{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,24]],"date-time":"2026-04-24T13:48:39Z","timestamp":1777038519517,"version":"3.51.4"},"reference-count":114,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2026,2,8]],"date-time":"2026-02-08T00:00:00Z","timestamp":1770508800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Science and Technology Innovation Fund-Major Science and Technology Innovation Research and Development Special Project","award":["KCZD202202"],"award-info":[{"award-number":["KCZD202202"]}]},{"name":"Capital's Funds for Health Improvement and Research","award":["CRF-2024-1-2062"],"award-info":[{"award-number":["CRF-2024-1-2062"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCDD"],"abstract":"<jats:p>Excessive right heart load imposes an acute or chronic injury on the right ventricle (RV), predisposing critically ill neonates and cardiac surgical patients to RV failure, low cardiac output syndrome, and death. Inhaled nitric oxide (iNO) is a selective pulmonary vasodilator that improves ventilation\u2013perfusion matching and unloads the RV without systemic hypotension; nonetheless, its application beyond established neonatal indications remains contentious. Our review synthesizes current mechanistic, translational, and clinical evidence regarding iNO use in three major settings characterized by excessive RV load: (1) neonatal pulmonary hypertension, particularly PPHN; (2) acute and chronic RV overload in older children and adults, including secondary pulmonary hypertension, acute respiratory distress syndrome (ARDS), and acute pulmonary embolism; and (3) perioperative and post-cardiopulmonary bypass (CPB) management in congenital and adult cardiac surgery. In term and near-term infants with hypoxic respiratory failure, pivotal randomized trials show that iNO consistently improves oxygenation and reduces extracorporeal membrane oxygenation (ECMO) use, but this has little effect on survival and long-term neurodevelopment. In ARDS and other adult critical-care indications, iNO provides transient improvements in gas exchange and RV performance without reducing mortality or ventilator duration, and meta-analyses signal an increased risk of acute kidney injury, particularly with prolonged use. In contrast, perioperative studies around CPB demonstrate that prophylactic postoperative iNO and intra-CPB nitric oxide administration can attenuate pulmonary hypertensive crises, facilitate separation from CPB, shorten ventilation and intensive care stay, and, in selected high-risk cohorts, may reduce cardiac surgery-associated acute kidney injury, although survival benefits remain unproven. Across these scenarios, iNO should be used judiciously and in a pathophysiology-driven manner as a time-limited, targeted adjunct to stabilize patients with documented or anticipated RV strain rather than a disease-modifying therapy. Future work should refine patient selection, timing, dosing, and weaning strategies, and define the long-term safety and cost-effectiveness of iNO within contemporary multimodal RV support pathways.<\/jats:p>","DOI":"10.3390\/jcdd13020081","type":"journal-article","created":{"date-parts":[[2026,2,9]],"date-time":"2026-02-09T14:05:15Z","timestamp":1770645915000},"page":"81","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Clinical Application of Inhaled Nitric Oxide in Conditions of Excessive Right Heart Load: A Review from Neonatal Pulmonary Hypertension to Perioperative Cardiac Surgery Management"],"prefix":"10.3390","volume":"13","author":[{"given":"Chengming","family":"Hu","sequence":"first","affiliation":[{"name":"Department of Pediatric Cardiac Surgery, Beijing Anzhen Hospital, Capital Medical University, No. 2 Anzhen Street, Chaoyang District, Beijing 100029, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhe","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Pediatric Cardiac Surgery, Beijing Anzhen Hospital, Capital Medical University, No. 2 Anzhen Street, Chaoyang District, Beijing 100029, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lizhi","family":"Lv","sequence":"additional","affiliation":[{"name":"Department of Pediatric Cardiac Surgery, Beijing Anzhen Hospital, Capital Medical University, No. 2 Anzhen Street, Chaoyang District, Beijing 100029, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yan","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of ICU in Pediatric Cardiology, Beijing Anzhen Hospital, Capital Medical University, No. 2 Anzhen Street, Chaoyang District, Beijing 100029, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yan","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of ICU in Pediatric Cardiology, Beijing Anzhen Hospital, Capital Medical University, No. 2 Anzhen Street, Chaoyang District, Beijing 