Effect of inhaled nitric oxide on the gas exchange and hemodynamic of ischemia-reperfusion lung in rabbit model

AIM:To evaluate the effect of pulmonary gas exchang and hemodynamic by inhaled nitric oxide on ischemia-reperfusion(I/R) lung in rabbit model.METHODS:Forty Newzealand rabbits were divided into four groups: group Ⅰ, sham-operated; group Ⅱ, sham-operated with inhaled nitric oxide (NO); group Ⅲ, I/R; group Ⅳ, I/R with Inhaled NO. Pulmonary artery pressure (PA), pulmonary vascular resistance(PVR), arterial oxygen tension(PaO₂), arterial carbon dioxide tension (PaCO₂), alveolar-arterial gradient (A-aDO₂), Shunt fraction (Qs/Qt) expression of CD₁₈, peripheral leukocyte, methemoglobin were continuetly quantitated. RESULTS:At the start of reperfusion inhaled NO significantly improved PaO₂ and decreased PA, PVR,PaCO₂,A-aDO₂,Qs/Qt.CONCLUSION:Inhaled NO ameliorated significantly the early gas exchange and hemodynamic of reperfusion lung.     

Effects of aminoguanidine on endotoxin-induced acute lung injury in rabbits

AIM: To observe the effect of aminoguanidine (AG) on hemodynamics and lung capillary permeability in acute lung injury (ALI) in rabbits. METHODS:24 rabbits were equally divided into four groups: saline group, endotoxin group, AG group and AG plus endotoxin group. In AG plus endotoxin group, endotoxin was injected to animals to make an ALI model, 25mg/kg AG was injected following that and let this sustain 3 hours. Meanwhile, mean arterial pressure (MAP), mean pulmonary arterial pressures (MPAP) and blood gas analyses were observed during this period. At the end of the experiment, broncho-alveolus lavage was performed, pathologic samples were treated routinely and lung wet weight/dry weight ratio was calculated. RESULTS:After endotoxin injection, MAP and arterial oxygen pressure (PaO₂) decreased, and MPAP increased significantly. The injection of AG had little effect on MAP, but AG could markedly decrease MPAP and increase PaO₂. Cell count in broncho-alveolus lavage fluid (BALF) was less in AG plus endotoxin group than in endotoxin group. Although AG did not affect total protein in BALF, low molecular weight proteins decreased in AG plus endotoxin group by the assay of electrophoresis. Tissue wet weight/dry weight ratio also decreased in this group. Pathologic study showed that there were fewer inflammatory cells and less lung edema in AG plus endotoxin group. CONCLUSION:AG could improve hemodynamics status and attenuate acute lung injury induced by endotoxin in rabbits.     

会讯

AIM:To investigate the pulmonary expresson of macrophage migration inhibitory factor(MIF) in acute lung injury (ALI) rats induced by intravenous injection of oleic acid and its correlation with blood gas change, pulmonary weight index (PWI) and pulmonary pathological injuries.METHODS: ALI rats model were made by injecting oleic acid as the oleic acid group while rats injection with saline solution as control. After injecting oleic acid or saline for six hours, the PaO₂ and PaCO₂ of the left heart and pulmonary weight index were measured. At the same time, by using a microwave-base double immunohistochemistry labeling, the number of MIF^＋, ED₁⁺ (anti-CD68 antibody), ED₁⁺/MIF^＋cell in pulmonary tissue of different groups and their correlation with blood gas and pulmonary weight index were examined. RESULTS: The blood gas parameters of the oleic acid group were far worse than that of the control group (P＜0.01). The PWI of the oleic acid group was significantly higher than that of the control group (P＜0.01). There was marked upregulation of MIF expression on injured lung tissue. The number of cell expressed MIF^＋ , ED₁⁺ and MIF with ED₁ showed a strong positive correlation with PaO₂, PWI and histological changes. CONCLUSION: MIF may play a pivotal role in mediation of progressive lung injuries induced by intravenous oleic acid injection. In addition, the number of cells expressed MIF, especially macrophage, may reflect the severity of lung injury.     

