Hypoxic pulmonary vasoconstriction in nonventilated lung areas contributes to differences in hemodynamic and gas exchange responses to inhalation of nitric oxide

Background: Enhancement of hypoxic pulmonary vasoconstriction (HPV) in nonventilated lung areas by almitrine increases the respiratory response to inhaled nitric oxide (NO) in patients with acute respiratory distress syndrome (ARDS). Therefore the authors hypothesized that inhibition of HPV in nonventilated lung areas decreases the respiratory effects of NO. Methods: Eleven patients with severe ARDS treated by venovenous extracorporeal lung assist were studied. Patients' lungs were ventilated at a fraction of inspired oxygen (FIO2) of 1.0, By varying extracorporeal blood flow, mixed venous oxygen tension (P-O2; partial oxygen pressure in mixed venous blood [P (V) over bar(O2)]) was adjusted randomly to four levels (means, 47, 54, 64 and 84 mmHg). Extracorporeal gas flow was adjusted to prevent changes in mined venous carbon dioxide tension [P (v) over bar(CO2)]). Haemodynamic and gas exchange variables were measured at each revel before, during, and after 15 ppm NO. Results: Increasing P (v) over bar(O2) from 47 to 84 mmHg resulted in a progressive decrease in lung perfusion pressure (PAP-PAWP; P < 0.05) and pulmonary vascular resistance index (PVRI; P < 0.05) and in an increase in intrapulmonary shunt (Q) over dot(S)/(Q) over dot(T); P < 0.05). P (v) over bar(CO2) and cardiac index did not change. Whereas the NO-induced reduction in PAP-PAWP was smaller at high P (v) over bar(O2), NO-induced decrease in in (Q) over dot(S)/(Q) over dot(T) independent of baseline P (v) over bar(2). In response: to NO, arterial P-O2 increased more and arterial oxygen saturation increased less at high compared with low P (v) over bar(O2). Conclusion: In patients with ARDS, HPV in nonventilated lung areas modifies time hemodynamic and respiratory response to NO. The stronger the HPV in nonventilated lung areas the more pronounced is the NO-induced decrease in PAP-PAWP. LPI contrast, the NO-induced decrease in (Q) over dot(S)/(Q) over dot(T) is independent of P (v) over bar(O2) over a wide range of P (v) over bar(O2) levels. The effect of NO on the arterial oxygen tension varies with the level of P (v) over bar(O2) by virtue of its location on the oxygen dissociation curve.