【摘要】 目的 探讨肺动脉高压患者药物靶向治疗的效果与耐受性。 方法 回顾分析2008年1月〖CD3/5〗2009年8月期间8例肺动脉高压患者分别接受波生坦及西地那非治疗的临床资料,评估其临床表现、WHO肺动脉高压功能分级、6 min步行距离及肺动脉收缩压在基线及治疗3个月后的变化。 结果 治疗后3个月,患者均能耐受药物治疗,无严重不良反应发生。WHO肺动脉高压功能分级在治疗前平均(31±04),治疗后为(23±09),明显得到改善(Plt;005)。肺动脉收缩压在治疗前平均(695±112 ) mm Hg(1 mm Hg=0133 kPa),治疗后为(483±124) mm Hg,明显降低(Plt;005)。6 min步行距离在治疗前平均(324±48) m,治疗后为(400±43) m,明显延长(Plt;005)。 结论 肺动脉高压患者药物靶向治疗的疗效显著,且耐受良好。【Abstract】 Objective To examine the effects of target medical therapy in patients with pulmonary arterial hypertension(PAH). Methods To determine the safety and efficacy of bosentan and sildenafil in eight patients with PAH.The patients’ clinical features, six minutes walking diastance, WHO functional class and systolic pulmonary arterial pressure (SPAP) were measured at baseline and at three months after initiating target medial treatment. Results At the three months followup assessments, WHO functional class was improved with 31±04 vs 23±09 (Plt;005); SPAP was significantly decreased with(695±112 ) mm Hg vs (483±124) mm Hg (Plt;005), the six minutes walking distance was significantly increased with(324±48) m vs(400±43) m (Plt;005). Target medical treatment was well tolerated. Conclusion Target medical treatment is well tolerated and has beneficial effects on PAH.
Objective To establish the reliable model of hepatocirrhosis with portal hypertension. Methods Carbon tetrachloride was subcutaneous injected after devascularization of the circumference of the left renal vein. The morphology of liver, the extrahepatic portal system and portcaval collateral circulation were observed. Results The liver of rats underwent degeneration and necrosis of hepatocytes, and the normal architecture of the liver lobules was replaced by pseudolobules, which consisted of regenerative hepatocytes and fibrous septa. After 5 weeks, the portal pressure was significantly higher than that of control (Ｐ＜0.05). The diameter of esophageal vein was significantly larger than that of control at 15th week (Ｐ＜0.05). Conclusion This technique is simple and reliable and can be applied for various experimental studies on portal hypertension.
42 Wistar rats were divided into three groups at random, liver cirrhosis (LC), portal vein stricture (PVS) and sham operation (SO) group. The changes of barrier capability of gastric mucosa in portal hypertensive rats were observed. The results demonstrated: the splanchnic blood flow of the portal hypertensive rats increased, as compared with the normal control group (Ｐ＜0.001), but actually gastric mucosa was under the condition of ischemia. Mucosa of gastric wall glycoprotein and PGE2 of gastric mucosa decreased, as compared with the normal control (Ｐ＜0.01); and more seriously decreased in cirrhotic portal hypertensive rats, there was no significant difference about amount of the basal acid secretion (BAS) among the three groups, but the amount of H＋ backdiffusion (H＋BD) was obviously increased, as compared with the normal control group (Ｐ＜0.001). The amount of H＋BD of cirrhotic portal hypertensive rats was the highest among this three groups. The results suggest that the barrier capability of gastric mucosa with portal hypertension is lower than that of the normal control group and much lower with cirrhotic portal hypertensive rats. The portal hypertensive gastropathy is associated with the lower capability of defense of gastric mucosa. The condition of liver function contributes to the change of barrier capability of gastric mucosa.
