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Biomedical subjects

S M Cobbe

Publications and source records attributed to S M Cobbe.

At least 109 records · Page 6Linked to original sources
PubMed1994

Increase in plasma beta endorphins precedes vasodepressor syncope.

BACKGROUND: Endogenous opioids have a tonic inhibitory effect on sympathetic tone and have been implicated in the pathophysiology of vasodepressor syncope. Plasma beta endorphin concentrations increase after vasodepressor syncope induced by exercise or by fasting. AIMS: To take frequent samples for plasma beta endorphin estimation during tilt testing, and to determine whether plasma beta endorphin increased before the start of syncope. PATIENTS: 24 patients undergoing tilt testing for investigation of unexplained syncope. SETTING: Tertiary referral centre. METHODS: Blood samples were obtained during 70 degrees head up tilt testing. Plasma beta endorphin concentrations were estimated by radioimmunoassay (mean(SD) pmol/l). RESULTS: Patients with a positive test showed a rise in beta endorphin concentrations before syncope (baseline 4.4(1.5) v start of syncope 8.5(3.1), p < 0.002). In contrast, patients with a negative test showed no change in beta endorphin concentrations (baseline 3.4(1.0) v end of test 4.5(2.3), NS). After syncope all patients showed a large secondary increase in beta endorphins (32.3(18.6)). CONCLUSION: An increase in plasma beta endorphins precedes vasodepressor syncope. This finding supports a pathophysiological role for endogenous opioids.

Adolescent↗
PubMed1994

Hypoxaemia during transoesophageal echocardiography.

OBJECTIVES: To establish the incidence and severity of arterial oxygen desaturation during transoesophageal echocardiography performed under light intravenous sedation; to determine which patients are at greatest risk; and to assess the effects of supplementary oxygen treatment. DESIGN: Prospective study of 150 patients referred for transoesophageal echocardiography. SETTING: Echocardiography laboratory in a tertiary cardiothoracic referral centre. MAIN OUTCOME MEASURE: Transcutaneous arterial oxygen saturation. RESULTS: During transoesophageal echocardiography mean (SD) arterial oxygen saturation (SaO2) fell in 144 of 150 patients (96%) from 95.4%(2.6%) to 90.7%(6.3%) (p < 0.001). Significant hypoxaemia, defined as SaO2 < 90%, was found in 27 of 150 patients (18%); in this group SaO2 fell from 92.9%(3.5%) to 81.8%(9.6%) (p < 0.001), but rose rapidly on oxygen to 95.5%(2.4%) (p < 0.001). Two patients became profoundly hypoxaemic with SaO2 values of 35% and 74%. The principal risk factors for hypoxaemia during transoesophageal echocardiography were mitral valve disease, severe mitral regurgitation, and New York Heart Association symptomatic class III or IV. CONCLUSIONS: Transcutaneous oximetry and supplementary oxygen should be available routinely during transoesophageal echocardiography.

Adult↗
PubMed1994

An audit of utilisation of Holter tape facilities at Glasgow Royal Infirmary.

Holter tape analysis is widely used to both confirm and exclude the presence of significant arrhythmias. We have studied the utilisation of the Holter service at Glasgow Royal Infirmary over a period of 6 months. During this period 305 x 24 hour Holter tapes were recorded. Out patient referrals generated 95% of these requests with only 5% of requests for in patient recordings. The median delay from request date to dispatch to the referring doctor was 14 days. No arrhythmia was detected in 77% and only 3% had a detectable symptomatic significant arrhythmia. The recording was felt to demonstrate the presence of a relevant arrhythmia in 17% of cases and to help exclude a possible arrhythmia in 61%. The capital cost per tape was 20.82 Pounds. In conclusion Holter monitoring is an inexpensive way of analysing the heart rhythm over an extended period which is probably underused.

Adolescent↗
PubMed1994

A characterized model of left ventricular hypertrophy in the rabbit.

