Propranolol, timolol and sotalol were compared regarding their toxicological effects on the cardiovascular and respiratory system. Each drug was administered intravenously to anaesthetized spontaneously breathing and artificially ventilated rats. After the start of infusion in spontaneously breathing rats each drug induced an expected decrease in arterial blood pressure and heart rate. An increase in PQ, QRS and QT interval was observed. From 5/8 of the survival time onwards these changes were accentuated. PaO2, pH and respiratory rate decreased and PaCO2 increased. The rats died as a result of respiratory arrest. Artificial ventilation of rats infused with the same doses increased the survival time significantly. The total doses administered before the animals died as a result of cardiovascular failure were significantly higher for each drug. The initial decreases in arterial blood pressure and heart rate were similar to those in spontaneously breathing rats. Thereafter, significantly smaller decreases were observed. The increases in PQ, QRS and QT interval were significantly less than in spontaneously breathing rats. Blood gases remained unchanged except for a decrease in pH in case of timolol.

Adrenergic beta-Antagonists↗

PubMed1985

Cardiorespiratory depression and haemolysis due to thioridazine overdose in the rat.

The cardiovascular and respiratory effects of an intravenous overdose of thioridazine (125 mg kg-1 h-1) were examined in either spontaneously breathing or artificially ventilated urethane-anaesthetized rats. In both groups PO2, heart rate and mean arterial pressure decreased and atrioventricular and intraventricular conduction time, as well as QT time, increased similarly. PCO2 and pH did not differ significantly except in spontaneously breathing rats where a severe acidosis occurred at the end of the experiments. Haemolysis was suspected. The same dose was administered intravenously to artificially ventilated rats. Plasma concentrations of the drug and its main metabolites, haematocrit and free plasma Hb were determined in separate groups. A severe haemolysis was observed. Thioridazine administered in the same doses intragastrically, intraduodenally or intraperitoneally resulted in lower plasma values than after intravenous administration and there was no haemolysis. Much higher oral doses produced haemolysis at 36 h, at which time plasma concentrations were not higher than those recorded after administration via the other non-intravenous routes. It is probable that the observed changes in cardiovascular and respiratory parameters are partly the result of haemolysis following thioridazine administration.

Anesthesia↗

PubMed1985

A case of fatal endrin poisoning.

Ingestion of 12 g of endrin by a 49-year-old man caused convulsions persisting for 4 days, hypersalivation, hyperthermia, renal insufficiency, thrombocytopenia and recurrent hypotension. Death followed after 11 days, due to pulmonary complications (infection and haemorrhage) and hypoxaemia causing bradycardia and cardiac arrest. Endrin and dieldrin concentrations in blood 4 hours, 6 and 11 days after ingestion were respectively 450, 86 and 71 micrograms/l for endrin and 60, 19 and 19 micrograms/l for dieldrin. Dieldrin was also present, possibly because the endrin preparation contained traces of dieldrin. Endrin concentrations 11 days after ingestion were 0.071 mg/l in blood, in adipose tissue 89.5 mg/kg, in the heart 0.87 mg/kg, in the brain 0.89 mg/kg, in the kidneys 0.55 mg/kg and in the liver 1.32 mg/kg.

Endrin↗

PubMed1985

Medical aspects of environmental pollution. Environmental incidents in the Netherlands 1980-1984.

In the Netherlands since 1980, 16 situations have been identified in which man might be exposed to environmental pollutants. This paper provides an overview of these incidents and describes how health risk assessments, public studies and provision of individual medical toxicological care are dealt with. The importance of involving general practitioners and other primary health care personnel at an early stage is stressed.

Air Pollution↗

PubMed1985

Dopamine and isoproterenol in imipramine intoxication in the dog.

Artificially ventilated anesthetized dogs were given imipramine 7.5 mg/kg/hr i.v. In the first group (n = 6) mechanical cardiac activity was no longer detectable after a cumulative dose of 20.0 +/- 6.6 mg/kg (mean +/- sd). When aortic flow had decreased to 75% of its initial value, in a second group (n = 5) of experiments dopamine 10 micrograms/kg/min and in a third group (n = 5) isoproterenol 1 microgram/kg/min were administered i.v.. The doses of dopamine and isoproterenol were doubled when aortic flow had again decreased to 75% and 100%, respectively, of the original values. Cardiac mechanical activity was not detectable after a cumulative dose of 43.8 +/- 13.3 in the dopamine and 42.5 +/- 8.0 mg imipramine/kg in the isoproterenol group. These values differed significantly from that in the reference group (both 0.01 greater than p greater than 0.001). In the first group plasma imipramine concentrations at the end of the experiments were 3.06 +/- 0.66, in the second 3.36 +/- 0.66 and in the third 3.32 +/- 1.10 mg/1. Desipramine concentrations were 0.078 +/- 0.06, 0.162 +/- 0.076 and 0.383 +/- 0.09 mg/1 respectively. Dopamine induced a hemodynamic profile of low output and high pressure and isoproterenol one of low pressure and high output. It is concluded that dopamine combined with isoproterenol might be effective in counteracting the cardiodepressant action of imipramine.

