MTX Treatment Does Not Improve Outcome in Mice with AMI

Abstract

<b><i>Background:</i></b> Targeting inflammation in patients with coronary artery disease and/or acute myocardial infarction (AMI) is a matter of debate. Methotrexate (MTX) is one of the most widely used immunosuppressants. Cardiovascular Inflammation Reduction Trial (CIRT) recently failed to demonstrate reduced cardiovascular events in MTX-treated patients. However, it is not known if long-term MTX treatment improves cardiac outcome in AMI. Therefore, in this study, we investigated the postischemic phase in MTX-treated mice undergoing AMI. <b><i>Methods:</i></b> Wild-type mice received MTX medication intraperitoneally for 2 weeks. Afterward, AMI was induced by transient left anterior ascending artery ligation. Postischemic cardiac damage after 24 h was assessed. <b><i>Results:</i></b> MTX treatment did not affect infarct size as compared to control (IS/AAR: Con 76.20% ± 12.37%/AAR vs. MTX 73.51 ± 11.72%/AAR, <i>p</i> = 0.64). Moreover, systolic function and structural parameters did not differ between groups (_24hejection fraction: Con 36.49 ± 3.23% vs. MTX 32.77 ± 2.29%, <i>p</i> = 0.41; _24hLVID; d: Con 3.57 ± 0.17 mm vs. MTX 3.19 ± 0.13 mm, <i>p</i> = 0.14). Platelets were increased by MTX (Con 1,442 ± 69.20 × 10³/mm³ vs. MTX 1,920 ± 68.68 × 10³/mm³, <i>p</i> &#x3c; 0.0001). White blood cell and RBC as well as rate of monocytes, granulocytes, lymphocytes, and serum amyloid P levels were equal. <b><i>Conclusion:</i></b> MTX medication did not improve postischemic cardiac damage in a murine model of AMI. Future trials are needed to identify and investigate other anti-inflammatory targets to improve cardiovascular outcome.