Beta-adrenoreceptor blockers and CaCl2-induced arrhythmias in the rat: discrepancies between antiarrhythmic properties and survival rate.
Although propranolol antagonized CaCl2-induced arrhythmias in the rat due to its local anaesthetic properties, arrhythmias-protected animals died because of respiratory failure. To assess the relative role played by beta 2-adrenoreceptor blocking and local anaesthetic properties in the genesis of this phenomenon, five beta-blockers with different degrees of local anaesthetic properties have been tested at their respective ED50 against CaCl2-induced arrhythmias in the rat and their respective surviving/arrhythmias-protected animals ratio (SAPAR) calculated. A highly significant correlation exists between local anaesthetic properties and SAPAR but not between SAPAR and beta 2-adrenoreceptor blocking properties. Further studies showed that (a) assisted ventilation but not picrotoxin or terbutaline pretreatment protected rats against propranolol-CaCl2-induced respiratory failure, and (b) intracerebroventricular propranolol failed to antagonize CaCl2-induced arrhythmias while producing a dose-dependent inhibition of breathing rate. These results suggest that, in this test model, local anaesthetic properties of beta-blockers are responsible for their antiarrhythmic effect at peripheral level, and superimpose to the effects of CaCl2 in inducing respiratory failure at central level.
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000779:Anesthetics, Local; D000818:Animals; D000889:Anti-Arrhythmia Agents; D001145:Arrhythmias, Cardiac / Q000139:chemically induced; D002122:Calcium Chloride; D008297:Male; D051379:Mice; D010852:Picrotoxin / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012119:Respiration / Q000187:drug effects; D012121:Respiration, Artificial; D013726:Terbutaline / Q000494:pharmacology
D000319:Adrenergic beta-Antagonists; D000779:Anesthetics, Local; D000889:Anti-Arrhythmia Agents; D002122:Calcium Chloride; D010852:Picrotoxin; D011433:Propranolol; D013726:Terbutaline