Investigation of the effects of sildenafil on bupivacaine cardiotoxicity in rats

There are various studies about the cardioprotective effects of sildenafil which is an inhibitor of phosphodiesterase type 5.In this experimental study; the effects of sildenafil on bupivacaine induced cardiotoxicity was investigated in anesthetized rats.Wistar Albino rats were anesthetized with intraperitoneal urethane (1g.kg-1), and the cannulations of the tail vein and common carotid artery were performed. Intravenous 0.9% sodium chloride was administered (0.5 mL) and infused at 2 mL.h-1 because of blood loss during cannulations. Experimental study was performed while the rats were breathing spontaneously.Following stabilization period (15 min), twenty four rats were equally divided into 4 groups. 200 µL İV bolus 0.9% sodium chloride was administered, then infusion of bupivacaine (3 mg.kg-1.min-1) was started to the rats in Group 1. Sildenafil with doses of 0.01 mg.kg-1, 0.1 mg.kg-1, and 1 mg.kg-1 in a volume of 100 µL İV given to the rats in Groups 2, 3 and 4, respectively. After then, 100 µL 0.9% sodium chloride was administered and bupivacaine was infused at 3 mg.kg-1.min-1 until asystole occured in these groups.At the end of the study, the following events were evaluated from the recorded data; Times to 25%, 50% and 75% reduction of heart rate and mean arterial pressure relative to baseline, time to first QRS complex alteration (prolongation of QRS complex duration by more than 20%), time to first dysrhythmia (first dysrhythmia accompanied by an abnormal systole on the arterial pressure trace and /or 2nd and 3rd degree AV conduction block), and time to asystole (the absence of pressure pulse on the arterial pressure trace).Kruskal-Wallis and Mann-Whitney-U tests were used for the statistical analysis.Baseline arterial pressures, heart rate, duration of QRS complex were similar in all groups (p>0.05). The reduction times in heart rate to 25%, 50% and 75 % and reductoin times in mean arterial pressure to 50% and 75% from the baseline were also similar in all groups (p>0.05). In Group 4, reduction time of mean arterial pressure to 25% from the baseline was significantly shorter compared to Group 1 (p= 0.009). In Group 2 (727.95 ± 59.14 s), the first dysrhytmia was observed significantly later than Group 1 (235.76 ± 67.496 s) (p= 0.002). Time to asystole was similar in all groups (p>0.05).In conclusion, sildenafil may have a cardioprotective effect during cardiotoxicity induced by bupivacaine infusion in rats. Further investigations are reqiured with more subjects.