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Biomedical subjects

S M Cobbe

Publications and source records attributed to S M Cobbe.

At least 163 records · Page 9Linked to original sources
PubMed1987

The influence of ischaemia on the electrophysiological properties of amiodarone in chronically treated rabbit hearts.

The effects of 30 min zero-flow ischaemia and reperfusion on the electrophysiological properties of amiodarone were studied in 11 rabbits treated with oral amiodarone (mean 117 mg kg-1, day-1) for 2-3 months, and 11 controls. Experiments were performed in vitro in the isolated perfused interventricular septum, and preischaemic values were compared with those obtained in right ventricular papillary muscles from the same hearts. Prior to ischaemia, mean values of action potential duration (APD90) and effective refractory period (ERP) were prolonged by 13% in the amiodarone-treated septa. Action potential upstroke velocity (Vmax) was reduced by 14% in the septa, but by 42% in papillary muscles. Ischaemia resulted in shortening of APD90 in both control and amiodarone-treated septa, with a loss of the ability of amiodarone to prolong APD90. In contrast, ischaemia resulted in a greater fall in Vmax, gross lengthening in conduction time and increase in stimulation threshold in the amiodarone-treated septa compared with controls. Reperfusion resulted in a restoration of the action of amiodarone on repolarization, and resolution of the marked effects on excitability and conduction. The electrophysiological properties of amiodarone are considerably altered in ischaemic myocardium, with a reversible loss of its ability to prolong repolarization, but evidence suggestive of a marked enhancement of its effect on the inward sodium current.

Action Potentials↗
PubMed1987

Adaptive processes after myocardial infarction.

Although much recent attention has focussed on the events of the first 12 hours of acute myocardial infarction, the local and systemic evolutionary changes which occur during the following days and weeks are of equal importance. The condition of the ischaemic and infarcted myocardium may be altered by spontaneous reperfusion or reocclusion, with effects on the mechanical and electrical sequelae of the initial infarction. The area of infarction undergoes "maturation" in its mechanical and electrical properties, which result in alterations in ventricular function and in the types of arrhythmias encountered. These changes occur against the background of the metabolic and neurohumoral response to infarction, which result in changes in catecholamine drive, plasma potassium, and free fatty acid levels, and in the renin-angiotensin-aldosterone system. The resolution of the initial metabolic response to infarction may be slowed or reversed by the development of heart failure. The varying speed of these adaptive processes has considerable influence on the optimal timing of investigations designed to identify "high-risk" patients. The appropriate time for the start of secondary prevention measures will likewise depend on the restoration process following the initial infarct.

Adaptation, Physiological↗
PubMed1987

A comparison of symptoms and intra-arterial ambulatory blood pressure during long term dual chamber atrioventricular synchronous (DDD) and ventricular demand (VVI) pacing.

Fifteen patients with dual chamber pacemakers implanted for atrioventricular block (11) or sinoatrial disease (4) completed a single blind within-patient comparison of symptoms and 24 hour intra-arterial blood pressure during long term atrioventricular synchronous (DDD) pacing and long term ventricular demand (VVI) pacing. The patients reported significantly less breathlessness, fatigue, and dizziness and a significantly greater sense of general well-being during DDD pacing than during VVI pacing. Twelve of the fifteen patients expressed a strong preference for DDD pacing. Systolic blood pressure tended to be lower and was significantly more variable during VVI pacing than during DDD pacing (mean (SD) daytime systolic blood pressure 132.4 (17.1) and 140.4 (13.1) mm Hg respectively). Accordingly, episodes of hypotension were more common during VVI pacing, which may partly explain why the patients reported more symptoms during this mode of pacing.

Aged↗
PubMed1986

Subsidiary class III effects of beta blockers? A comparison of atenolol, metoprolol, nadolol, oxprenolol and sotalol.

The electrophysiological effects of various concentrations of atenolol, metoprolol, nadolol, D-oxprenolol, L-oxprenolol, and D, L-oxprenolol and D-sotalol, L-sotalol, and D, L-sotalol were compared in rabbit right ventricular papillary muscle studied in vitro using intracellular microelectrodes. An assessment of the relative beta blocking effects of D-sotalol and D, L-sotalol against the inotropic action of isoprenaline was made in the same preparation. Of the drugs tested, only oxprenolol and sotalol showed prolongation of action potential duration and effective refractory period (class III action), with oxprenolol showing, in addition, depression of maximal upstroke velocity and the presence of post-repolarisation refractoriness (class I action). When contrasted at clinically relevant concentrations, only sotalol retained a class III effect, without any actions on variables related to fast inward current. The effects of oxprenolol and sotalol were not found to be stereospecific. The mechanical experiments indicate that, in this preparation, D-sotalol has approximately one-fourteenth of the beta blocking potency of the racemic compound. It therefore merits further consideration as a useful alternative class III antiarrhythmic agent, which would be free from the side effects of beta receptor blocking treatment.

