Class III antiarrhythmic drugs are most commonly used for atrial fibrillation. These drugs block potassium currents responsible for restoration of resting potential and increase action potential duration (APD) and excitation wavelength.
OBJECTIVE
To study the influence of Refralon, Sotalol and E-4031 on myocardium of the left atrium and pulmonary vein orifices under hypoxia and acidification (pH=6.6).
MATERIAL AND METHODS
We analyzed the effects of Refralon, Sotalol and E-4031 on the left atrium and distal part of pulmonary vein in rats using multichannel microelectrode technology.
RESULTS
Hypoxia insignificantly decreased effective refractory period in the atrium, pulmonary vein orifices and distal part of pulmonary vein. However, addition of Sotalol under hypoxia significantly reduced effective refractory period in the atrium, pulmonary vein orifices and distal part of pulmonary vein (77±4%, 78±5% and 76±3% of control values, respectively, p<0.05). Addition of E-4031 under hypoxia did not significantly change effective refractory period. At the same time, Refralon significantly increased effective refractory period under hypoxia (125±3%, 125±4%, 148±5% of control values in the atrium, pulmonary vein orifices and distal part of pulmonary vein, respectively, p<0.05). Acidification significantly reduced effective refractory period in the atrium, pulmonary vein orifices and distal part of pulmonary vein (76±3%, 75±4%, 74±5% of control values, respectively, p<0.05). Addition of Sotalol did not lead to recovery of effective refractory period (84±5%, 81±6%, 78±9% of control values in the atrium, pulmonary vein orifices and distal part of pulmonary vein, respectively, p<0.05). Refralon and E-4031 restored effective refractory period up to control values. In the control, the probability of premature heart beat was 42% (15/36). Under hypoxia, this value was the same (39%, 7/18). The probability was 61% (11/18) at pH=6.6. Addition of Sotalol under hypoxia increased the likelihood of premature heart beat to 80% (4/5), E-4031 did not significantly affect the likelihood of premature heart beat (40%, 2/5). No premature heart beats were observed under the action of Refralon (0/8). At pH=6.6 and addition of Sotalol, the probability of premature heart beat reached 83% (5/6). E-4031 and Refralon did not significantly affect the probability of premature heart beats (50%, 3/6).
CONCLUSION
Ikr current blockers (Refralon, E-4031) contribute to effective refractory period recovery and prevention of premature heart beats under acidification, except for Sotalol. Refralon increased effective refractory period under hypoxia in contrast to E-4031 and Sotalol, as well as reduced the likelihood of premature heart beats. Refralon also increased functional refractory period under hypoxia that can indicate its efficacy for correction of atrial fibrillation and atrial flatter under hypoxia.
