| PartⅠ: A randomized controlled clinical study of sildenafil for the interventionof early high altitude pulmonary hypertensionBackground and Objectives:Cardiovascular changes induced by high altitude chronic hypoxia gradually alter fromphysiological compensatory state to pathological formation. Those who have been living inthe plateau area for a long time, with increased pulmonary arterial pressure, but notdiagnosed with high altitude pulmonary hypertension（HAPH）, was intended to bediagnosed as early high altitude pulmonary hypertension. It is of great significance to slowdown and halt the pulmonary arterial pressure from further rising or decreasing the pressureto normal, and to prevent HAPH through drug intervention. In this randomized、controlledclinical trial, we aimed to evaluate the efficacy and safety of sildenafil for the interventionof early HAPH.Methods:From April2011to August2011, forty-six young males inhabiting above an altitude of4500m over three months，with clinical symptoms or signs of HAPH, with increasedsystolic pulmonary artery pressure (SPAP), but not fulfilling the standard of HAPH, wereenrolled in this trial. These subjects were randomly divided into two groups, supplementaloxygen group (2L/min1.5h/d，n=23，12weeks) and sildenafil group (supplemental oxygenand oral sildenafil50mg/d, n=23，12weeks) with the random number method. At the verybeginning of enrollment and the12th weeks in the trial, all subjects were inquired themedical history and subjected physical examination. SPAP was measured usingtransthoracic Doppler echocardiography and calculated using the modified Bernoulli equation. Six minutes walk distance and percutaneous oxygen saturation were alsomeasured, so as the Borg dyspnea scores blood routine, liver function and kidney function.During the medication, adverse effects of drugs were observed. All continuous data arepresented as mean±standard deviation. Data within each group was compared with pairedt-test, data between the supplemental oxygen and sildenafil groups was compared withindependent t-test.Results:1.In the baseline, SPAP, the6minute walk distance, Borg dyspnea score, percutaneousoxygen saturation, heart rate, blood pressure, liver function and kidney function betweensildenafil group and supplemental oxygen group do not differ significantly (P>0.05).2. After12weeks intervention，compared with the baseline, SPAP in sildenafil groupwas decreased from26.47±1.86mmHg to22.13±2.10mmHg (P<0.05), no significantchanges were observed in SPAP in supplemental oxygen group (P>0.05); the6minute walkdistance and Borg dyspnea scores of two groups compared with the baseline wereremarkably improved(P<0.05). Besides, there is no significant changes on percutaneousoxygen saturation, heart rate, blood pressure, liver function and kidney function betweenthe two groups (P>0.05).3. After12weeks intervention，SPAP in sildenafil group was significantly decreasedcompared with supplemental oxygen group (P<0.05). The6minute walk distance and Borgdyspnea scores of group sildenafil was significantly higher than that in supplementaloxygen group (P<0.05). No significant changes were observed on percutaneous oxygensaturation, heart rate, blood pressure, liver function and kidney function in the two groups(P>0.05).4. Among the23subjects in the sildenafil group, flush were observed in1case,headache in1case, abdominal distension in2cases. All the side effects were tolerated andno severe side effects were observed.Conclusion:For early HAPH， sildenafil significantly reduced pulmonary arterial pressure,improved the clinical symptoms，exercise capability and no serious side effects wereobserved. PartⅡ: Effects of three pharmaceutical treatment on high altitude pulmonaryhypertension: A randomized controlled clinical studyBackground and Objectives:High altitude pulmonary hypertension（HAPH） is one of the major cardiovasculardiseases that affects people for long-time living in plateau. Reducing the pulmonaryartery pressure is key to HAPH. At present, there are numerous strategies to treat HAPH,but few evidence base research was reported. This study aims to compare the efficacy andsafety of the current three kinds of main drug treatments for HAPH. Hopefully we canprovide some evidence to optimize the current domestic HAPH treatments.Methods:From June2011to October2011, sixty-nine young male patients living above analtitude of4500m over three months were diagnosed HAPH with Qinghai Standard andenrolled in this trial. These subjects were randomly divided into three groups with therandom number method, perindopril group (n=23), nifedipine group (n=23) and combinedgroup (n=23).Three groups were given oxygen therapy(2L/min1.5h/d), meanwhile,nifedipine group oral extended release nifedipine tablets（10mg，bid）, Perindopril grouporal Perindopril tablets（4mg, qd）, combination group oral aminophylline tablets（0.1g，tid）and compound danshen dripping pills（10pills，tid）,respectively. All subjects wereunderwent treatment for12weeks. In the baseline and the12th weeks of this trial, allpatients were inquired about medical history and subjected to physical examination. SPAPwas measured using transthoracic Doppler echocardiography and calculated using themodified Bernoulli equation. The6minutes walk test and percutaneous oxygen saturationwere measured, Borg dyspnea scores and WHO functional class were also assessed. Inaddition, routine blood test, liver function and kidney function were examined. During themedication, drug adverse effects were recorded. All continuous data was presented as mean±standard deviation. Data within each group was compared with paired t test. the data wascompared between three groups using One way ANOVA. WHO functional class wascompared using analysis of non-parametric Wilcoxon rank sum test.Results:1. In the baseline, there is no significant differences of SPAP, the6minute walkdistance, Borg dyspnea score, percutaneous oxygen saturation, heart rate, blood pressure, liver function and kidney function between the two groups (P>0.05).2. After12weeks treatment，compared with the baseline, SPAP of perindopril groupwas decreased from58.36±3.39mmHg to53.68±3.72mmHg (P<0.05), SPAP of nifedipinegroup compared with the baseline was decreased from58.71±3.05mmHg to52.76±3.70mmHg(P<0.05), SPAP of combination group did not change significantly (P>0.05), the6minute walk distance, Borg dyspnea scores and WHO functional class of three groupscompared with the baseline were significantly improved(P<0.05), Systolic bloodpressure(SBP) and diastolic blood pressure(DBP) of perindopril group and nifedipine groupcompared with the baseline were remarkably decreased(P<0.05). SBP and DBP ofcombination group did not change significantly (P>0.05), so as the percutaneous oxygensaturation, heart rate, liver function and kidney function of three groups compared with thebaseline (P>0.05),3. After12weeks treatment，SPAP of perindopril group and nifedipine group wassignificantly decreased compared with combination group, respectively (P<0.05). Nosignificant changes between SPAP in perindopril group and nifedipine group (P>0.05). The6minute walk distance, Borg dyspnea scores and WHO functional class of three groupswere not significantly ifferent (P>0.05). SBP and DBP of perindopril group andnifedipine group was markedly decreased respectively compared with combination group(P<0.05). SBP and DBP of perindopril group did not differ significantly from nifedipinegroup (P>0.05). Percutaneous oxygen saturation, heart rate, liver function and kidneyfunction of three groups did not change significantly (P>0.05).4. During the medication, nausea was observed in2case in the combination group, drycough was observed in1case in the perindopril group, side effects in the nifedipine groupwere flush in1case, edema in ankle joint in1cases. No severe side effects were observed.Conclusion:Three kinds of treatment programs of this study significantly improved the clinicalsymptoms, exercise capability and the WHO function class of subjects with HAPH.Perindopril and nifedipine effectively reduced SPAP. No significant pharmaceutical adverseeffects were observed. |
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