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Abstract: Purpose: The response to inhaled nitric oxide (iNO) is inconsistent in patients with acute respiratory distress syndrome (ARDS). We sought to determine whether the response to iNO, defined as 20% Pao 2/Fio 2 increase from baseline, depends on the level of cardiac natriuretic peptides. Materials and methods: This is a prospective cohort study including 11 consecutive patients with ARDS who were eligible to receive iNO. Measurements of plasma concentrations of atrial natriuretic peptide (ANP), N-Terminal-Pro-B-Type Natriuretic Peptide (NT-pro-BNP) and 3′,5′-cyclic guanosine monophosphate were obtained before initiating iNO and 30 minutes later during iNO. Baseline cardiac peptides, oxygenation, and hemodynamic variables and their change during iNO were compared among responders and nonreponders to iNO. Results: Baseline ANP and NT-pro-BNP concentrations were higher in patients that responded to iNO and tended to decrease during iNO in responders only. 3′,5′-Cyclic guanosine monophosphate concentrations were not different among responders and nonresponders and were unchanged during iNO. Baseline ANP was strongly correlated with change in intrapulmonary shunt, and baseline NT-pro-BNP and its change were correlated with the change in cardiac output. Conclusions: High ANP and NT-pro-BNP concentrations are associated with the response to iNO. These data suggest that cardiac peptides have the potential to identify a subgroup of patients with ARDS who might derive clinical benefit from iNO. [Copyright &y& Elsevier]