A rabbit model of left ventricular hypertrophy is characterized with respect to blood pressure, heart mass and ventricular refractoriness. Hypertension and left ventricular hypertrophy was induced by unilateral nephrectomy plus wrapping of the contralateral kidney in cellophane. Control or sham operated animals were subjected to a similar procedure except that the kidney was not wrapped in cellophane. No change in conscious mean arterial blood pressure was shown in the 11 sham operated animals (75 +/- 2 mmHg before operation and 75 +/- 3 mmHg 4-5 weeks after). Mean arterial pressure was increased from 73 +/- 2 to 99 +/- 3 mmHg by 4-5 weeks and had reached a plateau of 110 +/- 3 mmHg 5-6 weeks after operation in the 16 animals in which the kidney was wrapped. The ratios of left ventricular dry weight to body weight and of whole heart wet weight to body weight were significantly (p < 0.05) higher in the wrap group (0.38 +/- 0.01 and 2.97 +/- 0.12, respectively) than in the sham group (0.29 +/- 0.01 and 2.44 +/- 0.08 respectively). Effective refractory period, recorded from the left side of the arterially perfused interventricular septum, was greater in the wrap (266.1 +/- 8.9 ms) than in the sham group (228.2 +/- 3.5 ms). Linear correlations were shown between mean arterial pressure or effective refractory period vs the ratio of left ventricular dry weight to body weight or ratio of whole heart to body weight. This study has shown that hypertension induced by perinephritis caused left ventricular hypertrophy which was associated with a prolongation in ventricular refractoriness in the rabbit.

Animals↗
PubMed1993

Performance of an established system of first responder out-of-hospital defibrillation. The results of the second year of the Heartstart Scotland Project in the 'Utstein Style'.

The Heartstart Scotland project for out-of-hospital defibrillation covers the whole of Scotland, a population of approximately 5,102,400 (14.9% > 65 years, 48.3% male). All 395 ambulances in Scotland have been equipped with an automated external defibrillator and crews are trained in basic cardiopulmonary resuscitation and defibrillator use (EMT-D). Between 1 May 1990 and 30 April 1991 a total of 1700 cardiac arrests was reported by the ambulance service. Of the 1676 arrests which we could trace, 63% were witnessed. A total of 1383 (83%) of all patients were declared dead on arrival at hospital or in the emergency department, 119 (7%) died in hospital and 174 (10%) were discharged alive. Of the 174 survivors, 87% were conscious and normal at discharge, 9% had moderate residual disability and 2% severe disability. Survival of patients discharged alive from hospital was 85% at 1 year. Defibrillation was undertaken in 71% of the reported cardiac arrests. Survival of bystander witnessed arrests was increased from 7 to 15% with bystander CPR (P < 0.005). If the cardiac arrest was witnessed by the ambulance crew and required defibrillation, survival to discharge was 39%. Of bystander witnessed arrests reached while still in VF (n = 643), 11% were discharged alive. Patients who were defibrillated within 4 min of arrest had a 43% survival rate to hospital discharge.

Cardiopulmonary Resuscitation↗
PubMed1993

Influence of hyperkalaemia and ischaemia on non-receptor-mediated cardiac electrophysiological effects of naloxone.

OBJECTIVE: The aim was to investigate the cardiac electrophysiological effects of the opioid receptor antagonist naloxone and examine whether hyperkalaemia and ischaemia influence these effects. METHODS: The cardiac electrophysiological effects of racemic naloxone, nalmafene, and morphine were examined in superfused rabbit papillary muscles under normal conditions and in the case of naloxone under conditions of hyperkalaemia. The electrophysiological effects of racemic naloxone and d-naloxone were examined in arterially perfused rabbit interventricular septa before and during 30 min global zero flow ischaemia; the rate of rise of extracellular K+ concentration was also measured. RESULTS: Naloxone, nalmafene and morphine all prolonged action potential duration and effective refractory period in superfused papillary muscles (class III effects), suggesting that these effects are not receptor mediated. During hyperkalaemia, naloxone increased the depressant effect on the maximum upstroke velocity of the action potential and enhanced post-repolarisation refractoriness, further suggesting a class I effect. Both racemic naloxone (active at opioid receptors) and d-naloxone (inactive) prolonged action potential duration and effective refractory period in septa, again suggesting non-receptor-mediated effects. During myocardial ischaemia the class III effects of both compounds were gradually lost in such a way that post-repolarisation refractoriness developed. Both compounds reduced the rate of rise of extracellular K+ concentration and preserved resting membrane potential, but the fall in maximum upstroke velocity was enhanced, again suggesting that naloxone has an additional class I effect in partially depolarised ventricular myocardium. CONCLUSIONS: The antiarrhythmic activity of naloxone in models of myocardial ischaemia/reperfusion can be explained by non-opioid receptor mediated effects on the duration and maximum upstroke velocity of the action potential and on extracellular potassium accumulation during ischaemia.