Effect of the combination of positive end expiratory pressure and nitric oxide inhalation on oleic acid-induced acute lung injury in canine

AIM:To observe the effects of the combination of positive end expiratory pressure (PEEP) and 80×10^-6 nitric oxide (NO) inhalation on oleic acid induced acute lung injury (ALI) in canine.METHEDS:30 dogs were divided into 6 groups. Oleic acid was injected through Swan-Ganz catheter to induced ALI. Pulmonary and systemic hemodynamics,blood gas were measured in dogs before and after injection of oleic acid and the period of inhaled NO for 1-6 h. The methemoglobin(MHb) concentrations were measured. Histology and ultrastructure of the lung tissue were observed. RESULTS:(1) The combination of PEEP and 80×10^-6 NO inhalation rapidly reduced mean pulmonary arterial pressure (MPAP) and pulmonary vascular resistance (PVR), increased PaO₂/FiO₂, reduced A-aDO₂ without inducing significant change on systemic hemodynamics. Arterial blood levels of MHb did not change significantly. (2)The combination group was showed the lightest ALI change by HE stain and electron microscopy. CONCLUSION:The combination of PEEP and inhalation of 80×10^-6 NO significantly and rapidly increased PaO₂/FiO₂ without producing lung injury induced by high FiO₂ and high PEEP.     

Establishment of chronic obstructive pulmonary disease rat models by passive cigarette smoking and intratracheal instillation of lipopolysaccharide

AIM:To establish rat chronic obstructive pulmonary disease(COPD) models by passive cigarette smoking plus intratracheal instillation of lipopolysacchride(LPS) or passive cigarette smoking only, which would be similar to the pathogenesis of human COPD. METHODS:48 Wistar rats were randomly divided into 4 groups.(1) Healthy control I group(n=12), rats were bred 4 weeks;healthy control II group(n=12), rats were bred for 3months. (2) Model group I (n=12), 200μg lipopolysaccharide(LPS) was instilled intratracheally once for every two weeks and the rats were exposured to 5% of cigarette smoke, 0.5 h/d for 4 weeks.(3) Model group II(n=12),rats were exposed to 5% of cigarette smoke, 0.5 h/d for 3 months. The pathologic changes of airways and lung tissues, pulmonary function and blood gas analysis were determined. The airway wall lymphocytes and alveolar macrophages were counted. The cross areas of epithelial layer, smooth muscle layer and lamina propria of bronchi were measured. The hydroxyproline of lung tissue homogenates was determined by biochemistry method.RESULTS:The pathologic changes of airways and lung tissue of two models were similar to but milder than those of COPD patients(biopsy data). The collagen deposition and the cross areas of epithelial layer and smooth muscle layer in airway walls of two model groups were significantly increased than those of control groups(P＜0.01,P＜0.05).FEV_0.3/FVC% of two model groups, PaO₂ and SaO₂ of model I group were significantly decreased, while R_i and R_e in model I group were significantly increased than that of control I group(P＜0.05). The PaCO₂ and the counts of lymphocytes and alveolar macrophages of both model groups were significantly increased than those of the control groups (P＜0.01). Lots of alveolar macrophages had phagocyted smoke granules. The amounts of hydroxyproline of two model groups were significantly increased than those of control group((P＜0.05) and were negatively related to the FEV_0.3/FVC%, respectively (P＜0.01,P＜0.01) and positively related to airway resistance of model I group(P＜0.01). CONCLUSIONS:COPD rat models were successfully established by passive cigarette smoking plus intratracheal instillation of LPS and cigarette smoking only. The pathologic changes were similar but milder than those of COPD patients. The airway obstruction of model I group was more severe than that of model II group, but they have no significant difference.     