Objective To explore the methods， clinical effects， and application value of laparoscopic splenectomy combined with pericardial devascularization. Methods The clinical data of 23 patients with liver cirrhosis and portal hypertension who performed laparoscopic splenectomy combined with pericardial devascularization between july 2009 and july 2012 in our hospital were analyzed retrospectivly. Results In 23 cases， 2 cases were converted laparotomy due to bleeding， 21 cases were successfully performed laparoscopic splenectomy combined with pericardial devascularization. The operative time was 230-380 minutes （average 290 minutes）. The intraoperative blood loss was 300-1 500 mL （average 620 mL）. The postoperative fasting time was 1-3 days （average 2 days）. The postoperative hospital stay was 8-14 days （average 10 days）. Conclusion Laparoscopic splenectomy combined with pericardial devascularization is a feasible， effective， and safe procedure as well as minimally invasive hence is applicable for patients with portal hypertension and hypersplenism．
ObjectiveTo explore the hemodynamic effects of inhaled nitric oxide (iNO) on postoperative hemodynamic in patients with cyanotic congenital heart disease (CHD) combined with decreased pulmonary blood flow.MethodsFrom 2014 to 2018, there were 1 764 patients who received corrective repair of cyanotic CHD with decreased pulmonary blood flow in the Department of Pediatric Cardiac Surgery of Fuwai Hospital. We included 61 patients with the ratio of right ventricular systolic pressure to systolic blood pressure (SBP) ≥75% after weaning from cardiopulmonary bypass. There were 41 males and 20 females, with the age of 20.5 (9.0, 39.0) months and weight of 12.5±7.8 kg. The patients were divided into two groups: a conventional group (33 patients, conventional therapy only) and a combined therapy group (28 patients, iNO combined with conventional therapy). The hemodynamics during the first 24 hours after iNO therapy and the in-hospital outcomes of the two groups were investigated and compared.ResultsThere was no statistical difference between the two groups in demographic characteristics and surgical parameters (P>0.05). The hemodynamic effects of iNO within 24 hours included the decrease in the vasoactive inotropic score (VIS, 21.6±6.6 vs. 17.3±7.2, P=0.020) along with the increase in blood pressure (SBP: 73.7±9.7 mm Hg vs. 90.8±9.1 mm Hg, P<0.001) , the decrease in central venous pressure (10.0±3.1 mm Hg vs. 7.9±2.1 mm Hg, P=0.020), the decrease in lactate (2.2±1.7 mmol/L vs. 1.2±0.5 mmol/L, P<0.001) and increase in urine output [2.8±1.7 mL/(kg·h) vs. 4.9±2.2 mL/(kg·h), P<0.001]. The decrease of VIS at 24 h after the surgery in the conventional therapy group was not statistically significant (22.1±7.9 vs. 20.0±8.5, P=0.232). Besides, we discovered that the need for renal replacement therapy (RRT) was less in the combined therapy group than that in the conventional therapy group, especially in the moderate complicated surgery [risk adjustment in congenital heart surgery (RACHS-1) ≤3] subgroup (9.5% vs. 40.7%, P=0.016).ConclusionIn pediatric patients after corrective repair of cyanotic and pulmonary blood follow decreased CHD with increased pulmonary vascular resistance, iNO combined with conventional therapy can improve the hemodynamics effectively. Compared with the conventional therapy, the combined therapy with iNO can decrease the VIS and the need for RRT, which is beneficial to the postoperative recovery of patients.
Objective To evaluate the efficacy and safety of different doses of metoprolol in the treatment of primary hypertension.Methods We searched for randomized controlled trials of different doses of metoprolol in the treatment of primary hypertension. We screened relevant studies according to predefined inclusion and exclusion criteria, evaluated the quality of the included studies, and performed meta-analyses by using The Cochrane Collaboration’s Revman 4.2.8 software. Results Five randomized controlled trials of different doses of metoprolol in the treatment of primary hypertension were included. Two were of high quality and the other three were of low quality. No study reported mortality or the incidence of cardiovascular events, but four studies reported the means and standard deviations of systolic and diastolic blood pressures and heart rate. Based on the two self-control studies, meta-analyses of the levels of systolic and diastolic blood pressures before and after treatment of different doses of metoprolol showed that the combined OR for systolic blood pressure levels was -4.62 [95%CI (-7.77, -1.47), P=0.004]; and for the diastolic blood pressure levels, the combined OR was -5.71 [95%CI (-6.75, -4.68), Plt;0.000 01]. Four studies reported adverse reactions, and meta-analysis of the incidence of non-specific adverse reactions showed that the combined OR was 2.61 [95%CI (1.33, 5.13), P=0.005]. Conclusion A dose-effect relationship may exist between the dose of metoprolol and antihypertensive effect in the treatment of hypertension. When the antihypertensive effect of low-dose metoprolol was inadequate, an increase in the dose may lower blood pressure further. Although high-dose metoprolol has higher incidence of adverse reactions, it can be tolerated by most patients. Therefore, in the treatment of hypertension with metoprolol, an individualized dosing regimen can be applied according to the patient’s tolerance, and blood pressure may be controlled ideally by a gradual increase of the metoprolol dose to its maximum tolerated dose.
