Biomedical subjects

Stuart M Cobbe

Publications and source records attributed to Stuart M Cobbe.

24 records · Page 2Linked to original sources

PubMed2002

Potential impact of public access defibrillators on survival after out of hospital cardiopulmonary arrest: retrospective cohort study.

OBJECTIVE: To estimate the potential impact of public access defibrillators on overall survival after out of hospital cardiac arrest. DESIGN: Retrospective cohort study using data from an electronic register. A statistical model was used to estimate the effect on survival of placing public access defibrillators at suitable or possibly suitable sites. SETTING: Scottish Ambulance Service. SUBJECTS: Records of all out of hospital cardiac arrests due to heart disease in Scotland in 1991-8. MAIN OUTCOME MEASURES: Observed and predicted survival to discharge from hospital. RESULTS: Of 15 189 arrests, 12 004 (79.0%) occurred in sites not suitable for the location of public access defibrillators, 453 (3.0%) in sites where they may be suitable, and 2732 (18.0%) in suitable sites. Defibrillation was given in 67.9% of arrests that occurred in possibly suitable sites for locating defibrillators and in 72.9% of arrests that occurred in suitable sites. Compared with an actual overall survival of 744 (5.0%), the predicted survival with public access defibrillators ranged from 942 (6.3%) to 959 (6.5%), depending on the assumptions made regarding defibrillator coverage. CONCLUSIONS: The predicted increase in survival from targeted provision of public access defibrillators is less than the increase achievable through expansion of first responder defibrillation to non-ambulance personnel, such as police or firefighters, or of bystander cardiopulmonary resuscitation. Additional resources for wide scale coverage of public access defibrillators are probably not justified by the marginal improvement in survival.

Cardiopulmonary Resuscitation↗

PubMed2002

Depressed inotropic response to increased preload in rabbit hearts with left-ventricular dysfunction induced by chronic myocardial infarction.

Chronic (8 weeks) coronary artery ligation caused marked left-ventricular dysfunction (LVD) in rabbits. The positive inotropic effect observed in vivo with intraventricular injection of saline in sham-operated (control) animals was reversed in rabbits with LVD. In vitro, a step increase in filling pressure from 10 to 15 cm H(2)O caused an immediate increase, followed by a slow increase, in left-ventricular peak systolic pressure (LVP(max)) and cardiac output (CO) over 5-7 min in sham-operated hearts. No significant slow positive inotropic effect was observed in hearts with LVD in response to a standard increase in filling pressure. Progressive increases in filling pressure increased (LVP(max)) and CO to a maximum value at 20 cm H(2)O in control hearts. In the LVD group, progressive increases in filling pressure caused a negative inotropic response and reduced CO. Hearts from the LVD group were significantly dilated compared with control hearts but no significant changes in myocardial compliance were observed in beating or quiescent hearts. These studies reveal an impaired inotropic response to increased ventricular filling in LVD rabbit hearts; this defect included the depression of the slow inotropic response to an increased end-diastolic volume. These changes appear not to be accompanied by altered passive mechanical properties.

Animals↗

PubMed2002

Safety and tolerability of pravastatin in long-term clinical trials: prospective Pravastatin Pooling (PPP) Project.

BACKGROUND: Therapeutic decisions regarding pharmacological therapy should be based on safety and tolerability as well as efficacy data. Clinical trials designed to assess efficacy are often insufficiently powered to generate reliable safety data. METHODS AND RESULTS: The West of Scotland Coronary Prevention Study (WOSCOPS), the Cholesterol and Recurrent Events (CARE), and Long-term Intervention with Pravastatin in Ischemic Disease (LIPID) studies collectively accumulated >112 000 person-years of exposure in double-blind randomized trials comparing placebo and pravastatin (40 mg once daily). During 5 years of exposure, the incidence of fatal and nonfatal cancers was similar between pravastatin and placebo groups. No differences in noncardiovascular serious adverse events were detected. With >243 000 blood sample analyses, the percentage of patients with any abnormal liver function test after baseline sampling was similar (>3x the upper limit of normal for alanine aminotransferase: 128 [1.4%] versus 131 [1.4%] patients for pravastatin versus placebo, respectively). Study medication was withdrawn in 3 pravastatin and 7 placebo patients due to creatine phosphokinase elevations; no cases of mild or severe myopathy were reported. A Cox regression model considering treatment group, age, diabetes, smoking, whether primary or secondary prevention study, and cardiovascular serious adverse events indicates that the likelihood of discontinuing pravastatin was less than placebo. CONCLUSIONS: This prospective analysis indicates that during prolonged exposure, 40 mg of pravastatin is well tolerated, with no excess of noncardiovascular serious adverse events, including liver function abnormalities and laboratory and clinical evidence for myositis. These extensive safety and tolerability data provide important information for therapeutic decisions regarding this pharmacological agent.

Aged↗

PubMed2002

A Prospective Study of Pravastatin in the Elderly at Risk (PROSPER): Screening Experience and Baseline Characteristics.