Effects of different ventilation strategies on gas exchange and extravascular lung water during early stage of acute lung injury in a canine model

AIM: To evaluate the effects of different ventilation strategies on gas exchange and extravascular lung water during early stage of acute lung injury (ALI). METHODS: Upon the establishment of oleic acid-induced ALI (diagnostic standard: PaO₂/FiO₂ ≤ 300 mmHg), 24 adult mongrel dogs were randomly divided into 3 groups (n=8 each) according to different ventilation strategies: controlling high-concentration oxygen therapy (O₂) group, continuous positive airway pressure (CPAP) group and bi-level positive airway pressure (BiPAP) group. The parameters of gas exchange and hemodynamics including the values of normal baseline, at ALI early stage (positive control) and from 1 to 4 h after treatment were recorded continuously. RESULTS: Compared with the value at the beginning of ALI, after 4 h of artificial ventilation, the improvement in oxygenation index (PaO₂/FiO₂) in BiPAP group (375.83±81.55, P<0.01) and CPAP group (327.17±78.82, P<0.01) were better than that in O₂ group (255.00±49.85, P>0.05). The ratio of alveolar dead space to tidal volume [V_D(alv)/V_T]in O₂ group further increased (P<0.01), while it obviously declined in CPAP group and BiPAP group (P<0.01). Oxygen delivery (DO₂) in BiPAP group (P<0.01) was much higher than that in CPAP group and O₂ group, while oxygen consumption (VO₂) and oxygen extraction rate (O₂ER) in O₂ group were evidently higher than those in CPAP group and BiPAP group (P<0.05, P<0.01). After treatment, the alveolar-arterial oxygen differences [P_(A-a)O₂] of the 3 ventilation groups were significantly higher than the normal baseline values and the values at early ALI stage (P<0.01). BiPAP and CPAP greatly reduced the ratio of shunted blood to total perfusion (Qs/Qt) as compared with O₂ group (P<0.01). Some parameters including pulmonary arterial wedge pressure (PAWP) and index of cardiac output (CI) kept stable, while mean pulmonary arterial pressure (MPAP) and pulmonary vascular resistance index (PVRI) further increased in CPAP group and BiPAP group (P<0.05,P<0.01). Three ventilation strategies did not effectively control the increase in extravascular lung water index (ELWI). CONCLUSION: During early stage of ALI, BiPAP and CPAP make active effects on improving gas exchange and tissue oxygenation. BiPAP displays more significant therapeutic effect than CPAP and oxygen therapy. The 3 ventilation strategies have no obvious effects on reducing extravascular lung water.     

Effects of non-ventilated lung with nitrous oxide on intrapulmonary oxygenation and lactic acid level in arterial blood during one lung anesthesia

AIM: To investigate the effects of non-ventilated lung with N₂O on systemic oxygenation and lactic acid level in arterial blood during one lung anesthesia. METHODS: Twenty-two patients, ASA Ⅰ-Ⅲ, scheduled for selective pulmonary surgery, were randomly divided into two groups: control group (group A, n=11) and observation group (group B, n=11). Group A: the non-ventilated lung was kept open to the air; group B: N₂O 2 cmH₂O through CPAP system was insufflated into the non-ventilated lung during one lung ventilation. The anesthesia was induced with intravenous midazolam (0.05 mg·kg^-1), propofol (0.5-1.0 mg·kg^-1), fentanyl (4 μg·kg^-1), and vecuronium (0.1 mg·kg^-1) and was maintained with inhaling isoflurane. Blood gas analysis and lactic acid was recorded 20 min after two-lung ventilation (TLV) in the supine position, 20 min after one-lung ventilation (OLV) in the supine position, 20 min and 40 min after OLV in the lateral position and at the end of operation and the shunt fraction was calculated. RESULTS: PaO₂ in group B was significantly higher than that in group A (P＜0.05). Qs/Qt in group B was significantly lower than that in group A (P＜0.05), and lactic acid level in group B was significantly lower than that in group A during OLV. CONCLUSION: Non-ventilated lung with N₂O (2 cmH₂O) improves systemic oxygenation, reduces intrapulmonary shunt and prevents hypoxemia during OLV.     