Action Potentials↗
PubMed1993

Early treatment with captopril after acute myocardial infarction.

OBJECTIVES: To determine the effects of early treatment with captopril on haemodynamic function, neuroendocrine biochemistry, left ventricular structure, clinical outcome, and exercise capacity over one year from acute myocardial infarction. DESIGN: Randomised, double blind, placebo controlled comparison of captopril and placebo. SETTING: Coronary care units and cardiology departments of two university teaching hospitals in Glasgow. PATIENTS: 99 haemodynamically stable patients with acute myocardial infarction, selected on clinical grounds as being at risk of late ventricular dilatation. INTERVENTION: Captopril or identical placebo started between six and 24 hours after start of symptoms and continued for 12 months. Target maintenance dose was 25 mg three times a day. MAIN OUTCOME MEASURES: (a) Acute haemodynamic effects of treatment; (b) neuroendocrine biochemistry from admission to two months; and (c) change in echocardiographic measures of left ventricular size, clinical outcome, and exercise capacity after 12 months of treatment with a separate analysis of the effects of one month of treatment withdrawal on left ventricular volumes. RESULTS: Captopril caused acute reductions in mean (SEM) pulmonary artery pressure (2.48 (0.69) mm Hg) and systemic vascular resistance (260 (103)) dyn.s.cm-5). Over the first 10 hours captopril reduced mean arterial pressure by 12.1 (2.4) mm Hg compared with 3.8 (1.9) mm Hg in the placebo group. No patient had to be withdrawn from the captopril group because of hypotension. From day 1 onwards systolic and diastolic arterial pressures in the captopril treated group were slightly but not significantly lower than on placebo. There was no difference in the incidence of ventricular or supraventricular arrhythmia with treatment. Captopril prevented the day 3 peak in angiotensin II that occurred in the placebo group (peak concentration (interquartile range): 10.1 (4.8-19.4) pg/ml v 16.8 (4.3-46.3) pg/ml)) but had no effect on atrial natriuretic factor, arginine vasopressin, or catecholamines. Plasma atrial natriuretic factor remained above normal in both groups at two months after infarction. After one year left ventricular volume indices had increased less on captopril than on placebo: left ventricular end systolic volume index 5.4 ml/m2 v 14.7 ml/m2 (95% confidence interval (95% CI) of difference -14.6 to -3.9; p = 0.0011); left ventricular end diastolic volume index 8.4 ml/m2 v 19.0 ml/m2 (95% CI of difference, -17.0 to -4.2; p = 0.0016). Withdrawal of captopril for one month did not affect ventricular volumes. There was no difference in exercise capacity. CONCLUSIONS: Captopril started between six and 24 hours after acute myocardial infarction is not associated with significant hypotension. It suppresses activation of the renin angiotensin system but has no effect on plasma concentrations of other neurohormones. Atrial natriuretic factor remains raised at two months after myocardial infarction. Captopril significantly decreases left ventricular dilatation. This effect is not lost after one month of treatment withdrawal and is thus due to an alteration of left ventricular structure and not to a short lived haemodynamic action of captopril. Long-term treatment with captopril does not result in improved aerobic exercise capacity after acute myocardial infarction.

Adult↗
PubMed1992

Effects of the class III antiarrhythmic drug dofetilide on ventricular monophasic action potential duration and QT interval dispersion in stable angina pectoris.

