CARD17: Mitigation of the Inflammatory Response During Cardiopulmonary Bypass with Nitric Oxide Gas

Abstract

Background: Cardiopulmonary bypass (CPB) is associated with an inflammatory response that increases morbidity and mortality. Previous studies demonstrate that the air-blood interface plays an important role in CPB induced inflammation. Nitric oxide (NO) is known to mitigate the inflammatory response. We sought to examine the effect of NO on the inflammatory response resulting from a large air-blood interface during CPB in a porcine model. Methods: Twenty-one healthy swine (40-50 kg) were placed on CPB for 2h using central cannulation through a right mini thoracotomy. Following placement of an aortic cross clamp, the myocardium was preserved with antegrade cold del Nido cardioplegia. Cardiac arrest was maintained for 45min. Group 1 (n=11), swine supported on CPB with a controlled 20% air blood shunt at 3-4:1 air:blood ratio. Group 2 (n=10), as group 1 with the addition of NO (500 ppm) mixed in the sweep gas of the oxygenator. Following weaning from CPB, animals were recovered and monitored for 2d. Survival, clinical outcomes, and blood assays for inflammatory markers were collected prior, during, and postCPB. Mann -Whitney U test and log rank test were performed to determine statistical significance in both groups. Results: There was no difference in our ability to wean from CPB between Groups. Two-day survival rate was superior in Group 2 (80% vs 54%, p=0.24). Immediately after CPB the time to extubation (95.3 ±32.6min vs 70.6 ±13.7min, p=0.07) and lung compliance (LC) (86.1% vs 75.3%, p=0.056) were better in Group 2. Troponin-I levels were higher in group 2 overall (21,7702+/-18,108 pg/ml vs 8491+/- 6,686 p=.055). Preliminary results (n=2 in each group) show elevated IL-6 (3.89 pg/ml vs 3.3pg/ml) in Group 1 and 2 respectively. At necropsy LC was 82.6% in group 1 vs 86.4% in group 2, p= 0.43. There were no differences in P-selectin or Cd11-b. Conclusions: Nitric oxide administration at high dose during CPB with a large air-blood interface attenuates components of the IL-6 pathway. NO was associated with decrease in overall mortality post bypass and improved lung compliance. Further studies are needed to characterize these findings and optimize NO dosing prior to clinical application.