Plasma endothelin-1 and nitric oxide correlate with ligustrazine alleviation of pulmonary artery hypertension in patients of chronic cor pulmonale from high altitude plateau during acute exacerbation.

OBJECTIVE: To explore the mechanisms involved in the ligustrazine alleviation of the pulmonary artery hypertension (PAH) in patients of chronic obstructive pulmonary disease (COPD) associated with chronic cor pulmonale (CCP) during exacerbation. METHODS: Seventy patients of COPD and CCP with acute exacerbation were randomly and equally divided into control group and treatment group. The control group received standard treatment with antibiotics, antiasthmatic and expectorant medications, and oxygenation; and the ligustrazine treatment group received ligustrazine treatment (80 mg/d; i.v.; for 2 weeks) in addition to the standard treatment. Before and at the end of 2 week treatment, the clinic responses of the two regimens were evaluated, plasma levels of endothelin-1 (ET-1) and nitric oxide (NO) were determined; arterial oxygen partial pressure (PaO2, mean pulmonary arterial pressure (mPAP), outflow tract of right ventricle (RVOT), and internal diameter of right ventricle (RV) were measured. RESULTS: Good clinic benefits were achieved in both the standard and ligustrazine regimens, plasma level of ET-1, values of mPAP, RV and RVOT decreased significantly, plasma level of NO and PaO2 values decreased (all P < 0.01 vs pre-treatment to all parameters). Compared with the control group, ligustrazine greatly enhanced the clinic efficacy from 77.1% to 97.1% (P < 0.05), and also resulted in more significant changes of all these parameters (P < 0.01 vs control group for all parameters). For both groups, the levels of plasma ET-1 were positively correlated with values of mPAP, RVOT, and RV (r = 0.710, 0.853, and 0.766, respectively, all P = 0.000), and negatively correlated with plasma NO and PaO2 (r = - 0.823, and - 0.752, respectively, all P = 0.000). CONCLUSION: Ligustrazine is effective in treating pulmonary artery hypertension during acute exacerbation of COPD and CCP in patients from the plateau area. The observed changes in the plasma levels of NO and ET-1 in response to ligustrazine treatment suggest that ligustrazine may act through the selective effect on pulmonary blood vessels to enhance the synthesis and release of NO and suppress those of ET-1 from lung vascular endothelial cells, thus reducing pulmonary artery pressure and decreasing pulmonary arterial hypertension.

[Change in serum basic fibroblast growth factor level and its relationship to pulmonary arterial pressure in patients with acute exacerbation of chronic cor pulmonale on plateau].

OBJECTIVE: To assess the role of serum basic fibroblast growth factor (bFGF) in the development of hypoxic pulmonary hypertension in the patients with chronic cor pulmonale on highland (HACCP). METHODS: The levels of bFGF in serum of 38 patients with HACCP in the acute exacerbation stage, 30 patients with chronic obstructive pulmonary disease (COPD) in the remission stage and 30 normal control subjects were measured by sandwich enzyme-linked immunoadsorbent assay (ELISA). The mean pulmonary arterial pressure (MPAP) was measured by echocardiography. The partial pressure of oxygen in artery blood (PaO(2)) was measured by blood gas analyzer. RESULTS: The level of serum bFGF [(87.54+/-12.15) ng/L] and MPAP [(45.86+/-5.63)mm Hg (1 mm Hg=0.133 kPa)] in the patients with HACCP were significantly higher than those in the patients with COPD [(55.72+/-9.08) ng/L, (22.95+/-2.56)mm Hg, respectively, both P<0.01], those of the patients with COPD were both significantly higher than those of the normal control subjects [(49.83+/-8.78)ng/L, (20.34+/-2.23)mm Hg, respectively, both P<0.05]. The PaO(2) [(38.79+/-4.56)mm Hg] in the patients with HACCP was significantly lower than those in patients with COPD and normal subjects [(58.22+/-6.18) mmHg and (66.57+/-5.48)mm Hg, respectively, all P<0.01]. The level of serum bFGF in the patients with HACCP and the patients with COPD was positively correlated with MPAP (cor pulmonale group r=0.788, P<0.01; COPD group r=0.674, P<0.01)],negatively correlated with PaO(2) (cor pulmonale group r=-0.735, P<0.01; COPD group r=-0.587, P<0.01)). CONCLUSION: The level of serum bFGF in patients with HACCP is significantly increased; it may play an important role in the process of sustained hypoxic pulmonary hypertension in patients with HACCP.