Action Potentials↗
PubMed1986

Non-invasive assessment by Doppler ultrasound of 155 patients with bioprosthetic valves: a comparison of the Wessex porcine, low profile Ionescu-Shiley, and Hancock pericardial bioprostheses.

One hundred and fifty five patients with 167 bioprosthetic valves (68 Wessex porcine, 54 Hancock pericardial, and 45 low profile Ionescu-Shiley pericardial valves) were studied by Doppler ultrasound. Valve gradients were calculated from the mitral and aortic flow velocities by the modified Bernoulli equation. Mean mitral gradients were significantly smaller across the Ionescu-Shiley valves than across the Wessex porcine or Hancock pericardial valves. Mitral pressure half time was, however, significantly longer in the Hancock pericardial than in the Wessex porcine or Ionescu-Shiley valves. No significant differences were seen among the groups of aortic bioprostheses, though the comparable size of Wessex porcine valves showed significantly higher gradients. Bioprosthetic regurgitation was detected in 13 of 103 mitral and 11 of 59 aortic valves, though it was suspected clinically in only 12 mitral and six aortic bioprostheses. Doppler ultrasound is a repeatable non-invasive method of acquiring haemodynamic information in vivo from a variety of bioprostheses and it can detect bioprosthetic regurgitation at an early stage.

Adult↗
PubMed1986

Cardiovascular risk in patients with treated familial hypercholesterolaemia and patients with severe hypertriglyceridaemia.

A study was performed to determine the morbidity and mortality from ischaemic heart disease (IHD) in patients with heterozygous familial hypercholesterolaemia (FH) and severe hypertriglyceridaemia (pretreatment plasma triglyceride greater than 5 mmol/l). Twenty-nine (38%) of 76 patients with FH and 8(44%) of 18 patients with hypertriglyceridaemia had evidence of IHD. Over a mean follow-up period of 5.5 years, 2 patients with hypertriglyceridaemia died but there were no deaths in patients with FH. This contrasts with earlier reports which showed a high mortality in FH patients. The lower mortality may be due to improved treatment and consequent lower levels of cholesterol.

Adult↗
PubMed1985

The influence of acute myocardial ischaemia on the class III antiarrhythmic action of sotalol.

The effects of acute myocardial ischaemia on the Class III antiarrhythmic properties of dl-sotalol 10(-4) mol . litre-1 were studied in the isolated arterially perfused interventricular septum of the rabbit heart. Before ischaemia, sotalol increased mean action potential duration (APD90) from 267 +/- 6 to 406 +/- 19 ms (p less than 0.001 mean +/- SEM, n = 7 septa), and mean effective refractory period (ERP) from 222 +/- 7 to 291 +/- 10 ms. During 30 min zero flow global ischaemia, mean APD90 in the control group fell from 264 +/- 7 to 128 +/- 13 ms (n = 7). APD90 fell more rapidly in the sotalol group, so that the initial difference between the sotalol and control groups was abolished after 24 min ischaemia. In the sotalol group, ERP shortened rapidly during ischaemia, and was significantly less than in the control group after 30 min. These changes were associated with the development of substantial post-repolarisation refractoriness in the control but not in the sotalol group. There was a greater fall in action potential upstroke velocity in the controls than in the sotalol group. The results indicate that the Class III effect of sotalol gradually disappears during ischaemia. The effects on post-repolarisation refractoriness and upstroke velocity are compatible with the hypothesis that sotalol slows the rate of rise of extracellular potassium concentration in acute ischaemia. This is a potentially antiarrhythmic property.

Action Potentials↗
PubMed1985

Interaction of the effects of hypoxia, substrate depletion, acidosis and hyperkalaemia on the class III antiarrhythmic properties of sotalol.

