AIM To investigate the effect of CPU86017 on the changes of mRNA abundance of different calcium handling system in infarcted heart. METHODS Rats were subjected to left coronary ligation to induce myocardial infarction (MI). The treatment with either propranolol (Pro) 5 mg/kg ip or CPU86017 1, 2, and 4 mg/kg ip was initiated on the next day of operation and continued for 20 d. Medication with isoproterenol (Isop) 3 mg/kg sc started on the d 17-21. Ventricular mRNA abundance of ryanodine receptor 2 (RyR2), sarcoplasmic reticulum Ca(2+)-ATPase (SERCA2), L-type Ca(2+) channel, and Na(+)/Ca(2+)exchanger (NCX1) were measured. RESULTS Arrhythmic scores (AS) in the Isop group was raised up to 5.27+/-1.75 (P<0.01) vs myocardial infarction group 2.25+/-2.04 and sham group 1.50+/-1.73. The AS was depressed by Pro (1.63+/-1.53, P<0.01 vs Isop), and CPU86017 2 and 4 mg/kg (3.00+/-1.24, and 1.70+/-1.85, P<0.01 vs Isop). The significant dispersion of depressed mRNA abundance of RyR2 and SERCA2 was associated with an increase in AS in Isop group, and it was much depressed in the left than the right ventricle. The dispersion and depression of mRNA were restored significantly by Pro and CPU86017, associated with suppression on AS. In Isop group, the mRNA abundance of L-type Ca(2+) channel was not changed; and a moderate increase in the mRNA of NCX1 was seen, the changes were regressed by Pro and CPU86017. CONCLUSION Isop-induced arrhythmogenesis in MI heart was correlated mainly with a dispersion of depressed mRNA abundance in ventricle likely due to the consequence of PKA over-phosphorylation. A suppression of arrhythmia by Pro and CPU86017 resulted from a regression of the dispersion and depression of RyR2 and SERCA2.

中文翻译：

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RyR2和SERCA2的心室mRNA分散与大鼠心律失常相关。

目的探讨CPU86017对梗死心脏不同钙处理系统mRNA丰度变化的影响。方法对大鼠进行左冠状动脉结扎以诱发心肌梗塞（MI）。在手术的第二天开始使用普萘洛尔（Pro）5 mg / kg ip或CPU86017 1、2和4 mg / kg ip进行治疗，并持续20 d。从第17-21天开始以3 mg / kg异丙肾上腺素（Isop）进行药物治疗。ryanodine受体2（RyR2），肌质网Ca（2 +）-ATPase（SERCA2），L型Ca（2+）通道和Na（+）/ Ca（2+）交换子（NCX1）的心室mRNA丰度是。测量。结果与心肌梗死组2.25 +/- 2.04和假手术组1.50 +/- 1.73相比，Isop组的心律失常评分（AS）升高至5.27 +/- 1.75（P <0.01）。Pro压低了AS（1.63 +/- 1.53，与Isop相比，P <0.01），和CPU86017 2和4 mg / kg（3.00 +/- 1.24和1.70 +/- 1.85，P <0.01 vs Isop）。在Isop组中，RyR2和SERCA2的mRNA丰度下降的显着分散与AS的升高有关，并且在左心室比在右心室低得多。Pro和CPU86017可显着恢复mRNA的分散和抑制，并抑制AS。在Isop组中，L型Ca（2+）通道的mRNA丰度没有改变；并且观察到NCX1 mRNA的适度增加，然后Pro和CPU86017将该变化进行回归。结论异丙酚引起的心律失常主要与心室中mRNA丰度降低有关，可能是由于PKA过度磷酸化所致。