Carbon monoxide releasing molecule A1 reduces myocardial damage after acute myocardial infarction in a porcine model - Archive ouverte HAL Access content directly
Journal Articles Journal of Cardiovascular Pharmacology Year : 2021

Carbon monoxide releasing molecule A1 reduces myocardial damage after acute myocardial infarction in a porcine model

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Abstract

Infarct size is a major determinant of outcomes after acute myocardial infarction (AMI). Carbon monoxide releasing molecules (CORMs), which deliver nano-molar 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 4.27mM 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 mm2, 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 LV function tended to recover better in CORM-A1 treated group. There was no evidence of hepatic or renal toxicity with the doses used. The cardio-protective effects of CORM-A1 were associated with a significant reduction in cell proliferation and inflammation. CORM-A1 reduces infarct size and improves LV remodelling and function in a porcine model of reperfused MI via a reduction in inflammation. These potential cardio-protective effects of CORMs warrant further translational investigations.
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Dates and versions

inserm-03313135 , version 1 (03-08-2021)

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Javaid Iqbal, Janet Chamberlain, Mabruka Alfaidi, Matthew Hughes, Tooba Alizadeh, et al.. Carbon monoxide releasing molecule A1 reduces myocardial damage after acute myocardial infarction in a porcine model. Journal of Cardiovascular Pharmacology, 2021, Online ahead of print. ⟨10.1097/FJC.0000000000001067⟩. ⟨inserm-03313135⟩

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