The combination approach with Rhokinase inhibition and mechanical circulatory support in myocardial ischemia-reperfusion injury: Rho-kinase inhibition and ventricular unloading
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Media type:
E-Article
Title:
The combination approach with Rhokinase inhibition and mechanical circulatory support in myocardial ischemia-reperfusion injury: Rho-kinase inhibition and ventricular unloading
Description:
<jats:sec><jats:title>Background</jats:title><jats:p> It remains unclear whether the Rho-kinase (ROCK) inhibition in combination with mechanical circulatory support (MCS) had a synergic protective effect on myocardial ischemia (MI)/reperfusion injury in therapeutic strategies for acute myocardial infarction (AMI). We report the results of an approach using a rat model consisting of a miniaturized cardiopulmonary bypass (CPB) and AMI. </jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p> A total of 25 male Wistar rats were randomized into 5 groups: (1) Sham: a suture was passed under the left anterior descending artery (LAD) creating no MI. A vehicle solution (0.9% saline) was injected intraperitoneally. (2) Myocardial ischemia (MI) + vehicle (MI + V): LAD was ligated for 30 min and reperfused for 120 min, followed by administration of vehicle solution. (3) MI + fasudil (MI + F): the work sequence of group 2, but the selective ROCK inhibitor fasudil (10 mg/kg) was administered instead. (4) MI + V + CPB: CPB was initiated 15 min after the ligation of the LAD to the end of the reperfusion, in addition to the work sequence in group 2. (5) In the MI + F + CPB group, the work sequence of group 4, but with fasudil administration (10 mg/kg). </jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p> Measurements of cardiac function through conductance catheter indicated that the drop of + dP/dt after reperfusion was moderately limited in MI + F + CPB (vs. MI + V, dP/dt p = 0.22). The preload recruitable stroke work was moderately improved in the MI + F + CPB ( p = 0.23) compared with the corresponding control animals (MI + V). Phosphorylated protein kinase B expression in the MI + V + CPB and MI + F + CPB was higher than that in MI + V ( p = 0.33). </jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p> Therefore, fasudil administration with MCS resulted in a moderately better left ventricular performance. </jats:p></jats:sec>