Nuofu Zhang

Promising therapeutic effects of sodium tanshinone IIA sulfonate towards pulmonary arterial hypertension in patients

BACKGROUND Pulmonary hypertension (PH) is a lethal disease with no cure currently available. Sodium Tanshinone IIA sulfonate (STS) is a water-soluble derivative of tanshinone IIA isolated as the major active component from salvia miltiorrhiza, a kind of Chinese herbal medicine. We investigate the efficacy of STS towards treatment of PH patients. METHODS AND RESULTS Five hospitalized patients were randomly enrolled for this study. These patients were suffering from various types of serious PH without getting sufficient benefits from sildenafil treatment (20 mg tid) for at least three months. The efficacy of STS on PH was evaluated by measuring the pulmonary arterial systolic pressure (PASP), RV size by echocardiography, 6-minute walking distance (6MWD), Borg dyspnea score, and WHO functional class of PH. Patients aged from 17 to 46 (average 33±11) years old, pulmonary arterial systolic pressure (PASP) ranged from 60 to 140 mmHg, RV size ranged from 25 to 39 mm were included in study. At the endpoint of observation for 8 weeks of STS infusion, they obtained reduction of PASP in the range of 14-45 (average 28.6±12.5) mmHg, RV size in the range of 0-10 (average 4.2±1.6). All patients exhibited improved exercise capacity with an increase of 6MWD from 63 to 268 (average 138.4±40.7) meters, significantly reduced Borg dyspnea score from maximum 9 down to 1 or 0, and reduced WHO functional class of PH from III or IV down to II. CONCLUSIONS These results indicate that STS exhibits remarkable beneficiary effects on treating PH patients either alone or in concert with sildenafil.

Effectiveness of digital infrared thermal imaging in detecting lower extremity deep venous thrombosis

PURPOSE The authors aimed to determine the effectiveness of infrared thermal imaging (IRTI) as a novel, noninvasive technique in adjunctive diagnostic screening for lower limb deep venous thrombosis (DVT). METHODS The authors used an infrared thermal imaging sensor to examine the lower limbs of 64 DVT patients and 64 healthy volunteers. The DVT patients had been definitively diagnosed with either Doppler vascular compression ultrasonography or angiography. The mean area temperature (T_area) and mean linear temperature (T_line) in the region of interest were determined with infrared thermal imaging. Images were evaluated with qualitative pseudocolor analysis to verify specific color-temperature responses and with quantitative temperature analysis. Differences in T_area and T_line between the DVT limb and the nonaffected limb in each DVT patient and temperature differences (TDs) in T_area (TDarea) and T_line (TDline) between DVT patients and non-DVT volunteers were compared. RESULTS Qualitative pseudocolor analysis revealed visible asymmetry between the DVT side and non-DVT side in the presentation and distribution characteristics (PDCs) of infrared thermal images. The DVT limbs had areas of abnormally high temperature, indicating the presence of DVT. Of the 64 confirmed DVT patients, 62 (96.88%) were positive by IRTI detection. Among these 62 IRTI-positive cases, 53 (82.81%) showed PDCs that agreed with the DVT regions detected by Doppler vascular compression ultrasonography or angiography. In nine patients (14.06%), IRTI PDCs did not definitively agree with the DVT regions established with other testing methods, but still correctly indicated the DVT-affected limb. There was a highly significant difference between DVT and non-DVT sides in DVT patients (P < 0.01). The TDarea and TDline in non-DVT volunteers ranged from 0.19 ± 0.15 °C to 0.21 °C ± 0.17 °C; those in DVT patients ranged from 0.86 °C ± 0.71 °C to 1.03 °C ± 0.79 °C (P < 0.01). CONCLUSIONS Infrared thermal imaging can be effectively used in DVT detection and adjunctive diagnostic screening because of its specific infrared PDCs and TDs values.

Functional mutations in 5′UTR of the BMPR2 gene identified in Chinese families with pulmonary arterial hypertension

Pulmonary arterial hypertension (PAH) is a progressive pulmonary vasculopathy with significant morbidity and mortality. Bone morphogenetic protein receptor type 2 (BMPR2) has been well recognized as the principal gene responsible for heritable and sporadic PAH. Four unrelated Chinese patients with PAH and their family members, both symptomatic and asymptomatic, were genetically evaluated by sequencing all exons and the flanking regions of BMPR2. Functionality of the aberrant mutations at the 5′ untranslated region (UTR) of BMPR2 in the families with PAH was determined by site mutation, transient transfection, and promoter-reporter assays. Four individual mutations in the BMPR2 gene were identified in the 4 families, respectively: 10-GGC repeats, 13-GGC repeats, 4-AGC repeats in 5–UTR, and a novel missense mutation in exon 7 (c.961C>T; p.Arg321X). Moreover, we demonstrated that (1) these 5′UTR mutations decreased the transcription of BMPR2 and (2) the GGC repeats and AGC repeats in BMPR2 5′UTR bore functional binding sites of EGR-1 and MYF5, respectively. This is the first report demonstrating the presence of functional BMPR2 5′UTR mutations in familial patients with PAH and further indicating that EGR-1 and MYF5 are potential targets for correcting these genetic abnormalities for PAH therapy.

