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Biomedical subjects

S M Cobbe

Publications and source records attributed to S M Cobbe.

At least 73 records · Page 4Linked to original sources
PubMed1996

Survival of 1476 patients initially resuscitated from out of hospital cardiac arrest.

OBJECTIVES: To determine the short and long term outcome of patients admitted to hospital after initially successful resuscitation from cardiac arrest out of hospital. DESIGN: Review of ambulance and hospital records. Follow up of mortality by "flagging" with the registrar general. Cox proportional hazards analysis of predictors of mortality in patients discharged alive from hospital. SETTING: Scottish Ambulance Service and acute hospitals throughout Scotland. SUBJECTS: 1476 patients admitted to a hospital ward, of whom 680 (46%) were discharged alive. MAIN OUTCOME MEASURES: Survival to hospital discharge, neurological status at discharge, time to death, and cause of death after discharge. RESULTS: The median duration of hospital stay was 10 days (interquartile range 8-15) in patients discharged alive and 1 (1-4) day in those dying in hospital. Neurological status at discharge in survivors was normal or mildly impaired in 605 (89%), moderately impaired in 58 (8.5%), and severely impaired in 13 (2%); one patient was comatose. Direct discharge to home occurred in 622 (91%) cases. The 680 discharged survivors were followed up for a median of 25 (range 0-68) months. There were 176 deaths, of which 81 were sudden cardiac deaths, 55 were non-sudden cardiac deaths, and 40 were due to other causes. The product limit estimate of 4 year survival after discharge was 68%. The independent predictors of mortality on follow up were increased age, treatment for heart failure, and cardiac arrest not due to definite myocardial infarction. CONCLUSION: About 40% of initial survivors of resuscitation out of hospital are discharged home without major neurological disability. Patients at high risk of subsequent cardiac death can be identified and may benefit from further cardiological evaluation.

Age Factors↗
PubMed1996

Nitric oxide mediates the anti-adrenergic effect of adenosine on calcium current in isolated rabbit atrioventricular nodal cells.

The aim of this study was to determine if adenosine exerts an anti-adrenergic effect on rabbit isolated atrioventricular (AV) nodal cells and, if so, the dependence of this effect on nitric oxide (NO) production. Inward Ca current, ICa, was measured in AV nodal cells, enzymatically isolated from rabbit hearts. Isoprenaline (0.1 microM) increased ICa from 676 +/-59 to 1102 +/-86 pA (n =25). This isoprenaline-induced increase in ICa(178 +/-15% of control) was abolished in the presence of 10 microM adenosine (ICa100 +/-2% of control, n =9, P <0.05). This effect of adenosine was completely blocked by the A1 receptor antagonist CPDPX (8-cyclopentyl l, 3-dipropylxanthine, 0.1 microM). In cells pre-treated with the NO synthase inhibitor, L-nitro-arginine methyl ester (L-NAME, 1 mM) the isoprenaline-induced increase in ICa(208 +/-39% of control, n=7) was not reduced by the addition of 10 microM adenosine (195 +/-32% of control). Co-incubation of cells in L-NAME with L-arginine (1 mM, the endogenous substrate of NO synthase) restored the adenosine-induced attenuation of ICa. In these cells, isoprenaline increased ICa (157 +/-7% of control, n =6), and, following addition of adenosine (10 microM) ICa was reduced to 107 +/-8% (P <0.05). The NO-releasing agent SIN-1 (3-morpholino-sydnonimine, 100 microM), inhibited ICa augmented by isoprenaline (n=5). It is concluded that adenosine exerts an anti-adrenergic effect on the AV node via A1 receptors to attenuate a catecholamine-stimulated increase in ICa and that this action involves the intracellular production of NO.

Adenosine↗
PubMed1996

Arrhythmogenesis in experimental models of heart failure: the role of increased load.

