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Biomedical subjects

D J Coltart

Publications and source records attributed to D J Coltart.

At least 73 records · Page 4Linked to original sources
PubMed1981

Long-term beta-blockade: prolonged protective action on the ischaemic myocardium.

In this study we have assessed the possibility that long-term beta-blockade may offer additional protection against myocardial ischaemia that is separate from that afforded by acute beta-blockade. In addition, the effect of intrinsic sympathomimetic activity (ISA) on this additional protection was also investigated. Equipotent doses (4 mg . kg-1 body wt . day-1) of oxprenolol (possessing ISA) or propranolol (without ISA) were administered orally to rats for 3 weeks. Hearts were excised an perfused as isolated "working" heart preparations at variable times after the last dose. Hearts excised on the final day of drug administration showed significantly higher basal functional performance compared with untreated hearts. After 30 min reduced flow ischaemia (in the presence of exogenous catecholamine drive) hearts were aerobically reperfused and functional recovery measured. In both chronically beta-blocked groups, at times when plasma drug levels were undetectable, the number of hearts that recovered function and the cellular levels of creatine phosphate and glycogen were significantly increased. In addition, hearts from the oxprenolol-treated group perfused on the final day of drug administration, exhibited a greater recovery of heart rate compared with both propranolol treated and untreated groups. These results indicate that secondary consequences of long-term beta-blockade are beneficial to the ischaemic myocardium in the presence of high catecholamine drive. In addition, the possession of ISA by oxprenolol offered some advantages in terms of post-ischaemic functional recovery.

Adenosine Triphosphate↗
PubMed1981

The effects of chronic oral cimetidine therapy on the cardiovascular system in man.

1 The demonstration of histamine (H2) receptors in the cardiovascular system in man and the widespread use of the specific H2 receptor antagonist cimetidine for the treatment of peptic ulcer has necessitated assessment of the cardiovascular effects of this drug during oral therapy in man. 2 Consequently, nineteen patients with a history of peptic ulcer but in symptomatic remission underwent a double-blind crossover trial of oral cimetidine v placebo, each treatment period lasting 4 weeks. No significant difference in various cardiac parameters at rest (heart rate, blood pressure, ECG) or following a maximal treadmill exercise test (time-into-protocol, maximum heart rate and blood pressure) was found between the groups. Similarly, cimetidine produced no change in the incidence of ventricular ectopics or in heart rate on 24 h ambulatory monitoring and had no effect on left ventricular volume or contractility as measured by echocardiography. 3 Thus oral administration of cimetidine in a dose of 400 mg four times daily was associated with no demonstrable cardiovascular changes. In addition, since this dose is thought compatible with cardiovascular H2 receptor blockade this study favours the lack of a physiological role for these receptors in man.

Cardiovascular Diseases↗
PubMed1981

Advantages of technetium pyrophosphate scintigraphy over plasma enzyme analysis in estimation of anterior myocardial infarct size.

Infarct size was estimated by cumulative creatine kinase MB isoenzyme (CKMB-r) release and by technetium 99m stannous pyrophosphate (TcPYP) scintigraphy in 27 patients with acute anterior myocardial infarction. In eight patients, scintigraphy showed a central area of reduced tracer uptake surrounded by a peripheral rim of increased TcPYP accumulation ("doughnut" pattern). This appearance occurred only in large infarcts and the maximal scintigraphic area (51.3 +/- 2.8 cm2, mean +/- SEM) in this group was significantly greater than that in the remainder (28.1 +/- 2.5 cm2). Correlation between CKMB-r and maximal scintigraphic infarct area was moderate in the whole group. Exclusion of patients, however, with "doughnut" scintigrams in which correlation was very poor, resulted in substantial improvement in the remainder. It is suggested that in the central regions of large "doughnut" infarcts, reduced blood flow hinders the efflux of CKMB from the centre causing an underestimate of infarct size. Pyrophosphate scintigraphy appears to be more accurate than CKMB release in measuring the size of these large anterior infarcts.

Adult↗
PubMed1981

A model for the generation of spontaneous yet predictable ventricular arrhythmias.