100029, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qiang","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Pediatric Cardiac Surgery, Beijing Anzhen Hospital, Capital Medical University, No. 2 Anzhen Street, Chaoyang District, Beijing 100029, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,2,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"524","DOI":"10.1038\/327524a0","article-title":"Nitric Oxide Release Accounts for the Biological Activity of Endothelium-Derived Relaxing Factor","volume":"327","author":"Palmer","year":"1987","journal-title":"Nature"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1093\/eurheartj\/12.suppl_E.2","article-title":"Endothelium-Derived Nitric Oxide: The Endogenous Nitrovasodilator in the Human Cardiovascular System","volume":"12","author":"Loscher","year":"1991","journal-title":"Eur. Heart J."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1161\/01.CIR.87.2.447","article-title":"Inhaled Nitric Oxide in Congenital Heart Disease","volume":"87","author":"Roberts","year":"1993","journal-title":"Circulation"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"140","DOI":"10.15420\/cfr.2019.15.2","article-title":"Right Ventricular Failure: Pathophysiology, Diagnosis and Treatment","volume":"5","author":"Arrigo","year":"2019","journal-title":"Card. Fail. Rev."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1801900","DOI":"10.1183\/13993003.01900-2018","article-title":"Pathophysiology of the Right Ventricle and of the Pulmonary Circulation in Pulmonary Hypertension: An Update","volume":"53","author":"Chin","year":"2019","journal-title":"Eur. Respir. J."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"H1731","DOI":"10.1152\/ajpheart.00336.2006","article-title":"Quantification of Right Ventricular Afterload in Patients with and without Pulmonary Hypertension","volume":"291","author":"Lankhaar","year":"2006","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1186\/s13244-019-0695-9","article-title":"Pathophysiology of Right Ventricular Failure in Acute Pulmonary Embolism and Chronic Thromboembolic Pulmonary Hypertension: A Pictorial Essay for the Interventional Radiologist","volume":"10","author":"Bryce","year":"2019","journal-title":"Insights Imaging"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"2683","DOI":"10.1056\/NEJMra051884","article-title":"Inhaled Nitric Oxide Therapy in Adults","volume":"353","author":"Griffiths","year":"2005","journal-title":"N. Engl. J. Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"422","DOI":"10.1016\/j.freeradbiomed.2019.11.029","article-title":"Clinical Use of Inhaled Nitric Oxide: Local and Systemic Applications","volume":"152","author":"Barnes","year":"2020","journal-title":"Free Radic. Biol. Med."},{"key":"ref_10","unstructured":"Respiratory Care Group of Chinese Thoracic Society, Respiratory Therapist Working Group of Respiratory Career Development Committee, Chinese Association of Chest Physician, Liang, G., Luo, F., and Xie, L. (2024). Expert consensus on clinical application of inhaled nitric oxide therapy (2024 edition). Chin. Med. J., 104, 2386\u20132400."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"595","DOI":"10.1016\/j.clp.2021.05.009","article-title":"Pathophysiology and Management of Persistent Pulmonary Hypertension of the Newborn","volume":"48","author":"Singh","year":"2021","journal-title":"Clin. Perinatol."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Brown, T.N., and Brogan, T.V. (2023). Right Ventricular Dysfunction in Patients with Acute Respiratory Distress Syndrome Receiving Venovenous Extracorporeal Membrane Oxygenation. Front. Cardiovasc. Med., 10.","DOI":"10.3389\/fcvm.2023.1027300"},{"key":"ref_13","first-page":"CD000509","article-title":"Inhaled Nitric Oxide for Respiratory Failure in Preterm Infants","volume":"4","author":"Barrington","year":"2000","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Atlan, L., Berthomieu, L., Karsenty, C., Gascoin, G., Arnaud, C., and Breinig, S. (2024). Neurodevelopmental Outcome in Children between One and Five Years after Persistent Pulmonary Hypertension of Term and Near-Term Newborns. Front. Pediatr., 12.","DOI":"10.3389\/fped.2024.1450916"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1464","DOI":"10.1016\/S0140-6736(00)02869-5","article-title":"Inhaled Nitric Oxide and Prevention of Pulmonary Hypertension after Congenital Heart Surgery: A Randomised Double-Blind Study","volume":"356","author":"Miller","year":"2000","journal-title":"Lancet"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1907","DOI":"10.1016\/S0003-4975(00)01312-6","article-title":"Randomized Controlled Study of Inhaled Nitric Oxide after Operation for Congenital Heart Disease","volume":"69","author":"Day","year":"2000","journal-title":"Ann. Thorac. Surg."