OBJECTIVES: To assess the effects of cardiac failure due to doxorubicin cardiotoxicity or chronic myocardial infarction on arrhythmia induction, ventricular repolarization and refractoriness in isolated perfused rabbit hearts under different loading conditions. METHODS: Cardiac failure was induced by doxorubicin injection (1-1.25 mg.kg-1 twice weekly for 8 weeks, n = 16) or coronary ligation (n = 12), with 12 controls. Cardiac failure was defined by an echocardiographic ejection fraction < or = 0.40. Arrhythmia susceptibility was assessed by programmed ventricular stimulation and fibrillation threshold measurement during Langendorff and during working heart perfusion under baseline conditions and at maximum tolerated preload and afterload. Monophasic action potential duration, dispersion of refractoriness, conduction time and effective refractory period were measured at each level of load. RESULTS: During unloaded (Langendorff) perfusion, there was a low incidence of arrhythmia induction in all hearts. Increasing load did not alter arrhythmogenesis significantly in normal hearts, but led to increases in arrhythmia inducibility and falls in fibrillation threshold which were significantly greater in failing than in non-failing hearts. Monophasic action potential duration was significantly (P < 0.05) shorter in failing than in non-failing hearts in the doxorubicin-treated [mean (s.e.m.) 140(2) vs. 147(2) ms] and post-infarction groups [146(2) vs. 154 (3) ms] during working heart perfusion. The shortening in action potential duration and effective refractory period during increased preload tended to be greater in failing than in non-failing hearts. There were no changes in conduction times in response to changes in loading. CONCLUSIONS: The inducibility of ventricular arrhythmias is greater in failing than in non-failing hearts and is further enhanced by increases in preload. Shortening of repolarization and refractoriness due to increased preload may contribute to the increased risk of ventricular tachyarrhythmias and sudden death in cardiac failure.

Action Potentials↗
PubMed1996

Role of endogenous opioids and catecholamines in vasovagal syncope.

Head-up tilt testing demonstrates vasovagal mechanisms as a cause for syncope, but the pathophysiology underlying this condition remains unclear. The aim of this study was (i) to measure plasma beta-endorphins, adrenocorticotrophic hormone, cortisol, catecholamines, and brain natriuretic peptide during head-up tilt, and (ii) to assess the effect of naloxone infusion during head-up tilt in subjects with reproducible vasovagal syncope. During the assessment of unexplained syncope, 71 subjects underwent a total of 93 tilt tests (60-70 degrees head upwards for 40-45 min or until syncope occurred) during which frequent blood sampling was performed. Subjects with a positive tilt test (n = 56) (mean duration to syncope 23.6 min) showed a larger rise in beta-endorphin levels prior to syncope (baseline 4.7 +/- 2.2 vs syncope onset 6.9 +/- 3.2 pmol.l-1, P = 0.0001) than those with a negative test (n = 37) (baseline 3.9 +/- 3.9 vs end of test 4.9 +/- 2.3 pmol.l-1, P = 0.03). During tilting, adrenocorticotrophic hormone, cortisol, and noradrenaline increased; adrenaline and brain natriuretic peptide remained unchanged; and these responses were similar in positive and negative test groups. Naloxone (2.6 mg.kg-1 i.v. bolus followed by 20 micrograms.kg-1.min-1 infusion), administered in a double-blind fashion during head-up tilt in nine subjects, failed to modify either the time to syncope or the vasodepressor response. Thus, endogenous opioids appear not to be an important trigger for vasovagal syncope, and other pathophysiological mechanisms should be considered.

Adrenocorticotropic Hormone↗
PubMed1996

Coronary haemodynamics in left ventricular hypertrophy.

BACKGROUND: Left ventricular hypertrophy is associated with an increased risk of cardiovascular morbidity and mortality. Previous studies have shown that patients with left ventricular hypertrophy develop electrocardiographic changes and left ventricular dysfunction during acute hypotension, and suggest that the lower end of autoregulation may be shifted upwards. AIM: To measure coronary blood flow (velocity) and flow reserve during acute hypotension in patients with left ventricular hypertrophy. PATIENTS: Eight patients with atypical chest pain and seven with hypertensive left ventricular hypertrophy; all with angiographically normal epicardial vessels. SETTING: Tertiary referral centre. METHODS: The physiological range of blood pressure was determined by previous ambulatory monitoring. Left ventricular mass was determined by echocardiography. At cardiac catheterisation, left coronary blood flow velocity was measured using a Judkins style Doppler tipped catheter. During acute hypotension with sodium nitroprusside, coronary blood flow velocity was recorded at rest and during maximal hyperaemia induced by intracoronary injection of adenosine. Quantitative coronary angiography was performed manually. RESULTS: For both groups coronary blood flow velocity remained relatively constant over a range of physiological diastolic blood pressures and showed a steep relation with diastolic blood pressure during maximal hyperaemia with intracoronary adenosine. Absolute coronary blood flow (calculated from quantitative angiographic data), standardised for left ventricular mass, showed reduced flow in the hypertensive group at rest and during maximal vasodilatation. CONCLUSION: The results are consistent with an inadequate blood supply to the hypertrophied heart, but no upward shift of the lower end of the autoregulatory range was observed.

