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Biomedical subjects

J D Fitzgerald

Publications and source records attributed to J D Fitzgerald.

At least 37 records · Page 2Linked to original sources
PubMed1977

Reduction of intrinsic sinoatrial frequency and norepinephrine response of the exercised rat.

Physical training is associated with a reduction of intrinsic sinoatrial activity; the present study examined the role of the parasympathetic nervous system in this reduction. Six groups of rats were studied for 10 weeks: inactive control; treadmill exercised; parasympathetic receptor blockade with atropine; exercise plus atropine; parasympathetic receptor stimulation with carbachol; and exercise plus carbachol. In vivo ISF (cardiac frequency 20 min after injection of propranolol and atropine) was measured at 3-week intervals. At the end of 10 weeks the right atrium was excised, in vitro measurements were made of ISF, and chronotropic dose-response curves to acetylcholine and norepinephrine were established. In vivo, ISF was reduced with time, the greatest reduction being found in the exercise plus atropine group; the treadmill-exercised and the atropine-treated groups also had a greater reduction than the control group. In vitro, no differences were observed in acetylcholine responses. The maximum norepinephrine chronotropic response was reduced in the treadmill-exercised and the exercise plus atropine groups. The maximum norepinephrine-induced frequency correlated with the in vitro ISF (r = 0.75). Thus, ISF was reduced with training, but this effect was independent of parasympathetic activity. The properties of the sinoatrial node which set ISF also influenced the maximum norepinephrine response.

Acetylcholine↗
PubMed1976

Comparison of metoprolol and propranolol in modification of haemodynamic and renin-aldosterone responses to tilting in humans.

1. Acute oral administration of metoprolol and propranolol to ten normal males resulted in equal reduction in heart rate both supine and after passive tilting to 60 degrees. 2. Tilted systolic blood pressure was reduced by both agents but metoprolol alone reduced supine systolic blood pressure. 3. Tilted but not supine diastolic blood pressure was reduced by both agents. 4. Metoprolol and propranolol both reduced the rise in plasma renin activity induced by tilting. 5. No effect of tilting was observed on plasma aldosterone.

Adult↗
PubMed1976

Human pharmacokinetic and pharmacodynamic studies on the atenolo (ICI 66,082), a new cardioselective beta-adrenoceptor blocking drug.

The beta-adrenoceptor blocking effects of orally administered atenolol on tachycardia induced by intravenous isoprenaline or by exercise have been studied in normal volunteers, and compared with the effects of similar doses of propranolol. The blood levels of atenolol at various times after oral administration were determined by g.l.c. and correlated with the degree of inhibition of tachycardia. Atenolol was shown to be a beta-adrenoceptor blocker in man, as in animals, in that it antagonized the chronotropic effects of isoprenaline and of exercise. The inhibitory effect of atenolol on exercise-induced tachycardia was evident at a concentration in blood of 0.2 mug/ml and virtually complete at 0.5 mug/ml. Higher concentrations than this did not produce significantly greater blockade. The effects of atenolol on exercise-induced tachycardia were similar to those of propranolol but it was less effective in blocking the rise in heart rate and fall in diastolic blood-pressure induced by intravenous infusion of isoprenaline. This separation of effects is considered characteristic of drugs causing preferential blockade of cardiac beta-adrenoreceptors. The half-life of atenolol in blood was calculated to ablut 9 hours.

Adult↗
PubMed1976

The effect of beta-adrenoreceptive antagonists on the morbidity and mortality in cardiovascular disease.

The effect is critically reviewed of chronic administration of beta-adrenoreceptor antagonists on morbidity and mortality in angina pectoris and myocardial infarction. There is inconclusive evidence that the abrupt cessation of therapy with these agents may increase morbidity and mortality in angina pectoris. The type of anginal patient in which this may occur is not yet defined and neither is the mechanism. There is no evidence that beta-antagonists prolong the life of anginal patients. In the acute phase of experimental myocardial infarction, these drugs reduce mortality but do not do so in man. There is increasing evidence that they prolong life if administered to patients surviving the acute phase of myocardial infarction. The need for further studies is discussed.