Protective effects of hypercapnia on acute lung injury and it's mechanisms

AIM: To investigate whether hypercapnia is protective against acute lung injury (ALI) in a rabbit model, and study it's potential mechanisms. METHODS: Twenty-two healthy New Zealand white rabbits were involved in this study, and randomly allocated to control group (group C), normocapnic group (group N) and hypercapnic group (group H). Oleic acid (0.1 mL/kg) was injected intravenously to establish ALI model. Lung mechanics, hemodynamics, blood-gas analysis, the content of malondialdehyde (MDA) and superoxide dismutase (SOD) activity in lung tissue were measured. Apoptosis was analyzed after 3h mechanical ventilation. RESULTS: (1) Peak airway pressure in group H was significantly lower than that in group N (P<0.05) and the dynamic lung compliance was significantly higher than that in group N (P<0.05). (2) PaO₂ in group H was significantly higher than that in group N(P<0.05). (3) The content of MDA was significantly lower but the activity of SOD was significantly higher in group H than that in group N (P<0.05). (4) Apoptosis index in group H was significantly lower than that in group N (P<0.01). (5) Histologic damage was significantly severer in group N than group H. (6) PaCO₂ was correlated with pH, PaO₂, dynamic lung compliance, peak airway pressure and pulmonary permeability index (r=－0.928, P<0.01; r=0.511, 0.526, -0.506, -0.556, P<0.05, respectively). CONCLUSION: Hypercapnia protects lung from oleic acid-induced injury in rabbits. The mechanisms of protection might be associated with improvement of oxidation/anti-oxidation imbalance and inhibition of apoptosis.     

Effects of different β-adrenergic receptors on cardiac systolic and diastolic functions in hypoxic stress rats

AIM:To explore the effects of different β-adrenergic receptors (β-AR) on the left and right ventricular systolic and diastolic functions in rats under acute hypoxic stress. METHODS:The healthy male SD rats were randomly divided into 4 groups (n=7):control group, non-selected β-AR blocker propranolol group, selected β₁-AR blocker atenolol group and selected β₂-AR blocker ICI 118,551 group, and then the rats were exposed to normoxia (20.9% O₂, 79.1% N₂) and hypoxia (15.0% O₂, 85.0% N₂) condition respectively at the altitude of 2 260 m (Xining, China). The heart rate (HR), the left ventricular systolic pressure (LVSP), the right ventricular systolic pressure (RVSP), and the maximum raise/decline rate of left and right ventricular pressure (±dp/dt_max) were monitored, and the arterial blood gas in normoxia and hypoxia condition were compared to explore the effect of β-AR on the left and right ventricular systolic and diastolic functions in acute hypoxic stress rats. RESULTS:Under normoxia condition, the LVSP, ±dp/dt_max of left ventricular were decreased in propranolol group, atenolol group and ICI 118,551 group, the RVSP and ±dp/dt_max of right ventricle were decreased in propranolol group and atenolol group (P<0.05). Under hypoxia condition, the PaO₂, LVSP, ±dp/dt_max of left ventricle were decreased in all groups compared with the normoxia group, and the ±dp/dt_max of right ventricle was increased in all groups (P<0.05), also the degree of index change in control group was more obvious than that in propranolol group and atenolol group. CONCLUSION:The activation of β₁-AR is an important compensatory regulation for heart function during hypoxic stress. However, the compensatory enhancement of right heart function under acute hypoxia condition which through tonogenic dilation is more significant for maintaining the normal circulating blood flow.     

Effects of recruitment maneuvers on oxygen metabolism and hemodynamics in canine models of extrapulmonary and pulmonary ARDS

