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Biomedical subjects

T L Svendsen

Publications and source records attributed to T L Svendsen.

At least 55 records · Page 3Linked to original sources

Kinetics of disopyramide after intravenous infusion to patients with myocardial infarction and heart failure.

Total body clearance, half-life and volume of distribution of disopyramide (Norpace, Searle G.D.) was measured during a six to eight hour infusion to steady state in twenty four patients with either congestive heart failure or acute myocardial infarction and compared to eleven patients without these diseases. All patients were given a bolus injection of 150 mg disopyramide followed by a continuous infusion of 18-24 mg per hour. Serum concentration of disopyramide and its main dealkylated metabolite were determined by HPLC. The clearance in patients without myocardial infarction or congestive heart failure was 1.71 +/- 0.60 ml/min./kg (mean +/- S.D.), not significantly different from those who had either myocardial infarction, congestive heart failure or both. Half-life was 798 min. in patients without heart failure, not significantly different from the values in the other groups. The ratio between disopyramide and its metabolite varied between 3 to 10. Twenty-six % of the steady state serum concentrations of disopyramide were outside the recommended therapeutic range (2-5 micrograms/ml), but no adverse haemodynamic effects were observed in any of the patients. The suggested dosage regimen of disopyramide seems to result in a satisfactory response.

Aged↗

Treatment of malignant pleural effusion with drainage, with and without instillation of talc.

In order to determine whether pleural drainage with talc instillation was better than pleural drainage alone, in the treatment of malignant effusion, the present trial was initiated. Thirty-one patients with malignant pleural effusion and progressive disease, resistant to conventional therapy, were included. All patients had pleural drainage applied. After re-expansion of the lung, half of the patients had talc instilled through the chest tube. Twenty-one of the 31 treated patients were evaluable. After pleural drainage with talc instillation, all of 9 treated patients obtained complete resolution of the effusion and subjective improvement. After pleural drainage alone, 7 of 12 patients obtained complete resolution of the malignant effusion. If it is possible to re-expand the lung during pleural drainage in patients with a malignant pleural effusion, pleurodesis can be obtained in 60% of the treated patients with pleural drainage alone. This study showed a statistically significant improvement in the treatment associated with instillation of talc into the pleural cavity and this was achieved without causing increased discomfort to the patient.

Adult↗

Pulmonary lymphangioleiomyomatosis: a case of progesterone receptor positive lymphangioleiomyomatosis treated with medroxyprogesterone, oophorectomy and tamoxifen.

A 28-year-old woman with lymphangioleiomyomatosis had severe changes in the chest radiograph and recurrent pneumothoraces. Pathological tissue from the lung was progesterone receptor positive. After treatment with medroxyprogesterone her condition improved, but did not become clinically stable until after bilateral oophorectomy. Even after oophorectomy her condition deteriorated, when the dose of medroxyprogesterone was decreased. For one year after oophorectomy she has had no episodes of pneumothorax or breathlessness. In order to depress oestrogen activity further the anti-oestrogen drug tamoxifen was added to her usual treatment with medroxyprogesterone. During 2 weeks of treatment with tamoxifen and medroxyprogesterone marked increase of the changes in the chest radiograph were seen and a pneumothorax occurred. After discontinuation of tamoxifen the condition improved and has since been stable on medroxyprogesterone treatment.

Adult↗

Central hemodynamics of beta-adrenoceptor blocking drugs: beta 1 selectivity versus intrinsic sympathomimetic activity.

