Effects of simulated ischemia-reperfusion and atorvastatin on INa in rat left ventricular myocytes.

Objective To observe time dependent effects of simulated ischemia-reperfusion on transient sodium currents (INa) in rat left ventricular myocytes, and effects of atorvastatin on INa in the condition of ischemia and reperfusion. Methods Fifty-four Wistar rats were used for isolating left ventricular myocytes, which were randomly divided into four groups: ischemia group (normal→ischemia→ischemia), reperfusion group (normal→ischemia→reperfusion), statin-ischemia group (normal→ischemia with 5 μmol/l atorvastatin) and statin-reperfusion group (normal→ischemia→reperfusion with 5 μmol/l atorvastatin). Firstly, INa were recorded in normal INa solution (for control) by whole-cell patchclamp. Then, in simulated ischemia solution, INa were recorded from 3 min to 21 min. Finally, INa were recorded again in normal INa solution (simulate reperfusion). Results (1) Ischemia effects: In ischemia group, compared with normal (0.95±0.04), normalised currents (at −40 mV) of simulated ischemia were increased to peak at 3 min (1.15±0.08, p<0.01), returned at 9 min and 11 min (0.98±0.12 and 0.92±0.12, p>0.05, respectively), and decreased at 21 min (0.56±0.13, p<0.01). At simulated ischemia for 21 min, there were no significant differences among ischemia group, reperfusion group and statin-reperfusion group. (2) Effects of atorvastatin on ischemia myocytes: in statin-ischemia group, there were no differences between nomal and simulated ischemia for 3 min (0.97±0.04 vs 0.92±0.12, p>0.05). (3) Reperfusion effects: compared with ischemia for 21 min, normalised currents (at −40 mV) in reperfusion group were decreased at reperfusion for 3 min from 0.83±0.11 to 0.57±0.09 (p<0.05), and decreased to 0.50±0.09 at reperfusion for 9 min (compared with 3 min p<0.05), while in ischemia group normalised currents were not changed again. And compared with ischemia group, normalised currents (at −40 mV) in reperfusion group were decreased at reperfusion for 3 to 9 min (p<0.01). (4) Effects of atorvastatin on reperfusion myocytes: compared with ischemia for 21 min, normalised currents (at −40 mV) in statin-reperfusion group were decreased at reperfusion for 3 min from 0.92±0.04 to 0.72±0.05 (p<0.01). And at reperfusion for 3 to 9 min, normalised currents in statin-reperfusion group were decreased compared with ischemia group, but increased compared with reperfusion group (p<0.01, respectively). Conclusions (1) The effects of simulated ischemia on INa are time dependent, while INa is transient increased at 3 min, but decreased 21 min (2) Simulated reperfusion make INa more decreased from ischemia condition. (3) Atorvastatin can depress increased INa at the period of early ischemia, and depress decreased INa at the time of reperfusion.