AIM: To determine the effects of recruitment maneuver(RM) strategy on oxygen metabolism and hemodynamics in canine models of extrapulmonary acut respiratory distress syndrome(ARDSexp) and pulmonary acute respiratory distress syndrome(ARDSp). METHODS: Twelve healthy canines were randomly divided into ARDSexp group and ARDSp group with 6 dogs each. To induce lung injury, the ARDSexp dogs were injected with oleic acid through femoral vein, and hydrochloric acid were administered by lung lavage to the ARDSp dogs. Pressure control ventilation (PCV) with lung protective ventilation strategy (LPVS) was employed to RM. P_high was set to upper inflection point (UIP), and P_low was set to lower inflection point (LIP)+2 cmH₂O.The duration of RM was 60 s and followed by baseline ventilatory settings. The indexes of oxygen metabolism and hemodynamics were measured before and after RM. RESULTS: After RM, arterial partial pressure of oxygen (PaO₂), venous partial pressure of oxygen (PvO₂), mixed venous oxygen saturation (SvO₂) and oxygen delivery (DO₂) obviously increased, and oxygen extraction ratio (ERO₂) gradually decreased in both groups. PaO₂, PvO₂, SvO₂ and DO₂ in ARDSexp group were significantly higher than those in ARDSp group, and ERO₂ in ARDSexp group were significantly lower than that in ARDSp group. Although mean pulmonary arterial pressure (MPAP), central venous pressure (CVP) and pulmonary artery wedge pressure (PAWP) significantly increased and mean arterial pressure (MAP) and cardiac index (CI) obviously decreased in both groups during RM, they reversed rapidly after RM. During RM, MPAP, CVP and PAWP were significantly higher, and MAP and CI were significantly lower in ARDSp group than those in ARDSexp group. CONCLUSION: RM increases oxygen delivery and improves tissue anoxia, and the better effects are obtained in ARDSexp dogs than those in ARDSp dogs. The effects of RM on hemodynamics are temporary and the ill effects are worse in ARDSp dogs than those in ARDSexp dogs.     

Acute pulmonary injury caused by echinococcus granulosus cyst fluid

AIM:to establish an animals model of pulmonary embolism caused by echinococcus granulosus (E.g)cyst fluid.METHODS:Cyst fluid were isolated from sheep liver . Twenty-one rabbits were randomized into 3 groups: group Ⅰ(saline group), group Ⅱ(clear cyst fluid group), group Ⅲ (sand-contained cyst fluid group). Operation was performed on each animal to place a femoral artery catheter and a femoral vein catheter. Saline, clear cyst fluid or sand-contained cyst fluid were given to rabbits at a dose of 3 mL/kg body weigh . Observations were then made at 10, 30, 60 minutes to determine the changes of MAP, blood gas and vaso-active substance. Then ECT scanning image was obtained .After observation, all animals were killed and the lungs were harvested for histological examination by light microscopy.RESULTS:Remarkable decline of PaO₂, MAP and rise of TXB₂, 6-keto-PGF_1α were observed in group Ⅲ and group Ⅱ(P＜0.05). ECT examination showed radioactivity defect in group Ⅲ and radioactivity weakening of the lung in group Ⅱ. Histological examination of the lungs showed that sand-contained cyst fluid may cause an "ARDS-like" change.CONCLUSION:Animals in group Ⅲ basically simulated the clinical situation of pulmonary embolism caused by E.g cyst content. The sand contained in the fluid played an important role in damaging the lung. Vaso-active substance had relevance to the lung injury.     

Effects of partial liquid ventilation on acute lung injury in piglets

AIM: To observe the effect of partial liquid ventilation with perfluorocarbon on gas exchange, hemodynamics and lung histological change in the piglets with surfactant depletion-induced acute lung injury. METHODS: 12 piglets were treated by lung lavage to a partial pressure of oxygen in arterial blood (PaO₂) below 100 mmHg for one hour and randomly divided into gas ventilation group (control group) and partial liquid ventilation (PLV) group, in PLV group, piglets received PFC (FC3280) intratracheally at doses of 15 mL/kg. The parameters of gas exchange and hemodynamics were measured before lung lavage, after lung lavage when the acute lung injury (ALI) was established, and 1 hour, 2 hours after ALI. Animals underwent euthanasia at the end of the study, lung histologic analysis followed. RESULTS: Surfactant depletion by lung lavage induced a stable acute lung injury.Gas exchange increased markedly in the animals that underwent PLV, less hemodynamic damage was observed in PLV group compared with the animals in GV group. Lung histologic analysis demonstrated a less lung damage, including atelectasis, neutrophil excudation, intra-alveolar hemorrhage and interstitial edema in PLV group compared with control group. CONCLUSION: In piglets with surfactant depletion-induced acute lung injury, partial liquid ventilation with perfluorocarbon can improve the gas exchange with less adverse hemodynamic effect and less lung injury compared with conventional gas ventilation.     