Visualization of Peripheral Pulmonary Artery Red Thrombi Utilizing Optical Coherence Tomography

Optical coherence tomography (OCT) is a new imaging technique capable of obtaining high-resolution intravascular images and has been used in interventional cardiology. However, an application of OCT in pulmonary arteries had seldom been documented. In this case, OCT imaging is performed in peripheral pulmonary arteries and shows mural red thrombi. Subsequently, the red thrombi are aspirated and confirmed by a histological examination. These findings suggest that OCT may be a useful tool to depict peripheral pulmonary artery thrombi.

Optical coherence tomography in imaging of peripheral pulmonary arteries

BACKGROUND To establish an optical coherence tomography (OCT)-based method for imaging peripheral pulmonary arteries. METHODS We recruited eight patients (five men; average age, 48±12 years; peripheral pulmonary artery thrombosis, three patients; idiopathic pulmonary hypertension, three patients; interstitial lung disease, two patients) who underwent OCT of the peripheral pulmonary arteries in the First Affiliated Hospital of Guangzhou Medical University and Guangzhou Institute of Respiratory Diseases, between September 2009 and September 2010. OCT was performed using both the conventional OCT imaging method (COI) and the improved pulmonary artery imaging method (IPI). In the IPI, contrast agent was used as an indicator of balloon inflation meanwhile increases in flushing speed of the replacement fluid. The percentage of optimal images, inflation pressure, flushing speeds and complications were compared between the two methods. RESULTS We performed OCT of 33 vessel segments by both methods. IPI produced more optimal images than COI (88% vs. 24%). Mean inflation pressure and flushing speed were higher during IPI than COI (0.62±0.15 vs. 0.43±0.08 atm; 1 atm =101.3 kPa; 0.82±0.10 vs. 0.42±0.06 mL/s; both P<0.01). Decreased blood oxygen saturation (SaO2) was associated with 9% and 30% segments (P<0.01) in the COI (mean decrease, 8.4%±3.6%) and IPI groups (mean decrease, 12.1%±5.3%; P<0.05) respectively. SaO2 recovered to pre-imaging levels after oxygen inhalation. CONCLUSIONS IPI is safe and effective for OCT of peripheral pulmonary arteries.

A 50‐year‐old woman with haemoptysis, cough and tachypnea: cholesterol pneumonia accompanying with pulmonary artery hypertension

Lipoid pneumonia is an uncommon disease caused by the presence of lipid in the alveoli. Here we described a case of a 50‐year‐old woman with haemoptysis, cough and tachypnea, who was diagnosed with cholesterol pneumonia accompanying with pulmonary artery hypertension. The extremely high pulmonary artery pressure achieved, in this case, is alarming and should alert the physicians that the cholesterol pneumonia may be one of the underlying causes of pulmonary artery hypertension. After a treatment of methylprednisolone, her clinical symptoms were significantly improved, which suggested that steroid might be a promising therapeutic for patients with cholesterol pneumonia.

Pulmonary Capillary Hemangiomatosis without Pulmonary Hypertension: An Early Stage of Disease?

A 14‐year‐old male visited the First Affiliated Hospital of Guangzhou Medical University with a complaint of a 2‐year history of progressive exertional dyspnea and fingertips cyanosis. Physical examination revealed remarkable desaturation measured by pulse oximetry (80% at rest) and marked cyanosis of lips. The high‐resolution computed tomography scanning revealed no significant abnormality in the lung field [Figure 1a and 1b]. Computed tomography of pulmonary angiography showed no filling defect in trunk or branches of pulmonary arteries, no dilated central pulmonary arteries, and no cardiomegaly [Figure 1c and 1d]. Cardiac catheterization showed a mean right atrial pressure of 6 mmHg, pulmonary artery pressure with mean of 12 mmHg, pulmonary capillary wedge pressure of 9 mmHg, cardiac output of 6.2 L/min, and cardiac index of 4.10 L·min−1·m−2. Pulmonary vascular resistance was slightly elevated at 4.52 wood units. Lung biopsy revealed that lower lobe alveolar spaces were filled with red blood cells or hemosiderin cells, and alveolar septum was wider than normal. Hematoxylin and eosin staining shows that capillary proliferations within alveolar and bronchiolar walls were visible throughout most areas [Figure 2a‐2c]. Immunostaining of lung section was strongly positive for CD34 [Figure 2d], CD31 [Figure 2e], and F8 [Figure 2f]. The clinical manifestations, pathological findings, and immunohistochemistry supported definitive diagnosis of pulmonary capillary hemangiomatosis (PCH) with normal pulmonary artery blood pressure and normal radiological appearance. Because of financial difficulties, the patient abandoned heart–lung transplantation and left hospital without therapeutic intervention. Follow‐up to nearly a years, the patient was stable with no prominent hypoxia on 2 L/min supplemental nasal cannula oxygen at home. Written informed consent was obtained from the parents of patient for publication of this case report and any accompanying images. All patients with PCH usually have elevated pulmonary arterial pressures measured by right heart catheterization with normal or low pulmonary capillary wedge pressure and this have been demonstrated.[1] The infiltration of pulmonary vessel and intrapulmonary shunting caused by uncontrolled proliferation of the pulmonary capillaries might be responsible for the pulmonary hypertension and Pulmonary Capillary Hemangiomatosis without Pulmonary Hypertension: An Early Stage of Disease?