Animals↗

PubMed1985

Science and technology in an institute of public and environmental health.

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Academies and Institutes↗

PubMed1984

[Paraquat poisoning in the Netherlands, 1972-1982].

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Acute Kidney Injury↗

PubMed1984

[Dioxins].

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Abnormalities, Drug-Induced↗

PubMed1984

Urinary excretion of cadmium, protein, beta-2-microglobulin and glucose in individuals living in a cadmium-polluted area.

Urine was collected from 289 inhabitants of a cadmium-polluted quarter of Stadskanaal. The excretion of cadmium, protein, beta-2-microglobulin and glucose were determined. After being divided according to sex and to smoking habits, the results of the inhabitants were compared with those of 293 controls. In inhabitants as well as controls, cadmium excretion was age-dependent. Cadmium excretion in females increased faster with age than in males. In male-smoker controls, cadmium excretion was significantly higher (p less than 0.001) than in male-non-smoker controls. In male-non-smoker inhabitants, cadmium excretion (p = 0.05), protein excretion (p less than 0.01) and glucose excretion (p less than 0.01) were significantly higher than in corresponding controls. In male-smoker inhabitants, protein excretion (p less than 0.01) and glucose excretion (0.01 less than p less than 0.05) were significantly higher than in corresponding controls. In female-non-smoker inhabitants glucose excretion was significantly higher (0.01 less than p less than 0.05) than in corresponding controls. For some categories, living in the polluted area was associated with an increased cadmium excretion in urine and a slight difference in renal function, possibly related to a difference in cadmium body burden. It was concluded that, considering the actual values of each parameter, the observed differences were not relevant in terms of potential health hazards.

Adolescent↗

PubMed1984

Different toxicological profiles for various beta-blocking agents on cardiac function in isolated rat hearts.

Propranolol, timolol and sotalol were compared regarding their cardiotoxic properties in isolated, perfused and catecholamine depleted rat hearts. Catecholamine depletion was performed in order to exclude interference of the drugs with beta-adrenergic receptors. The results demonstrate that both in spontaneously beating and atrial- stimulated hearts propranolol (3 - 30 micrograms/ml) and timolol (30 - 300 micrograms/ml) induced a dose dependent decrease in myocardial contractility, stimulus formation and stimulus conduction. Lacking local anesthetic properties as evidenced by effects on coronary flow and threshold voltage in the heart it can be deduced that the negative inotropic effect and an impaired stimulus conduction due to timolol can neither attributed to beta-adrenoceptor antagonism nor membrane stabilising activity. In addition, both propranolol (5 micrograms/ml) and timolol (200 micrograms/ml) reduced myocardial contractility to the same extent in ventricular-paced hearts. Therefore, a direct myocardial depressive effect rather than an indirect effect due to a reduced heart rate must be responsible for the negative inotropy. The hydrophilic beta-blocker sotalol demonstrated a slight cardiodepressant activity either in the spontaneously beating and atrial-stimulated hearts (30 - 300 micrograms/ml) or ventricular-paced hearts (300 micrograms/ml). It is concluded that the toxicological profile of various beta-blocking drugs might be determined by an yet unknown pharmacological property apart from beta-adrenoceptor blockade or membrane stabilising activity. Furthermore, the degree of lipophilicity of the drug might be an important determinant for the cardiotoxic profile of this class of drugs.

Animals↗

PubMed1984

Treatment of 4-aminopyridine-poisoning after oral overdose; a proposal.

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4-Aminopyridine↗

PubMed1983

The influence of haemoperfusion on white cells, immunoglobulin concentrations and the complement system in the treatment of intoxications.

The influence of haemoperfusion on some immunological parameters was investigated in a pilot study involving two groups of three patients each. In columns containing cellulose-coated activated charcoal or polystyrene resin a temporary reduction of the total white cell number, particularly involving the segmented and band neutrophils, was demonstrated. Cellulose-coated activated charcoal and, to a lesser extent, polystyrene resin induced activation of the complement system using C3d as a parameter. An appreciable decrease of immunoglobulin or complement levels could not be demonstrated in either column.

Adult↗

PubMed1983

An evaluation of derived aortic flow parameters as indices of myocardial contractility in rats.

Potential indices of myocardial contractility derived from aortic blood flow, measured by means of electromagnetic flowmetry, were evaluated in rats under different ventricular loading conditions and were compared with the familiar contractility index dP/dt max. Aortic flow acceleration (dF/dt max) appeared to increase in a direct relationship to dP/dt max following inotropic stimulation by either dobutamine or isoprenaline. Since the former drug hardly influenced cardiac frequency, the increase in both variables could be attributed to a positive inotropic action. Also, afterload reduction by both drugs as a possible factor for increase in dF/dt max might be excluded since reduction in afterload by prazosin did not influence this variable, although dP/dt max was slightly reduced. However, dF/dt max was significantly decreased when afterload was markedly increased by methoxamine, whereas dP/dt max was slightly augmented. Therefore, this variable fails to satisfy the criterium of insensitivity to a certain level of aortic pressure rise. It is concluded that dF/dt max can serve as contractility index in rats, provided the influence of afterload conditions on this variable are taken into account.

Animals↗