A Study to Evaluate the Efficacy, Safety and Tolerability of PDNO Infusion in Patients With Pulmonary Hypertension After Cardiopulmonary Bypass Surgery

Inclusion Criteria:

• Ability to understand and willing to sign an informed consent form (ICF)
• Male and female patients, age ≥ 18 years
• Planned to undergo elective cardiopulmonary bypass (CPB) for coronary artery bypassgrafting (CABG), aortic valve repair (AVR) or mitral valve repair (MVR) with orwithout CABG
• Diagnosed with echocardiographic signs of pulmonary artery systolic pressure (PASP) >50 mmHg , as estimated by doppler defined echocardiography using a modified Bernoulliequation: PASP ≈ 4 (tricuspid regurgitant jet velocity)^2 + central venous pressure (CVP)

Exclusion Criteria:

• History of chronic pulmonary hypertension (PH) (WHO group 1, 3, 4 or 5), not group 2due to left heart disease
• Patients with contraindications for pulmonary artery catheter (PAC)
• History of severe chronic obstructive pulmonary disease
• Left heart failure with ejection fraction (EF) <35%
• Non-ST elevation myocardial infarction (non-STEMI) or ST elevation myocardialinfarction (STEMI) within 1 months prior to informed consent
• Stroke (cerebrovascular lesion [CVL]), transient ischemic attack (TIA), AV block IIIwithin 3 months prior to informed consent or QTcF >450ms at the time of screening
• High inotropic requirement (no more than one inotrope treatment and the vasopressornorepinephrine at time of screening/postoperative evaluation)
• (Increased) mediastinal bleeding >100 mL/hour in mediastinal drainage at postoperativeevaluation
• Mechanical circulatory assistance (intra aortic balloon pump [IABP] orright/left-ventricular assist device [R/L VAD])
• Echocardiographic evidence of significant tricuspid insufficiency
• Body Mass Index (BMI) >40 kg/m^2
• Estimated glomerular filtration rate (eGFR) < 30 mL/min preoperative value
• Methemoglobin >3%
• Indication of liver disease, defined by serum levels of either alanineaminotransferase (ALT), aspartate aminotransferase (AST) or alkaline phosphatase (ALP)above 3 x upper limit of normal (ULN) (preoperative value)
• Preoperative haemoglobin <10 g/dL, postoperative: Hb < 9 g/dL
• Thrombocytopenia (platelet count <100,000/mm^3), preoperative value
• Prothrombin time International ratio (INR) > 1.3, preoperative value
• Pregnant or lactating women, or with a positive pregnancy test at screening (forfertile women only)
• Ongoing daily treatment the last 3 days with non-steroidal anti-inflammatory drugs (NSAIDs, excluding low dose, i.e. 75 mg, acetylsalicylic acid), new oralanticoagulants (NOACs), warfarin, heparin, clopidogrel (last 5 days). Low molecularweight heparin (LMWH) is not an exclusion criterion. Any use of PDE5 inhibitors (sildenafil, tadalafil, vardenafil and avanafil) within 48 hours prior to theadministration of PDNO.
• Known active malignancy within the past 3 years except for localized prostate cancer,cervical carcinoma in situ, breast cancer in situ, or nonmelanoma skin cancer that hasbeen definitively treated
• History of allergy/hypersensitivity to PD or ongoing allergy/hypersensitivity orhistory of hypersensitivity to drugs with a similar chemical structure or class toPDNO
• History of any other clinically significant disease or disorder
• Participation in any interventional clinical study or has been treated with anyinvestigational research products within 30 days or 5 half-lives, whichever is longer,prior to the initiation of screening