Inhibition of Small‐Conductance Ca2+‐activated K+ Channels Protects Against Ventricular Fibrillation (VF) In Rats With Acute Myocardial Infarction (AMI)

Abstract

In vitro study has shown that up‐regulation of SK channels in the ventricular epicardial myocytes is responsible for the spontaneous VF in failing ventricle. The present study determined the role of SK channels in regulating VF in AMI rats. AMI was induced by coronary artery ligation and ventricular programmed stimulation was used to evaluate ventricular vulnerable period (VVP), VF threshold (VFT) and ventricular effective refractory period (VERP) in anesthetized rats. In AMI animals, VVP was prolonged and VERP was shortened (p<0.05, n=6). Pre‐treatment in the AMI group with the SK channel blocker UCL1684 significantly shortened VVP and prolonged VERP (p<0.05, n=6). No effects were observed in sham‐operated controls (n=9). Additionally, VT was reduced in the AMI group, and UCL1684 increased VFT in the AMI group (p<0.05, n=6), but, again, was without effect in sham‐operated controls (n=9). Finally, monophasic action potential duration (MAPD90) was examined using an electrode placed on the left ventricular epicardium. The data showed that MAPD90 was shortened in AMI group (p<0.05, n=7), and UCL1684 significantly prolonged the MAPD90 (p<0.05, n=5), but was without effect in sham‐operated controls (n=9). We conclude that activation of SK channels may underlie the mechanisms of VF. Inhibition of SK channels reduced shorting of MAPD90, which may be responsible for the inhibitory effect on VF in AMI rats. Support: NNSF‐30971223 (JHZ); AHA 10SDG2640130 (QHC).