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1744","DOI":"10.1007\/s00134-016-4420-6","article-title":"Nitric Oxide Administration during Paediatric Cardiopulmonary Bypass: A Randomised Controlled Trial","volume":"42","author":"James","year":"2016","journal-title":"Intensive Care Med."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"3106","DOI":"10.1161\/01.CIR.0000134595.80170.62","article-title":"Inhaled Nitric Oxide: A Selective Pulmonary Vasodilator: Current Uses and Therapeutic Potential","volume":"109","author":"Ichinose","year":"2004","journal-title":"Circulation"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Grotberg, J.C., Reynolds, D., and Kraft, B.D. (2024). Extracorporeal Membrane Oxygenation for Respiratory Failure: A Narrative Review. J. Clin. Med., 13.","DOI":"10.20944\/preprints202405.0185.v1"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"e578","DOI":"10.1161\/CIR.0000000000000560","article-title":"Evaluation and Management of Right-Sided Heart Failure: A Scientific Statement From the American Heart Association","volume":"137","author":"Konstam","year":"2018","journal-title":"Circulation"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1317","DOI":"10.1161\/CIR.0000000000001136","article-title":"Evaluation and Management of Pulmonary Hypertension in Noncardiac Surgery: A Scientific Statement From the American Heart Association","volume":"147","author":"Rajagopal","year":"2023","journal-title":"Circulation"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"S1688","DOI":"10.21037\/jtd.2019.05.73","article-title":"Extracorporeal Membrane Oxygenation as Rescue Therapy for Severe Hypoxemic Respiratory Failure","volume":"11","author":"Patel","year":"2019","journal-title":"J. Thorac. Dis."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1186\/s40560-015-0082-7","article-title":"Extracorporeal Membrane Oxygenation for Acute Respiratory Distress Syndrome","volume":"3","author":"Aokage","year":"2015","journal-title":"J. Intensive Care"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"2401180","DOI":"10.1183\/13993003.01180-2024","article-title":"Management of Pulmonary Hypertension in Special Conditions","volume":"64","author":"Preston","year":"2024","journal-title":"Eur. Respir. J."},{"key":"ref_25","first-page":"e70307","article-title":"Current Pharmaceutical Strategies in the Management of Persistent Pulmonary Hypertension of the Newborn (PPHN): A Comprehensive Review of Therapeutic Agents","volume":"16","author":"Kaplish","year":"2024","journal-title":"Cureus"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"2038","DOI":"10.1161\/01.CIR.83.6.2038","article-title":"Inhaled Nitric Oxide. A Selective Pulmonary Vasodilator Reversing Hypoxic Pulmonary Vasoconstriction","volume":"83","author":"Frostell","year":"1991","journal-title":"Circulation"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"2884","DOI":"10.1161\/01.CIR.88.6.2884","article-title":"Selective Pulmonary Vasodilation by Inhaled Nitric Oxide Is Due to Hemoglobin Inactivation","volume":"88","author":"Rimar","year":"1993","journal-title":"Circulation"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1186\/cc7734","article-title":"Bench-to-Bedside Review: Inhaled Nitric Oxide Therapy in Adults","volume":"13","author":"Griffiths","year":"2009","journal-title":"Crit. Care"},{"key":"ref_29","first-page":"100391","article-title":"Management of Pediatric Pulmonary Vein Stenosis","volume":"1","author":"Callahan","year":"2022","journal-title":"J. Soc. Cardiovasc. Angiogr. Interv."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"2200879","DOI":"10.1183\/13993003.00879-2022","article-title":"2022 ESC\/ERS Guidelines for the Diagnosis and Treatment of Pulmonary Hypertension","volume":"61","author":"Humbert","year":"2023","journal-title":"Eur. Respir. J."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"The Neonatal Inhaled Nitric Oxide Study Group (1997). Inhaled Nitric Oxide in Full-Term and Nearly Full-Term Infants with Hypoxic Respiratory failure (Neonatal Inhaled Nitric Oxide Study Group). N. Engl. J. Med., 336, 597\u2013604.","DOI":"10.1056\/NEJM199702273360901"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1056\/NEJM200002173420704","article-title":"Low-Dose Nitric Oxide Therapy for Persistent Pulmonary Hypertension of the Newborn","volume":"342","author":"Clark","year":"2000","journal-title":"N. Engl. J. Med."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Nelin, L.D., and Potenziano, J.L. (2019). Inhaled Nitric Oxide for Neonates with Persistent Pulmonary Hypertension of the Newborn in the CINRGI Study: Time to Treatment Response. BMC Pediatr., 19.","DOI":"10.1186\/s12887-018-1368-4"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"661","DOI":"10.1002\/ppul.25073","article-title":"Persistent Pulmonary Hypertension of the Newborn","volume":"56","author":"Mandell","year":"2021","journal-title":"Pediatr. Pulmonol."