The effects of intravenous dofetilide on ventricular monophasic action potential duration and effective refractory period at the right ventricular apex and outflow tract were studied in 18 patients (aged 37 to 70 years) with ischemic heart disease. Six patients received low-dose dofetilide as a 3 micrograms/kg loading dose over 15 minutes and a 1.5 micrograms/kg maintenance dose over 45 minutes; 6 received high-dose dofetilide 6 + 3 micrograms/kg and 6 placebo. During atrial pacing at a cycle length of 800 ms high-dose dofetilide prolonged right ventricular apex monophasic action potential duration by 45 ms (16%) and the effective refractory period by 40 ms (16%). At the right ventricular outflow tract, monophasic action potential duration was prolonged by 45 ms (15%) and effective refractory period by 55 ms (21%). During atrial pacing at a cycle length of 500 ms high-dose dofetilide prolonged the right ventricular apex monophasic action potential duration by 40 ms (18%) and the effective refractory period by 43 ms (21%). The right ventricular outflow tract monophasic action potential duration was prolonged by 33 ms (14%) and effective refractory period by 45 ms (21%). Dofetilide produced no increase in the dispersion of repolarization between the 2 sites. During the maintenance infusion QTc prolongation by high-dose dofetilide averaged 43 ms (10%) with no increase of interlead QT dispersion. The effects of dofetilide on QT interval and effective refractory period are shown to be due to a direct effect on action potential duration with no effect on dispersion. No rate dependence of monophasic action potential prolongation was detected at these cycle lengths.

Action Potentials↗
PubMed1992

Significance of ventricular arrhythmias in systemic hypertension with left ventricular hypertrophy.

Hypertensive patients with the electrocardiographic (ECG) pattern of left ventricular (LV) hypertrophy and strain are at increased risk of sudden death. It has been suggested that ventricular arrhythmias may be responsible. The prevalence and significance of ventricular arrhythmias was therefore studied in 90 hypertensive patients with LV hypertrophy and strain by undertaking 48-hour ambulatory ECG monitoring, ECG signal-averaging and programmed ventricular stimulation. Complex ventricular ectopic activity (Lown grade greater than or equal to 3) was detected in 59 patients (66%). Eleven patients (12%) had episodes of nonsustained ventricular tachycardia. There were no sustained arrhythmias either on ambulatory ECG monitoring or induced by programmed ventricular stimulation. Only 1 patient had ventricular late potentials recorded by the signal-averaged electrocardiogram. Therefore, there was little to suggest an underlying arrhythmogenic substrate in these patients. In conclusion, whereas ventricular arrhythmias occur often in patients with LV hypertrophy associated with systemic hypertension, their significance, if any, remains to be established.

Adult↗
PubMed1992

Clinical and electrophysiologic effects of intravenous dofetilide (UK-68,798), a new class III antiarrhythmic drug, in patients with angina pectoris.

Dofetilide (UK-68,798) is a new class III antiarrhythmic agent. In animal experiments it selectively prolongs the refractory periods parallel to the action potential duration without any influence on upstroke velocity or conduction parameters. The present double-blind, placebo-controlled study was designed to show the effect of dofetilide on basic electrophysiologic parameters in patients with coronary artery disease. Eighteen patients (aged 31 to 64 years) with symptoms of stable angina pectoris admitted for routine coronary angiography were recruited. They were randomly allocated to receive either placebo or 1 of 2 dose levels of dofetilide intravenously with 6 patients in each group. Paired electrophysiologic variables were compared before and after administration of dofetilide. Both active dose levels produced significant prolongations (p less than 0.05) of 10 to 23% in atrial effective refractory period, 6 to 16% in ventricular effective refractory period and 11 to 15% in ventricular functional refractory period. Atrial functional refractory period was prolonged by 14 to 22% at the high-dose level (p less than 0.05). No effect was observed on conduction parameters (PA, AH, HV, PR or QRS intervals), sinus cycle length or sinus node recovery. The selective prolongation of the refractory periods in both atrium and ventricle, combined with a lack of effect on cardiac conduction parameters, indicates that this drug could be useful in the treatment of both atrial and ventricular reentrant tachyarrhythmias and fibrillation.

