The investigation of the effects of 44bu, a newly sodium channel blocker, against reperfusion arrhythmias in vivo

The aim of this study was to investigate protective effects of 44Bu that is one of the transient Na+ channel blockers which inhibit intracellular Na+ and Ca2+ overloading against in vivo İ/R injury especially in terms of arrhythmias and tissue damage occuring as result of this damage and to compare ranolazine (persistent Na+ channel blocker) and lidocaine (a well known Na+ channel blocker)In the experiments, after anaesthetized rats were placed on a water-filled heating pad and during the study body temperatures measured with rectal thermometer and maintained temperature 37±1 °C. Rats were then mechanically ventilated using rodent respirator after the trachea was entubated . To constitute I/R damage, a left thoracotomy between the fourth and fifth rimbs was performed and passed surgical silk suture to area that close to the center of left descending coronary artery in back side of the heart and to cerate a snare suture was threaded through a hollow polyethylene tube. After stabilization period for 15 minutes, rats were subjected to 15 minutes of ischemia by compressing tube with a metal clamp onto left descending coronary artery and after 15 minutes of coronary artery occlusion,the clamp was released,the snare loosened, and reperfusion protocol performed for 15 minutes. During I/R, we measured arterial pressure with right carotid artery cannulation and we measured EKG with needle electrodes that applied to left arm, right arm and left leg constantly. All drugs applied as bolus through femoral vein 5 minutes before iscemia. İmprovement in ventricular arrhythmia evaluated with ventricular tachycardia (VT) and alteration in ventricular fibrilation (VF) incidence and count of ventricular ectopic beat (VEB). Myocardial tissue damage determined by mesuring LDH levels from blood which was collected at the end of the reperfusion.In this study it is shown that, 44Bu reduced significantly the number of VEB and the incidence of VT and VF which are observed during reperfusion, to control. At the same time it is determined that lidocaine and ranolazine prevented significantly the reperfusion-induced VT beter than 44Bu and protective effect of 44Bu on VF was strong than the other two drugs. Also LDH levels, used as a marker of myocardial demage, decreased with the administration of ranolazine and lidocaine but were not affected with 44Bu.In conclusion, our findings in this thesis shows that 44Bu may be an agent which is as effective as lidocaine and ranolasine used at the clinic, in preventing against I/R injury which results in ventricular arrhythmias