Effects of Rotigotine Extended‐release Microspheres Therapy on Myocardial Ischemia Injury in Mice

Objective Dopamine receptor agonists are important drugs for the therapy of Parkinson's disease (PD), but have a potential to increase the risk of myocardial ischemia. Rotigotine extended‐release microspheres (RoMS) was developed by Shandong Luye Pharmaceutical Co., Ltd. A single RoMS administration continuously releases rotigotine for 2 weeks. This study aims to determine the effect of RoMS therapy on myocardial ischemia injury in mice. Methods The mice were intramuscularly administered with a single RoMS (10 mg/kg or 40 mg/kg). At 5 th or 12 th day after RoMS treatment, myocardial ischemia model was established using subcutaneous injection with isoproterenol (10 mg/kg, once a day for three days). Then Troponin I level, CK‐MB activity and rotigotine concentration in serum were assayed. Furthermore, histopathological examination of heart tissues was performed. To investigate whether dopamine receptor blocker can abrogate the effect of RoMS on the myocardial ischemia injury, the mice were treated with a single RoMS at dose of 40 mg/kg and co‐administered with chlorpromazine at dose of 2 mg/kg (once a day for 7 d or 14 d). Results After a single intramuscular injection of RoMS at dose of 10 or 40 mg/kg, the rotigotine concentrations were 7.7 ± 2.1, 21.6 ± 4.1 ng/mL on the 7 th day. On the 14 th day, the rotigotine concentrations were 1.4 ± 0.4, 3.4 ± 1.1 ng/mL, respectively. On the 7 th day, the Troponin I level and the CK‐MB activity in the control group were 30.8 ± 11.0 pg/mL, 116.8 ± 8.7 U/L. The Troponin I and the CK‐MB in the model group were increased (2829.1 ± 433.2 pg/mL, 274.9 ± 21.2 U/L, P<0.01). The Troponin I and the CK‐MB in RoMS groups were decreased (P<0.01). On the 14 th day, the Troponin I level and the CK‐MB activity in the control group were 41.3 ± 12.6 pg/mL, 128.5 ± 16.4 U/L. The Troponin I and the CK‐MB in the model group were augmented (2766.5 ± 311.4 pg/mL, 273.5 ± 20.7 U/L, P<0.01). The Troponin I and the CK‐MB in the RoMS groups were reduced (P<0.01). On the 7 th and 14 th day, the cardiomyocytes in the control group displayed normal morphology. In the model group, focal necrosis, interstitial edema and inflammatory cells infiltration were observed. In the RoMS groups, the focal necrosis, the degree of interstitial edema and the infiltration of inflammatory cells were alleviated. Compared with the RoMS group, the Troponin I levels (303.6 ± 42.8 pg/mL versus 800.6 ± 103.5 pg/mL on the 7 th day, 906.8 ± 63.4 pg/mL versus 1741.8 ± 146.9 pg/mL on the 14 th day) and the CK‐MB activities (136.4 ± 9.1 U/L versus 189.6 ± 14.1 U/L on the 7 th day, 196.4 ±13.9 U/L versus 280.6 ± 13.9 U/L on the 14 th day) in RoMS plus chlorpromazine group were increased (P<0.05 or P<0.01). Furthermore, chlorpromazine partially abrogated the protective effect of RoMS on the cardiomyocyte injury caused by ischemia. Conclusion If the animals treated with RoMS are on an attack of myocardial ischemia, the injury of cardiomyocyte will be alleviated. RoMS therapy for PD patients with high risk factor for cardiovascular diseases does not increase the degree of cardiomyocyte injury caused by ischemia, which has a protective effect on cardiomyocyte. Support or Funding Information Natural Science Foundation of Shandong Province (no. ZR2015HM034), Taishan Scholar Project (For Prof. Rong Zhai). This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .