[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.

[Analysis of prognostic risk factors in the patients with acute exacerbation of chronic cor pulmonale and obstructive sleep apnea-hypopnea syndrome in high altitude area].

OBJECTIVE: To assess the prognostic risk factors in the patients with acute exacerbation of chronic cor pulmonale (AEHACCP) and obstructive sleep apnea-hypopnea syndrome (OSAHS) in high altitude area. METHODS: The relations between neck circumference (Nc), body mass index (BMI), arterial blood gases, polysomnography (PSG) parameters and prognosis from 66 patients with AEHACCP and OSAHS (31 survivors, 35 non-survivors) were studied by one variable analysis and multivariable Logistic regression analysis. RESULTS: The results of one variable analysis showed that in patients with AEHACCP and OSAHS, Nc> or =45 cm, BMI > or =28 kg/m(2) , arterial oxygen partial pressure (PaO(2))< or =40 mm Hg (1 mm Hg= 0.133 kPa), mean pulmonary arterial pressure (mPAP)> or =45 mm Hg, apnea-hypopnea index (AHI)> or = 40 times/h, sleep mean arterial oxygen saturation (MSaO(2))< or =0.70, percentage of the duration of SaO(2)<0.70 during sleep(T(70) )> or =50% and difference between basic and minimum SaO(2) during sleep(Delta SaO(2))> or = 0.20 were closely correlated with prognosis. The Logistic regression models showed that Nc> or =45 cm [odds ratio (OR)=6.781, 95% confidence interval (95%CI)=1.153-17.502, P=0.007], BMI> or =28 kg/m(2) (OR=7.562, 95%CI=1.012-23.457, P=0.004), mPAP> or =45 mm Hg (OR=6.991, 95%CI=1.353-20.155, P=0.003), AHI> or =40 times/h (OR=7.258, 95%CI=1.526-18.022, P=0.006), MSaO(2)< or =0.70 (OR=6.488, 95%CI=1.562-26.878, P=0.008), T(70) > or =50% (OR=5.593, 95%CI=1.265-21.589, P=0.008) and Delta SaO(2)> or =0.20 (OR=6.551, 95%CI=1.495-18.920, P=0.007) were independent significant risk factors in prognosis of patients with AEHACCP and OSAHS. CONCLUSION: The patients with AEHACCP and OSAHS, Nc> or =45 cm, BMI> or =28 kg/m(2), mPAP> or =45 mm Hg, AHI> or = 40 times/h, MSaO(2)< or =0.70, T(70) > or =50% and Delta SaO(2)> or =0.20 are risk factors leading to a rise in mortality. It is important to use these parameters to guide clinical therapy, and to judge the prognosis so as to reduce the mortality of patients with AEHACCP and OSAHS by monitoring the above risk factors in clinical practice.

[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.

[Study on the clinical significance of plasma adrenomedullin and brain natriuretic polypeptide in the patients with chronic cor pulmonale on highland].

OBJECTIVE: To study the clinical significance of plasma adrenomedullin (ADM) and brain natriuretic polypeptide (BNP) in the patients with chronic cor pulmonale on highland (HACCP). METHODS: The levels of ADM and BNP in plasma of 44 patients with HACCP in the acute and in the remission stages were determined with radioimmunoassay. Their correlations with partial pressure of oxygen in arterial blood (PaO(2)), endothelin-1 (ET-1), and the ratio of right ventricular pre-ejection time to the pulmonary flow acceleration time (RVPEP/AT), which reflected the degree of pulmonary hypertension, were investigated. Twenty healthy subjects served as a normal control group. RESULTS: The levels of ADM [(38.8+/-7.2)ng/L and (26.2+/-5.3)ng/L] and BNP [(81.4+/-13.8)ng/L and (58.9+/-9.3)ng/L] in the acute and remission stages of cor pulmonale groups were both significantly higher than those in the normal control group [(15.0+/-3.2)ng/L, (38.6+/-3.4)ng/L, respectively, all P<0.01]. The levels of ADM and BNP in acute stage were both significantly higher than those in remission stage (both P<0.01). In the acute and in the remission stages, the levels of ADM in plasma were negatively correlated with PaO(2) (r(a)=-0.826, P<0.01; r(r)=-0.783, P<0.01), positively correlated with ET-1 (r(a)=0.755, P<0.01; r(r)=0.668, P<0.01) and RVPEP/AT ratio (r(a)=0.788, P<0.01; r(r)=0.734, P<0.01). In the acute and in the remission stages, the levels of BNP in plasma were negatively correlated with PaO(2) (r(a)=-0.787, P<0.01; r(r)=-0.554, P<0.01), positively correlated with ET-1 (r(a)=0.725, P<0.01; r(r)=0.679, P<0.01) and RVPEP/AT ratio (r(a)=0.771, P<0.01; r(r)=0.722, P<0.01). CONCLUSION: The study suggests that ADM and BNP are involved in the pathophysiological process of HACCP in the patients and may play a compensatory role in the disease.

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.

[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.