Acute blood loss anemia aggravates endothelial dysfunction after acute myocardial infarction

Anemia is frequently observed in patients with acute myocardial infarction (AMI) and is known to be associated with poor prognosis. We recently demonstrated that acute blood loss anemia is associated with a compensatory increase in endothelial nitric oxide (NO)-dependent flow-mediated dilation (FMD) responses. However, the effects of acute anemia on systemic endothelial function after AMI remain unclear. In this study, we evaluated systemic endothelial function following AMI in an established murine model of acute blood loss anemia. We hypothesize that acute anemia aggravates systemic endothelial dysfunction (ED) after AMI.

Acute anemia was induced in male C57BL/6J mice by repeated blood withdrawal for three consecutive days. Separate groups of anemic and non-anemic mice underwent AMI via left anterior descending artery (LAD) ligation (45 min), followed by reperfusion. Endothelial function was assessed using both in vivo and in vitro methods 24 h post-AMI. Impaired FMD (in vivo) and endothelium-dependent relaxation (EDR) responses were observed in the aorta, femoral, and saphenous arteries of AA mice compared to their respective control groups 24 h post-AMI. Analysis of oxidative products of NO in plasma revealed reduced nitrite and nitrate levels in acute anemia compared to controls 24 h post-AMI. Immunohistochemistry of aortic tissues from both anemic groups showed increased reactive oxygen species (ROS) product 4-Hydroxynonenal (4-HNE). Co-incubation of RBCs from anemic mice or anemic acute coronary syndrome (ACS) patients with aortic rings from wild-type mice demonstrated attenuated EDR responses. Supplementation with the ROS scavenger N-acetyl cysteine (NAC) for four weeks improved both in vivo and ex vivo EDR in acute anemic mice 24 h post-AMI.

After AMI, acute anemia is associated with ROS-mediated severe endothelial dysfunction, which is partly mediated by RBCs. Antioxidant supplementation with NAC is a potential therapeutic option to reverse the severe ED in anemia following AMI.