Adrenergic beta-Antagonists↗
PubMed1976

Beta-blockade and mechanisms of disease.

In this review an attempt has been made to define the contribution of beta-antagonists to out understanding of the mechanisms of disease. It is concluded that beta-antagonists, and propranolol in particular, have clarified mechanisms in angina pectoris, cardiac arrhythmias and some aspects of essential hypertension as well as hypertrophic obstructive cardiomyopathy. The study of beta-antagonists in anxiety states shows that they can help to define the somatic component but give no clue as to central mechanisms involved. There is no substantial evidence that beta-antogonists are of value in the psychoses and these negative findings suggest that disturbances of brain catecholamines contribute little to the pathogenesis of these conditions.

Adrenergic beta-Antagonists↗
PubMed1975

Beta blocking drugs as anti-arrhythmic agents.

Fifteen years after the introduction of beta adrenergic blocking drugs into clinical medicine, there is satisfactory evidence indicating that this class of drug has significant anti-arrhythmic activity. The chief indications for using these drugs are for the control of sinus tachycardia digitalis dysrhythmias and for the control of rapid ventricular rates atrial and ventricular dysrhythmias. The mode of action is by antagonizing the cardiac actions of catecholamines on cardiac automaticity and conduction.

Action Potentials↗
PubMed1972

A comparison of the haemodynamic effects of propranolol, 4-hydroxypropranolol and practolol in anaesthetized dogs.

1. The haemodynamic effects of propranolol, practolol and 4-hydroxypropranolol have been compared in anaesthetized dogs both at free heart rates and at heart rates fixed by electrical pacing. All three drugs produced a fall in heart rate at the lowest dose of 0.09 mg/kg.2. Practolol caused less change in dP/dt, cardiac output and blood pressure than did propranolol. 4-Hydroxypropranolol had intermediate effects. Since the changes in dP/dt caused by these three drugs were still present when the heart rate was fixed by pacing, it is concluded that these were independent of changes in heart rate.3. The fact that practolol and 4-hydroxypropranolol cause less change in haemodynamic function than propranolol may be associated with the intrinsic sympathomimetic activity possessed by the first two of these drugs.

Adrenergic beta-Antagonists↗
PubMed1971

Pharmacology of 4-hydroxypropranolol, a metabolite of propranolol.

1. 4-Hydroxypropranolol, a metabolite produced after oral administration of propranolol, has been shown to be a beta-adrenoceptor blocking drug. It is of similar potency to propranolol in antagonizing the effects of isoprenaline on heart rate and blood pressure in cats and against isoprenaline protection of guinea-pigs from bronchospasm. It is not cardioselective.2. In rats depleted of catecholamine 4-hydroxypropranolol produced an increase in heart rate, suggesting that it has intrinsic sympathomimetic activity.3. In anaesthetized dogs 4-hydroxypropranolol produced a decrease in heart rate and dP/dt and an increase in A-V conduction time at doses within the range 0.09-1.25 mg/kg. These effects are a result of beta-adrenoceptor blockade. In dogs depleted of catecholamines these same doses produced an increase in heart rate and dP/dt and a decrease in A-V conduction time. These responses were antagonized by propranolol, and were due to the intrinsic sympathomimetic activity of the compound. At higher doses (5.25 and 13.25 mg/kg) a further dose dependent decrease in heart rate and dP/dt and an increase in A-V conduction time occurred. This trend was also seen in animals depleted of catecholamines. These changes represent membrane stabilizing activity of 4-hydroxypropranolol.4. 4-Hydroxypropranolol is a potent beta-adrenoceptor blocking drug with both intrinsic sympathomimetic activity and membrane stabilizing activity.

Adrenergic beta-Antagonists↗