Effects of ambroxol combined with low-dose heparin on production of ICAM-1 and E,P-selectin in acute lung injury

AIM: To study the production of intercellular adhesion molecule-1(ICAM-1), E-selectin and P-selectin in serum, lung tissues and bronchoalveolar lavage fluid(BALF)of acute lung injury(ALI) model and to observe the effects of ambroxol combined with low-dose heparin on the changes of the 3 factors above.METHODS: Twenty-four healthy rabbits were randomly divided into 3 groups: normal saline control group (NC), oleic acid injury group (OA), ambroxol+ heparin treatment group (AH). The rabbit ALI model was induced by oleic acid injection through auricular vein. Partial pressure of O₂ in artery(PaO₂) was analyzed.The concentrations of ICAM-1 and E-selectin were detected by ELISA.The apoptosis index(AI) was measured by TUNEL method.The expression of P-selectin was determined by immunohistochemical method.The ultrastructural changes of the lung tissues were observed under electron microscope, and the lung wet/dry ratio(W/D) was calculated.RESULTS: PaO₂ in AH group and OA group was significantly lower (P<0.01) than that in NC group, and PaO₂ in AH group was significantly higher than that in OA group (P<0.01). The concentrations of ICAM-1 and E-selectin in serum, lung tissues and BALF, and AI and W/D in lung tissues in AH group were higher (P<0.05 or P<0.01) than those in NC group, and was lower than those in OA group (P<0.05 or P<0.01). In NC group, no significant change of the above parameters at all time points was observed (P>0.05). In OA group, PaO₂ was significantly decreased (P<0.01) with the pathological process developed, and the concentrations of ICAM-1 and E-selectin were significantly increased. In AH group, PaO₂ was decreased (P<0.05),and the concentrations of ICAM-1 and E-selectin were increased with the process of ALI developed. The P-selectin expression in lung tissues of OA group was distributed mainly in inflammatory cells, capillary endothelial cells and plasma. From low to high levels, the order was NC group < AH group < OA group in the expression of P-selectin. The most obvious apoptosis was observed in OA group. No apoptosis or occasional positive cells were found in NC group. The apoptotic rate in AH group was significantly reduced compared with that in OA group.CONCLUSION: In ALI induced by OA, ICAM-1, E-selectin and P-selectin are significantly increased and are involved in the occurrence and development of ALI. Ambroxol combined with low-dose heparin reduces the levels of ICAM-1, E-selectin and P-selectin, the pulmonary edema and the lung injury, improves pulmonary functions, and plays an important role in the prevention and treatment of acute lung injury.     

Effects of imidapril on blood gas,oxidative stress and inflammatory factors in rats with acute lung injury induced by ammonium chloride

AIM: In this study, the rat lung injury model was induced by ammonium chloride for studying the effect of imidapril on blood gas, serum TNF-α, IL-6 and MDA concentrations, and AngⅡ and CD54 protein expression in rat lung tissue. METHODS: Male rats were randomly divided into 3 groups: control group, lung injury model group and drug group. The rats in control group were given saline (2 mL/kg), while the rats in lung injury model group were given 6% ammonium chloride (2 mL/kg). In drug group, imidapril (3 mg·kg^-1·d^-1) was given to the rats once daily for 1 week by intragastric gavage after given 6% ammonium chloride. On the 7th day, the rats were anesthetized with 2% so-dium pentobarbital. Abdominal aorta blood, venous blood and lung tissue were collected. The blood gas indexes and serum TNF-α, IL-6 and MDA concentrations were determined. The lung tissues were fixed and sliced, and the expression of AngⅡ and CD54 proteins was detected by immunohistochemistry. RESULTS: The PaCO₂ increased in lung injury model group compared with control group and drug group (P < 0.05).The expression of AngⅡ and CD54, and the concentrations of TNF-α, IL-6 and MDA also increased significantly (P < 0.01) in model group. Pulmonary edema, inflammation, alveolus congestion, hemorrhage and hyperplasia in model group were obvious compared with control group and drug group. CONCLUSION: Imidapril improves blood gas indexes, and reduces lipid peroxidation and inflammatory responses in the rats with lung injury induced by ammonium chloride.     