It was the purpose of the present study to assess the hemodynamic effects of adrenergic beta-receptor blocking drugs possessing intrinsic sympathomimetic activity (ISA) and/or beta 1 selectivity, both at rest and during exercise. The hemodynamic effects of seven different beta-blockers (propranolol, atenolol, acebutolol, ICI 72,222, ICI 89,406, and pindolol) were studied at rest in patients with ischemic heart disease. Heart rate (HR), cardiac output (CO), arterial blood pressure (BP), and pulmonary artery pressure (PP) were determined. At rest, it was possible to subdivide the various beta-blockers into three main groups according to the degree of ISA. One group without ISA, including propranolol and atenolol, reduced CO by 25% and HR by 15%. A second group with moderate ISA, represented by practolol, acebutolol and ICI 72,222, reduced CO only by 15% and HR by 10%. A third group with pronounced ISA, represented by pindolol and ICI 89,406, did not change CO and HR significantly. All three groups consisted of drugs both with and without beta 1 selectivity. During exercise, pindolol and propranolol reduced CO, HR, and BP to the same extent. In conclusion, the central hemodynamic response to beta-blockers at rest is determined by the degree of ISA, whereas beta 1 selectivity does not modify the central hemodynamic response to beta-blockade. However, the hemodynamic differences between adrenergic beta-blocking drugs with and without ISA disappear in situations with increased sympathetic drive, such as exercise.

Adrenergic beta-Antagonists↗

Haemodynamic and metabolic effects of diazoxide during rest and forearm exercise.

The immediate haemodynamic and metabolic effects of acute dose of diazoxide 300 mg i.v. were studied in six healthy subjects at rest and during dynamic forearm exercise. Control periods of rest, exercise and recovery were compared with corresponding periods after drug administration. Resting forearm blood flow was almost doubled after diazoxide, and during forearm exercise it increased by about 24%. Systolic blood pressure did not change significantly, but diastolic blood pressure was moderately decreased (5-10 mm Hg). The mean heart rate increased from 57 to 92 beats/min immediately after diazoxide administration and remained about 20% higher throughout the study. There was a sustained increase in arterial blood glucose of almost 1 mmol/l. The arterial concentration of free fatty acids increased transiently just after diazoxide and then returned to the pre-drug level. The arterial concentration of triglycerides after diazoxide was decreased by about 15% throughout the study. Arterial blood lactate remained unchanged. Forearm uptake of oxygen and glucose tended to increase during the exercise and recovery periods, whereas lactate release remained unchanged.

Adult↗

Effects of propranolol and pindolol on plasma lignocaine clearance in man.

1 Steady state concentrations and clearance of lignocaine were determine in eight healthy volunteers during 360 min continuous lignocaine infusion (2 mg/min). Before the infusion propranolol (0.18 mg/kg i.v.), pindolol (0.023 mg/kg i.v.) or placebo were administered in a random double-blind, cross over design. 2 During the infusion of lignocaine heart rate, cardiac output and arterial blood pressure were measured every 60 min. 3 Propranolol decreased heart rate and cardiac output significantly by 10--20%, while pindolol or lignocaine did not change cardiac output or heart rate significantly. None of the drugs changed the arterial blood pressure. 4 Propranolol pretreatment decreased lignocaine significantly by 14.7% and the steady state concentration was increased by 22.5%. Pindolol produced no significant change in steady state concentration or clearance of lignocaine.

Adult↗

Beta-adrenoceptor blockade and psychic stress in man. A comparison of the acute effects of labetalol, metoprolol, pindolol and propranolol on plasma levels of adrenaline and noradrenaline.

1 A random double-blind study was performed in healthy volunteers. The immediate effects of three different beta-adrenoceptor blocking agents, metoprolol, pindolol and propranolol, on the plasma concentrations of adrenaline and noradrenaline were compared in a situation of pleasant psychic stimulation during a television-game of tennis. The immediate effects of labetalol in a group of patients with arterial hypertension were studied in a similar experimental situation. 2 During psychic stress the plasma concentration of noradrenaline rose significantly by 85% after placebo, by 95% after labetalol, by 63% after metoprolol and by 55% after propranolol. After pindolol the noradrenaline concentration remained unchanged. 3 During psychic stress the plasma concentration of adrenaline rose significantly by 135% after labetalol, by 110% after metoprolol and by 83% after propranolol. After pindolol and placebo the adrenaline concentration remained unchanged. 4 The present results are taken to indicate that the intrinsic sympathomimetic activity possessed by pindolol prevents the rise in plasma noradrenaline normally seen during psychic stress. It is suggested that beta-adrenoceptor blockers with strong intrinsic sympathomimetic effect reduce the release of catecholamines during psychic stress.