Adult↗
PubMed1992

Pacing termination of spontaneous ventricular tachycardia in the coronary care unit.

We reviewed our experience with the use of pacing techniques in the acute treatment of spontaneous ventricular tachycardia occurring outside the context of acute myocardial ischaemia. Over a consecutive 18 month period 23 patients (20 male, aged 38-76 yr) admitted to our coronary care unit experienced a total of 75 episodes of haemodynamically tolerated sustained ventricular tachycardia. Pace termination was attempted in 18 patients in a total of 58 episodes of ventricular tachycardia using a standard temporary external pacemaker. Pacing was successful in 32/58 (55%) attempts vs 13/49 (27%) with intravenous antiarrhythmic drug therapy p = 0.003. The superior success rate of pacing was apparent whether or not patients were receiving chronic antiarrhythmic drug therapy. Pace termination should be considered in the treatment of haemodynamically tolerated spontaneous ventricular tachycardias.

Adult↗
PubMed1992

Beta endorphin release in patients after spontaneous and provoked acute myocardial ischaemia.

BACKGROUND: In animal models of circulatory shock and heart failure concentrations of the endogenous opioid peptide beta endorphin are raised and opioid receptor blockade improves haemodynamic variables and survival. This study was performed to identify whether acute myocardial ischaemia provokes the release of beta endorphin in humans. METHODS: Observational study in a university cardiology centre. Serial measurements of beta endorphin made by specific radioimmunoassay were correlated with other clinical and neuroendocrine variables that were measured prospectively. Fifty five patients with acute myocardial ischaemia and 26 patients undergoing elective coronary angioplasty of the left anterior descending coronary artery were studied. RESULTS: beta endorphin concentrations were raised above the upper limit of normal in 31/42 (74%) patients with confirmed myocardial infarction, 3/13 (23%) patients with unstable angina, and 10/24 (42%) patients after coronary angioplasty. There was no evidence of myocardial release of beta endorphin. There were significant positive correlations between beta endorphin and the concentrations of adrenocorticotrophic hormone, cortisol, and arginine vasopressin. In patients with acute myocardial ischaemia there was a significant positive correlation between the peak concentrations of creatine kinase and beta endorphin but no correlation with visual analogue scores of the intensity of chest pain. The highest beta endorphin concentrations were seen in patients whose clinical course was complicated by the development of heart failure. CONCLUSIONS: beta endorphin release is a component of the neuroendocrine activation associated with myocardial ischaemia/infarction.

Acute Disease↗
PubMed1992

Symptomatic and silent myocardial ischaemia in hypertensive patients with left ventricular hypertrophy.

OBJECTIVE: To assess the prevalence of symptomatic and silent myocardial ischaemia in patients with hypertensive left ventricular hypertrophy. DESIGN: Cross sectional study. SETTING: University department of medical cardiology. PATIENTS: 90 patients (68 men and 22 women; mean age 57 (range 25 to 79)) with left ventricular hypertrophy due to essential hypertension. INTERVENTIONS: 48 hour ambulatory ST segment monitoring (all patients), exercise electrocardiography (n = 79), stress thallium scintigraphy (n = 80), coronary arteriography (n = 35). RESULTS: 43 patients had at least one episode of ST segment depression on ambulatory electrocardiographic monitoring. The median number of episodes was 16 (range 1 to 84) with a median duration of 8.6 (range 2 to 17) min. Over 90% of these episodes were clinically silent. 26 patients had positive exercise electrocardiography and 48 patients had reversible thallium perfusion defects despite chest pain during exercise in only five patients. 18 of the 35 patients who had coronary arteriography had important coronary artery disease. Seven of these patients gave no history of chest pain. CONCLUSIONS: Symptomatic and silent myocardial ischaemia are common in hypertensive patients with left ventricular hypertrophy, even in the absence of epicardial coronary artery disease.

Adult↗