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Biomedical subjects

J C Forfar

Publications and source records attributed to J C Forfar.

At least 55 records · Page 3Linked to original sources
PubMed1985

Control of myocardial catecholamine release during acute ischemia.

Regional myocardial catecholamine release during graded stimulation of the left ansa subclavia has been assessed in open-chest anaesthetised dogs during left anterior descending coronary artery (LAD) occlusion and reperfusion. Frequency-dependent release of noradrenaline (NA) in response to stimulation of the ansa was maintained across the ischaemic area during the two early phases of enhanced vulnerability to arrhythmias at 5 and 17 min, but was selectively inhibited after 30 min. Spontaneous NA release from the ischaemic heart did not occur with either alpha 2-adrenoceptor (yohimbine) or neuronal reuptake (desmethylimipramine) blockade alone, but was unmasked by the drug combination. Intracoronary potassium infusions, designed to mimic the concentration range seen in ischaemia, exerted biphasic effects on stimulation-induced NA release, being inhibitory at low dose and stimulatory at high dose. High-dose intracoronary adenosine inhibited NA release in response to high-frequency ansa stimulation but basal release was slightly increased. Thus, catecholamine release from ischaemic myocardium has multifactorial determinants and may be limited by enhanced reuptake, adrenoceptor-mediated negative feedback, and metabolite accumulation. Lack of nerve-terminal response to sympathetic stimulation coincides with the later period of myocardial electrical stability.

Adenosine↗
PubMed1985

End-organ responses to thyroxine therapy in subclinical hypothyroidism.

We studied variables known to change with thyroid hormone status in 18 patients with subclinical hypothyroidism before and during treatment with thyroxine in a dose sufficient to restore the plasma TSH response to TRH to normal. There was an associated increase in both plasma total T4 and free T4 within the normal range but plasma total T3 and free T3 were unchanged. As a result of thyroxine treatment there was a small but significant increase (P less than 0.05) in left ventricular ejection fraction (LVEF) with maximal exercise but no significant changes in LVEF at rest and moderate exercise, continuously monitored mean sleeping heart rate, day/night ratios of urinary sodium excretion, peripheral nerve conduction velocities, fasting serum triglycerides, total cholesterol (TC), high density lipoproteins (HDL) or TC/HDL ratios. On this evidence we do not consider that thyroxine replacement therapy is indicated in patients with subclinical hypothyroidism.

Adult↗
PubMed1985

Functional and anatomical correlates in atrial septal defect. An echocardiographic analysis.

The results of cross sectional echocardiography, intracardiac contrast echocardiography, and balloon sizing techniques and conventional haemodynamic assessment were correlated in 40 consecutive patients evaluated for an isolated left to right shunt at atrial level. Echo free areas along the septum were identified in 23 of 25 patients with a secundum defect, but not in two with a fenestrated defect, and in the upper atrial septum in three of four patients with a sinus venosus defect. No false positive results occurred in 11 patients with a probe patent foramen ovale. Saline contrast injection into the left atrium showed significant left to right shunting in all patients with atrial septal defect; inferior vena caval injection produced right to left shunting in 15 of 29 patients and a negative contrast effect in eight of 29 patients with an atrial septal defect, although neither correlated quantitatively with defect diameter or magnitude of the left to right shunt. Echocardiographic assessment of defect size as small, moderate, or large showed a highly significant correlation with balloon measurement of defect diameter, although some overlap between the groups was evident. In contrast, the correlation between defect diameter and pulmonary to systemic blood flow ratio was poor, mainly because of highly variable shunting in patients with an anatomically large defect. Cross sectional echocardiography has high sensitivity and specificity in the diagnosis of the non-fenestrated atrial septal defect and provides quantitative information about defect diameter. Contrast studies do not add to the diagnostic value of imaging from the subcostal position. The poor correlation between defect size and the measured shunt suggests that the latter may not be the best criterion for surgical management and that size could be an important factor likely to influence both the long term prognosis and the decision for closure.

Adolescent↗
PubMed1985

Left ventricular performance in subclinical hypothyroidism.