Adenosine↗
PubMed1996

Enhanced SR function in saponin-treated ventricular trabeculae from rabbits with heart failure.

Cardiac sarcoplasmic reticulum (SR) Ca(2+)-loading ability was assessed in a coronary artery ligation model of heart failure. Heart failure was produced in New Zealand White rabbits by ligation of the left marginal coronary artery. Sham-operated animals were used as controls. After hemodynamic and echocardiographic assessment 8 wk after coronary ligation, a free-running trabecula was isolated from the left or right ventricle, mounted for isometric tension measurement, and permeabilized with the chemical skinning agent saponin, leaving the SR functionally intact. The SR was Ca2+ loaded by exposure of the preparation to a mock intracellular solution with a Ca2+ concentration ([Ca2+]) of 150-300 nM. The amplitude of the caffeine-induced contracture was used as a measure of Ca2+ loaded by the SR. The same preparation was then treated with Triton X-100 to disrupt all cell membranes, and Ca2+ sensitivity {expressed as [Ca2+] required to produce 50% of maximal activation (pCa50)} of isometric tension production and maximum Ca2+ activated force (Cmax) were measured. Ligated animals demonstrated enhanced SR Ca(2+)-loading ability that correlated with the degree of left ventricular dysfunction. Enhanced SR Ca2+ loading was associated with evidence of SR Ca2+ overload revealed as spontaneous tension oscillations. Cmax and pCa50 were not significantly different from controls. Increased SR Ca(2+)-loading ability may predispose the SR to Ca2+ overload and could contribute to both contractile dysfunction and arrhythmogenesis in heart failure.

Actin Cytoskeleton↗
PubMed1996

Comparison of in vivo and in vitro haemodynamic function in experimental heart failure: use of echocardiography.

OBJECTIVE: To compare in vivo and in vitro haemodynamic performance in two models of experimental cardiac failure. To validate echocardiography as a means of non-invasive assessment of left ventricular dysfunction in rabbits. METHODS: Cardiac failure was induced by doxorubicin injection (1-1.25 mg.kg-1 twice weekly for 8 weeks (n = 16)) or coronary ligation (n = 12), with 12 controls. Left ventricular diastolic dimension and ejection fraction were assessed in vivo by echocardiography. The doxorubicin-treated and ligation hearts were subdivided by ejection fraction > 0.40 or < or = 0.40 into non-failing and failing groups. Thermodilution cardiac output was measured in vivo at baseline and after a fluid load. Basal cardiac output and peak cardiac output achieved by increased preload were measured in vitro in the working heart mode. RESULTS: The mean ejection fractions in the doxorubicin-treated and ligation groups were significantly (P < 0.001) lower than in controls, but there was wide inter-individual variability ranging from normal to severely impaired function [mean +/- s.d. (range) controls 0.65 +/- 0.03 (0.59-0.72), doxorubicin 0.45 +/- 0.11 (0.30-0.67), ligation 0.42 +/- 0.12 (0.25-0.65)]. Basal and peak cardiac outputs in vivo and in vitro were significantly lower in the doxorubicin and coronary ligation groups than in controls, although there was a wider scatter of values in the pathological groups. Among the doxorubicin and coronary ligation groups, hearts with ejection fractions < or = 0.40 demonstrated significantly impaired haemodynamic function compared with those with ejection fractions > 0.40. There were significant correlations between ejection fraction and all indices of haemodynamic function in vivo and in vitro. CONCLUSIONS: Simple non-invasive measurement of ejection fraction allowed improved characterization of haemodynamic responses in vivo and in vitro. Individual assessment of animals by echocardiography will improve interpretation of cellular or molecular studies in experimental heart failure by relating observed abnormalities to the degree of global cardiac dysfunction.

Animals↗
PubMed1995

Prevention of coronary heart disease with pravastatin in men with hypercholesterolemia. West of Scotland Coronary Prevention Study Group.

