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.

[Relationship of high altitude de-adaptation with acute high altitude response and cardiac function].

OBJECTIVE: To assess the relationship of high altitude de-adaptation response (HADAR) with acute high altitude response (AHAR) and cardiac function. METHODS: Ninety-six military personnel of rapid entering into high altitude (3 700 to 4 800 m) with strong physical work were analyzed, all subjects were male, aged 18 - 35 years. According to the symptomatic scores of AHAR were divided into 3 groups: sever AHAR (group A, 24), mild to moderate AHAR (group B, 47) and non-AHAR (group C, 25) at high altitude. According to the symptomatic scores of HADAR were divided into 3 groups: severe HADAR (group E, 19), mild to moderate HADAR (group F, 40) and non-HADAR (group G, 37) after return to lower altitude (1 500 m). Mean pulmonary arterial pressure (mPAP), right ventricular internal dimension (RVID), outflow tract of right ventricle (RVOT), left ventricular internal dimension (LVID), left ventricular ejection fraction (LVEF), cardiac muscle work index (Tei index), creatine kinase isoenzymes-MB (CK-MB), lactic dehydrogenase isoenzyme-1 (LDH-1) were measured at high altitude stayed 50 days and after return to lower altitude 12 h, 15 d, and 30 d. Fifty healthy volunteers (group D) at 1 500 m altitude served as control. RESULTS: Level of mPAP, RVID, RVOT, RVID/LVID ratio, Tei index, CK-MB,and LDH-1 were higher, and LVEF was lower in group A than those in group B, C and D, there were significant differences between group B and C, C and D (all P < 0.01). AHAR scores were positively correlated with HADAR scores (r = 0.863, P < 0.01). Twelve hours after return to lower altitude, level of mPAP, RVID, RVOT, RVI/LVID ratio, Tei index, CK-MB, and LDH-1 were higher, and LVEF was lower in group E than those in group F, G and D, there were significant differences between group F and G, G and D (all P < 0.01). Fifteen days after return to lower altitude, level of mPAP, RVID, RVOT, RVID/LVID ratio were higher in group E than those in group F, G, and D, there were significant differences between group F and G, and D (P < 0.01 or P < 0.05), there were no significant differences between group G and D (all P > 0.05), LVEF, Tei index, CK-MB, LDH-1 showed no significant differences among groups (all P > 0.05). Thirty days after return to lower altitude, these parameters in group E, F, and G showed no significantly differences compared with those of group D (all P > 0.05). CONCLUSION: The severity of HADAR is associated with severity of AHAR and cardiac injury, the more serious of AHAR and cardiac injury at high altitude, the more serious of HADAR and cardiac injury after return to lower altitude, the more long of restore of right cardiac morphologic injury.

[The role of hypoxia inducible factor-1α and vascular endothelial growth factor in hypoxic pulmonary hypertension in patients with acute high altitude reaction of rescue workers in Yushu earthquake].