},{"key":"ref_35","first-page":"1717","article-title":"Evidence-Based Clinical Practice Guideline: Inhaled Nitric Oxide for Neonates with Acute Hypoxic Respiratory Failure","volume":"55","author":"DiBlasi","year":"2010","journal-title":"Respir. Care"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"803","DOI":"10.1016\/j.clp.2006.09.006","article-title":"Hypoxic Respiratory Failure in the Late Preterm Infant","volume":"33","author":"Dudell","year":"2006","journal-title":"Clin. Perinatol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"655","DOI":"10.1016\/j.clp.2012.06.006","article-title":"The Pulmonary Circulation in Neonatal Respiratory Failure","volume":"39","author":"Lakshminrusimha","year":"2012","journal-title":"Clin. Perinatol."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Muenster, S., Zarragoikoetxea, I., Moscatelli, A., Balcells, J., Gaudard, P., Pouard, P., Marczin, N., and Janssens, S.P. (2024). Inhaled NO at a Crossroads in Cardiac Surgery: Current Need to Improve Mechanistic Understanding, Clinical Trial Design and Scientific Evidence. Front. Cardiovasc. Med., 11.","DOI":"10.3389\/fcvm.2024.1374635"},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Kamenshchikov, N.O., Duong, N., and Berra, L. (2023). Nitric Oxide in Cardiac Surgery: A Review Article. Biomedicines, 11.","DOI":"10.3390\/biomedicines11041085"},{"key":"ref_40","first-page":"292","article-title":"Inhaled Nitric Oxide in Adult Patients with Acute Respiratory Distress Syndrome","volume":"41","year":"2017","journal-title":"Farm. Hosp."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"e605","DOI":"10.1097\/CCM.0000000000000395","article-title":"Meta-Analysis of Nitric Oxide in Acute Respiratory Distress Syndrome: Dosage?","volume":"42","author":"Baird","year":"2014","journal-title":"Crit. Care Med."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1111\/bph.14512","article-title":"Inhaled Nitric Oxide","volume":"176","author":"Yu","year":"2019","journal-title":"Br. J. Pharmacol."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Zhang, J., Zhang, H., Wang, J., Wang, T., Bian, L., Li, Z., Wang, J., Teng, Y., Liu, G., and Yan, S. (2025). The Organ-Protective Effects of Nitric Oxide in Adult Patients Undergoing Cardiac Surgery with Cardiopulmonary Bypass: A Systematic Review and Meta-Analysis. BMC Anesthesiol., 25.","DOI":"10.1186\/s12871-025-03207-7"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1007\/s11748-023-01971-2","article-title":"Real-World Safety and Effectiveness of Inhaled Nitric Oxide Therapy for Pulmonary Hypertension during the Perioperative Period of Cardiac Surgery: A Post-Marketing Study of 2817 Patients in Japan","volume":"72","author":"Matsugi","year":"2024","journal-title":"Gen. Thorac. Cardiovasc. Surg."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1016\/j.ahj.2017.01.011","article-title":"Randomized Trial of Inhaled Nitric Oxide to Treat Acute Pulmonary Embolism: The iNOPE Trial","volume":"186","author":"Kline","year":"2017","journal-title":"Am. Heart J."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1435","DOI":"10.1016\/j.jacc.2010.05.046","article-title":"Medical and Surgical Treatment of Acute Right Ventricular Failure","volume":"56","author":"Lahm","year":"2010","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"e680","DOI":"10.1542\/neo.16-12-e680","article-title":"Persistent Pulmonary Hypertension of the Newborn","volume":"16","author":"Lakshminrusimha","year":"2015","journal-title":"Neoreviews"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"424","DOI":"10.1152\/japplphysiol.00204.2021","article-title":"Arterial Load and Right Ventricular-Vascular Coupling in Pulmonary Hypertension","volume":"131","author":"Oakland","year":"2021","journal-title":"J. Appl. Physiol. (1985)"},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Li, Y., Guo, D., Gong, J., Wang, J., Huang, Q., Yang, S., Zhang, X., Hu, H., Jiang, Z., and Yang, Y. (2021). Right Ventricular Function and Its Coupling With Pulmonary Circulation in Precapillary Pulmonary Hypertension: A Three-Dimensional Echocardiographic Study. Front. Cardiovasc. Med., 8.","DOI":"10.3389\/fcvm.2021.690606"},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Mathew, B., and Lakshminrusimha, S. (2017). Persistent Pulmonary Hypertension in the Newborn. Children, 4.","DOI":"10.3390\/children4080063"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1111\/jth.13194","article-title":"The Contact Activation and Kallikrein\/Kinin Systems: Pathophysiologic and Physiologic Activities","volume":"14","author":"Schmaier","year":"2016","journal-title":"J. Thromb. Haemost."