BACKGROUND: Lowering the blood cholesterol level may reduce the risk of coronary heart disease. This double-blind study was designed to determine whether the administration of pravastatin to men with hypercholesterolemia and no history of myocardial infarction reduced the combined incidence of nonfatal myocardial infarction and death from coronary heart disease. METHODS: We randomly assigned 6595 men, 45 to 64 years of age, with a mean (+/- SD) plasma cholesterol level of 272 +/- 23 mg per deciliter (7.0 +/- 0.6 mmol per liter) to receive pravastatin (40 mg each evening) or placebo. The average follow-up period was 4.9 years. Medical records, electrocardiographic recordings, and the national death registry were used to determine the clinical end points. RESULTS: Pravastatin lowered plasma cholesterol levels by 20 percent and low-density-lipoprotein cholesterol levels by 26 percent, whereas there was no change with placebo. There were 248 definite coronary events (specified as nonfatal myocardial infarction or death from coronary heart disease) in the placebo group, and 174 in the pravastatin group (relative reduction in risk with pravastatin, 31 percent; 95 percent confidence interval, 17 to 43 percent; P < 0.001). There were similar reductions in the risk of definite nonfatal myocardial infarctions (31 percent reduction, P < 0.001), death from coronary heart disease (definite cases alone: 28 percent reduction, P = 0.13; definite plus suspected cases: 33 percent reduction, P = 0.042), and death from all cardiovascular causes (32 percent reduction, P = 0.033). There was no excess of deaths from noncardiovascular causes in the pravastatin group. We observed a 22 percent reduction in the risk of death from any cause in the pravastatin group (95 percent confidence interval, 0 to 40 percent; P = 0.051). CONCLUSIONS: Treatment with pravastatin significantly reduced the incidence of myocardial infarction and death from cardiovascular causes without adversely affecting the risk of death from noncardiovascular causes in men with moderate hypercholesterolemia and no history of myocardial infarction.

Anticholesteremic Agents↗
PubMed1995

Electrophysiologic profile and efficacy of intravenous dofetilide (UK-68,798), a new class III antiarrhythmic drug, in patients with sustained monomorphic ventricular tachycardia. Dofetilide Arrhythmia Study Group.

There is increasing evidence that class III antiarrhythmic agents may be superior to class I agents for the long-term treatment of life-threatening ventricular tachyarrhythmias. This open study evaluated the acute electrophysiologic effects, antiarrhythmic efficacy, and safety of different doses of intravenous dofetilide, a new class III drug, in 50 patients with sustained monomorphic ventricular tachycardia inducible by programmed electrical stimulation who had previously been unsuccessfully treated with 0 to 7 (median 3) other drugs. Intravenous dofetilide was administered over 60 minutes at the following dose levels: 1.5, 3.0, 6.0, 9.0, and 15.0 micrograms/kg. Significant class III activity was apparent at doses of 3.0 to 15.0 micrograms/kg, as evidenced by dose-related prolongation of the QTc interval by 13.4% to 14.2%, ventricular effective refractory period by 7.9% to 20.6%, and ventricular functional refractory period by 7.3% to 25.0%. The corresponding mean +/- SD plasma dofetilide concentrations ranged from 1.45 +/- 0.52 to 6.48 +/- 1.31 ng/ml. There was no evidence of reverse use-dependence. At these electrophysiologically active dose levels, intravenous dofetilide suppressed (complete response) or slowed (partial response) inducible ventricular tachycardia in 17 of 41 patients (41%) compared with 0 of 9 patients receiving only 1.5 micrograms/kg. The response rate was fairly uniform among the groups receiving 3.0, 6.0, 9.0, and 15.0 micrograms/kg. Intravenous dofetilide was hemodynamically well tolerated. Torsades de pointes (which was self-limiting) developed in only 1 patient, who was allocated to receive 15.0 micrograms/kg. There were no other proarrhythmic episodes or serious adverse effects. Further evaluation of the therapeutic potential of dofetilide in the management of life-threatening ventricular arrhythmias is justified.

Aged↗
PubMed1995

When is it futile for ambulance personnel to initiate cardiopulmonary resuscitation?

OBJECTIVE: To determine whether patients with unexpected prehospital cardiac arrest could be identified in whom ambulance resuscitation attempts would be futile. DESIGN: Review of ambulance and hospital records; detailed review of automated external defibrillator rhythm strips of patients in whom no shock was advised. SETTING: Scottish Ambulance Service; all cardiopulmonary resuscitation attempts after cardiorespiratory arrest during 1988-94 included in the Heartstart Scotland database. SUBJECT: 414 cardiorespiratory arrest patients with no pulse or breathing on arrival of ambulance personnel, no bystander cardiopulmonary resuscitation performed, and more than 15 minutes from time of arrest to arrival of ambulance. Patients were stratified into those with "shockable" and "non-shockable" rhythms. MAIN OUTCOME MEASURES: Return of spontaneous circulation, or survival to reach hospital alive, or survival to discharge, or all three. RESULTS: No patient with a non-shockable rhythm who met the entry criteria for analysis survived a resuscitation attempt. Review of the defibrillator rhythm strips of these patients failed to find any case in which the tracing was deemed compatible with survival. CONCLUSION: On the basis that it would be inappropriate to initiate vigorous resuscitation in patients who can be identified as "dead" and beyond help an algorithm was prepared to guide ambulance personnel.

