Abstract 3773: Selective Inhibition of iNOS Alone Offers Protection Against Left Ventricular Remodeling Similar to the Combination of ACE-Inhibition and Beta-Blockade in a Murine Model of Reperfused Myocardial Infarction: A Cardiac MR Study
Introduction: Post-MI LV remodeling is greatly reduced in iNOS knock-out mice. This study tests the hypothesis that selective inhibition of iNOS protects against post-MI LV remodeling similar to conventional therapy.
Methods: A total of 19 male C57BL/6 mice (8–10 wks) received 1h coronary occlusion and 28d of reperfusion. Seven of these were left untreated, 5 were treated with 1400W (a highly selective iNOS inhibitor) and 7 with ACE inhibition + β-blockade. Mice were studied by CMR at 4.7T before and at 1, 7 & 28 days post-MI. Alzet minipumps (Durect Corp) were used to deliver 1400W (30 mg/kg-d) from 1h post-reperfusion until Day 14. Captopril & metoprolol were mixed and 50 mg/kg-d of each were similarly applied to 7 mice (AI+BB) from 1h post-reperfusion until Day 28. CMR studies included short-axis black-blood cines covering the entire heart. On Day 1, Gd-DTPA was infused for Gd-enhanced inversion recovery imaging. Myocardial volumes and EF were measured from cine images. Day 1 infarct size was measured as %LV mass from Gd-enhanced images.
Results: Infarct sizes at Day 1 were similar in the 3 groups (Untreated: 37±3, AI+BB: 44±5, 1400W: 39±10%, p=NS). Panels A-C show ED images at Day 28 from A:Untreated, B:AI+BB & C:1400W groups. Panels D-F show ESV, EDV and EF where * denotes p<0.05 vs Untreated. AI+BB reduced ESV at Days 7&28, whereas both AI+BB & 1400W reduced ESV at Day 28 (p<0.05). ANOVA found no difference in Day 28 ESV between AI+BB & 1400W, but Day 28 EF in AI+BB was improved over 1400W.
Conclusions: 1400W preserves post-MI ESV similar to AI+BB, but EF was improved by AI+BB over 1400W. Selective iNOS inhibition shows promise as an alternative when ACE inhibition or β-blockade are contraindicated.