Arrhythmogenic and antiarrhythmic actions of substances of abuse: effects on triggered activity.
Substances of abuse exert adrenergic and/or depressant actions on the cellular processes responsible for cytosolic calcium overload. This investigation attempted to determine whether substances of abuse, through catechol-mediated effects or cellular actions, elicit or inhibit the production of arrhythmias caused by delayed afterdepolarizations (DADs) and triggered activity (TA). The papillary muscles of rats and Purkinje fibers of dogs were superfused in vitro with Tyrode's solution at 37 degrees C. Intracellular microelectrodes were used to record membrane potentials. Overdrives failed to induce DADs and TA in the canine Purkinje fibers exposed to either Tyrode's solution alone, or containing ethanol or harmine. Instead, ethanol and harmine inhibited DADs and TA induced by overdrives in the presence of strophanthidin. On the contrary, in the presence of acetaldehyde and amphetamine, overdrives did produce TA, which was inhibited by propranolol. In conclusion, substances of abuse may either elicit or inhibit the production of DADs and TA, depending on the balance between adrenergic and depressant actions on the cellular mechanisms responsible for the calcium overload of the cytosol.
Gallardo-Carpentier
A
A
Department of Pharmacology, Howard University College of Medicine, Washington, DC 20059, USA.
Aileru
A A
AA
Carpentier
R G
RG
D000661:Amphetamine; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000009:adverse effects / Q000494:pharmacology*; D001145:Arrhythmias, Cardiac / Q000139:chemically induced* / Q000378:metabolism / Q000503:physiopathology; D002118:Calcium / Q000378:metabolism; D002492:Central Nervous System Depressants / Q000009:adverse effects / Q000494:pharmacology*; D000697:Central Nervous System Stimulants / Q000009:adverse effects / Q000494:pharmacology*; D003600:Cytosol / Q000187:drug effects / Q000378:metabolism; D004285:Dogs; D066298:In Vitro Techniques; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D008839:Microelectrodes; D010210:Papillary Muscles / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D011690:Purkinje Fibers / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley
D000889:Anti-Arrhythmia Agents; D002492:Central Nervous System Depressants; D000697:Central Nervous System Stimulants; D000661:Amphetamine; D002118:Calcium