The Study On The Effect Of Sildenafil In Pulmonary Hypertension Therapy

Objective:Pulmonary arterial hypertension is a progressive disease characterized by progressive pulmonary vascular resistance increased,eventually leading to right heart failure and death.Right heart failure is a common means of death and disability in patients with all types of pulmonary arterial hypertension,and pulmonary arterial hypertension is also the main reason for right heart failure.The complexity cause and difficult treatment are the main reason for long-term development in the field. Therefore the treatment of pulmonary arterial hypertension is a major challenge. Traditional vasodilator in the treatment of pulmonary arterial hypertension has the different efficacy.However,because of the efficacy,side effects and other reasons, these drugs are not ideal.Now people are trying hard to finding one drug which can selectively dilate pulmonary vessel and have slighter side,effect.It has been approved that vascular endothelial cells can produce and release vasoactive substances "endothelium-derived relaxing factor",that is Nitric oxide(NO),which can diastolic vascular smooth muscle by increasing the cell inner cyclic guanosine monophosphate (cGMP).And 5 phosphodiesterase(PDE5) can degradate cGMP in lung tissue. phosphodiesterase inhibitor inhibit phosphodiesterase,increase the endogenous NO and thus to reduce pulmonary hypertension.Sildenafil is a selective inhibitor of phosphodiesterase-5,which has been widely used to treat male sexual dysfunction in the past.In recent years,studies have reported that it can be used in the treatment of pulmonary hypertension.Sildenafil selectively inhibit phosphodiesterase 5(cGMP monophosphoryl of metabolizing enzymes),thereby enhance the cyclic guanosine monophosphate mediated relaxation of vascular smooth muscle and inhibit the growth of smooth muscle cells,including pulmonary vascular smooth muscle cells,resulting in a decline in pulmonary arterial pressure.In animal studies,sildenafil have been widely confirmed in the treatment of pulmonary hypertension in recent years.There are many clinical reports about the application of sildenafil in the treatment of pulmonary hypertension in foreign country.However,there are few researches about it used in domestic clinic.So this study is to explore the therapeutic effects and mechanism of sildenafil on idiopathic pulmonary hypertension and pulmonary hypertension in congenital heart disease.Method:Randomly select 12 cases from the patients hospitalized in our infirmary from June 2007 to February 2009,all of them were diagnosed of congenital heart disease with pulmonary hypertension or idiopathic pulmonary hypertension through Color Doppler and right heart cardiac catheterization.In these patients,there were 9 females and 3 males,mean age 42.10 pulmonary hypertension in congenital heart disease,2 idiopathic pulmonary hypertension.All these patients oral sildenafil 3 months.Before and after medication,we collect the baseline data(blood,blood biochemistry,electrocardiogram,chest X-ray);6 minutes walk test and Borg dyspnea rating;Determination of pulmonary artery systolic pressure,average pressure and ventricular end-diastolic pressure,right atrium mean pressure,right ventricular systolic pressure and ventricular end-diastolic pressure,pulmonary capillary wedge pressure which used right heart catheterization;Sub-blood oxygen saturation measurements(superior vena cava,inferior vena cava,pulmonary artery,right atrium, right ventricle) to calculate the pulmonary vascular resistance,cardiac output,cardiac index;through the detection of arterial blood gas analysis of PaO₂,PaCO₂,SaO₂ and PH value.According to the changes of the exercise tolerance in patients, emodynamics and arterial blood gas,we analyzed the therapeutic effects of sildenafil and its mechanism in idiopathic pulmonary hypertension and pulmonary hypertension in congenital heart disease.Results:10/12 patients have complete data acquisition,one Case withdrawal because of short-term visual impairment and one patient for drug costs,others are successfully completed.Sildenafil can increase the 6-minute walking distance(from 299±45.26m to 346±46.17m,P=0.004,an average of 47m) and reduce Borg score(Z=-0.33,P＜0.05).At the same time,cardiac output and cardiac index increase significantly, cardiac output(from 4.11±0.48L/min to 4.50±0.64L/min,P=0.048),cardiac index (from 2.31±0.33 L/min/m² to 2.67±0.67 L/min/m²,P=0.047),whole lung resistance decrease(from 922.60±104.43dyn.s.cm^-5 to 892.20±103.58 dyn.s.cm^-5,P = 0.014).The pulmonary artery systolic pressure-and mean pressure have been a downward trend,but have not reach statistical significance,pulmonary artery systolic pressure(from 96.9±6.19mmHg to 92.2±6.64mmHg,P=0.075),mean pressure(from 67.7±8.69mmHg to 65.1±9.39mmHg,P=0.059),right atrium mean pressure(from 7.60±1.71mmHg to 7.10±1.52mmHg,P=0.177).There are no significant changes in blood pressure and heart rate:heart rate(from 78.21±9.59/min to 78.95±9.97/min,P = 0.163);systolic blood pressure(from 118.10±11.4mmHg to 116.50±7.76mmHg,P = 0.368);diastolic pressure(from 78.70±8.29mmHg to 78.60±7.75mmHg,P=0.94). Partial pressure of oxygen and oxygen saturation in arterial blood gas analysis increased,reaching statistical significance(Partial pressure of oxygen:from 68.40±5.64mmHg to 72.00±7.72mmHg,P=0.047,oxygen saturation from 85.70±3.92%to 89.20±4.05%,P=0.014);Arterial blood carbon dioxide and PH value has no significant changes.Objective examination including electrocardiogram,chest X-ray,liver and kidney reactive have no significant changes.In this study,there are no serious adverse reactions.Conelusion:According to the result of our clinical study,we can draw the following conclusions:1.We use the right heart catheterization for the determination of pulmonary artery pressure,and measure 6-minute walking accurately,this method is simple and reliable.2.Through the 6 minutes walking distance test and WHO functional classification of pulmonary hypertension before and after oral sildenafil,we find that sildenafil can improve the quality of life and improve exercise capacity in patients with pulmonary hypertension. 3.Although the decline of pulmonary arterial pressure in patients did not reach statistical significance,there has the lower trend.Oral sildenafil improve heart function,while show few influence on systemic circulation pressure.There are no phenomenon of instable hemodynamics about low cardiac output,low blood pressure and so on.4.Oral sildenafil can improve pulmonary arterial oxygenation by expand pulmonary arterial and increase organizational oxygen,escalate arterial oxygen content,while has no influence on balance of acid and base in body fluid.5.Sildenafil plays an important role in treatment Of pulmonary hypertension for high selectivity of pulmonary circulation,the application of convenience and less side-effect.