Adrenergic beta-Antagonists↗

Beta 2-adrenoceptor agonists and thyroid hormones.

The potential influence of the selective beta 2-adrenoceptor agonist terbutaline on the serum concentration of the thyroid hormones in humans was studied in 11 healthy euthyroid subjects. Five served as a control group without medication while six received 5 mg terbutaline three times daily for 2 weeks. No significant differences were found between the two groups by measuring the serum concentrations of thyroxine, triiodothyronine, reverse triiodothyronine and resin-triiodothyronine uptake. The use of a beta 2-adrenergic receptor stimulating drug is relatively contraindicated in untreated thyrotoxicosis. This recommendation is based upon a summation of clinical adverse reactions and not due to an effect on the serum concentrations of thyroid hormones.

Adrenergic beta-Agonists↗

Systemic and forearm haemodynamic and metabolic effects of racemic propranolol or D-propranolol in healthy subjects.

1. The immediate haemodynamic and metabolic effects of intravenous administration of DL-propranolol and D-propranolol were studied in healthy male subjects at rest and during dynamic forearm exercise. The dose of DL-propranolol and of D-propranolol was 0.1 and 1.0 mg/kg body weight respectively. 2. DL-Propranolol reduced heart rate significantly at rest, during forearm exercise and post-exercise, whereas D-propranolol had a lesser effect on heart rate which was significant only at the end of the exercise period. Arterial blood pressure and forearm blood flow were unchanged after either drug. 3. Both drugs reduced the release of lactate from the exercising forearm. Forearm exchange of oxygen, glucose, free fatty acids and triglycerides remained unchanged. 4. The arterial blood glucose concentration increased after D-propranolol, but was unchanged after DL-propranolol. The arterial serum free fatty acid concentration decreased after DL-propranolol, but was not changed after D-propranolol. Arterial concentrations of lactate and triglycerides were not influenced by the drugs. 5. The chronotropic response to beta-adrenoceptor blockade appears to be stereoselective, suggesting specific blockade of beta-adrenoceptors. Metabolic responses to beta-adrenoceptor blockade are difficult to explain in terms of the known adrenoceptor system and may be due to non-specific actions of beta-adrenoceptor antagonists. An exception is inhibition of lipolysis, which is probably mediated via beta-adrenoceptors.

Adult↗

Central and peripheral haemodynamic effects of prenalterol in patients with coronary heart disease.

The acute haemodynamic effects of prenalterol, a selective adrenergic beta-I-receptor agonist were studied in eight patients with coronary heart disease. Prenalterol was administered intravenously in four increasing doses to a cumulative dose of 5.6 mg. Fifteen minutes after the last dose of prenalterol two doses of the selective adrenergic beta-I-receptor antagonist metoprolol were administered intravenously to a cumulative dose of 17-5 mg. Ten minutes after each dose cardiac output, heart rate, arterial blood pressure, pulmonary artery pressure, systolic time intervals and forearm blood flow were determined. Haemodynamic effects of prenalterol: cardiac index and heart rate increased maximally by 38% and 39% respectively. Stroke index was increased by 6-9% after the first and second dose. Mean blood pressure was increased by 9.8 mmHg. Total peripheral resistance index was reduced by 19%. The mean pulmonary artery pressure decreased by 3.8 mmHg and pulmonary resistance index was reduced by 48%. Systolic time intervals were all reduced significantly after the second dose, which reflected the positive inotropic effects of prenalterol. Forearm blood flow increased by 29% and forearm vascular resistance was decreased by 20%. Haemodynamic effects of metoprolol: the haemodynamic changes induced by prenalterol were stepwise counteracted by metoprolol. After the second dose all the haemodynamic variables had returned to the control levels. It is concluded that prenalterol possesses a considerable positive inotropic as well as positive chronotropic effect on the myocardium. Both the chronotropic and inotropic effect of prenalterol was counteracted by metoprolol.

Blood Pressure↗