Abstract Background Inhaled nitric oxide (iNO) is approved by the FDA solely for treating persistent pulmonary hypertension (PH) in newborns, but also by the European Medicines Agency for treating patients with peri- and post-operative PH. Although evidence suggests its safe use in cardiac surgery, others call for more evidence, and clinically relevant large animal models seem to be lacking. Purpose To test the effects of iNO on hemodynamic parameters in a clinically relevant porcine model of heart transplantation. Methods 10 female Danish Landrace pigs (≈80kg) underwent orthotopic heart transplantation with directly procured hearts following either circulatory death (n=5) or brain death (n=5), and 24 hours of hypothermic machine perfusion. In the recipient pig, inhaled nitric oxide (iNO) was initiated at 20 ppm during reperfusion, 15 minutes before weaning from cardiopulmonary bypass (CPB). At 120 minutes after weaning from CPB, iNO was gradually reduced from 20 ppm to 1 ppm over 5-minute intervals, then discontinued after 40 minutes. Finally, iNO was reinstituted at 20 ppm for an additional 5 minutes. Results Cessation of iNO caused a significant rise in mean pulmonary artery pressure (MPAP), already evident at 15 ppm (P 0.05). At 0 ppm, MPAP rose by 17.75 mmHg (P 0.01). When iNO was reintroduced, MPAP decreased, but remained 7 mmHg above baseline (P 0.01). Similarly, pulmonary vascular resistance (PVR) increased significantly following the first reduction of iNO (P 0.05). Following iNO cessation, PVR increased by 4.28 mmHg·L⁻¹·min (P 0.001), and after reinitiation, the increase was reduced to 1.84 mmHg·L⁻¹·min, yet still significant compared to baseline (P 0.01). Mean arterial pressure (MAP) decreased by 14.25 mmHg at 0 ppm (P 0.05) but returned to a level not significantly different from baseline after iNO was restarted. Similarly, mixed venous oxygen saturation dropped by 14.0% at 0 ppm (P 0.01) and rose to a non-significant level after iNO reinitiation. Conclusion Gradual cessation of iNO led to a severe hemodynamic compromise, characterised by a marked increase in pulmonary vascular resistance. Although the evidence is indirect and derived from an experimental model, the findings strongly support the protective contribution of iNO and the need for gradual, carefully monitored weaning protocols after heart transplantation.
Lenbroch et al. (Fri,) studied this question.