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1016\/j.ppedcard.2005.09.011","article-title":"Cardiopulmonary Bypass and the Coagulation System","volume":"21","author":"Yeh","year":"2005","journal-title":"Prog. Pediatr. Cardiol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"731","DOI":"10.1016\/S0003-4975(99)00096-X","article-title":"Effects of Ischemia on Pulmonary Dysfunction after Cardiopulmonary Bypass","volume":"67","author":"Chai","year":"1999","journal-title":"Ann. Thorac. Surg."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"5269","DOI":"10.1111\/jocs.17160","article-title":"Pulmonary Hypertension Associated with Cardiopulmonary Bypass and Cardiac Surgery","volume":"37","author":"Fayad","year":"2022","journal-title":"J. Card. Surg."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1248","DOI":"10.1016\/S0022-5223(96)70228-3","article-title":"Effects of Cardiopulmonary Bypass and Circulatory Arrest on Endothelium-Dependent Vasodilation in the Lung","volume":"111","author":"Kirshbom","year":"1996","journal-title":"J. Thorac. Cardiovasc. Surg."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"755","DOI":"10.1038\/nrd2038","article-title":"NO-Independent Stimulators and Activators of Soluble Guanylate Cyclase: Discovery and Therapeutic Potential","volume":"5","author":"Evgenov","year":"2006","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"2465","DOI":"10.1111\/jth.15844","article-title":"The NO\/cGMP\/PKG Pathway in Platelets: The Therapeutic Potential of PDE5 Inhibitors in Platelet Disorders","volume":"20","author":"Degjoni","year":"2022","journal-title":"J. Thromb. Haemost."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1084","DOI":"10.1161\/CIRCRESAHA.107.162511","article-title":"Phosphodiesterase Type 5: Expanding Roles in Cardiovascular Regulation","volume":"101","author":"Kass","year":"2007","journal-title":"Circ. Res."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1053\/j.semperi.2015.12.004","article-title":"Pharmacologic Strategies in Neonatal Pulmonary Hypertension Other than Nitric Oxide","volume":"40","author":"Lakshminrusimha","year":"2016","journal-title":"Semin. Perinatol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"219","DOI":"10.4187\/respcare.03278","article-title":"Nitric Oxide Delivery by Neonatal Noninvasive Respiratory Support Devices","volume":"60","author":"DiBlasi","year":"2015","journal-title":"Respir. Care"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"11795484211047065","DOI":"10.1177\/11795484211047065","article-title":"Inhaled Nitric Oxide via High-Flow Nasal Cannula in Patients with Acute Respiratory Failure Related to COVID-19","volume":"15","author":"Chandel","year":"2021","journal-title":"Clin. Med. Insights Circ. Respir. Pulm. Med."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"11482","DOI":"10.1073\/pnas.97.21.11482","article-title":"Role of Circulating Nitrite and S-Nitrosohemoglobin in the Regulation of Regional Blood Flow in Humans","volume":"97","author":"Gladwin","year":"2000","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1038\/nrd4623","article-title":"Strategies to Increase Nitric Oxide Signalling in Cardiovascular Disease","volume":"14","author":"Lundberg","year":"2015","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"H287","DOI":"10.1152\/ajpheart.00108.2024","article-title":"Effects of Nitric Oxide Inhalation on Pulmonary Arterial Impedance: Differences between Normal and Pulmonary Hypertension Male Rats","volume":"327","author":"Fukumitsu","year":"2024","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"665","DOI":"10.1177\/10742484211014162","article-title":"Nitric Oxide-cGMP Pathway Modulation in an Experimental Model of Hypoxic Pulmonary Hypertension","volume":"26","author":"Reinero","year":"2021","journal-title":"J. Cardiovasc. Pharmacol. Ther."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"R835","DOI":"10.1152\/ajpregu.00362.2020","article-title":"Carbonic Anhydrase Inhibition Improves Pulmonary Artery Reactivity and Nitric Oxide-Mediated Relaxation in Sugen-Hypoxia Model of Pulmonary Hypertension","volume":"320","author":"Christou","year":"2021","journal-title":"Am. J. Physiol. Regul. Integr. Comp. Physiol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"2101153","DOI":"10.1183\/13993003.01153-2021","article-title":"Myeloid-Cell-Specific Deletion of Inducible Nitric Oxide Synthase Protects against Smoke-Induced Pulmonary Hypertension in Mice","volume":"59","author":"Gredic","year":"2022","journal-title":"Eur. Respir. J."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"153","DOI":"10.2174\/1874192401105010153","article-title":"Regulation of Inducible Nitric Oxide Synthase (iNOS) and Its Potential Role in Insulin Resistance, Diabetes and Heart Failure","volume":"5","author":"Sudar","year":"2011","journal-title":"Open Cardiovasc. Med. J."