POLYCYTHEMIA IMPAIRS VASODILATOR RESPONSE TO ACETYLCHOLINE IN PATIENTS WITH CHRONIC HYPOXEMIC LUNG-DISEASE

To investigate whether polycythemia associated with chronic hypoxemic lung disease (CHLD) increases vascular resistance by altering endothel ium-derived nitric oxide (NO), we examined the responses to acetylchol ine (ACh) infusions (5, 10, and 15 mg/min) on hemodynamics and gas exc hange in 21 patients with CHLD of varying severity. Patients were clas sified into two groups based on whether their hemoglobin (Hb) level wa s less or greater than 15.5 g/dl. In the normocythemic patients (Hb = 13.6 +/- 0.3 g/100 mi, n = 10), ACh decreased pulmonary artery pressur e (Ppa) from 30 +/- 2 mm Hg 26 +/- 2 mm Hg (p < 0.01); pulmonary vascu lar resistance (PVR), from 5.1 +/- 0.4 U/m(2) to 3.4 +/- 0.3 U/m(2) (p < 0.001); systemic arterial pressure (Psa), from 111 +/- 4 mm Hg to 1 08 +/- 4 mm Hg (p < 0.05); and systemic vascular resistance (SVR), fro m 27 +/- 2 U/m(2) to 22 +/- 2 U/m(2) (p < 0.01); and also increased th e cardiac index (CI), from 3.8 +/-: 0.2 to 4.7 +/-: 0.3 L/min/m(2) (p < 0.001). Pa-O2 fell from 59 +/- 3 mm Hg to 48 +/- 3 mm Hg (p < 0.001) whereas venous admixture (Qs/Qt) rose from 32 +/- 4% to 44 +/- 4% (p < 0.01). In contrast, in patients with polycythemia (17.7 +/- 0.5 g/10 0 mi, n = 11) ACh failed to produce any changes in Pa-O2 (49 +/- 2 mm Hg versus 51 +/- 2 mm Hg, p = NS), Ppa (34 +/- 1 mm Hg versus 33 +/- 1 mm Hg, p = NS), PVR (6.7 +/- 0.9 U/m(2) versus 6.9 +/- 0.8 U/m(2), p = NS) or Psa, but slightly increased the CI, from 3.6 +/- 0.3 L/min/m( 2) to 3.9 +/- 0.3 L/min/m(2) (p < 0.01), and Qs/Qt, from 40 +/- 4% to 45 +/- 3% (p < 0.05). In the 21 patients, negative correlations with H b concentrations were found for ACh-induced changes in PVR (r = -0.57, p < 0.01), Ppa (r = -0.46, p < 0.01), CI (r = -0.5, p < 0.05), Pa-O2 (r = -0.79, p < 0.01), and Qs/Qt (r = -0.79, p < 0.01). In the six pol ycythemic patients who received isovolemic hemodilution, with a decrea se in Hb concentration from 18.6 +/- 0.9 g/dl to 15.3 +/- 0.3 g/dl as a result, infusion of ACh, which was without effect before hemodilutio n, caused decreases in Ppa from 28 +/- 1 mm Hg to 23 +/- 1 mm Hg (p < 0.05) and in PVR from 5.7 +/- 0.8 U/m(2) to 3.6 +/- 0.5 U/m(2) (p < 0. 02), as well as an increase in CI from 3.4 +/- 0.4 L/min/ m(2) to 4.1 +/- 0.4 L/min/m(2) (p < 0.05). In contrast to ACh, inhaled NO (40 ppm) induced pulmonary vasodilation in both the normocythemic and polycyth emic groups. Our results show that high hematocrit (Hct) levels inhibi t endothelium-dependent vasodilation in response to ACh in patients wi th CHLD, possibly through inactivation of endothelial-derived NO by Hb .