title: Comparative effects of sodium bicarbonate and sodium chloride on reversing cocaine-induced changes in the electrocardiogram.
abstract: Cocaine abuse is associated with a number of cardiovascular complications that include arrhythmias and sudden cardiac death. Although the mechanism(s) remain unclear, cocaine-induced block of sodium channels resulting in slowed cardiac conduction is thought to play an important role. Several reports suggest that the effects of cocaine effects on cardiac sodium channels can be reversed by administration of sodium bicarbonate. Whether the beneficial effects of sodium bicarbonate are due to sodium ions or an increase in blood pH is unknown. Therefore the purpose of this study was to compare the effects of sodium loading alone (by using sodium chloride) versus sodium loading with an associated increase in arterial pH (by using sodium bicarbonate) on reversing cocaine-induced effects on the electrocardiogram (ECG) in a canine model. Seventeen anesthetized dogs received three i.v. injections of cocaine, 5 mg/kg, with each dose separated by 15 min. Two minutes after the third cocaine dose, each dog was randomly assigned to receive 2 mEq/kg i.v. sodium bicarbonate (1 mEq/ml) or 2 mEq/kg i.v. sodium chloride (1 mEq/ml). ECG, electrophysiologic, and hemodynamic data were recorded at baseline, after each cocaine injection, and after administration of sodium bicarbonate or sodium chloride. In both groups of animals, the first cocaine injection significantly (p < 0.05) prolonged the PR, QTc, AH, and HV intervals, and QRS duration compared with baseline. All intervals continued to lengthen in a dose-dependent manner after the second and third cocaine doses. Sodium bicarbonate significantly (p < 0.05) reduced cocaine-induced prolongation of PR [(147 +/- 5-130 +/- 5 ms), AH (81 +/- 6 - 72 +/- 6 ms), and HV intervals (55 +/- 2 - 39 +/- 1 ms). and QRS duration (96 +/- 6 - 66 +/- 4 ms), peak effect after third cocaine dose versus after sodium bicarbonate, respectively]. Sodium chloride had no effect on reversing cocaine-induced effects on the ECG. Cocaine produces dose-dependent slowing of cardiac conduction that is effectively reversed by sodium bicarbonate. The lack of efficacy of sodium chloride suggests that the increase in arterial pH associated with sodium bicarbonate is responsible for reversal of the effects of cocaine on the ECG. Therefore sodium bicarbonate may be clinically useful in the treatment of cocaine-induced cardiac arrhythmias, primarily as a result of its effects on arterial pH.
authors.affiliation: Department of Clinical Pharmacy, College of Pharmacy, University of Tennessee, Memphis 38163, USA. rparker@utmem.edu
authors.forename: R B
authors.initials: RB
authors.lastname: Parker
authors.forename: G Y
authors.initials: GY
authors.lastname: Perry
authors.forename: L G
authors.initials: LG
authors.lastname: Horan
authors.forename: N C
authors.initials: NC
authors.lastname: Flowers
mesh_terms: D000818:Animals; D003042:Cocaine / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D004285:Dogs; D004562:Electrocardiography / Q000187:drug effects*; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D008297:Male; D012964:Sodium / Q000097:blood; D017693:Sodium Bicarbonate / Q000494:pharmacology*; D026941:Sodium Channel Blockers; D012965:Sodium Chloride / Q000494:pharmacology*; D014662:Vasoconstrictor Agents / Q000037:antagonists & inhibitors* / Q000494:pharmacology
chemical_list: D026941:Sodium Channel Blockers; D014662:Vasoconstrictor Agents; D012965:Sodium Chloride; D017693:Sodium Bicarbonate; D012964:Sodium; D003042:Cocaine