OBJECTIVE: To assess the effects of hypoxia inducible factor-1α (HIF-1α) and vascular endothelial growth factor (VEGF) on hypoxic pulmonary hypertension(HPH) in patients with acute high altitude reaction(AHAR) and its change after return to lower altitude. METHODS: Ninety-six officers and soldier participating in rescue of Yushu megaseism on April 14th in 2010, leaving low altitude area (1 500 m) rapidly to high altitude area(3 700 m) to undertake strenuous physical work were enrolled for study. All of them were male, aged 18-35 years, and they were divided into three groups according to the symptomatic scores of AHAR: without AHAR(group B, n=25), mild to moderate AHAR (group C, n=47 ) and severe AHAR (group D, n=24). Mean pulmonary artery pressure (mPAP), levels in serum HIF-1α and VEGF were measured at high altitude area after a stay of 50 days, and also after their return to lower altitude area (1 500 m) for 12 hours and 15 days. Fifty healthy volunteers at low altitude area served as control (group A). RESULTS: Level of mPAP (mm Hg, 1 mm Hg=0.133 kPa), serum HIF-1α (pg/L) and VEGF (ng/L) in group B (24.23±1.56, 68.80±7.52 and 82.56±6.32) were significantly higher than those in group A (18.50±1.30, 50.95±3.33 and 65.78±4.03), respectively (all P<0.01). Moreover, the value of all the parameters increased with increase in severity of AHAR, the respective value in group C were 28.42±1.32, 88.10±9.20 and 104.82±10.36, and in group D were 34.70±2.94, 117.93±13.46 and 136.77±12.03, and there were significant differences in comparing two groups (all P<0.01). At high altitude area, AHAR total score was positively correlated with mPAP, serum HIF-1α and VEGF (r=0.672, 0.737 and 0.634, respectively, all P<0.01), mPAP was positively correlated with serum HIF-1α and VEGF (r=0.706, 0.638, both P<0.01). Compared with group A, level of mPAP (29.08±4.22), serum HIF-1α (91.16±20.58) and VEGF (107.11±10.32) were significantly increased in 96 officers and soldiers who stayed for 50 days at an altitude of 3 700 m (all P<0.01), and the values were significantly decreased after returning to lower altitude area for 12 hours(23.05±3.18, 70.99±8.22 and 78.65±6.47) and 15 days(18.96±1.75, 52.31±4.92 and 63.08±4.55). The values showed significant difference between 12 hours and 15 days stay at 1 500 m (all P<0.01). The values of the determined parameters 15 days after return to lower altitude area showed no difference compared with those of group A (all P>0.05). CONCLUSION: Strenuous physical work at high altitude area, AHAR becomes more serious, and it is accompanied by higher values of HIF-1α, VEGF and mPAP, indicating that HPH is closely associated with elevation of HIF-1α and VEGF. These changes are improved after returning to lower altitude area for 12 hours, and they recover to normal lever after 15 days.

[Effect of oxidative stress in development of acute high altitude response during the process of strong physical work at high altitude].

OBJECTIVE: To assess the effect of oxidative stress in development of acute high altitude response (AHAR) during the process of strong physical work at high altitude and its change after return to lower altitude. METHODS: Ninety-six officers and soldiers of rapid entering into high altitude (3 700 m) with strong physical work were analyzed, all subjects were male, aged 18-35 years. According to the symptomatic scores of AHAR were divided into 3 groups: severe AHAR (group A, n = 24), mild AHAR (group B, n = 47) and without AHAR (group C, n = 25). Levels in serum 8-iso prostaglandinF2alpha(8-iso-PGF2alpha), superoxide dismutase (SOD) and malonaldehyde (MDA) were measured at higher altitude stayed 50 d and after return to lower altitude (1 500 m) 12 h and 15 d, and 50 healthy volunteers (group D) at 1 500 m altitude served as controll. RESULTS: Levels of serum 8-iso-PGF2alpha and MDA [(9.53 +/- 0.47) microg/L, (8.91 +/- 0.39) micromol/L] were significantly higher in group A than those in group B [(8.34 +/- 0.42) microg/L, (7.31 +/- 0.32) micromol/L] , group C [(7.02 +/- 0.48) microg/L, (6.41 +/- 0.23) micromol/L] and group D [(5.13 +/- 0.56) microg/L, (5.48 +/- 0.33) micromol/L], (all P < 0.01), and serum SOD [(52.08 +/- 3.44) micro/ml] was significantly lower in group A than that in group B [62.27 +/- 2.54) micro/ml], group C [(71.99 +/- 3.35) micro/ml] and group D [(80.78 +/- 3.44) micro/ ml] (all P < 0.01), there were significant differences between group B and C, C and D (all P < 0.01). At altitude 3 700 m 50 d, AHAR scores was positively correlated with serum 8-iso-PGF2alpha and MDA (all P < 0.01), negatively correlated with SOD (P < 0.01). Serum 8-iso-PGF2alpha and MDA were negatively correlated with SOD (all P < 0.01). Levels of serum 8-iso-PGF2alpha and MDA were significantly higher at altitude of 3 700 m 50 d than those at altitude of 1 500 m 12 h,15 d in group D (all P < 0.01), and serum SOD was significantly lower than that at 1 500 m 12 h,15 d in group D (all P < 0.01), there were significantly difference between at 1 500 m 12 h and 15 d (all P < 0.01), there were no difference between at 15 d in group D (all P > 0.05). CONCLUSION: The more serious of oxidative stress and oxidative/antioxidative imbalance, the more serious of AHAR, oxidative stress and oxidative/antioxidative imbalance may be involved in the development of AHAR. The changes were obviously improved after return to lower altitude 12 h, and recovered to normal after 15 d.