INHALED NITRIC-OXIDE DOES NOT CHANGE TRANSPULMONARY ANGIOTENSIN-II FORMATION IN PATIENTS WITH ACUTE RESPIRATORY-DISTRESS SYNDROME

Study objective: To investigate the effect of short-term inhalation of nitric oxide (NO) on transpulmonary angiotensin II formation in patie nts with severe ARDS. Design: Prospective, clinical study. Setting: An esthesiology ICU of a university hospital. Patients: Ten ARDS patients who responded to inhalation of 100 ppm NO by decreasing their pulmona ry vascular resistance (PVR) by at least 20 dyne.s.cm(-5) were include d in the study. Interventions and measurements: In addition to standar d treatment, the patients inhaled 0, 1, and 100 ppm NO in 20-min inter vals. Fraction of inspired oxygen was 1.0. Hemodynamics were measured and recorded online. Mixed venous (pulmonary arterial catheter) and ar terial (arterial catheter) blood samples were taken simultaneously for hormonal analyses at the end of each inhalation period.Results: Pulmo nary arterial pressure decreased from 33 +/- 2 mm Hg (0 ppm NO, mean /- SEM) to 29 +/- 2 mm Hg (1 ppm NO, p < 0.05), and to 27 +/- 2 mm Hg (100 ppm NO, p < 0.05, vs 0 ppm). PVR decreased from 298 +/- 56 (0 ppm NO) to 243 +/- 45 dyne.s.cm(-5) (1 ppm NO, not significant [NS]), and to 197 +/- 34 dyne.s.cm(-5) (100 ppm NO, p < 0.05, vs 0 ppm). Arteria l oxygen pressure increased from 174 +/- 23 mm Hg (0 ppm NO) to 205 +/ - 26 mm Hg (1 ppm NO, NS), and to 245 +/- 2.5 mm Hg (100 ppm NO, p < 0 .05, vs 0 ppm). Mean plasma angiotensin II concentrations were 85 +/- 20 (arterial) and 57 +/- 13 pg/mL (mixed venous) during 0 ppm NO and d id not change during inhalation of 1 and 100 ppm NO. Mean transpulmona ry plasma angiotensin II concentration gradient (= difference between arterial and mixed venous blood values) was 28 +/- 8 pg/mL (range, 0 t o 69) during 0 ppm NO and did not change during inhalation of 1 and 10 0 ppm NO. Mean transpulmonary angiotensin II formation (transpulmonary angiotensin II gradient multiplied with the cardiac index) was 117 +/ - 39 ng/min/m(2) (range, 0 to 414) during 0 ppm NO and did not change during inhalation of 1 and 100 ppm NO. Mean arterial plasma cyclic gua nosine monophosphate concentration was 11 +/- 2 pmol/mL (0 ppm NO), di d not change during 1 ppm NO, and increased to 58 +/- 8 pmol/mL (100 p pm NO, p < 0.05). Arterial plasma concentrations of aldosterone (142 /- 47 pg/mL), atrial natriuretic peptide (114 +/- 34 pg/mL), angiotens ion-converting enzyme (30 +/- 5 U/L), and plasma renin activity (94 +/ - 26 ng/mL/h of angiotensin I) did not change. Conclusion: The decreas e of PVR by short-term NO inhalation in ARDS patients was not accompan ied by changes in transpulmonary angiotensin II formation. Our results do not support an relationship between transpulmonary angiotensin II formation and the decrease in PVR induced by inhaled NO.