Normal plasma thyroid hormones with elevation of thyrotrophin levels in asymptomatic patients is known as subclinical hypothyroidism. Radionuclide angiography was used to study left ventricular function in 10 such patients before and after establishment of normal thyrotrophin levels with thyroxine. Resting left ventricular ejection fraction was similar in both states but exercise left ventricular ejection fraction was less in the subclinical hypothyroid (61 +/- 3 per cent) compared with the euthyroid (68 +/- 3 per cent; p less than 0.025) state. Sodium nitroprusside caused similar increases in resting cardiac output but in subclinical hypothyroidism this resulted from a large increase in heart rate (26 +/- 4 beats/min) and reduction in stroke volume (11 +/- 4 per cent) whereas in the euthyroid state, the heart rate increment was less (14 +/- beats/min) and stroke volume was unchanged. Analysis of left ventricular pressure-volume relationships at end-systole during exercise showed a steeper pressure-volume slope in the euthyroid compared with the subclinical hypothyroid state (p less than 0.05). Subtle impairment of left ventricular function is detectable in subclinical hypothyroidism and may justify use of hormone replacement.

Adult↗
PubMed1984

Graves' disease and atrial fibrillation: the case for even higher doses of therapeutic iodine-131.

Seventy five consecutive patients with Graves' disease complicated by atrial fibrillation were given a large single therapeutic dose of 600 MBq (16.2 mCi) iodine-131 in an effort to control their hyperthyroidism rapidly and thus restore sinus rhythm. Patients were initially followed up every three months after treatment and then at yearly intervals. The mean period of follow up was 3.1 years. A total of 44 of the patients became hypothyroid and 31 euthyroid, and 33 (75%) and 14 (45%) of these patients, respectively, reverted to sinus rhythm (p less than 0.01). Of the 33 who became hypothyroid and reverted to sinus rhythm, 30 had developed the hypothyroidism within six months after treatment. These results are a strong case for increasing the dose of radioiodine in patients with Graves' disease complicated by atrial fibrillation in an effort to speed the onset of thyroid failure and thus maximise the rate of reversion to sinus rhythm.

Adult↗
PubMed1984

Relationship of neurosympathetic responsiveness to early ventricular arrhythmias in ischaemic myocardium.

Myocardial catecholamine overflow has been measured in open-chest anaesthetised dogs after graded stimulation of the left ansa subclavia before and during left anterior descending coronary artery occlusion and on reperfusion. Sequential 1 min periods of ansa stimulation over 3 h resulted in reproducible, frequency dependent regional myocardial noradrenaline (NA) overflow without tachyphylaxis. In seven dogs, two successive 10 min periods of LAD occlusion did not modify peak myocardial NA overflow from the predominantly ischaemic (I) or non-ischaemic (NI) areas at either low (1 Hz) or high (10 Hz) frequency ansa stimulation. In a second group of nine dogs, myocardial catecholamine overflow was related to changes in ischaemic area epicardial activation delay during repeated ansa stimulation on four occasions during 75 min of ischaemia. Stimulation at the period of peak spontaneous arrhythmias 5 and 17 min after coronary occlusion resulted in NA overflow from I of 2.8 +/- 1.3 and 3.0 +/- 1.6 pmol X ml-1 respectively and a significant increase in mean activation delay in I of 12 +/- 4 ms at 5 min and 9 +/- 4 ms at 17 min (p less than 0.05). In contrast, stimulation 30 and 60 min after coronary occlusion, when spontaneous arrhythmias are rare, was not associated with NA overflow from ischaemic areas (0.3 +/- 0.3 and 0.9 +/- 0.5 pmol X ml-1 respectively) and resulted in a minor reduction in mean activation delay in ischaemic areas of 2 +/- 3 ms at 30 min and 3 +/- 4 ms at 60 min. NA overflow from non-ischaemic areas and increases in blood pressure and myocardial lactate release were similar during each period of ansa stimulation. Coronary reperfusion induced massive overflow of NA (11.4 +/- 2.8 pmol X ml-1) and reduced extraction of adrenaline (A) from ischaemic areas with a time course similar to early reperfusion arrhythmias. Stimulation-evoked release of NA in ischaemic myocardium is thus maintained during the early period of enhanced vulnerability to arrhythmias and during reperfusion but is inhibited after 30 min. This temporal variability may be a factor in the time course of spontaneous arrhythmias in this model.

Animals↗
PubMed1984

Delayed recovery of left ventricular function after antithyroid treatment. Further evidence for reversible abnormalities of contractility in hyperthyroidism.

