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.
Langemeijer
J
J
de Wildt
D
D
de Groot
G
G
Sangster
B
B
D000319:Adrenergic beta-Antagonists / Q000037:antagonists & inhibitors / Q000506:poisoning*; D000818:Animals; D002118:Calcium / Q000494:pharmacology / Q000502:physiology*; D002395:Catecholamines / Q000502:physiology; D003326:Coronary Circulation / Q000187:drug effects; D004558:Electric Stimulation; D006321:Heart / Q000187:drug effects*; D006329:Heart Conduction System / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D011433:Propranolol / Q000037:antagonists & inhibitors / Q000506:poisoning; D051381:Rats; D011919:Rats, Inbred Strains; D013015:Sotalol / Q000037:antagonists & inhibitors / Q000506:poisoning; D013999:Timolol / Q000037:antagonists & inhibitors / Q000506:poisoning
D000319:Adrenergic beta-Antagonists; D002395:Catecholamines; D013999:Timolol; D011433:Propranolol; D013015:Sotalol; D002118:Calcium