ObjectiveTo determine the ability of cardiopulmonary exercise testing (CPET) to distinguish chronic thromboembolic pulmonary hypertension (CTEPH) from chronic thromboembolic disease (CTED). MethodsFifty patients diagnosed with CTED and fifty-eight patients with CTEPH in the the First Affiliated Hospital of Guangzhou Medical University from April 2019 to February 2022 were retrospectively included. The basic characteristics including age, gender, body mass index, symptom duration, and N-terminal prohormone of brain natriuretic peptide (NTpro-BNP), parameters of arterial blood gas analysis, right heart catheterization, echocardiography, pulmonary function, and CPET were all compared between patients with CTED and those with CTEPH. ResultsPatients with CTEPH displayed longer symptom duration, increased NTpro-BNP, decreased arterial partial pressure of oxygen, larger right atrial and ventricular diameters, and impaired worse resting pulmonary diffusing function compared with those with CTED (P<0.05). However, there was no statistically significant difference in the resting pulmonary ventilation function between the two groups (P>0.05). Among the CPET parameters of the CTEPH group, peak exercise oxygen uptake per kilogram, oxygen uptake at anaerobic threshold, oxygen pulse, oxygen uptake efficiency slope and oxygen saturation were all decreased, while the minute ventilation-carbon dioxide production at anaerobic threshold (VE/VCO2@AT) and VE/VCO2 slope were increased (P<0.05). However, there was no statistically significant difference in heart rate reserve and breathing reserve (P>0.05). Furthermore, VE/VCO2@AT showed high accuracy for distinguishing CTEPH from CTED (sensitivity, 0.825; specificity, 0.860; and the area under the receiver operating characteristic curve 0.897). ConclusionsPatients with CTEPH showed more significant decreased exercise endurance, diffusion dysfunction, and hypoxemia during exercise and insufficient increase in cardiac output compared with CTED patients. Therefore, it is feasible to apply CPET as a new objective examination to distinguish CTED from CTEPH.
ObjectiveTo systematically review the risk factors in elderly patients with primary hypertension with morning blood pressure surge in China, so asto provide references for clinical treatment and prevention of complications. MethodsSuch databases as PubMed, EMbase, The Cochrane Library (Issue 11, 2013), CNKI, VIP and WanFang Data were electronically searched for the case-control studies about morning blood pressure surge (MBPS) among elderly patients with primary hypertension in China from January 2006 to June 2014 were collected. Literature was screened according to inclusion and exclusion criteria, data were extracted and the methodological quality of the included studies was assessed, and then meta-analysis was conducted using RevMan 5.2 software. ResultsA total of 16 studies involving 2 007 cases were finally included, of which 956 cases were detected with MBPS. The results of meta-analysis showed that significant differences were found in glucose levels (MD=0.42, 95%CI 0.04 to 0.81, P=0.03), urinary microalbumin levels (MD=23.85, 95%CI 6.64 to 41.07, P=0.007), incidences of cerebrovascular events (OR=1.96, 95%CI 1.25 to 3.08, P=0.004), carotid atherosclerosis (OR=5.13, 95%CI 1.70 to 15.45, P=0.004) and left ventricular hypertrophy (OR=2.49, 95%CI 1.70 to 3.64, P < 0.000 01), left ventricular mass (MD=12.89, 95%CI 3.94 to 21.84, P=0.005), and carotid artery intima-media thickness (MD=0.08, 95%CI 0.02 to 0.14, P=0.009); while no significant difference was found in gender (OR=1.12, 95%CI 0.84 to 1.49, P=0.44), total cholesterol levels (MD=0.01, 95%CI-0.11 to 0.12, P=0.92), and creatinine levels (MD=1.77, 95%CI-1.16 to 4.70, P=0.24) between patients with or without MBPS. ConclusionCurrent evidence shows that glucose levels, early kidney damage, emergent cerebrovascular events and the reconstruction of the artery and the left ventricle are risk factors of abnormal MBPS in China. However, the above conclusion needs to be verified by further conducting high quality prospective studies.
