Characteristics Of Cardiac And Pulmonary Arterial Pressure Responses To Acute High Altitude Exposure And Its Association With The Incidence Of High-altitude Fatigue

Backgroud:Our country is famous with the large areas of high altitude(HA),which is characterized by hypobaric hypoxia.When unacclimatized lowlanders rapidly ascend to HA,a series of adaptive changes in the circulation system may occur in response to the HA hypoxic stress.Whereas well-adapted cardiac performance may facilitate oxygen delivery to tissues.It has been reported that the global left ventricular(LV)and right ventricular(RV)systolic functions are well preserved,but both ventricles show altered filling patterns.However,recent study has shown that acute HA hypoxia induces the increase in LV twist,but sub-endocardial systolic dysfunction.Previous studies have shown that baseline heart rate(HR)may directly impact cardiac function.However,whether the baseline HR of lowlanders exhibits diverse cardiac responses during HA travels is still unclear.Moreover,acute HA exposure always induce hypoxic pulmonary vasoconstriction,and result in the elevation of pulmonary artery pressure,which may increase RV afterload and impair RV function.Furthermore,acute extreme altitude exposure may result in RV dilatation,increase in RV Tei index and decrease in RV free wall longitudinal systolic strain,suggesting that RV longitudinal systolic function may be impaired.Previous study have showed that acute hypoxia could trigger RVD,whether acute HA exposure can induce the incidence of RVD and its impact on RV function have not been fully elucidated.Furthermore,our previous data have shown that elevated RV afterload is associated with impaired cardiorespiratory fitness in healthy subjects after acute HA exposure.However,the association between HA induced elevated RV afterload and high-altitude fatigue(HAF)is still unknown.Objectives:1.To investigate the cardiac and pulmonary arterial pressure responses under acute HA exposure in different baseline heart rate(HR).2.To investigate the effect of acute HA exposure on the incidence of RVD,and the association between RVD and RV function.3.To investigate the association of the onset of HAF under acute HA exposure,and correlation with cardiac function and pulmonary arterial pressure.Methods:1.A total of 240 healthy young men were enrolled and ascended to 4100 m by bus within 7 days.The basic characteristics and physiologic parameters of participants were collected before and after ascent.Standard echocardiography was performed to detect cardiac function at sea level and at 4100m.The subjects were divided into three groups based on the tertiles of their baseline HR at SL:lowest tertile HR(LT),middle tertile HR(MT)and highest tertile HR(HT).Comparison of these parameters in different groups of subjects.2.A total of 108 healthy young men were enrolled and ascended to 4100 m by bus within 7 days.The basic characteristics and physiologic parameters of participants were collected before and after ascent.Standard echocardiography was performed to detect cardiac function at sea level and at 4100m.By using 2-dimensional speckle-tracking echocardiography,RVD was evaluated by calculating the R-R interval-corrected standard deviation of the time-to-peak systolic strain for the 4 mid-basal RV segments(RVSD4)and defined by RVSD4>18.7 ms.The subjects were divided into RVD-groups and RVD-groups.Comparison of these parameters in different groups of subjects.3.A total of 136 healthy Han men were enrolled and ascended to 4100m by bus within7 days,and divided into HAF+group(n=78)and HAF-group(n=58)according to the fatigue assessment instrument.The basic characteristics and physiologic parameters of participants were collected before and after ascent.Standard echocardiography was performed to detect cardiac function at sea level and at 4100m.Comparison of these parameters in different groups of subjects.The risk factors of the incidence of HAF at HA were analysed by logistic regression analysis.Results:1.In all subjects,baseline HR was negatively correlated with HA exposure-induced changes in HR(r=-0.410,P<0.001)and CI(r=-0.314,P<0.001).Following HA exposure,subjects with lowest tertile of baseline HR showed an increased HR[56(53,58)vs.65(58,73)beats/min,P<0.001],left ventricular ejection fraction(LVEF)[61.7(56.5,68.0)vs.66.1(60.7,71.5)%,P=0.004]and mitral S'velocity[5.8±1.4 vs.6.5±1.9 cm/s,P=0.04].However,subjects with highest tertile of baseline HR showed an unchanged HR,LVEF and mitral S'velocity,but a decreased E'velocity[9.2±2.0 vs.8.4±1.8 cm/s,P=0.003].2.Following HA exposure,RVSD4 was significantly increased,and induce RVD in 35subjects.RVD+group showed lower pulse oxygen saturation(SpO2),higher mean pulmonary artery pressure(mPAP)and systolic pulmonary artery pressure(SPAP).Moreover,RV isovolumetric velocity(Tricuspid IVV)and isovolumetric acceleration(Tricuspid IVA)was increased in total subjects and RVD-group but not in those with RVD+group.In addition,RVD+group showed lower RV global longitudinal strain(RVGLS),and no additional changes were found in the RV fractional area change and tricuspid S'velocity between subjects with and without RVD-.3.Following HA exposure,78(57.4%)of all participants suffered from a clinical symptom of HAF;moreover,the mPAP,systolic pulmonary artery pressure(SPAP)and pulmonary vascular resistance(PVR)were significantly increased;compared with subjects in HAF-group,subjects in HAF+group showed higher values of mPAP[20.6(18.5,26.1)vs.17.9(15.5,21.6)mmHg,P<0.001],SPAP[30.4(27.0,39.4)vs.26.1(22.1,32.1)mmHg,P<0.001],PVR[5.56(4.21,7.45)vs.4.41(3.61,5.69)Woods,P=0.002],right ventricular end-diastolic area(RVEDA)(22.0±3.8 vs.20.5±3.6 cm~2,P=0.019),right ventricular end-systolic area(RVESA)(13.1±2.7 vs.12.1±2.3 cm~2,P=0.032)and right ventricular basal dimension(RVD-basal)(3.92±0.45 vs.3.72±0.41 cm,P=0.008).Logistic regression analysis indicated that mPAP was an independent factor for the onset of HA fatigue[OR=1.130,95%CI:(1.034,1.235),P=0.007].Conclusions:1.The baseline HR of subjects at sea level could determine the cardiac responses to acute HA exposure,which were characterized by enhanced LV function in subjects with a low baseline HR and by reduced LV myocardial velocity in early diastole in subjects with a high baseline HR.2.Acute HA exposure could induce RVD in healthy subjects by a combination of RV afterload and hypoxia;the incidence of RVD at HA was associated with reduced RV regional function and blunted myocardial acceleration.3.Acute HA exposure leads to the onset of HAF and increase of pulmonary artery pressure.The mPAP is an independent risk factor for the occurrence of HAF.