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"9898","DOI":"10.1039\/c3dt50945a","article-title":"Decomposition Kinetics of Peroxynitrite: Influence of pH and Buffer","volume":"42","author":"Molina","year":"2013","journal-title":"Dalton Trans."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"C1424","DOI":"10.1152\/ajpcell.1996.271.5.C1424","article-title":"Nitric Oxide, Superoxide, and Peroxynitrite: The Good, the Bad, and Ugly","volume":"271","author":"Beckman","year":"1996","journal-title":"Am. J. Physiol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"112705","DOI":"10.1016\/j.biopha.2022.112705","article-title":"Nitric Oxide Releasing Nanoparticles Reduce Inflammation in a Small Animal Model of ARDS","volume":"148","author":"Jani","year":"2022","journal-title":"Biomed. Pharmacother."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1023\/A:1009920724708","article-title":"Inhaled Nitric Oxide Delivery and Monitoring","volume":"15","author":"Montgomery","year":"1999","journal-title":"J. Clin. Monit. Comput."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1186\/s12938-016-0227-5","article-title":"An Injection and Mixing Element for Delivery and Monitoring of Inhaled Nitric Oxide","volume":"15","author":"Martin","year":"2016","journal-title":"Biomed. Eng. Online"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"1021","DOI":"10.4187\/respcare.08856","article-title":"Inhaled Nitric Oxide Delivery Systems for Mechanically Ventilated and Nonintubated Patients: A Review","volume":"66","author":"Gianni","year":"2021","journal-title":"Respir. Care"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/S0022-3476(97)70124-0","article-title":"Randomized, Multicenter Trial of Inhaled Nitric Oxide and High-Frequency Oscillatory Ventilation in Severe, Persistent Pulmonary Hypertension of the Newborn","volume":"131","author":"Kinsella","year":"1997","journal-title":"J. Pediatr."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1183\/09031936.98.11010234","article-title":"High-Frequency Ventilation Augments the Effect of Inhaled Nitric Oxide in Persistent Pulmonary Hypertension of the Newborn","volume":"11","author":"Hoehn","year":"1998","journal-title":"Eur. Respir. J."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"954","DOI":"10.1007\/BF02044122","article-title":"Occupational Exposure during Nitric Oxide Inhalational Therapy in a Pediatric Intensive Care Setting","volume":"22","author":"Markhorst","year":"1996","journal-title":"Intensive Care Med."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"147","DOI":"10.4037\/ajcc2003.12.2.147","article-title":"Exposure of Intensive Care Unit Nurses to Nitric Oxide and Nitrogen Dioxide during Therapeutic Use of Inhaled Nitric Oxide in Adults with Acute Respiratory Distress Syndrome","volume":"12","author":"Qureshi","year":"2003","journal-title":"Am. J. Crit. Care"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1097\/MAT.0000000000001153","article-title":"Extracorporeal Life Support Organization (ELSO): Guidelines for Neonatal Respiratory Failure","volume":"66","author":"Wild","year":"2020","journal-title":"ASAIO J."},{"key":"ref_80","first-page":"CD002787","article-title":"Inhaled Nitric Oxide for Acute Respiratory Distress Syndrome (ARDS) in Children and Adults","volume":"2016","author":"Gebistorf","year":"2016","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"779","DOI":"10.1136\/bmj.39139.716794.55","article-title":"Effect of Nitric Oxide on Oxygenation and Mortality in Acute Lung Injury: Systematic Review and Meta-Analysis","volume":"334","author":"Adhikari","year":"2007","journal-title":"BMJ"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1186\/s13054-015-0880-2","article-title":"Inhaled Nitric Oxide Therapy and Risk of Renal Dysfunction: A Systematic Review and Meta-Analysis of Randomized Trials","volume":"19","author":"Ruan","year":"2015","journal-title":"Crit. Care"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"1293","DOI":"10.1164\/rccm.202304-0637OC","article-title":"High-Dose Inhaled Nitric Oxide in Acute Hypoxemic Respiratory Failure Due to COVID-19: A Multicenter Phase II Trial","volume":"208","author":"Shetty","year":"2023","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"404","DOI":"10.1097\/CCM.0b013e3182a27909","article-title":"Inhaled Nitric Oxide Does Not Reduce Mortality in Patients with Acute Respiratory Distress Syndrome Regardless of Severity: Systematic Review and Meta-Analysis","volume":"42","author":"Adhikari","year":"2014","journal-title":"Crit. Care Med."