Sequential measurements of systolic time intervals, left ventricular dimensions, and the derived indices of contractility were undertaken at rest and during isometric exercise in 15 hyperthyroid patients before, during, and after antithyroid treatment. At rest hyperthyroidism was characterised by a shortened pre-ejection period and increased velocity of circumferential shortening of the left ventricle. During isometric exercise, however, the pre-ejection period increased significantly beyond that predicted for normal subjects, and the velocity of circumferential fibre shortening fell by 30%. In contrast, both the pre-ejection period and the velocity of circumferential fibre shortening were unchanged during exercise after a stable euthyroid state had been achieved for at least three months. Comparison between exercise responses and thyroid status during antithyroid treatment showed that a biochemical euthyroid state may be achieved many weeks before normalisation of contractile response to exercise. These findings support the hypothesis of reversible depression of left ventricular function in hyperthyroidism. Responses at rest principally reflect the peripheral actions of thyroid hormone excess.

Adult↗
PubMed1983

The effect of minor increments in plasma thyroxine on heart rate and urinary sodium excretion.

We studied day/night (D:N) patterns of urinary sodium excretion and the 24 hour ambulatory electrocardiogram in seven normal subjects before and during the administration of T4. Thyroxine increased thyroid hormone levels within the normal range and inhibited the plasma TSH response to TRH. This was associated with a significant decrease in D:N sodium excretion (P less than 0.01) and D:N urine flow (P less than 0.01), a significant increase in mean nocturnal heart rate (P less than 0.01), and a lesser increment in mean daytime heart rate (P less than 0.05). These responses to small changes in thyroid hormone levels suggest that the anterior pituitary is not alone in recognising minor thyroid hormone excess. The clinical implication is that some patients with a normal T3 and T4 but an impaired TSH response to TRH might benefit from antithyroid treatment.

Adult↗
PubMed1982

Abnormal left ventricular function in hyperthyroidism: evidence for a possible reversible cardiomyopathy.

We assessed the effects of exercise and beta-adrenoceptor blockade on left ventricular ejection fraction (LVEF) measured by radionuclide ventriculography in nine patients with uncomplicated hyperthyroidism. Patients were studied in both the hyperthyroid and euthyroid states. The hyperthyroid state was characterized by a high LVEF at rest but--paradoxically--by a significant fall (P less than 0.01) in LVEF during exercise. At the same workload and at the same heart rate, patients had a restoration of the normal rise in LVEF during exercise when they were euthyroid. The LVEF was greater during exercise (P less than 0.02) when the patients were euthyroid than when they were hyperthyroid. Pretreatment with propranolol caused similar reductions in resting LVEF in the hyperthyroid and euthyroid states; the drug attenuated the rise in LVEF during exercise when the patients were euthyroid, but did not influence the exercise-induced reduction in LVEF in hyperthyroidism. The abnormal left ventricular function observed during exercise in hyperthyroidism suggests a reversible functional cardiomyopathy, independent of beta-adrenoceptor activation, that is presumably a direct effect of an excess in circulating thyroid hormones.

Adult↗
PubMed1982

Cardiovascular responses in hyperthyroidism before and during beta-adrenoceptor blockade: evidence against adrenergic hypersensitivity.

The relationship between the sympathetic nervous system and cardiovascular responses has been studied indirectly in ten hyperthyroid patients and age matched euthyroid controls. Nyctohemeral variations in heart rate, and heart rate and blood pressure responses to exercise were measured before and during beta-blockade with slow-release propranolol. Both groups showed a parallel variation in heart rate over 24 h, with an increase in heart rate inthe hyperthyroid group that was the same during the day (27.9 +/- 0.95 beats/min) and during the night (26.7 +/- 0.75 beats/min). Similarly, the increase in resting heart rate (32.7 +/- 4.4 beats/min) in the hyperthyroid group was close to the increase in peak exercise-induced heart rate (25.0 +/- 4.7 beats/min). Adequate beta-blockade was achieved in all subjects as evidenced by a percentage reduction in peak exercise heart rate of 25-45%. Propranolol caused a greater reduction in daytime than night-time heart rate in both groups and blunted the response to exercise. Following beta-blockade, the mean percentage reduction in heart rate and systolic blood pressure during exercise, and heart rate responses over 24 h were similar in hyperthyroid and euthyroid groups. The closest correlation between thyroid hormone levels and heart rate was that of serum total tri-iodothyronine (T3) and nocturnal heart rate during beta-blockade (r=0.92; P less than 0.0001). It is concluded that excess circulating thyroid hormones exert a direct effect on the cardiovascular system additive to the sympathetic nervous system and that there is no evidence of adrenergic hypersensitivity in hyperthyroidism.

