Interaction of the effects of hypoxia, substrate depletion, acidosis and hyperkalaemia on the class III antiarrhythmic properties of sotalol.
The effects of hypoxia on the actions of dl-sotalol 10(-4) mol . litre-1 were studied in rabbit papillary muscles at 32 degrees C. Superfusion for 30 min with a hypoxic solution (95% N2, 5% CO2) in the presence of 5 mmol . litre-1 glucose caused moderate shortening of control action potential duration from 208 +/- 3 to 138 +/- 9 ms (mean +/- SEM). In the presence of sotalol, hypoxia caused shortening of APD90 from 399 +/- 9 ms to 249 +/- ms, but the value after 30 min was still significantly greater than in controls (p less than 0.001). Superfusion with a hypoxic, glucose-free solution, however, caused profound shortening of APD90 in controls to 80 +/- 7 ms at 30 min. The highly significant lengthening of APD90 produced by sotalol in control conditions was abolished after 5 min hypoxia. The effects of hypoxia on the effective refractory period (ERP) paralleled those on APD90. Exposure to a hypoxic, acidotic, hyperkalaemic solution (80% N2, 20% CO2, pH 6.8; K+ 12 mmol . litre-1) produced moderate shortening of APD90 with convergence of the two groups. There was an increase in ERP, with the development of an equal degree of post-repolarisation refractoriness in the control and sotalol groups. The Class III effect of sotalol is preserved under mild but lost under severely hypoxic conditions. Using "simulated ischaemic" conditions, with controlled extracellular potassium concentrations, there was no difference in the relationship between APD90 and ERP in the control and sotalol groups.
D000138:Acidosis / Q000378:metabolism; D000200:Action Potentials / Q000187:drug effects; D000208:Acute Disease; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D003327:Coronary Disease / Q000378:metabolism / Q000503:physiopathology*; D003470:Culture Media; D004558:Electric Stimulation; D005947:Glucose / Q000378:metabolism; D000860:Hypoxia / Q000378:metabolism; D066298:In Vitro Techniques; D010210:Papillary Muscles / Q000378:metabolism / Q000503:physiopathology*; D011817:Rabbits; D013015:Sotalol / Q000494:pharmacology*
D000889:Anti-Arrhythmia Agents; D003470:Culture Media; D013015:Sotalol; D005947:Glucose