Splenic Modulation of Early Post-Infarction Inflammation and Left Ventricular Function in Swine
Authors: ROLLAND Tyler , Hudson Emily , Zahra Sumbule , Fees Alex , Cucinotta Daniel , Young Rebeccah , Weil Brian 
Published: May 2023

Objective: Despite a growing body of evidence that the spleen contains a reservoir of leukocytes that can be rapidly mobilized following ischemic injury, the extent to which splenic leukocytes contribute to the early inflammatory response to myocardial infarction (MI) is unclear. Accordingly, we employed a surgical approach to assess the role of the spleen in modulating early post-MI inflammation in swine. Methods: Swine (n=12) were randomized to splenectomy (SPLX; n=6) or sham surgery (SHAM; n=6) 1-week prior to undergoing a 75-minute balloon occlusion of the left anterior descending coronary artery (LAD) to produce MI. Hemodynamic assessment, echocardiography, and venous blood sampling were performed before and up to 3 hours after MI, at which time the heart was collected for post-mortem analysis of infarct size via TTC staining. Flow cytometry was utilized to quantify leukocyte sub-populations in blood and myocardial tissue, while plasma concentrations of cardiac troponin I (cTnI), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) were measured via porcine-specific ELISA. Results: The severity of myocardial injury was comparable in both groups, as evidenced by measurement of infarct size (SPLX vs. SHAM: 18±2 vs. 17±3 % of LV mass; p=0.84) and peak post-MI cTnI levels (101±20 vs. 72±9 ng/mL; p=0.21). Early post-MI leukocyte mobilization was also similar between groups (20±6 vs. 20±13 % change from baseline; p=0.97), with no significant between-group differences in circulating neutrophils nor monocytes within the first 3-hours after reperfusion. Quantification of blood and myocardial leukocyte subpopulations based on expression of CD14, CD16, CD163, and CD172 failed to reveal any differences between groups, while each group exhibited a similar rise in circulating levels of IL-6 (p=0.35) and TNF-α (p=0.54). Despite the absence of evidence that splenectomy influenced early post-MI inflammation, LV function was significantly better in SPLX vs. SHAM animals throughout the post-reperfusion period, as indicated by significant elevations in peak LV pressure (104±5 vs. 90±5 mmHg) and LV dP/dtmax (1816±108 vs. 1367±107 mmHg/s; both p<0.05) at the 3-hour timepoint. Conclusion: In contrast to prior studies in rodents demonstrating a contribution of splenic leukocytes to post-MI inflammation at later timepoints, our results indicate that the spleen is not a primary source of circulating or infiltrating leukocytes within the first few hours after reperfusion in swine. Nevertheless, splenectomized animals exhibited improved LV function early after MI despite a comparable infarct size, suggesting that the spleen may modulate post-ischemic cardiac function through leukocyte-independent mechanisms. Supported by funding from the National Institutes of Health (1R01HL160538) and the US Dept. of Veteran's Affairs (1I0BX002659) This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.