Myocardial infarction rapidly induces diaphragm muscle weakness (1102.11)

Abstract

Chronic heart failure (CHF) induced by myocardial infarction (MI) results in diaphragm muscle weakness, with increased inflammation and oxidative stress directly implicated. It remains unknown, however, if diaphragm muscle function is impaired immediately post‐MI and whether this is associated with increased markers of inflammation and oxidative stress. Methods: Ligation of the left coronary artery to induce MI (n=21; confirmed by echocardiography) or sham operation (n=22) was performed on 8 wk old C57BL/6 mice. Three days later, in vitro isometric force of diaphragm muscle fibre bundles was assessed. Results: Specific force was depressed (p<0.05) between frequencies of 80‐300 Hz post‐MI, as was maximal tetanic force (25±1 vs. 21±1 N/cm²). MI had no influence on local mRNA expression of TNF‐α and IL‐6, but both were increased (p<0.05) at the systemic level. Compared to sham, MI increased (p<0.05) mRNA expression and enzyme activity of xanthine oxidase (65% and 19%, respectively) and NADPH oxidase (140% and 44%, respectively), however antioxidant enzymes remained unchanged. Conclusion: Diaphragmatic contractile dysfunction is rapidly induced following MI, and this is associated with increased systemic inflammation and markers of local oxidant production. These findings suggest diaphragm muscle weakness is early‐onset in CHF, potentially mediated by inflammation and oxidative stress. Grant Funding Source: Supported by the Alexander von Humboldt Foundation