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s00408-005-2550-7","article-title":"Inhaled Nitric Oxide Improves Pulmonary Functions Following Massive Pulmonary Embolism: A Report of Four Patients and Review of the Literature","volume":"184","author":"Szold","year":"2006","journal-title":"Lung"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"444","DOI":"10.4187\/respcare.01373","article-title":"Inhaled Nitric Oxide as Salvage Therapy in Massive Pulmonary Embolism: A Case Series","volume":"57","author":"Summerfield","year":"2012","journal-title":"Respir. Care"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3909\/ricm0718","article-title":"Inhaled Nitric Oxide in Acute Pulmonary Embolism: A Systematic Review","volume":"16","author":"Bhat","year":"2015","journal-title":"Rev. Cardiovasc. Med."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1136\/emermed-2013-202426","article-title":"Pilot Study of a Protocol to Administer Inhaled Nitric Oxide to Treat Severe Acute Submassive Pulmonary Embolism","volume":"31","author":"Kline","year":"2014","journal-title":"Emerg. Med. J. EMJ"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1016\/j.niox.2019.01.006","article-title":"Inhaled Nitric Oxide to Treat Intermediate Risk Pulmonary Embolism: A Multicenter Randomized Controlled Trial","volume":"84","author":"Kline","year":"2019","journal-title":"Nitric Oxide"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1186\/s40560-024-00761-z","article-title":"Impact of Inhaled Nitric Oxide Therapy in Patients with Cardiogenic Shock Treated with Veno-Arterial Extracorporeal Membrane Oxygenation Combined with Impella: A Retrospective Cohort Study","volume":"12","author":"Yamada","year":"2024","journal-title":"J. Intensive Care"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"2652","DOI":"10.1002\/ehf2.15305","article-title":"Percutaneous Mechanical Circulatory Support for Acute Right Heart Failure: A Practical Approach","volume":"12","author":"Gramegna","year":"2025","journal-title":"ESC Heart Fail."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1016\/S1010-7940(01)01099-5","article-title":"Cardiopulmonary Bypass Induced Inflammation: Pathophysiology and Treatment. An update","volume":"21","author":"Paparella","year":"2002","journal-title":"Eur. J. Cardiothorac. Surg."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"346","DOI":"10.1016\/S1010-7940(99)00017-2","article-title":"Acute Pulmonary Hypertension after Cardiopulmonary Bypass in Pig: The Role of Endogenous Endothelin","volume":"15","author":"Carteaux","year":"1999","journal-title":"Eur. J. Cardiothorac. Surg."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"530","DOI":"10.1016\/j.jtcvs.2012.09.100","article-title":"Nitric Oxide Delivery during Cardiopulmonary Bypass Reduces Postoperative Morbidity in Children\u2014A Randomized Trial","volume":"146","author":"Checchia","year":"2013","journal-title":"J. Thorac. Cardiovasc. Surg."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1016\/j.jtcvs.2002.08.001","article-title":"Supplemental Nitric Oxide and Its Effect on Myocardial Injury and Function in Patients Undergoing Cardiac Surgery with Extracorporeal Circulation","volume":"127","author":"Gianetti","year":"2004","journal-title":"J. Thorac. Cardiovasc. Surg."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"2328","DOI":"10.1016\/j.jtcvs.2018.08.117","article-title":"Nitric Oxide Provides Myocardial Protection When Added to the Cardiopulmonary Bypass Circuit during Cardiac Surgery: Randomized Trial","volume":"157","author":"Kamenshchikov","year":"2019","journal-title":"J. Thorac. Cardiovasc. Surg."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"1425","DOI":"10.1007\/s00228-023-03554-9","article-title":"The Beneficial Use of Nitric Oxide during Cardiopulmonary Bypass on Postoperative Outcomes in Children and Adult Patients: A Systematic Review and Meta-Analysis of 2897 Patients","volume":"79","author":"Abouzid","year":"2023","journal-title":"Eur. J. Clin. Pharmacol."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1001\/jama.2022.9376","article-title":"Effect of Nitric Oxide via Cardiopulmonary Bypass on Ventilator-Free Days in Young Children Undergoing Congenital Heart Disease Surgery: The NITRIC Randomized Clinical Trial","volume":"328","author":"Schlapbach","year":"2022","journal-title":"JAMA"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1213\/00000539-199807000-00011","article-title":"The Effects of Inhaled Nitric Oxide on Postoperative Pulmonary Hypertension in Infants and Children Undergoing Surgical Repair of Congenital Heart Disease","volume":"87","author":"Russell","year":"1998","journal-title":"Anesth. Analg."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"300","DOI":"10.1016\/0003-4975(95)00408-D","article-title":"Nitric Oxide Is Superior to Prostacyclin for Pulmonary Hypertension after Cardiac Operations","volume":"60","author":"Goldman","year":"1995","journal-title":"Ann. Thorac. Surg."