Splenic modulation of the early inflammatory response to regional and global ischemia/reperfusion injury in swine

The spleen has been identified as a source of proinflammatory leukocytes mobilized after local ischemic injury in rodents. However, the role of the spleen in the inflammatory response to regional or global ischemia/reperfusion injury (IRI) in larger mammals is unknown. We investigated the spleen's contribution to early IRI-associated inflammation in porcine models of acute reperfused myocardial infarction (AMI) and sudden cardiac arrest (SCA). Swine were randomized to splenectomy (SPLX; <i>n</i> = 15) or sham surgery (SHAM; <i>n</i> = 15) 1 wk before a 75 min coronary occlusion (AMI; <i>n</i> = 6/group) or 8 min of ventricular fibrillation and cardiopulmonary resuscitation (CPR) (SCA; <i>n</i> = 9/group). Hemodynamic assessment and echocardiography were performed before and after IRI, with serial blood sampling to assess leukocyte mobilization and cytokine release. Heart and brain samples were collected for postmortem evaluation of injury and leukocyte infiltration. Early post-IRI leukocyte mobilization, cytokine levels, and leukocyte infiltration were similar between groups in each protocol. After SCA, SHAM animals showed a significant 41 ± 15% increase in hematocrit and 30 ± 12% rise in arterial O₂ content during CPR that was absent after SPLX. These differences persisted for up to 90 min and were associated with prolonged time to return of spontaneous circulation (ROSC) and increased vasopressor support in the SPLX group. Contrary to findings in rodents, the spleen is not required for the early inflammatory response to regional or global IRI in swine. However, splenic erythrocyte mobilization during SCA leads to an increase in arterial O₂ content that is associated with earlier ROSC and reduced reliance on vasopressors during CPR and the postresuscitation period.<b>NEW & NOTEWORTHY</b> Acute reperfused myocardial infarction (AMI) and sudden cardiac arrest (SCA) are characterized by ischemia-reperfusion injury (IRI) and inflammation. Although prior studies implicated the spleen as a primary source of inflammatory leukocytes after regional IRI in rodents, our findings indicate that, in swine, the spleen is not required for leukocyte mobilization after AMI or SCA. However, splenic erythrocyte mobilization during whole body IRI increases arterial oxygen content during CPR and may influence outcomes after SCA.