Abstract 5419: Nitric Oxide For Inhalation Reduces Left Ventricular Remodeling After Myocardial Infarction In Pigs
Background: We previously showed in pigs that breathing nitric oxide (NO) during coronary reperfusion improves microvascular perfusion and reduces infarct size at 4h. Here, we tested whether short-term benefits of NO inhalation translate into less adverse LV remodeling at long-term follow-up.
Methods: In 11 pigs, the proximal LAD was occluded for 45 min followed by 4 h of reperfusion. Pigs were randomized to saline infusion (CON, n=5) or inhaled NO (iNO, n=6) at 80 parts per million, beginning 10 min before and continued throughout reperfusion. We measured cardiac necrosis markers during ischemia and reperfusion (I/R). At 2 days and 11 weeks after I/R, global and regional LV function was assessed by cine-MRI (3T), and infarct size was measured by delayed enhanced MRI after gadolinium injection. LV remodeling was measured by comparing changes in LV end-diastolic and end-systolic volumes (LVEDV, LVESV) over time.
Results: Four hours after I/R, serum troponin, CK, and CK-MB levels were greater in CON than in iNO pigs (P<0.05 for all). MRI measurements at 2d after I/R showed LV ejection fraction (LVEF) decreased similarly in CON and iNO pigs (28±2 vs 32±3%, respectively). Infarct size tended to be less in iNO pigs in CON pigs (15±2 vs 22±3%, P=0.06). After 11 weeks, LVEDV increased in CON from 74±5 to 210±33 ml (P<0.05), whereas in iNO pigs, LVEDV increased from 83±6 to 150±14 ml (P<0.05). LVEDV increased to a greater extent in CON than in iNO pigs (P <0.05). After 11 weeks, LVESV increased from 53±3 to 147±23 ml in CON and from 57±6 to 97±14 ml in iNO (P<0.05). LVESV increased to a greater extent in CON than in iNO pigs (P<0.05). LVEF at 11 weeks was similar in both groups (36±3 vs 30±2% in iNO and CON, respectively), while infarct size tended to decrease more in iNO than CON (20±3 vs 13±2%, P=0.06). Moreover, end-diastolic wall thickness in the infarct zone 11 weeks after I/R was greater in iNO than in CON pigs (9.6±0.3 vs 6.9±0.2, P<0.001).
Conclusion: Inhalation of NO just before and during coronary reperfusion significantly protects against adverse LV remodeling and preserves wall thickness in the infarct zone. Short-term NO inhalation may prevent development of heart failure following myocardial infarction.