[Effects of ryanodine receptors block on spontaneous initiation of atrial fibrillation in the intact canine heart].
To study the possible role of intracellular Ca2+ overload in initiation of cholinergic-dependent atrial fibrillation (AF), we tested the effects of ryanodine in canine models of AF. In anesthetized open-chest dogs (n=10) AF was induced by two methods: (I) perfusion (9 ml/min) with normal Tyrode solution containing acetylcholine (ACh) into the sinus node artery (SNA) and (II) stimulation of the right vagal nerve (VS, 5 sec train). AF was induced in all dogs: by perfusion with ACh (3.7-/+1.5 mcM) into the SNA in 97-/+3% of attempts and by VS in 78-/+6% of attempts. Intravenous infusion of ryanodine (5 mg/kg) did not prevent induction of AF during ACh perfusion (84-/+5%, NS) but completely prevented the induction of AF by VS (4-/+3%, p<0.001). Atrial activation mapping (112 unipolar electrodes) did not show any significant differences between the beginning of ACh-dependent AF in control and after ryanodine treatment. Ryanodine significantly reduced both systolic and diastolic arterial pressures but had no effect on heart rate, atrial effective refractory period (AERP) and conduction velocity for one hour after infusion. Ryanodine, itself, did not exert antivagal activity, so after ryanodine treatment in the presence of VS (8 Hz) the reduction of AERP and the deceleration of heart rate were similar to that in control. These data suggest that ryanodine can suppress the initiation of AF induced by VS but not AF induced by ACh perfusion. We can conclude that the initiation of AF during ACh perfusion unlikely relates to triggering activity induced by intracellular Ca2+ overload. In addition, we suggest that besides ACh some 'unclear' ryanodine sensitive factor(s) contribute to the initiation of AF induced by VS.
Fedorov
V V
VV
Sharifov
O F
OF
Piatakova
O P
OP
Beloshapko
G G
GG
Iushmanova
A V
AV
Rozenshtraukh
L V
LV
D000818:Animals; D001281:Atrial Fibrillation / Q000188:drug therapy / Q000378:metabolism / Q000517:prevention & control*; D015220:Calcium Channels / Q000378:metabolism; D002799:Cholinergic Fibers / Q000378:metabolism; D004195:Disease Models, Animal; D004285:Dogs; D004594:Electrophysiology / Q000295:instrumentation; D012433:Ryanodine / Q000494:pharmacology* / Q000627:therapeutic use*; D019837:Ryanodine Receptor Calcium Release Channel / Q000187:drug effects*; D014630:Vagus Nerve / Q000502:physiology
D015220:Calcium Channels; D019837:Ryanodine Receptor Calcium Release Channel; D012433:Ryanodine