Objective To explore the pulmonary arterial pressure level in patients with predialysis chronic kidney disease ( CKD) and its relationship to cardiac structure and function. Methods 397 patients with predialysis CKD and 50 healthy subjects were enrolled. Cardiac structure was evaluated by Doppler echocardiography. Glomerular filtration rate ( GFR ) were assessed by radiant 99mTc-DTPA.Differences of PAP, BNP, LA, IVST, LVDd, LVDs, LVEF, LVMI and the correlation of PAP with cardiac structure and function were examined. Results The PAP level in the predialysis CKD patients was much higher than that in the healthy subjects [ ( 33. 13 ±9. 00) mm Hg vs. ( 29. 43 ±3. 71) mmHg, P lt;0. 01] .18. 9% of the CKD patients were complicated with pulmonary hypertension. PAP was higher in the CKD patients in stages 4-5 than those CKD patients in stages 1-3 [ ( 35. 90 ±9. 34) mmHg vs. ( 32. 08 ±8. 62)mmHg, P lt;0. 01) ] , so as to the prevalene of pulmonary hypertension ( 21. 60% vs. 13. 47% , P lt;0. 01) .Compared with the healthy, the level of lnBNP [ ( 3. 59 ±1. 63) pg/mL vs. ( 2. 88 ±1. 51) pg/mL, P lt;0. 01] , LA [ ( 40. 42 ±6. 77) mmvs. ( 36. 75 ±4. 94) mm, P lt; 0. 01) ] , LVPW [ ( 9. 55 ±1. 96) mm vs.( 8. 54 ±0. 88) mm, P lt; 0. 01) ] , IVST [ ( 9. 76 ±1. 75) mm vs. ( 8. 71 ±0. 90) mm, P lt; 0. 01) ] , LVMI[ ( 105. 61 ±36. 47) g/m2 vs. ( 87. 41 ±17. 08) g/m2 , P lt; 0. 01) ] were all much higher. There was a negative correlation between PAP and GFR( r = - 0. 461, P lt;0. 01) , and positive correlations between PAP and LA ( r=0. 491, P lt; 0. 01) , LVPW ( r =0. 298, P lt;0. 01) , IVST ( r = 0. 613, P lt;0. 01) , lnBNP ( r =0. 536, P lt;0. 01) , LVMI ( r = 0. 382, P lt;0. 01) . LVMI and lnBNP were both independent risk factors of PAP. The regression equation: y = 16. 447 + 0. 105x1 + 1. 724x2 ( F = 23. 482, P = 0. 000) , y: PAP( mm Hg) , x1 : LVMI( g/m2 ) , x2 : lnBNP( pg/mL) . Conclusions Pulmonary hypertension is a common morbidity of predialysis CKD patients, and deteriorates with degression of renal function. PAP is related to indexes of cardiac structure ( LVMI, LA, LVPW, IVST) and index of cardiac function ( lnBNP) . LnBNP and LVMI are independent risk factors of PAP.
Abstract： Objective To study the effect of different numbers of bone marrow mesenchymal stem cells（MSCs） transplanted into rats with pulmonary arterial hypertension （PAH）induced by monocrotaline（MCT）and their influence on the expression of endothelin-1（ET-1）. Methods Forty healthy male Wistar rats（weight，from 180 to 250 g） were divided into four groups by random number table（n=10）：group A：Wistar rats were intraperitoneally injected with MCT 60 mg/ kg， and then injected with 1×106 MSCs via the external jugular vein；group B：Wistar rats were intraperitoneally injected with MCT 60 mg/kg，and then injected with 5×105 MSCs via the external jugular vein；MCT group：Wistar rats were intraperitoneally injected with MCT 60 mg/kg， and then injected with equal amount of PBS via the external jugular vein； control group：Wistar rats were intraperitoneally injected with equal amount of saline and then injected with equal amount of PBS via the external jugular vein. Four weeks after MSCs transplantation，right ventricular systolic pressure（RVSP） and ventricular weight ratio of right ventricle/ （left ventricle＋ventricular septum）were measured. Histomorphology of lung tissue was observed. Genetic expression of ET-1 in lungs and serum peptide of ET-1 were also measured. Results Four weeks after MSCs transplantation，both RVSP and ventricular weight ratio decreased significantly in rats of group Acompared with those of MCT group（RVSP：35.8±4.2 mm Hg vs. 47.2±10.1 mm Hg，P＜ 0.01； ventricular weight ratio：0.357±0.032 vs. 0.452±0.056，P＜0.01）， but these two parameters didn’t decrease significantly in rats of group B（P＞ 0.05）. By histopathological staining， the percentage of medial wall thickness of the pulmonary arterioles was significantly less in rats of group A than that of MCT group（19.7%±3.0% vs. 26.8%±3.6%， P＜ 0.01）. There was no statistical difference in the percentage of medial wall thickness of the pulmonary arterioles between group B and MCT group. Reverse transcriptase-polymerase chain reaction （RTase-PCR）results showed that ET-1messenger ribonucleic acid（mRNA）expression was highest in MCT group and MSCs transplantation significantly decreasedits expression in group A， while its expression was similar between group B and MCT group. The expression ofET-1 in plasma was also significantly decreased in group A than that in MCT group. Conclusion Intravenous MSCs transplantation can significantly inhibit MCT-induced PAH，and reduce both ET-1 mRNA expression in lung and ET-1 peptide level in plasma. It’s a better choice to transplant 1×106 MSCs to inhibit PAH in rats.