New Technology for the Use of Inhaled Nitric Oxide to Protect the Heart and Lungs during Operations with Cardiopulmonary Bypass

The aim of the study was to evaluate the effectiveness of a new technology for the use of inhaled nitric oxide (NO) for the heart and lung protection during operations with cardiopulmonary bypass (СРВ).

Materials and Methods. The study included 90 patients who underwent heart valve surgery and combined procedures under CPB and pharmacological cardioplegia. Three groups were created: group 1 (control, n=30); group 2 (n=30) — NO inhalation (20 ppm) was conducted traditionally, that is, before and after CPB; group 3 (n=30) — NO inhalation was performed using a new technology — during the entire operation, with pulmonary artery perfusion and lung ventilation performed during CPB. Troponin I (cTn I) level, changes in the pulmonary function parameters, and clinical indicators were studied.

Results. Statistically significant lower levels of postoperative cTn I were registered in the patients of groups 2 and 3, at the same time, the levels were significantly lower in group 3 compared to group 2. The patients in group 1 (standardized anesthesia protocol) demonstrated an increase in the alveolar-arterial oxygen difference, an increase in intrapulmonary shunting, a decrease in blood oxygenation, and static lung compliance after СРВ. In both cases, NO inhalation retained the values of lung compliance and pulmonary oxygenating function after CPB, and in the patients of group 3, it also significantly reduced intrapulmonary shunting and alveolar-arterial difference after CPB. NO inhalation allowed a statistically significant decrease in the incidence of pulmonary dysfunction, acute respiratory failure, as well as the time of respiratory support in the ICU.

Conclusion. The developed technology for the use of inhaled NO in surgery with CPB provides a clinically marked protective effect on the heart and lungs. The effectiveness of the protective action of NO depends on the duration of its administration and is most pronounced when used during the entire operation, including CPB time.

