Role of action potential shortening in the prevention of arrhythmias in canine cardiac tissue.
1. The effects of the K+ channel opener diazoxide and the oxime-containing Ca2+ and K+ channel blocker salicylaldoxime were tested in canine cardiac Purkinje tissue. 2. Both drugs shortened action potential duration (APD). For salicylaldoxime (0.1-1.0 mmol/L), the reductions in APD were statistically significant at the 25% level of repolarization (APD25) for 0.1 mmol/L (P < 0.05, n = 14) and 0.5 and 1.0 mmol/L (P < 0.01, n = 6), at the 50% level of repolarization (APD50) for 0.1 mmol/L (P < 0.05, n = 14) and 0.5 and 1.0 mmol/L (P < 0.01, n = 6) and at the 90% level of repolarization (APD90) for 0.5 and 1.0 mmol/L (P < 0.01, n = 6). In contrast, diazoxide (0.05-0.1 mmol/L) significantly shortened APD at all levels of repolarizations, with the APD50 and APD90 reduced most significantly (P < 0.01, n = 6) for higher concentrations of the drug (0.07-0.1 mmol/L). Both drugs significantly reduced the force of contraction. 3. Diazoxide (10 experiments) was more potent in suppressing strophanthidin-induced arrhythmias than salicylaldoxime (three of seven experiments). Salicylaldoxime reduced APD even further in the presence of diazoxide. 4. Although salicylaldoxime and diazoxide modulate different ion channels, it appears APD shortening may be a necessary, but insufficient, factor for the suppression of strophanthidin-induced arrhythmias.
Mull
K P
KP
Department of Anatomy and Physiology, Meharry Medical College, Nashville, TN 37208, USA.
Debnam
Q
Q
Kabir
S M
SM
Bhattacharyya
M L
ML
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000139:chemically induced / Q000503:physiopathology* / Q000517:prevention & control*; D003981:Diazoxide / Q000494:pharmacology; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D005260:Female; D006321:Heart / Q000187:drug effects / Q000503:physiopathology*; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D010091:Oximes / Q000494:pharmacology; D015221:Potassium Channels / Q000187:drug effects; D011690:Purkinje Fibers / Q000187:drug effects; D013327:Strophanthidin / Q000009:adverse effects
D010091:Oximes; D015221:Potassium Channels; C005704:salicylaldoxime; D013327:Strophanthidin; D003981:Diazoxide