BACKGROUND: PROSPER was designed to investigate the benefits of treatment with pravastatin in elderly patients for whom a typical doctor might consider the prescription of statin therapy to be a realistic option. METHODS: The PROspective Study of Pravastatin in the Elderly at Risk (PROSPER) is a randomised, double blind, placebo-controlled trial to test the hypothesis that treatment with pravastatin (40 mg/day) will reduce the risk of coronary heart disease death, non-fatal myocardial infarction, and fatal or non-fatal stroke in elderly men and women with pre-existing vascular disease or with significant risk of developing this condition. RESULTS: In Scotland, Ireland, and the Netherlands, 23,770 individuals were screened, and 5,804 subjects (2,804 men and 3,000 women), aged 70 to 82 years (average 75 years) and with baseline cholesterol 4.0-9.0 mmol/l, were randomised. Randomised subjects had similar distributions with respect to age, blood pressure, and body mass index when compared to the entire group of screenees, but had a higher prevalence of smoking, diabetes, hypertension, and a history of vascular disease. The average total cholesterol level at baseline was 5.4 mmol/l (men) and 6.0 mmol/l (women). CONCLUSIONS: Compared with previous prevention trials of cholesterol-lowering drugs, the PROSPER cohort is significantly older and for the first time includes a majority of women. The study, having achieved its initial goal of recruiting more than 5,500 elderly high-risk men and women, aims to complete all final subject follow-up visits in the first half of 2002 with the main results being available in the fourth quarter of 2002.

Journal Article↗

PubMed2002

Assessment of sarcoplasmic reticulum Ca(2+) flux pathways in cardiomyocytes from rabbits with infarct-induced left-ventricular dysfunction.

The aim of the study was to correlate intracellular Ca(2+) transients with Ca(2+) uptake and efflux characteristics of the sarcoplasmic reticulum (SR) in ventricular myocytes isolated from rabbits with left-ventricular dysfunction (LVD). Chronic (8 weeks) ligation of a coronary artery caused marked LVD in rabbits. Measurements of intracellular [Ca(2+)] were made using Fura-2 on intact, single, left-ventricular myocytes. SR Ca(2+) flux rates associated with sarco-endoplasmic reticulum Ca(2+) ATPase type 2 (SERCA2)-mediated uptake, ryanodine receptor type 2 (RyR2)-mediated Ca(2+) efflux and background SR Ca(2+) leak were measured in suspensions of permeabilised myocytes. Measurements on single, permeabilised myocytes were used to assess the steady-state Ca(2+) content of the SR and the characteristics of spontaneous SR Ca(2+) release. Peak systolic [Ca(2+)] was significantly lower; time-to-peak and Ca(2+) transient duration were significantly longer in LVD myocytes. SERCA2-mediated Ca(2+) uptake was reduced to approximately 50% in myocytes from the LVD group. Ruthenium red (RuR)-sensitive Ca(2+) efflux (mediated by the RyR2) was also reduced in the LVD group by approximately 50%, as was the remaining (RuR-insensitive) background Ca(2+) leak. Measurements from single, permeabilised myocytes showed a lower steady-state SR Ca(2+) content. The frequency and amplitude of spontaneous SR Ca(2+) release from LVD hearts was also reduced. Partial inhibition of SERCA2 by thapsigargin depressed both the amplitude and the frequency of spontaneous release. Partial inhibition of RyR2-mediated-Ca(2+) efflux with tetracaine enhanced spontaneous Ca(2+) release amplitude and decreased frequency. Increased background Ca(2+) leak with ionomycin decreased the frequency of spontaneous release. It is concluded that partial inhibition of SERCA2 mimics some aspects of altered SR function in LVD, but reduced RyR2 function cannot explain the other functional alterations observed. Reduced background Ca(2+) leak from the SR may compensate partly for the reduced Ca(2+) uptake capacity of the SR in the LVD group.

Animals↗

PubMed2002

Apex-to-base dispersion of refractoriness underlies the proarrhythmic effect of hypokalaemia/hypomagnesaemia in the rabbit heart.

Apex-to-base differences in the density of potassium currents have been recently described in isolated rabbit myocytes. The significance of those findings for arrhythmogenesis in the whole heart is not known. We aimed to examine electrophysiological effects of hypokalaemia/hypomagnesaemia in isolated working rabbit hearts. Monophasic action potential duration (MAPD(90)), effective refractory period (ERP) and conduction delay were measured at 3 left ventricular sites (basal epicardium, apical epicardium, apical endocardium) in control (K(+) = 4mmol/L, Mg(2+) = 1mmol/L) and hypokalaemia/hypomagnesaemia (K(+) = 2mmol/L, Mg(2+) = 0.5mmol/L) groups. It was found that hypokalaemia/hypomagnesaemia shortened ERP in the apical epicardial region (by 22 +/- 6ms), without any significant effect in the basal area. Consequently, hypokalaemia/hypomagnesaemia increased transepicardial dispersion of refractoriness (from 10 +/- 3 to 25 +/- 7ms, P <.05) and increased inducibility of ventricular fibrillation (from 10% to 100%, P <.05). Similar effects were seen in hearts with left ventricular hypertrophy secondary to perinephritis-induced hypertension. These results suggest that hypokalaemia/hypomagnesaemia is pro-arrhythmic in normal or hypertrophied hearts due to an increase in apex-to-base dispersion of refractoriness.

Action Potentials↗