Key result
Novel adenosine agonists improve EF ~69% and reduce cardiac fibrosis in a rat MI model.
Why the study?
Current treatments for AMI include pain relief and attempts to improve survival, prompting investigation into the effects of two new adenosine receptor ligands, LASSBio-1027 and LASSBio-1860, on cardiac function.
Do novel adenosine receptor agonists (LASSBio-1027 and LASSBio-1860) improve cardiac function and reduce remodeling in a rat model of acute myocardial infarction?
Do novel adenosine receptor agonists (LASSBio-1027 and LASSBio-1860) improve cardiac function and reduce remodeling in a rat model of acute myocardial infarction?
Absolute Event Rate: 61.8% vs 36.6%
p-value: p=<0.05
The novel adenosine receptor agonists LASSBio-1027 and LASSBio-1860 attenuate cardiac remodeling and improve ventricular function in a rat model of acute myocardial infarction, highlighting a potential therapeutic pathway for post-MI heart failure.
Does not change post-MI care; hypothesis-generating for adenosine agonism in remodeling.
Background and Purpose: Current treatments for acute myocardial infarction (AMI) include pain relief and attempts to improve survival. This study investigated the effects of two new ligands of the adenosine receptor, LASSBio-1027 and LASSBio-1860, on cardiac function in an experimental model of AMI. Methods: AMI was induced in Wistar rats by ligating the anterior descending coronary arteries. Infarcted animals were treated orally with vehicle (DMSO), LASSBio-1027 (30 and 70 μmol/kg), or LASSBio-1860 (70 μmol/kg) for seven days. Hemodynamic parameters were observed using echocardiography, whereas inflammation and fibrosis were detected using histological analysis. Results: MI increased the filling pressure from 23.0 ± 1.6 and 14.0 ± 2.0 to 37.0 ± 3.7 and 33.2 ± 8.0, respectively indicating diastolic dysfunction. However, treatment with LASSBio-1027 (70 μmol/kg) and LASSBio-1860 (70 μmol/kg) reduced this parameter to 23.9 ± 5.4 and 17.1 ± 6.7. An impairment in ejection fraction from 57.1 ± 3.2 to 36.6 ± 2.0% was observed after MI, partially recovered to 47.0 ± 7.4% by LASSBio-1027 and fully restored to 61.8 ± 4.3% after 7 days of treatment with LASSBio-1860. After MI, collagen deposition in LV free wall was increased to 31.4 ± 11.0% and treatment with LASSBio-1027 reduced to 23.4 ± 6.0 and 19.7 ± 8.0% at 30 and 70 μmol/kg, respectively. Similarly, LASSBio-1860 reduced collagen levels to 63.1 ± 2.0%. Conclusion: Fibrosis and inflammatory components of MI reduced following treatment with agonist of adenosine receptor subtype A2A. Cardiac remodeling induced by LASSBio-1027 and LASSBio-1860 may be responsible for the improvement in cardiac function in AMI through the activation of A2A adenosine receptors.
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Beltrame et al. (2024) studied Acute Myocardial Infarction (n=35). LASSBio-1027 and LASSBio-1860 vs. Vehicle (DMSO) was evaluated on Ejection fraction (p=<0.05). Treatment with the novel adenosine receptor agonists LASSBio-1027 and LASSBio-1860 significantly improved ejection fraction and reduced cardiac fibrosis in a rat model of acute myocardial infarction.
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