(NVKP-16-1-2016-0017 National Heart Program) Funder: NRDIO
(2020-1.1.6-JOVO-2021-00013)
(K139237)
(K139105)
(RRF-2.3.1-21-2022-00003)
(2020-4.1.1.-TKP2020)
(Therapeutic Development and Bioimaging thematic programmes of the Semmelweis University)
(TKP2021-EGA-23) Funder: Ministry for Innovation and Technology
(2019-1.1.1-PIACI-KFI-2019-00367)
(Semmelweis 250+ Kiválósági PhD Ösztöndíj)
Az orvos-, egészségtudományi- és gyógyszerészképzés tudományos műhelyeinek fejlesztése(EFOP-3.6.3-VEKOP-16-2017-00009)
Funder: EFOP-VEKOP
(Gedeon Richter Ph.D. Scholarship grant)
(ÚNKP-21-4-I-60)
(VEKOP-2.3.3-15-2016-00006)
Subjects:
Pharmacology, pharmacogenomics, drug discovery and design, drug therapy
Lipid-lowering drugs have been shown to have cardioprotective effects but may have
hidden cardiotoxic properties. Therefore, here we aimed to investigate if chronic
treatment with the novel lipid-lowering drug bempedoic acid (BA) exerts hidden cardiotoxic
and/or cardioprotective effects in a rat model of acute myocardial infarction (AMI).
Wistar rats were orally treated with BA or its vehicle for 28 days, anesthetized and
randomized to three different groups (vehicle + ischemia/reperfusion (I/R), BA + I/R,
and positive control vehicle + ischemic preconditioning (IPC)) and subjected to cardiac
30 min ischemia and 120 min reperfusion. IPC was performed by 3 × 5 min I/R cycles
before ischemia. Myocardial function, area at risk, infarct size and arrhythmias were
analyzed. Chronic BA pretreatment did not influence cardiac function or infarct size
as compared to the vehicle group, while the positive control IPC significantly reduced
the infarct size. The incidence of reperfusion-induced arrhythmias was significantly
reduced by BA and IPC. This is the first demonstration that BA treatment does not
show cardioprotective effect although moderately reduces the incidence of reperfusion-induced
arrhythmias. Furthermore, BA does not show hidden cardiotoxic effect in rats with
AMI, showing its safety in the ischemic/reperfused heart.