Inducible nitric oxide synthase and arterial pressure regulation

AIM and METHODS:To clarify the role of inducible nitric oxide synthase (iNOS) in the regulation of blood pressure,in the present study, we examined the effect of aminoguanidine (AG), a selective inhibitor of iNOS on the hemodinamical response of Dahl salt-sensitive (DS) and Dahl salt-resistant (DR) rats to low (0.3%) or high (8%) sodium chloride (NaCl) infusion by chronical in vivo hemodynamic experiment, and the effect of NaCl or NaCl plus AG infusion on urinary nitrate (NO₃)/nitrite (NO₂), the end product of nitric oxide (NO), excretion by Greiss Reaction. Furthermore, NOS activity assay was also carried out to probe the effect of NaCl and AG on calcium-dependent or independent NOS activity in renal tissue. RESULTS:1. High or low NaCl-infused DR rats and low NaCl-infused DS rats have no hemodinamical response to AG, however, the hypertensive effect of high NaCl (8%) infusion on DS rats were greatly amplified by co-infusion of AG. 2. Administration of high NaCl significantly elevated the iNOS activity of renal tissue, and greatly increased urinary NO₃/NO₂ excretion. CONCLUSION:Inducible NOS is an important modulator of arterial pressure, especially in case of higher blood pressure.     

The augmentative effect of inducible nitric oxide synthase on pulmonary fibrosis progression

AIM: To study the up-regulation of inducible nitric oxide synthase (iNOS) in lung of pulmonary fibrosis and its relationship with fibrosis. METHODS: The changes of amount of iNOS positive stain cells and type Ⅰ?Ⅲ collagen were examined on the day 7, 14 and 30 after intratracheal administration of bleomycin A₅. The contents of NO₂^-/NO₃^- (nitrite/nitrate) in out-flowing pulmonary blood (OPB), hydroxyproline in lung and the histological changes were detected after iNOS was blocked by aminoguanidine (AG). RESULTS: (1) The number of iNOS-positive stain cells increased significantly in BLMA₅ 7 d, 14 d and 30 d groups compared with that in control group (P<0.01). Furthermore, the increment of the number of iNOS-positive stain cells in BLMA₅ 7 d, 14 d groups was more than that in BLMA₅ 30 d group. There was an increment of collagen in BLMA₅ 14 d group and in BLMA₅ 30 d group , with an increase in type Ⅲ collagen in BLMA₅ 14 d group and an increase in type Ⅰcollagen in BLMA₅ 30 d group. (2) The high level of NO₂^-/NO₃^- in OPB and hydroxyproline level in lung could be reversed by AG, a selective inhibitor of iNOS. Large amount of fibroblasts and macrophages were also abated by AG. CONCLUSION: In the development of pulmonary fibrosis, the expression of iNOS is up-regulated, which induces nitric oxide (NO) production and promotes propagation of pulmonary fibrosis.     

