Key result
Fasudil administration combined with mechanical circulatory support moderately limited the drop in left ventricular contractility (+dP/dt) after myocardial ischemia-reperfusion injury in rats compared to vehicle control (p=0.22).
Why the study?
It remained unclear whether Rho-kinase inhibition combined with mechanical circulatory support exerts a synergistic protective effect against myocardial ischemia/reperfusion injury in acute myocardial infarction.
Does fasudil combined with mechanical circulatory support improve left ventricular performance and reduce myocardial ischemia/reperfusion injury in a rat model of acute myocardial infarction?
Does fasudil combined with mechanical circulatory support improve left ventricular performance and reduce myocardial ischemia/reperfusion injury in a rat model of acute myocardial infarction?
In a rat model of myocardial ischemia/reperfusion injury, the combination of the Rho-kinase inhibitor fasudil and mechanical circulatory support resulted in a non-significant trend toward better left ventricular performance.
Answers are grounded in this paper and cite their sources.
May support adjunctive ROCK inhibition during MCS for AMI; leaves open clinical translation pending human trials.
Background 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. Methods 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). Results 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). Conclusion Therefore, fasudil administration with MCS resulted in a moderately better left ventricular performance.
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Miyahara et al. (2022) studied Myocardial ischemia-reperfusion injury (n=25). Fasudil and mechanical circulatory support (cardiopulmonary bypass) vs. Vehicle (0.9% saline) without cardiopulmonary bypass was evaluated on Cardiac contractility evaluated by +dP/dt after reperfusion (p=0.22). Fasudil administration combined with mechanical circulatory support moderately limited the drop in left ventricular contractility (+dP/dt) after myocardial ischemia-reperfusion injury in rats compared to vehicle control (p=0.22).
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