Development of an experimental preparation aided to investigate arrhythmogenic and antiarrhythmogenic factors influencing incidence of spontaneous and yet predictable ventricular arrhythmias is described. Using the isolated perfused guinea-pig heart and a system for quantitating rhythm disturbances based on computer-aided statistical analysis of beat-to-beat intervals, a number of factors influencing the incidence of rhythm disturbances were investigated. Manipulation of perfusate composition revealed that, after 'moderate' ischaemia, reperfusion arrhythmias were increased in the presence of noradrenaline and non-glucose fuels. Free fatty acids, unless in the presence of catecholamines, were not particularly arrhythmogenic. In contrast, the presence of pyruvate or lactate, endproduct inhibitors of glycolysis, significantly increased incidence of reflow rhythm disturbances. The dose-dependent arrhythmogenic effects of pyruvate and anti-arrhythmogenic effects of glucose support the thesis that inadequate glycolytic flux could be important in the development of arrhythmias.

Acetates↗
PubMed1980

Coxsackie-B-virus-specific IgM responses in patients with cardiac and other diseases.

An enzyme-linked immunosorbent assay (ELISA) test using polyvalent antigens and antisera was developed to detect Coxsackie-B-virus-specific IgM responses. The sera of 24 of 64 (37.5%) patients with acute pericarditis and 14 of 38 (36%) with acute myocarditis were positive for Coxsackie-B-virus-specific IgM. 4 of 30 (13.3%) patients with acute ischaemic heart disease and 2 of 28 (7.1%) patients with congestive cardiomyopathy were also positive. Coxsackie-B-virus-specific IgM was detected in the sera of 21 of 57 (36.8%) patients with Bornholm disease and 2 of 4 patients with acute-onset juvenile diabetes. Coxsackie-B-virus-specific IgM responses persisted for 6-8 weeks. Sera from patients with chronic valvular heart disease, Mycoplasma pneumoniae infections, and virus infections caused by viruses other than Coxsackie-B viruses were all negative. False-positive results did not occur when sera containing high titres of rheumatoid factor were tested.

Acute Disease↗
PubMed1980

Myocardial electrical instability after abrupt withdrawal of long-term administration of propranolol to guinea pigs.

1. Abrupt termination of chronic propranolol therapy has baeen suggested to cause a 'rebound' phenomenon. To investigate this possibility guinea pigs were given propranolol orally for 21 days. 2. At various times over a 10 day period after the last dose hearts were removed and subjected to aerobic perfusion, ischaemia and reperfusion. Rhythm disturbances were measured and compared with corresponding values in control hearts from the control untreated animals. 3. Three to 6 days after termination of drug administration a pronounced increase in myocardial electrical instability was observed. During pre-ischaemic aerobic perfusion the incidence of arrhythmias was increased and during reperfusion the incidence of ventricular fibrillation rose dramatically.

Animals↗
PubMed1980

Beta-blockade and ischaemic injury: effects of partial agonist activity.

In this study we have attempted: firstly to assess the extent to which the presence of partial agonist activity in a beta-blocking compound and/or sympathetic drive, influence ischaemic injury, and secondly to determine if any of the observed differences are due to changes in contractile activity. In the isolated, globally ischaemic (low flow) rat heart, oxprenolol (which possesses partial agonist activity) did not reduce creatine kinase leakage to the same extent as propranolol (no partial agonist activity) regardless of the background level of catecholamine drive. However, increasing background catecholamine drive increased the relative protection against enzyme leakage, of both beta-blockers. Under conditions of zero contractile activity (high K+ - medium) neither beta-blocker reduced enzyme leakage. Thus at equi-blocking doses oxprenolol and propranolol reduce enzyme leakage to different extents and the lesser protection afforded by oxprenolol is likely to be attributed to the presence of partial agonist activity. In addition, the reduction in enzyme leakage caused by both these compounds is due to reductions in contractile activity.

Animals↗
PubMed1980

Cardiac involvement in secondary haemochromatosis: a catheter biopsy study and analysis of myocardium.

