The antiarrhythmic effect of ryanodine in guinea pigs with glycoside poisoning

Many forms of rhythm disturbances in pathological states such as ischemia, glycoside poisoning, and hypokaliemia, have been shown to arise through calcium overloading. An increase in the intracellular calcium ion concentration [Ca++] i leads to diastolic waves of membrane potential (MP) which, on reaching the threshold level, induce extra-excitation of the he$$t [i0]. The pharmacotherapyof these forms of arrhythmias is thus aimed at reducing the Ca inflow into the cells, by the use of blockers of the inward Ca and Na currents. At the same time, we know that diastolic fluctug_~ionsof MP and of myocardial tone in calcium overloading are based on oscillations of [Ca"]i, the source of which is the sarcoplasmic reticulum (SR) [2, 14]. It is therefore interesting to study the antiarrhythmic properties of preparations which modify SR function. The list of these preparations includes caffeine and ryanodine. We know that caffeine exhausts the calcium reserves in SR [4]T ' There are data in the literatume on the blocking action of caffeine on oscillations of [Ca~-~]i, and on fluctuations of MP and myocardial tone in calcium overloading [3, 7]..i However, it is impossible to study the action of caffeine in animals in vivo because its antiarrhythmic activity is exhibited only if present in high concentrations (over 3 mM). All the available physiological data indicate that the main site of action of ryanodine is also SR [2, 3, 8, 13]. Unlike caffeine, ryanodine exhibits its antiarrhythmic properties in nanomolar concentrations [13], as has Been demonstrated in experiments in vivo [II]. It must be pointed out that so far an antiarrhythmic action of ryanodine in vivo has been obtained only in experiments on dogs [ii], and in vitro, on guinea pigs and calves [13]. It was therefore decided to study the antiarrhythmic activity of ryanodine in vitro and in vivo on the same object.