The effects of hypoxia on the actions of dl-sotalol 10(-4) mol . litre-1 were studied in rabbit papillary muscles at 32 degrees C. Superfusion for 30 min with a hypoxic solution (95% N2, 5% CO2) in the presence of 5 mmol . litre-1 glucose caused moderate shortening of control action potential duration from 208 +/- 3 to 138 +/- 9 ms (mean +/- SEM). In the presence of sotalol, hypoxia caused shortening of APD90 from 399 +/- 9 ms to 249 +/- ms, but the value after 30 min was still significantly greater than in controls (p less than 0.001). Superfusion with a hypoxic, glucose-free solution, however, caused profound shortening of APD90 in controls to 80 +/- 7 ms at 30 min. The highly significant lengthening of APD90 produced by sotalol in control conditions was abolished after 5 min hypoxia. The effects of hypoxia on the effective refractory period (ERP) paralleled those on APD90. Exposure to a hypoxic, acidotic, hyperkalaemic solution (80% N2, 20% CO2, pH 6.8; K+ 12 mmol . litre-1) produced moderate shortening of APD90 with convergence of the two groups. There was an increase in ERP, with the development of an equal degree of post-repolarisation refractoriness in the control and sotalol groups. The Class III effect of sotalol is preserved under mild but lost under severely hypoxic conditions. Using "simulated ischaemic" conditions, with controlled extracellular potassium concentrations, there was no difference in the relationship between APD90 and ERP in the control and sotalol groups.

Acidosis↗
PubMed1985

Effects of elevated extracellular potassium concentrations on the class III antiarrhythmic action of sotalol.

The electrophysiological and mechanical effects of sotalol, a beta-adrenergic blocker with Class III antiarrhythmic properties, were compared with those of atenolol in rabbit right ventricular papillary muscles studied in vitro using intracellular microelectrodes. Sotalol produced a dose-dependent increase in action potential duration and effective refractory period without any effect on parameters of rapid inward current. Atenolol had no Class I or Class III effect. The actions of equipotent beta-blocking concentrations of sotalol (10(-4) mol X litre-1) and of atenolol (10(-5) mol X litre-1) in elevated extracellular potassium concentrations of 8 and 12 mmol X litre-1 were investigated. There were reductions in membrane potential, action potential amplitude and upstroke velocity in elevated potassium which were not influenced by sotalol and atenolol, apart from a small additional depression of action potential amplitude and membrane potential in 12 mmol X litre-1 potassium. Hyperkalaemia caused shortening in action potential duration but lengthening in effective refractory period (post-repolarisation refractoriness). The increase in effective refractory period over control produced by sotalol in normal potassium was preserved in elevated potassium. This effect was attributable to lengthening of action potential duration rather than alteration in the duration of post-repolarisation refractoriness. The Class III effects of sotalol are preserved even in partially depolarised fibres where rapid inward current is depressed.

Action Potentials↗
PubMed1985

Contribution of delayed ventricular repolarization to the anti-arrhythmic efficacy of sotalol.

Eighteen patients with sustained ventricular tachycardia underwent serial electrophysiological studies to establish the therapeutic efficacy of sotalol as compared to other available anti-arrhythmic agents. One or more acutely effective drug was found in 14 of the 18 patients (78%). Sotalol was tested in all 18 patients and was effective in 12 of them (67%). For assessment of the prophylactic efficacy of other anti-arrhythmic agents, an average of 3.5 additional studies per patient were performed resulting in successful prevention of ventricular tachycardia in a total of 10 of 63 (16%) additional trials. Nine patients were placed on chronic oral therapy with sotalol. In these nine patients long-term prophylaxis against ventricular tachycardia was documented over a mean follow-up period of 9.6 months (range 2-18 months). The study suggests that sotalol can provide effective prophylaxis against ventricular tachycardia in a significant proportion of patients refractory to other available drugs and that this prophylactic efficacy is predominantly due to its Class III anti-arrhythmic properties. Experimental studies were performed in eight conscious dogs 3-7 days following proximal LAD ligation. Epicardial recordings were obtained using implanted composite electrodes. Sotalol prevented sustained VT by a predominant increase in refractoriness of the infarcted zone. In vitro, sotalol caused a significant prolongation of the action potential of epicardial and endocardial fibres within both the infarcted and noninfarcted myocardium. Refractoriness of epicardial ventricular fibres was significantly more prolonged in ischemically damaged cells as compared to normal fibres.

Animals↗
PubMed1985

Day to day variations in morphology and duration of fragmented ventricular potentials during the late post-myocardial infarction phase in conscious dogs.

The relationship between the inducibility of ventricular tachyarrhythmias and the presence of fractionated epicardial ventricular electrograms ('late potentials') was studied daily between days 3 and 8 after experimental myocardial infarction in 15 conscious dogs. Before each programmed stimulation, epicardial infarct zone electrograms were recorded from implanted 'composite' electrodes during sinus rhythm. There was considerable daily variation in the morphology and duration of delayed ventricular activation, but no significant difference in duration of infarct zone electrograms was seen between studies resulting in ventricular fibrillation (108 +/- 62 ms, mean +/- SD), sustained ventricular tachycardia (87 +/- 18 ms), nonsustained (94 +/- 41 ms) or no tachycardia (78 +/- 5 ms). Although fractionated ventricular electrograms were commonly recorded early after infarction, their presence and duration could not predict the inducibility of malignant ventricular tachyarrhythmias. Similar limitations may apply in clinical practice to the use of surface signal averaging of ventricular late potentials in the early post-myocardial infarction period.

