Background:

I_Ks is upregulated by tachycardia. Reperfusion fololowing ischemia increases heart rate and triggers arrhythmias. The present study explored whether a block of I_Ks could reduce malignant reperfusion arrhythmias increasing thus the time of normal sinus rhythm (SN) after a global no-flow ischemia.

Methods:

Isolated rat hearts (control group n=13, I_Ks-blocker group n=9) were perfused with a modified Krebs-Henseleit solution containing 3 mM K⁺ to lower fibrillation threshold. In the I_Ks-blocker group, HMR1556 (1µmol/l) was added to the perfusion 10 minutes before ischemia and during reperfusion. Ischemia and reperfusion were 20 and 30 minutes respectively. Monophasic action potentials in addition to ECG were recorded.

Results:

During the reperfusion, irreversible ventricular fibrillation (VF) occured in all -excepted one- control hearts. Blocking I_Ks reduced VF and increased periods of SN (1.9±3.2 vs 11.5±10.2 min, p=0.025). In 2 hearts of this group, VF could be reversed to SN and, in 2 other hearts completely suppressed. In the first minutes of ischemia, heart rate decreased markedly until the ventricle stopped. Bradycardia was more marked in the I_Ks-blocker group (1^st minute: 11.3±11.6% control vs 26.8±9.7% I_Ks-blocker, p=0.045; 5^th minute: 40.5±21.3% control vs 71.5±10.0% I_Ks-blocker, p=0.008). Moreover, the perfusion of HMR1556 extended the time of ventricle beating significantly (16.2±3.8 vs 11.8±3.4 min, p=0.038). Duration of action potential at 90% repolarization (APD₉₀) was not significantly modified by HMR1556.

Conclusions:

These results demonstrate the antiarrhythmic effect of I_Ks block in preventing from malignant reperfusion arrhythmias and suggest possible therapeutic applications.