Clinical characteristics and risk factors of pulmonary hypertension associated with chronic respiratory diseases: a retrospective study

BACKGROUND Chronic respiratory disease-associated pulmonary hypertension (PH) is an important subtype of PH, which lacks clinical epidemiological data in China. METHODS Six hundred and ninety three patients hospitalized from 2010 to 2013 were classified by echocardiography according to pulmonary arterial systolic pressure (PASP): mild (36≤ PASP <50 mmHg); moderate (50≤ PASP <70 mmHg) and severe (PASP ≥70 mmHg). RESULTS Dyspnea (93.51%) was the most common symptom. Hemoptysis observed in the severe group (6.42%) was significantly higher than the other two groups (P<0.05). COPD (78.35%), lung bullae (44.16%), tuberculosis (including obsolete pulmonary tuberculosis) (38.82%), and bronchiectasis (30.45%) were frequently present. Mild group occupied the highest proportion (84.7%) in COPD, while severe group occupied the highest proportion (19.3%) in pulmonary embolism (P<0.01). Age, partial pressure of oxygen (PaO2), hematocrit (HCT), partial pressure of carbon dioxide (PaCO2), increase of N-terminal pro brain natriuretic peptide (NT-proBNP) and right ventricular (RV) diameter (>20 mm) were associated with moderate-to-severe PH, while RV [odds ratio (OR) =3.53, 95% CI, 2.17-5.74], NT-proBNP (OR=2.44, 95% CI, 1.51-3.95), HCT (OR=1.03, 95% CI, 1.00-1.07) and PaCO2 (OR=1.01, 95% CI, 1.00-1.03) were independent risk factors. CONCLUSIONS PH related to respiratory diseases is mostly mild to moderate, and the severity is associated with the category of respiratory disease. Increased HCT can be an independent risk factor for PH related to chronic respiratory diseases.

Comparison of rivaroxaban mono-therapy and standard-therapy adjusted by CYP2C9 and VKORC1 genotypes in symptomatic pulmonary embolism

RATIONALE Pulmonary embolism (PE) is a life-threatening manifestation of venous thromboembolism. Rivaroxaban is an oral anticoagulant, which directly inhibits Factor Xa. The objective of the current study was, in comparison to the standard-therapy method, to investigate the potential of rivaroxaban to improve the treatment of patients with PE, and to reduce hemorrhage in the standard-therapy group through adjusting the dose of warfarin by CYP2C9 and VKORC1 genotypes. METHODS Sixty-two PE patients with or without deep venous thrombosis (DVT) was randomized to rivaroxaban mono-therapy or standard-therapy with enoxaparin followed by vitamin K antagonist (VKA). Concentration of the anticoagulants was adjusted according to the results of CYP2C9 and VKORC1 genotypes in order to stabilize the international normalized rate (INR) at 2.0-3.0 range. Length of hospital stay at initial hospitalization was compared, therapeutic efficacy was examined by computed tomographic pulmonary angiography (CTPA) and ventilation/perfusion (V/Q) scan, and side-effect of anti-coagulants was monitored at 1-month, and 3- or 6-months follow-up check points. RESULTS We found that, overall, patients who received rivaroxaban mono-therapy had a significantly shorter length of hospital stay compared with patients who received standard-therapy of enoxaparin followed by VKA (9.29±3.70 versus 11.38±3.12days, P=0.021). The therapeutic efficacy was of no marked difference between these two groups. However, after one month treatment, 50% (16/32) of the standard-therapy group had mild hemorrhage, which was significantly higher than that of rivaroxaban mono-therapy group (16.7%, 5/30, P=0.006). Moreover, a significantly higher rate in the standard-therapy group (22.2% versus 3.4%, P=0.032) was found after 3 or 6months therapy. Major bleeding was slightly but not significantly higher in the standard-therapy group than that in the rivaroxaban therapy group. In addition, 2 (6.3%) patients died from Life-threatening bleeding in the standard-therapy group. CONCLUSION Findings of the current study suggested that rivaroxaban mono-therapy result in shorter hospital stay compared to the standard-therapy. Implication of CYP2C9 and VKORC1 genotypes in determining dose of warfarin, however, remains to be further examined in larger cohort studies.