In:
Journal of Cardiovascular Pharmacology, Ovid Technologies (Wolters Kluwer Health), Vol. 78, No. 5 ( 2021-11), p. e656-e661
Abstract:
Infarct size is a major determinant of outcomes after acute myocardial infarction (AMI). Carbon monoxide–releasing molecules (CORMs), which deliver nanomolar concentrations of carbon monoxide to tissues, have been shown to reduce infarct size in rodents. We evaluated efficacy and safety of CORM-A1 to reduce infarct size in a clinically relevant porcine model of AMI. We induced AMI in Yorkshire White pigs by inflating a coronary angioplasty balloon to completely occlude the left anterior descending artery for 60 minutes, followed by deflation of the balloon to mimic reperfusion. Fifteen minutes after balloon occlusion, animals were given an infusion of 4.27 mM CORM-A1 (n = 7) or sodium borate control (n = 6) over 60 minutes. Infarct size, cardiac biomarkers, ejection fraction, and hepatic and renal function were compared amongst the groups. Immunohistochemical analyses were performed to compare inflammation, cell proliferation, and apoptosis between the groups. CORM-A1–treated animals had significant reduction in absolute infarct area (158 ± 16 vs. 510 ± 91 mm 2 , P 〈 0.001) and infarct area corrected for area at risk (24.8% ± 2.6% vs. 45.2% ± 4.0%, P 〈 0.0001). Biochemical markers of myocardial injury also tended to be lower and left ventricular function tended to recover better in the CORM-A1 treated group. There was no evidence of hepatic or renal toxicity with the doses used. The cardioprotective effects of CORM-A1 were associated with a significant reduction in cell proliferation and inflammation. CORM-A1 reduces infarct size and improves left ventricular remodeling and function in a porcine model of reperfused MI by a reduction in inflammation. These potential cardioprotective effects of CORMs warrant further translational investigations.
Type of Medium:
Online Resource
ISSN:
0160-2446
DOI:
10.1097/FJC.0000000000001067
Language:
English
Publisher:
Ovid Technologies (Wolters Kluwer Health)
Publication Date:
2021
detail.hit.zdb_id:
2049700-3
SSG:
15,3
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