Adult↗
PubMed1982

Left ventricular function in hypothyroidism. Responses to exercise and beta adrenoceptor blockade.

The effects of exercise and beta adrenoceptor blockade on left ventricular function were assessed in eight patients with hypothyroidism before and during thyroxine replacement treatment. Left ventricular ejection fraction, measured by radionuclide ventriculography, was reduced in hypothyroid patients at rest and on exercise. The rise in ejection fraction with exercise was, however, similar in both groups. Pretreatment with intravenous propranolol reduced the ejection fraction at rest 9% in both hypothyroid and euthyroid patients and reduced the rise on exercise. Directional changes in a second index of myocardial contractility based on the shape of the ventricular volume curve paralleled the changes in the ejection fraction. Left ventricular function is therefore reversibly depressed by thyroid hormone deficiency but responses to exercise and beta adrenoceptor blockade are normal. There is no evidence of altered adrenergic sensitivity in the control of myocardial contractility in hypothyroidism.

Adult↗
PubMed1981

Atrial fibrillation and isolated suppression of the pituitary-thyroid axis: response to specific antithyroid therapy.

Four patients are described with persistent atrial fibrillation associated with normal plasma total thyroxine (T4) and triiodothyronine (T3) but an absent plasma thyrotrophin (TSH) response to intravenous thyrotrophin releasing hormone (TRH). Initial cardioversion failed to establish sinus rhythm in three of the four patients. Following specific antithyroid therapy to lower thyroid hormone levels sufficient to allow a normal TSH response to TRH sinus rhythm was established in all four patients, one spontaneously and three after cardioversion. Stable sinus rhythm has persisted in three patients over a 2-yr follow-up period. In the presence of atrial fibrillation, an absent plasma TSH response to TRH should be considered sufficient grounds for antithyroid therapy even if plasma total T4 and T3 are within the expected normal range.

Atrial Fibrillation↗
PubMed1980

Haemodynamic effects of sulphinpyrazone on exercise responses in normal subjects.

The effects of sulphinpyrazone on heart-rate and blood-pressure responses to exercise were assessed in 15 normal volunteers by a randomised double-blind crossover technique. Submaximal exercise tests were performed 1 and 2 hours after either sulphinpyrazone (SPZ) 200 mg orally or placebo. Heart-rate and blood-pressure responses were unchanged at rest and during exercise 1 hour after SPZ but after 2 hours there was a significant fall in the product of heart-rate and blood-pressure during exercise (peak 35.8 +/- 1.5 x 10(-3) mmHg beats/min, placebo: 33.0 +/- 1.3 x 10(-3) sulphinpyrazone, p < 0.005) and for the first 2 minutes of recovery. This was mainly due to a decreased exercise-induced rise in systolic blood-pressure with lesser effects on heart-rate. This haemodynamic effect of SPZ has a potentially protective oxygen-sparing effect on the normal myocardium during exercise and may explain its apparent benefit in reducing sudden cardiac death after myocardial infarction.

Adult↗
PubMed1980

Paracetamol pharmacokinetics in thyroid disease.

The absorption, distribution and elimination of oral paracetamol have been studied in patients before and after treatment of thyrotoxicosis (n = 7) and hypothyroidism (n = 4). Absorption was faster in patients with untreated thyrotoxicosis than when subsequently euthyroid. The peak paracetamol concentration, however, was lower in thyrotoxic patients due to an apparent increase in the total body clearance and a shorter plasma half-life. Both absorption and elimination rates were reduced in hypothyroid patients, but were not significantly different from the euthyroid results. When estimated using a two compartment model the total volume of distribution and the hybrid distribution rate constants were unrelated to thyroid status, but the apparent volume of the central compartment was significantly greater in the thyrotoxic group. These changes in drug disposition may contribute to differences in drug response seen in thyroid disease.

Acetaminophen↗