Animals↗
PubMed1985

Day-to-day variations in inducibility of ventricular tachyarrhythmias during the late postmyocardial infarction phase in conscious dogs.

The inducibility of ventricular tachyarrhythmias was studied daily on days 3 through 8 after experimental myocardial infarction in 15 conscious dogs. Although a sustained ventricular tachyarrhythmia was produced on one or more occasions in 11 of 15 dogs (73%), there was marked daily variation in the results of programmed stimulation. Ventricular fibrillation or sustained ventricular tachycardia was elicited in six dogs on day 3 after infarction. In two of these dogs, no sustained tachycardia could be induced by day 7. In nine dogs sustained ventricular arrhythmias were not inducible on day 3. By day 6 to 7, sustained ventricular tachycardia was inducible in five of these dogs. In clinical practice similar variation in the inducibility of sustained ventricular arrhythmias may conceivably complicate the use of results of programmed ventricular stimulation as determinants of risk of sudden death after myocardial infarction.

Animals↗
PubMed1984

Actions of disopyramide on potential reentrant pathways and ventricular tachyarrhythmias in conscious dogs during the late post-myocardial infarction phase.

The effect of intravenous disopyramide (plasma level 3.7 +/- 1.6 micrograms/ml, mean +/- standard deviation) on reentrant ventricular tachyarrhythmias was studied by programmed ventricular stimulation in 11 conscious dogs 3 to 8 days after experimental myocardial infarction. Sustained ventricular tachycardia (VT) was induced in 4 dogs (mean cycle length 173 +/- 14 ms) and nonsustained VT in 7 (8 +/- 4 beats, mean cycle length 136 +/- 18 ms). Disopyramide prevented induction of VT in 1 of 4 dogs with sustained VT and 3 of 7 with nonsustained VT, and increased VT cycle length by more than 30% in 2 dogs with sustained VT and 2 of 7 with nonsustained VT. Disopyramide prolonged refractoriness in the infarct zone, measured by analysis of electrograms from an implanted "composite" electrode, by 38 to 53%, depending on the mode of pacing. These values were significantly greater than the increase produced by disopyramide in ventricular effective refractory period (13 +/- 12%), QRS duration and QT interval. Disopyramide has a selective effect on potential reentry circuits in ischemic myocardium, and prolongs refractoriness in abnormal myocardium to a greater extent than its effect on the normal ventricle.

Animals↗
PubMed1984

A comparison of cholestyramine and probucol in the treatment of familial hypercholesterolaemia.

Twelve patients with familial hypercholesterolaemia (FH) who had not achieved satisfactory cholesterol levels on dietary advice alone were treated with cholestyramine for 6 months and probucol for 6 months in a randomised cross-over study to compare the relative effectiveness of the two drugs. Over the 6-month period, mean total cholesterol fell by 16.4% on cholestyramine and 12.7% on probucol. Cholestyramine produced a 17.4% fall in low density lipoprotein (LDL) cholesterol, no significant changes in very low density lipoprotein (VLDL) cholesterol or high density lipoprotein (HDL) cholesterol, a 21.4% increase in HDL cholesterol subfraction HDL2 and a 24.1% increase in the HDL/LDL cholesterol ratio. Triglyceride levels rose by 29.6% but remained within the normal range. Probucol produced a 11.7% fall in LDL cholesterol, a 9.9% fall in VLDL cholesterol, a 10% fall in total HDL cholesterol, a 37% fall in HDL cholesterol subfraction HDL2 and no change in the HDL/LDL cholesterol ratio. Triglyceride levels fell by 14%. The mean corrected QT interval increased from 0.418 to 0.434 s (P less than 0.01) on probucol but did not change significantly on cholestyramine (from 0.405 to 0.41 s). The two drugs have different metabolic effects on FH. Cholestyramine has a more marked effect on LDL cholesterol, favourably influences the HDL/LDL cholesterol ratio and is therefore considered to be the drug of choice.

Cholesterol↗
PubMed1984

Serum sickness complicating intravenous streptokinase therapy in acute myocardial infarction.

A case of delayed serum sickness with transient renal impairment is described in a patient who received early high dose intravenous streptokinase following acute myocardial infarction. Review of the literature suggests that serum sickness after streptokinase may occur independently of the dose or route of administration, and could potentially complicate intracoronary streptokinase therapy.

Acute Kidney Injury↗