossover comparison of the effects of dual chamber pacing (DDD) and ventricular rate adaptive (VVIR) pacing on neuroendocrine variables, exercise performance, and symptoms in complete heart block.

OBJECTIVE: To compare the effects of dual chamber pacing (DDD) and ventricular rate adaptive pacing (activity sensing) (VVIR) in patients with complete heart block. DESIGN: Double blind crossover comparison with one month in each pacing mode. PATIENTS: 10 consecutive patients aged 23-74 presenting with complete anterograde atrioventricular block at rest and on exercise and with an intact atrial rate response received Synergyst I (Medtronic) pacemakers. MAIN OUTCOME MEASURES: Symptom scores, maximal exercise performance on a treadmill, and the plasma concentrations of atrial natriuretic peptide, adrenaline, and noradrenaline. RESULTS: No significant differences were identified between pacing modes in symptom scores for dyspnoea, fatigue, and mood disturbance; exercise time; and maximal oxygen consumption. One patient with intact ventriculoatrial conduction developed pacemaker syndrome during VVIR pacing. Resting plasma concentrations of atrial natriuretic peptide were raised in complete heart block and were restored to normal by DDD pacing but not by VVIR pacing. Resting plasma catecholamine concentrations were normal in complete heart block and in both pacing modes. During exercise the increase in the concentrations of all three hormones was similar in both pacing modes. CONCLUSIONS: In patients with complete anterograde and retrograde atrioventricular block, symptoms and maximal exercise performance were no better during DDD than during VVIR pacing.

Adult↗
PubMed1990

Quantification of aortic regurgitation using continuous and pulsed wave Doppler echocardiography.

In a prospective blind study, continuous and pulsed wave Doppler echocardiography were used to predict the severity of angiographically assessed aortic regurgitation in 36 patients. High quality continuous wave spectral recordings of the regurgitant jet were obtained in 32 patients but four patients with mild aortic regurgitation had dropout of high velocity signals precluding accurate assessment. The deceleration slope of the peak to end-diastolic velocity measured by continuous wave Doppler, and pulsed wave Doppler mapping of the regurgitant jet in the left ventricle were compared with angiographic severity. The deceleration slope was significantly steeper in patients with severe rather than mild or moderate aortic regurgitation (3.65 +/- 1.04 vs. 1.89 +/- 0.42 vs. 1.52 +/- 0.59 m sec-2). A decay slope of greater than 3 m sec-2 was observed only in patients with 3+ or 4+ aortic regurgitation and a decay slope less than 1.2 m sec-2 was seen only in mild 1+ aortic regurgitation but there was considerable overlap between groups, making it difficult in individual cases to assess severity on the basis of the continuous wave deceleration slope. The pulsed wave Doppler technique was more time consuming, added little to the continuous wave Doppler assessment and underestimated severe regurgitation in almost 50% of cases. Hence, there are significant problems using either Doppler technique in quantitatively assessing aortic regurgitation.

Adolescent↗
PubMed1990

Adenosine or adenosine triphosphate for supraventricular tachycardias? Comparative double-blind randomized study in patients with spontaneous or inducible arrhythmias.

The effects of intravenous adenosine and adenosine triphosphate (ATP) were studied in a double-blind randomized study during 68 episodes of supraventricular tachycardia in 39 patients. Adenosine restored sinus rhythm in 20 patients (25 of 27 episodes) and produced atrioventricular block to reveal atrial arrhythmias in nine. ATP restored sinus rhythm in 17 patients (22 of 25 episodes) and revealed atrial tachyarrhythmias in six. In patients receiving both compounds, the effective dosage of adenosine was 3.8 mg and of ATP it was 6.6 mg (p less than 0.05), suggesting molar equipotency. Transient side effects were common, occurring in 81% of episodes with adenosine and in 94% with ATP. Symptom scores (0 to 10) were not significantly different (median score for adenosine was 5, for ATP it was 6). Adenosine and ATP were equally effective for the diagnosis and treatment of supraventricular tachycardias and the incidence and severity of side effects were similar. Adenosine has the advantage of being more stable.

Adenosine↗
PubMed1990

Electrophysiological changes in animal model of chronic cardiac failure.