Effect of polidatin on the activity of phospholipase A2and pulmonary structural remodeling in rats with hypoxia-induced pulmonary hypertension

AIM: To study the relationship between the activity of phospholipase A₂ (PLA₂) and pulmonary structural remodeling with the model of chronic isobaric hypoxic pulmonary hypertension. METHODS: 29 healthy Sprague-Dawley rats were randomly divided into normal control group, chronic hypoxic group and hypoxia plus Polidatin (PD) group. By diameter, the arteries were divided into two groups: arteries of group I (30 μm-100 μm) and group II (101 μm-200μm). The mean pulmonary arterial pressure (mPAP) was measured by inserting a microcatheter into the pulmonary artery. The PLA₂ activity was measured with modified microtitrimetic method. The pulmonary tissue and arterioles morphology changes were examined under light microscope. RESULTS: It was found that after 21 days hypoxia, the mean pulmonary arterial pressure (mPAP), the PLA₂ activity in blood and lung homogenate increased significantly. The media thickness of group I arteries increased (P<0.01) while that of group II arteries had no significant changes. The ratio of media area and adventitia of both groups was raised. Under light microscope, it was observed that pulmonary vascular endothelium proliferated, media became thickening and adventitia matrix increased. Pretreatment with PD could attenuate the changes mentioned above. CONCLUSION:PLA₂ plays an important inducing role through promotion of the pulmonary vascular structural remodeling in the formation of chronic hypoxic pulmonary hypertension.     

Effects of hypoxia inhalation therapy on the number of eosinophil and CD4+T-lymphocyte in remission stage in asthmatic guinea pigs

AIM:To explore the mechanism underlying the therapeutic effects of hypoxia inhalation on asthma. METHODS:Guinea pigs were randomized into the normal group(NG), asthmatic group(AG) and the hypoxia inhalation-treated group(HITG). The model of asthma was established in the latter two groups through sensitization and induction with 10% ovalbumin(OA) and 1% OA, respectively. The animals in HITG were treated with hypoxia inhalation (13.0%±0.5% O₂/N₂ mixed gas). The content of serum cortisol, the number of eosinophils(EOS) and percentage of hypodense eosinophils(HEOS) in bronchoalveolar lavage fluid(BALF),the number of CD₄⁺T-lymphocyte in peripheral blood(PB) and the tension of airway muscle were determined. RESULTS:(1)The content of serum cortisol was significantly higher in NG and HITG than in AG(P＜0.01); (2)The number of EOS and percentage of HEOS in BALF was significantly lower in HITG than in AG(P＜0.01); (3) The number of CD₄⁺T-lymphocyte in PB was significantly higher in AG than in HITG(P＜0.01).CONCLUSION:After treatment with hypoxia inhalation, the content of serum cortisol in asthmatic guinea pigs was significantly increased to result in marked decreased of the number of EOS, the percentage of HEOS in BALF, and the number of CD₄⁺T-lymphocyte in PB, thus result in the tension of airway muscle and alleviation of the airway hyperresponsiveness. All these may be beneficial to preventing the relapse of asthma.     

The euthyroid sick syndrome in severe SIRS patients

AIM: To assay the pattern of thyroid hormone alternations in systemic inflammatory response syndrome (SIRS) patients. METHODS: 50 SIRS patients were enrolled, divided into two groups as to whether they got MODS. Thyroid hormone measurements were taken, including total T3 (TT3), total T4 (TT4), free T3 (FT3), free T4 (FT4) and TSH. The acute physiology and chronic health evaluationⅡ (APACHEⅡ) score was calculated according to clinical data. Outcome (recovery or deterioration) was recorded, as well as the length of time from the onset of SIRS to the day when thyroid hormones were measured (the duration of SIRS). RESULTS: Euthyroid sick syndrome (ESS) was presented in 45 cases. TT3 level was negatively correlated with APACHEⅡscore (r＝-0.330, P<0.05), and TT3/TT4 value was negatively correlated with the duration of SIRS (r=-0.316, P<0.05). TT3, TT4 and FT3 levels in the MODS patients were significantly lower than those in the patients without MODS (P<0.05). MODS patients got low TT4 or FT4 levels more frequently than those without MODS (P<0.05). Compared to the normal TSH group, patients with low TSH had lower T3 and T4, higher APACHEⅡscores, higher proportion of MODS, and higher proportion of recovery, but no differences were observed (P>0.05). CONCLUSION: SIRS patients has high possibility to get ESS, which happens more frequently and severely in MODS patients. With the persistence and aggravation of SIRS, there is a progression of thyroid hormone reduction.