ANTIARRHYTHMIC EFFECTS OF MONOAMINE OXIDASE INHIBITION IN RAT HEARTS SUBJECTED TO REGIONAL ISCHEMIA/REPERFUSION INJURY
Background: Increasing experimental evidence indicates that monoaminooxidase (MAO)-derived reactive oxygen species (ROS) play a major role in postischemic cardiac damage and irreversible MAO inhibitors elicit protective effects in both in vitro and in vivo animal models. The present study was aimed at characterizing the effects of a reversible MAO-A inhibitor, moclobemid (Mocl), in a rat model of regional ischemia.
Methods: Anesthetized rats subjected to 30 min ischemia by coronary ligation and 2 h reperfusion were randomized to receive: (i) no additional interventions (Ctrl), (ii) acute administration of 4 mg/kg Mocl IV 15 minutes before ischemia (MoclAc) and (iii) chronic administration of 4 mg/kg IP, daily for 3 weeks (MoclChr). Occurrence of arrhythmias (premature ventricular beats, PVBs; ventricular tachycardia, VT and ventricular fibrillation, VF) was assessed according to a modified arrhythmic score (0 = No arrhythmia, 1 = 1-30 PVB, 2 > 30 PVB, 3 < 3 episodes of VT/VF, 4 = 3-5 episodes of VT/VF, 5 > 5 episodes of VT/VF).
Results: No arrhythmias were observed in MoclAc group (arrhythmia score 0), whereas < 30 VPBs (arrhythmia score 1) appeared during ischemia in MoclChr group as compared to arrhythmia scores of 2 (>30 VPBs) and 3 (< 3 episodes of VF/VT) seen in controls.
Conclusion: Acute and chronic administration of a reversible inhibitor of MAO-A isoform elicited an important antiarrhythmic effect in the in vivo model of regional ischemia-reperfusion injury in rat hearts.