Although high blood transfusion regimens have improved the life expectancy of the patient with Thalassemia Major, cardiac failure and arrhythmias remain a cause of early death. It is not certain whether the massive myocardial iron deposition found in such patients is preventable by intensive chelation therapy. This study evaluates endomyocardial biopsy as a method of assessing myocardial iron deposition. Of four patients with clinical and biochemical evidence of severe haemochromatosis, only one had a myocardial iron content comparable to that found in severe haemochromatotic myocardium. The one patient with cardiac failure had an endomyocardial iron content within the normal range. Studies of the iron distribution in haemochromatotic myocardium demonstrate that the subendocardial myocardium contains only half the iron content of the subepicardial layer, and there is a large sampling variation. It is concluded that catheter endomyocardial biopsy is an insensitive method of determining early myocardial deposition because of the location of iron and the variability of the sampling. Studies of the nature of the myocardial iron protein with CM32 cation exchange resin chromatography show that there is a large increase in the haemosiderin: ferritin ratio (5:1) in iron overload myocardium as compared with the normal heart (2:1). Similar results have been observed in the liver with iron overload, where the increase in hepatic haemosiderin was associated with greater lysosomal fragility. It is possible that myocardial cell damage may also occur by the rupture of iron engorged lysosomes.

Adolescent↗
PubMed1980

Haemodynamic and metabolic effects of atenolol in patients with angina pectoris.

Myocardial substrate extraction, coronary sinus flow, left ventricular pressure, and cardiac output were measured in 11 patients with angina pectoris at three pacing rates before and after atenolol (0.2 mg/kg). Left ventricular pressures, and the product of systolic pressure time index and heart rate did not change, but max dP/dt and KV max fell after atenolol. Only at the lowest pacing rate did the drug reduce cardiac output. Coronary sinus blood flow and myocardial oxygen uptake did not change after atenolol. At the highest pacing rate before atenolol four patients developed angina, accompanied by a rise in end-diastolic pressure. After atenolol angina was abolished in three, but the end-diastolic pressure still rose at the highest pacing rate. Myocardial lactate extraction ratio fell as heart rate increased, and was lower in the patients who developed angina. After atenolol, lactate extraction ratio increased significantly at the highest and lowest pacing rates. Myocardial pyruvate extraction rose after the drug. Arterial concentrations of hydroxybutyrate and acetoacetate fell after atenolol, but the decrease in their extraction was not significant. Myocardial extraction of free fatty acids was related to arterial concentration, which fell after atenolol. The changes in lactate and pyruvate extraction after atenolol were related inversely to changes in arterial free fatty acid concentration suggesting that the improvement in myocardial metabolism could have been secondary to reduced peripheral lipolysis. The increase in lactate extraction was associated with relief of angina, but did not abolish the rise in end-diastolic pressure induced by pacing.

Adult↗
PubMed1980

Assessment of prognostic factors in patients undergoing surgery for non-rheumatic mitral regurgitation.

Twenty-four patients who had undegone mitral valve surgery for pure non-rheumatic mitral regurgitation were studied non-invasively six months to six years postoperatively. The long-term results of operation were assessed on the basis of clinical history, echocardiography, and treadmill stress testing using a points scoring system. The score so obtained was used to divide the patients into those with a good response to surgery (group 1) and those responding poorly (group 2). The effects on the long-term surgical outcome of several intraoperative and preoperative factors were then analysed both together and separately. A short symptomatic history (less than 1 year), a normal left ventricular end-diastolic volume index (less than or equal to 100 ml per m2), and a large post-ectopic potentiation of KV max (greater than 50 s-1) were found to be favourable prognostic factors when analysed independently. An angiographic ejection fraction less than 0.5 was uniformly associated with a poor outcome, and 71 per cent of patients in atrial fibrillation at the time of operation also responded badly. In those patients with good long-term function, cold potassium cardioplegia was more commonly used than intermittent aortic cross clamping as the means of intraoperative myocardial preservation, though this difference did not reach conventional significance. A standard analysis of variance allowed assessment of length of history, left ventricular end-diastolic volume index, and type of valve prosthesis simultaneously. This indicated that both length of history and left ventricular end-diastolic volume index were highly significant prognostic factors. The use of a Björk-Shiley as opposed to a Starr-Edwards prosthesis also emerged as significantly favouring a good long-term result. The state of the left ventricular myocardium before operation and the type of valve prosthesis used were thus shown to be the prime determinants of surgical outcome in these patients. The optimum time for operation was shown to be within one year of the onset of symptoms, and before the left left ventricular end-diastolic volume index exceeds 100 ml per m2, or the ejection fraction falls to less than 0.5. At such a time, irreversible changes in myocardial function sufficient to negate the beneficial effects of mitral valve surgery have not yet occurred.

