Abstract 1501: Knockout of p47phox Reduces Left Ventricular Remodeling Comparable to iNOS Knockout in a Murine Model of Reperfused Myocardial Infarction: A Cardiac MR Study
Introduction: Past studies have shown post-MI LV remodeling is greatly reduced in iNOS KO mice. This study tests the hypothesis that p47phox KO also protects against post-MI LV remodeling similar to iNOS KO.
Methods: A total of 28 male mice (8–10 wks) comprised of 8 C57BL/6 (Untreated), 11 iNOS KO and 9 p47phox KO mice received 1h coronary occlusion and 28d of reperfusion. All mice were studied by 4.7T CMR imaging before and at 1, 7 & 28 days post-MI. CMR imaging included short-axis black-blood cines covering the entire heart, and on Day 1, Gd-DTPA was infused IP for Gd-enhanced inversion recovery imaging. Myocardial LV volumes, EF & LV mass were measured from cine images. Day 1 infarct size was measured as %LV mass from Gd-enhanced images.
Results: Day 1 infarct sizes were similar in the 3 groups (Untreated: 38±4, iNOS KO: 35±4, p47phox KO: 37±6%, p=NS). Panels A–C show ED images at Day 28 from A: Untreated, B: iNOS KO & C: p47phox KO groups. Panels D–G show group means with SEM bars for EDV, ESV, EF & LV mass where * denotes ANOVA p<0.05 vs Untreated. Both iNOS KO & p47phox KO reduced EDV & ESV at Days 7 & 28 and LV mass at Day 28 (all p<0.05). There was no significant difference between iNOS KO & p47phox KO in Day 28 EDV, ESV or LV mass, however iNOS KO EF was improved over p47phox KO at Days 7 & 28. LV mass at Day 1 in p47phox KO mice was significantly greater than in Untreated mice, but similar to iNOS KO.
Conclusions: p47phox KO preserves post-MI EDV, ESV & LV mass similar to iNOS KO by Day 28 post-MI. However, EF was improved in iNOS KO vs p47phox KO mice. The similarity in phenotypic responses provides evidence that both superoxide and nitric oxide contribute to post-MI LV remodeling, perhaps through peroxynitrite formation.