STUDY OBJECTIVE: The aim of the study was to examine right ventricular electrophysiological changes in an animal model of chronic cardiac failure. DESIGN: Cardiac failure was induced in rabbits by intravenous doxorubicin 1 mg.kg-1 twice weekly for 8 weeks. Controls were injected with saline. Electrophysiological recordings were made in conscious animals using bipolar pacing electrodes implanted in the right ventricular apex. SUBJECTS: Adult male New Zealand white rabbits, weight 2.5-3.5 kg, were used (n = 27 doxorubicin treated, 20 control). MEASUREMENTS AND MAIN RESULTS: Recordings were made of effective refractory period and of the stimulus-T interval (Stim-T) of the paced evoked response, an index of ventricular repolarisation time. Progressive shortening of Stim-T and effective refractory period occurred in doxorubicin treated animals, with a reduction of 12% in repolarisation and 14% in refractoriness by week 10. No significant changes in Stim-T or effective refractory period occurred in controls. Right ventricular papillary muscles from doxorubicin treated animals in vitro also showed shortening of intracellular action potential duration and effective refractory period compared with controls. Changes in the doxorubicin treated animals were not attributable to a direct acute electrophysiological effect of doxorubicin or to differences in plasma electrolytes, noradrenaline or renin. CONCLUSIONS: Shortening of ventricular repolarisation and refractory period in heart failure may represent an intrinsic mechanism predisposing to arrhythmia and sudden death.

Action Potentials↗
PubMed1990

Attenuation of the rise in extracellular potassium concentration during myocardial ischaemia by d.l-sotalol and d-sotalol.

STUDY OBJECTIVE: The aim was to study the effects of d.l-sotalol, d-sotalol or atenolol on the rate of rise of extracellular potassium concentration [( K+]o) and the electrophysiological changes that occur during myocardial ischaemia. DESIGN: The study was performed in isolated, arterially perfused interventricular septa from rabbit. Six septa were treated with d.l-sotalol 10(-4) mol.litre-1, six with d-sotalol 10(-4) mol.litre-1, six with atenolol 10(-5) mol.litre-1, and there were seven untreated controls. At these concentrations d.l and d-sotalol are equipotent in their class III effect, though d-sotalol has only 7% of the beta blocking activity of the racemic form, and atenolol is equipotent in its beta blocking activity to d.l-sotalol. [K+]o and electrophysiological variables were compared before and during a 30 min period of global zero flow ischaemia. MEASUREMENTS AND MAIN RESULTS: Prior to ischaemia [K+]o, measured using potassium sensitive valinomycin electrodes, was similar in all the groups. [K+]o rose during ischaemia in all the groups, and at 30 min was 13.0 (SEM 0.7) mmol.litre-1 in the control group which was not different from 12.7(0.5) mmol.litre-1 in the atenolol group. In the d.l and d-sotalol groups the increases were markedly attenuated, reaching 9.2(1.0) and 8.8(0.7) mmol.litre-1 respectively. During ischaemia the class III effect of d.l and d-sotalol was lost within 6 min though the fall in maximum upstroke velocity of the action potentials (dV/dtmax) and the extent of resting membrane potential (Em) depolarisation were less in comparison to the control and atenolol groups. CONCLUSIONS: The results indicate an attenuation by sotalol of the ischaemic rise in [K+]o, with preservation of dV/dtmax and Em, despite the loss of an effect on action potential duration. This potentially antiarrhythmic effect of sotalol in ischaemic myocardium is attributable to a direct membrane effect rather than beta adrenoceptor antagonism.

Action Potentials↗
PubMed1990

Doppler echocardiographic characteristics of normal and dysfunctioning prosthetic valves in the tricuspid and mitral position.

The Doppler echocardiographic characteristics of 70 prosthetic valves in 35 patients are reported. Twenty nine patients had a Björk-Shiley prosthesis in both mitral and tricuspid positions and six had Carpentier-Edwards valves in both sites. Five of the patients had abnormal tricuspid prostheses on the basis of clinical and echocardiographic criteria. Pulsed wave Doppler echocardiography was used in all examinations. The pressure half times for the normal tricuspid prosthetic valves, 105 (40) ms (Björk-Shiley) and 97 (53) ms (Carpentier-Edwards), were significantly longer than those of normal mitral prosthetic valves, 75 (18) ms (Björk-Shiley) and 83 (15) ms (Carpentier-Edwards). The range of pressure half times for the abnormal tricuspid valves (237-530 ms) was distinct from that of the apparently normal tricuspid prosthetic valves (38-197 ms). There was an increase in the peak velocity of the obstructed tricuspid prosthetic valves (1.69 (0.12) m/s) in comparison with normal prostheses (1.06 (0.26) m/s). The normal range of pressure half times for the Björk-Shiley and Carpentier-Edwards valves in the mitral position is not applicable to the same valves in the tricuspid position. The valve appears to function well with very long pressure half times but a pressure half time of greater than 200 ms coupled with a peak velocity of greater than 1.60 ms without significant valve regurgitation indicates tricuspid obstruction of the tricuspid prosthetic valve.

Adult↗