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1080\/07853890.2020.1746826","article-title":"Comparison of Inhaled Nitric Oxide with Aerosolized Prostacyclin or Analogues for the Postoperative Management of Pulmonary Hypertension: A Systematic Review and Meta-Analysis","volume":"52","author":"Chen","year":"2020","journal-title":"Ann. Med."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1016\/S1053-0770(00)90048-X","article-title":"A Comparison of Inhaled Nitric Oxide and Milrinone for the Treatment of Pulmonary Hypertension in Adult Cardiac Surgery Patients","volume":"14","author":"Solina","year":"2000","journal-title":"J. Cardiothorac. Vasc. Anesth."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"2512","DOI":"10.1053\/j.jvca.2018.02.003","article-title":"Nitric Oxide in Cardiac Surgery: A Meta-Analysis of Randomized Controlled Trials","volume":"32","author":"Sardo","year":"2018","journal-title":"J. Cardiothorac. Vasc. Anesth."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"1759","DOI":"10.1016\/S0003-4975(96)00542-5","article-title":"Rebound Pulmonary Hypertension after Inhalation of Nitric Oxide","volume":"62","author":"Atz","year":"1996","journal-title":"Ann. Thorac. Surg."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"H777","DOI":"10.1152\/ajpheart.2001.280.2.H777","article-title":"Inhaled Nitric Oxide-Induced Rebound Pulmonary Hypertension: Role for Endothelin-1","volume":"280","author":"McMullan","year":"2001","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1542\/peds.114.2.417","article-title":"Cost-Effectiveness of Inhaled Nitric Oxide for the Management of Persistent Pulmonary Hypertension of the Newborn","volume":"114","author":"Lorch","year":"2004","journal-title":"Pediatrics"},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"650","DOI":"10.1007\/s00246-018-2042-1","article-title":"Practice Variation, Costs and Outcomes Associated with the Use of Inhaled Nitric Oxide in Pediatric Heart Transplant Recipients","volume":"40","author":"Bearl","year":"2019","journal-title":"Pediatr. Cardiol."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1542\/peds.113.3.559","article-title":"A randomized trial of early versus standard inhaled nitric oxide therapy in term and near-term newborn infants with hypoxic respiratory failure","volume":"113","author":"Konduri","year":"2004","journal-title":"Pediatrics"},{"key":"ref_109","first-page":"CD000509","article-title":"Inhaled nitric oxide for respiratory failure in preterm infants","volume":"1","author":"Barrington","year":"2017","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"1603","DOI":"10.1001\/jama.291.13.1603","article-title":"Inhaled Nitric Oxide in ARDS Study Group. Low-dose inhaled nitric oxide in patients with acute lung injury: A randomized controlled trial","volume":"291","author":"Taylor","year":"2004","journal-title":"JAMA"},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"1279","DOI":"10.1164\/rccm.201710-2150OC","article-title":"Nitric Oxide Decreases Acute Kidney Injury and Stage 3 Chronic Kidney Disease after Cardiac Surgery","volume":"198","author":"Lei","year":"2018","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"1393","DOI":"10.1016\/j.jtcvs.2020.03.182","article-title":"Nitric oxide delivery during cardiopulmonary bypass reduces acute kidney injury: A randomized trial","volume":"163","author":"Kamenshchikov","year":"2022","journal-title":"J. Thorac. Cardiovasc. Surg."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1186\/s13613-019-0605-9","article-title":"Effect of nitric oxide on postoperative acute kidney injury in patients who underwent cardiopulmonary bypass: A systematic review and meta-analysis with trial sequential analysis","volume":"9","author":"Hu","year":"2019","journal-title":"Ann. Intensive Care"},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"652","DOI":"10.1097\/ALN.0000000000005861","article-title":"Nitric Oxide to Reduce Acute Kidney Injury in Patients with Preexisting Endothelial Dysfunction Requiring Prolonged Cardiopulmonary Bypass: A Randomized Clinical Trial","volume":"144","author":"Arora","year":"2026","journal-title":"Anesthesiology"}],"container-title":["Journal of Cardiovascular Development and Disease"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2308-3425\/13\/2\/81\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,12]],"date-time":"2026-02-12T05:18:26Z","timestamp":1770873506000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2308-3425\/13\/2\/81"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,8]]},"references-count":114,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2026,2]]}},"alternative-id":["jcdd13020081"],"URL":"https:\/\/doi.org\/10.3390\/jcdd13020081","relation":{},"ISSN":["2308-3425"],"issn-type":[{"value":"2308-3425","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2,8]]}}}