Biomedical subjects

J Langemeijer

Publications and source records attributed to J Langemeijer.

3 recordsLinked to original sources

PubMed1986

Calcium interferes with the cardiodepressive effects of beta-blocker overdose in isolated rat hearts.

Propranolol, timolol and sotalol were compared with respect to their cardiotoxic properties in isolated, spontaneously beating rat hearts. Propranolol and timolol induced a dose-dependent decrease in myocardial contractility. A high dose of sotalol had only modest negative inotropic effects. Similar reductions in myocardial contractility were observed in isolated, ventricle-stimulated rat hearts. These observations were similar to those in a previous study in which spontaneously beating and ventricle-stimulated reserpinized rat hearts were investigated. Spontaneously beating rat hearts were perfused with a high-, a normal- and a low-Ca++ medium, each with and without propranolol, timolol and sotalol. Addition of each beta-blocker to a normal-Ca++ medium induced a decrease of myocardial contractility and of heart rate and an increase of AV-conduction time when compared with the drug-free medium. In a high-Ca++ medium containing the same concentration of each beta-blocker, a less pronounced decrease of myocardial contractility was observed. Heart rate decreased and AV-conduction time increased to the same extent as after perfusion with the drug containing normal-Ca++ medium. With respect to the corresponding drug-free medium perfusion with a low-Ca++ medium with each beta-blocker enhanced the decline in myocardial contractility, most pronounced in propranolol and timolol containing media. For propranolol and sotalol the decrease in heart rate and increase in AV-conduction time were similar to the results after administration of the same beta-blocker in a high- and a normal-Ca++ perfusion media. Timolol caused an electromechanical dissociation. It was concluded that in beta-blocker intoxication the negative-inotropic phenomena cannot be explained by an action of the drugs on the beta-receptor since the results in reserpinized and non-reserpinized rat hearts were similar. Other effects have to be responsible for the observed cardiotoxic phenomena. The present results indicate that these phenomena can be influenced by Ca++ and or can be attributed to differences in lipophilicity.

Adrenergic beta-Antagonists↗

PubMed1985

Respiratory arrest as main determinant of toxicity due to overdose with different beta-blockers in rats.

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↗

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↗