1. Naveed A., Azam H., Murtaza H.G., Ahmad R.A., Raza Baig M.A. Incidence and risk factors of pulmonary complications after cardiopulmonary bypass. Pak J Med Sci 2017; 33(4): 993–996, https://doi.org/10.12669/pjms.334.12846.
2. Apostolakis E., Filos K.S., Koletsis E., Dougenis D. Lung dysfunction following cardiopulmonary bypass. J Card Surg 2010; 25(1): 47–55, https://doi.org/10.1111/j.1540-8191.2009.00823.x.
3. Hirao S., Masumoto H., Minatoya K. Rat cardiopulmonary bypass models to investigate multi-organ injury. Clin Surg 2017; 2: 1509.
4. Shlyakhto E.V., Nifontov E.M., Galagudza M.M. Pre- and postconditioning as methods of cardiocytoprotection: pathophysiological and clinical aspects. Serdechnaa nedostatochnost’ 2008; 9(1): 4–10.
5. Laletin D.A., Bautin A.E., Rubinchik V.E., Naumenko V.S., Alekseyev A.A., Mikhailov A.P. Parallels between the hemodynamic profile and biomarkers activity in different forms of acute heart failure in the early period after aortocoronary bypass. Vestnik anesteziologii i reanimatologii 2015; 12(2): 27–33.
6. Hataishi R., Rodrigues A.C., Neilan T.G., Morgan J.G., Buys E., Shiva S., Tambouret R., Jassal D.S., Raher M.J., Furutani E., Ichinose F., Gladwin M.T., Rosenzweig A., Zapol W.M., Picard M.H., Bloch K.D., Scherrer-Crosbie M. Inhaled nitric oxide decreases infarction size and improves left ventricular function in a murine model of myocardial ischemia-reperfusion injury. Am J Physiol Heart Circ Physiol 2006; 291: H379–H384, https://doi.org/10.1152/ajpheart.01172.2005.
7. Liu X., Huang Y., Pokreisz P., Vermeersch P., Marsboom G., Swinnen M., Verbeken E., Santos J., Pellens M., Gillijns H., Van de Werf F., Bloch K.D., Janssens S. Nitric oxide inhalation improves microvascular flow and decreases infarction size after myocardial ischemia and reperfusion. J Am Coll Cardiol 2007; 50(8): 808–817, https://doi.org/10.1016/j.jacc.2007.04.069.
8. Nagasaka Y., Fernandez B.O., Garcia-Saura M.F., Petersen B., Ichinose F., Bloch K.D., Feelisch M., Zapol W.M. Brief periods of nitric oxide inhalation protect against myocardial ischemia-reperfusion injury. Anesthesiology 2008; 109(4): 675–682, https://doi.org/10.1097/ALN.0b013e318186316e.
9. Nagasaka Y., Buys E.S., Spagnolli E., Steinbicker A.U., Hayton S.R., Rauwerdink K.M., Brouckaert P., Zapol W.M., Bloch K.D. Soluble guanylate cyclase-α1 is required for the cardioprotective effects of inhaled nitric oxide. Am J Physiol 2011; 300: H1477–H1483, https://doi.org/10.1152/ajpheart.00948.2010.
10. Nagasaka Y., Fernandez B.O., Steinbicker A.U., Spagnolli E., Malhotra R., Bloch D.B., Bloch K.D., Zapol W.M., Feelisch M. Nitric oxide pharmacological preconditioning with inhaled nitric oxide (NO): organ-specific differences in the lifetime of blood and tissue NO metabolites. Nitric Oxide 2018; 80: 52–60, https://doi.org/10.1016/j.niox.2018.08.006.
11. Passero D., Martin E.L., Davi A., Mascia L., Rinaldi M., Ranieri V.M. The effects of inhaled nitric oxide after lung transplantation. Minerva Anestesiol 2010; 76(5): 353–361.
12. Schütte H., Witzenrath M., Mayer K., Rosseau S., Seeger W., Grimminger F. Short-term “preconditioning” with inhaled nitric oxide protects rabbit lungs against ischemia-reperfusion injury. Transplantation 2001; 72(8): 1363–1370, https://doi.org/10.1097/00007890-200110270-00005.
13. Waldow T., Alexiou K., Witt W., Wagner F.M., Kappert U., Knaut M., Matschke K. Protection of lung tissue against ischemia/reperfusion injury by preconditioning with inhaled nitric oxide in an in situ pig model of normothermic pulmonary ischemia. Nitric Oxide 2004; 10(4): 195–201, https://doi.org/10.1016/j.niox.2004.04.006.
14. Waldow T., Witt W., Ulmer A., Janke A., Alexiou K., Matschke K. Preconditioning by inhaled nitric oxide prevents hyperoxic and ischemia/reperfusion injury in rat lungs. Pulm Pharmacol Ther 2008; 21(2): 418–429, https://doi.org/10.1016/j.pupt.2007.10.005.
15. Pichugin V.V., Mel’nikov N.Yu., Sandalkin E.V., Medvedev A.P., Gamzaev A.B., Zhurko S.A., Chiginev V.A. Heart and lungs protection techniques in anesthetic and perfusion management of heart valves surgery. Klinicheskaa fiziologia krovoobraschenia 2014; 4: 50–59.
16. Pichugin V.V., Bober V.V., Domnin S.E., Nikol’skiy V.O., Bogush A.V., Chiginev V.A. The effectiveness of lung protection methods in patients with high pulmonary hypertension in the correction of valvular heart disease. Medicinskij al’manah 2017; 3: 130–136.
17. Glants S. Mediko-biologicheskaja statistika [Biomedical statistics]. Moscow: Praktika; 1998; 459 p.
18. Gianetti J., Del Sarto P., Bevilacqua S., Vassalle C., De Filippis R., Kacila M., Farneti P.A., Clerico A., Biagini M.A. Supplemental nitric oxide and its effect on myocardial injury and function in patients undergoing cardiac surgery with extracorporeal circulation. J Thorac Cardiovasc Surg 2004; 127(1): 44–50, https://doi.org/10.1016/j.jtcvs.2002.08.001.
19. Checchia P.A., Bronicki R.A., Muenzer J.T., Dixon D., Raithel S., Gandhi S.K., Huddleston C.B. Nitric oxide delivery during cardiopulmonary bypass reduces postoperative morbidity in children — a randomized trial. J Thorac Cardiovasc Surg 2013; 146(3): 530–536, https://doi.org/10.1016/j.jtcvs.2012.09.100.
20. James Ch., Millar J.C., Horton S., Brizard C.P., Molesworth C., Butt W. Nitric oxide administration during paediatric cardiopulmonary bypass: a randomised controlled trial. Intensive Care Med 2016; 42(11): 1744–1752, https://doi.org/10.1007/s00134-016-4420-6.
21. Kamenshchikov N.O., Mandel I.A., Podoksenov Yu.K., Svirko Yu.S., Lomivorotov V.V., Mikheev S.L., Kozlov B.N., Shipulin V.M., Nenakhova A.A., Anfinogenova Ya.J. Nitric oxide provides myocardial protection when added to the cardiopulmonary bypass circuit during cardiac surgery: randomized trial. J Thorac Cardiovasc Surg 2019; 157(6): 2328–2336.e12018, https://doi.org/10.1016/j.jtcvs.2018.08.117.
22. Macedo F.I., Carvalho E.M., Gologorsky E., Salerno T. Gas exchange during lung perfusion/ventilation during cardiopulmonary bypass: preliminary results of a pilot study. Open J Cardiovasc Surg 2010; 3: 1–7, https://doi.org/10.4137/OJCS.S4109.
23. Schlensak C., Doenst T., Preusser S., Wunderlich M., Kleinschmidt M., Beyersdorf F. Bronchial artery perfusion during cardiopulmonary bypass does not prevent ischemia of the lung in piglets: assessment of bronchial artery blood flow with fluorescent microspheres. Eur J Cardiothorac Surg 2001; 19(3): 326–331, https://doi.org/10.1016/s1010-7940(01)00581-4.
24. Schlensak C., Doenst T., Preusser S., Wunderlich M., Kleinschmidt M., Beyersdorf F. Cardiopulmonary bypass reduction of bronchial blood flow: a potential mechanism for lung injury in a neonatal pig model. J Thorac Cardiovasc Surg 2002; 123(6): 1199–1205, https://doi.org/10.1067/mtc.2002.121977.

Pichugin V.V., Seyfetdinov I.R., Ryazanov M.V., Domnin S.E., Gamzaev A.B., Chiginev V.A., Bober V.V., Medvedev A.P. New Technology for the Use of Inhaled Nitric Oxide to Protect the Heart and Lungs during Operations with Cardiopulmonary Bypass. Sovremennye tehnologii v medicine 2020; 12(5): 28, https://doi.org/10.17691/stm2020.12.5.03