Angiocardiography↗
PubMed1980

Effects of propranolol on myocardial oxygen consumption, substrate extraction, and haemodynamics in hypertrophic obstructive cardiomyopathy.

Myocardial substrate extraction, coronary sinus flow, cardiac output, and left ventricular pressure were measured at increasing pacing rates before and after propranolol (0.2 mg/kg) in 13 patients with hypertrophic obstructive cardiomyopathy (HOCM) during diagnostic cardiac catheterisation. At the lowest pacing rate myocardial oxygen consumption varied considerably between patients and very high values were found in several individuals (range 10.1 to 57.5 ml/min). These large differences between patients were not explicable by differences in cardiac work; consequently, cardiac efficiency, estimated from the oxygen cost of external work, varied between patients and was lower than normal in all but two. The pattern of substrate extraction at the lowest pacing rate was similar to results reported for the normal heart, and measured oxygen consumption could be accounted for by complete oxidation of the substrates extracted; thus there was no evidence of a gross abnormality of oxidative metabolism, suggesting that low efficiency lay in the utilisation rather than in the production of energy. Each of the four patients with the highest myocardial oxygen consumption and lowest values of efficiency sustained progressive reductions in lactate and pyruvate extraction as heart rate increased, and at the highest pacing rate had low (< 3%) or negative lactate extraction ratios. In three of these four, coronary sinus flow did not increase progressively with each increment in heart rate. One patient with low oxygen consumption and normal efficiency also failed to increase coronary flow with the final increment in heart rate, and produced lactate at the highest pacing rate. Thus the five patients in whom pacing provoked biochemical evidence of ischaemia all had excessive myocardial oxygen demand and/or limited capacity to increase coronary flow. Propranolol did not change lactate extraction significantly at any pacing rate in either the ischaemic or non-ischaemic groups. In only one patient was ischaemia at the highest pacing rate abolished after propranolol, and this was associated with a 30 per cent reduction in oxygen consumption. These results do not demonstrate a direct effect of propranolol upon myocardial metabolism in patients with HOCM, but emphasise the potential value of beta-blockade in protecting these patients from excessive increases in heart rate.

Adolescent↗
PubMed1980

Correlations of fibrosis in endomyocardial biopsies from patients with aortic valve disease.

The amount of fibrosis in endomyocardial biopsies from 55 patients with aortic stenosis and 42 patients with aortic regurgitaion was measured. Sixty per cent of the patients with aortic stenosis had some degree of fibrosis; the degree of fibrosis correlated strongly with ejection fraction, peak systolic gradient, symptoms of cardiac failure, and mortality. In patients with aortic regurgitation, fibrosis was found in 40 per cent and was never severe. A correlation was found with symptoms of cardiac failure and mortality at follow-up, but not with ejection fraction or degree of regurgitation.

Adult↗
PubMed1980

Controlled study of 24-hour ambulatory electrocardiographic monitoring in patients with transient neurological symptoms.

Sixty unselected patients with transient neurological symptoms underwent 24-hour ambulatory electrocardiographic (ECG) monitoring. Haemodynamically significant arrhythmias were observed in 32% of patients, but in only 3% of an age- and sex-matched control group. Nine patients received specific anti-arrhythmic therapy, which resulted in marked symptomatic improvement in each case. It is argued that 24-hour ECG monitoring is a valuable diagnostic tool in the investigation of transient neurological symptoms.

Adolescent↗
PubMed1980

Myocardial ischaemia: an isolated, globally perfused rat heart model for metabolic and pharmacological studies.

A model of myocardial ischaemia is described and has been characterized in terms of functional, ultrastructural, electrophysiological and metabolic changes. The model fulfills a number of criteria considered to be of importance in any model of myocardial ischaemia namely (1) the myocardium is ischaemic as opposed to hypoxic, (2) the coronary flow is reduced but not totally abolished, (3) that flow reaching the ischaemic myocardium is fully oxygenated and contains a mixture of substrates. It is proposed that this model is of value for the investigation and assessment of pharmacological interventions during myocardial infarction.

Animals↗