Algorithms↗
PubMed1995

Chemical cardioversion of atrial fibrillation with intravenous dofetilide.

We studied the effects of two active dose levels of dofetilide (8 and 12 micrograms/kg) and placebo in 16 patients with recent onset atrial fibrillation. The study was of a crossover design such that all patients received a therapeutic agent, 15 patients completed the study. Cardioversion was achieved in 2/6 patients receiving 8 micrograms/kg dofetilide and in 2/9 patients receiving 12 micrograms/kg. No patients cardioverted as a result of the placebo infusion. Two patients who cardioverted suffered episodes of torsades de pointes following the active drug. Electrical cardioversion was attempted in eight patients who remained in atrial fibrillation and was successful in six. The average duration of atrial fibrillation was 35 days in those who cardioverted and 83 days in those who did not. The compound appears to have only limited effect in cardioversion of atrial fibrillation of moderate duration.

Adult↗
PubMed1995

Randomised, prospective evaluation of a new pericardial heart valve: outcome after seven years.

Between 2 February 1987 and 20 March 1990, 170 patients were randomly allocated to receive a new pericardial heart valve (the Bioflo) or the Carpentier-Edwards supra-annular porcine bioprosthesis. Eighty-five patients (mean age 61 years, range 38-77) received 93 Bioflo valves, 46 having aortic valve replacement (AVR), 31 mitral valve replacement (MVR) and 8 aortic and mitral valve replacement (A+MVR); 85 patients (mean age 62.1 years, range 41-77) received 99 Carpentier-Edwards porcine valves (48 AVR, 23 MVR and 14 A+MVR). Cumulative follow-up totals 926 patient-years (mean 5.45 +/- 1.93, median 6.03, maximum 7.47 years). The overall operative mortality rate for the Bioflo group was 2.4%, and 5.9% for the Carpentier-Edwards group. At 7 years, there was no statistically significant difference in survival or in any prosthesis-related complication between the pericardial and porcine valve recipients overall, or when the data were analysed according to valve implant position. The actuarial survival rate at 7 years for the Bioflo group was 80.1 +/- 5.1% and 72.3 +/- 5.9% for the Carpentier-Edwards group. Freedom from structural valve deterioration (SVD) at 7 years for Bioflo patients was 98.5 +/- 1.5% and for Carpentier-Edwards patients 91.2 +/- 4.1%. No patient in the Bioflo group has required reoperation for SVD. The randomised prospective trial has proven practical and effective and has shown the pericardial valve to perform at least as well as the porcine valve up to 7 years when all of the standard outcome measures of valve performance are assessed.

Actuarial Analysis↗
PubMed1995

Effects of the new class III antiarrhythmic drug dofetilide on the atrial and ventricular intracardiac monophasic action potential in patients with angina pectoris.

The class III antiarrhythmic drug dofetilide is known to prolong action potential duration by specific blockade of the delayed rectifier potassium channel Ik. As dofetilide is likely to be used in the treatment of atrial arrhythmias it is important to determine the relative sensitivity of the atrium and ventricle in man. Twelve male patients underwent monophasic action potential and refractory period recordings from the high right atrium and right ventricular septum. The patients received either 8 micrograms.kg-1 dofetilide or placebo intravenously. The mean QTc was prolonged by 11% (SD 5%, P < 0.00001) in the active group; the mean monophasic action potential increased by 31% (SD 15%, P < 0.0005) in the atrium and 27% (SD 9%, P < 0.00005) in the ventricle; the mean effective refractory period increased by 30% (SD 16%, P < 0.0005) in the atrium and 20% (SD 6%, P < 0.0001) in the ventricle. No significant change occurred in the placebo group. There was no significant difference in effect between the two chambers. The change in QTc did not accurately reflect acute changes in refractory period or monophasic action potential duration. This has important implications for the use of QT prolongation to assess the acute effect of class III drugs.

Action Potentials↗