Effect of safflower injection on endoplasmic reticulum stress-induced apoptosts in rats with hypoxic pulmonary hypertension / 中国应用生理学杂志

<p><b>OBJECTIVE</b>To explore the effects of safflower injection on prevention and treatment of hypoxic pulmonary hypertension and clarify the function of the endoplasmic reticulum stress apoptosis pathway during the process.</p><p><b>METHODS</b>Thirty male SD rats were randomly grouped as normal control group, hypoxia-hypercapnia group and hypoxia+safflower group. The latter two groups were put in the cabin with oxygen concentration ranged from 9% to 11% and carbon dioxide concentration from 5% to 6%. The pulmonary artery pressure and the index of right ventricular hypertrophy were determined after hypoxia exposure (8 h/dx28 d). Changes in morphology of lung tissue were observed by electron microscopy. To explore the possible mechanisms, we also detected apoptosis and apoptosis-related genes/proteins in lung tissue by TUNEL reactivity and PCR and Western blot.</p><p><b>RESULTS</b>Compared with the normal control group, pulmonary artery pressure and the index of right ventricular hypertrophy in hypoxia group were 45% and 33.4% higher, respectively. Tiny blood vessel wall of lungs was thickened and edema, and proliferation of collagen fibers was obvious under the electron microscope. TUNEL staining of apoptotic cells in lung tissues showed more high brightness green fluorescence (+-++), but less green fluorescence showed in the pulmonary vascular smooth muscle cell layer, and apoptosis index (AI) value was 150% higher; gene and protein expression levels of endoplasmic reticulum stress pathway were increased. Compared with hypoxia-hypercapnia group, pulmonary artery pressure and the index of right ventricular hypertrophy in the hypoxia+safflower group were 18% and 15.6% lower, respectively; collagen fibers were decreased, and smooth muscle cells and epithelial cells were got apoptotic-like changes under the electron microscope. TUNEL staining of apoptotic cells in lung tissues showed brighter green fluorescence (++-+++); the high brightness green fluorescence showed in pulmonary vascular smooth muscle cell layer, and apoptotic index (Al) value was 40% higher; gene and protein expressions of endoplasmic reticulum stress pathway were significantly upregulated.</p><p><b>CONCLUSION</b>Our findings demonstrate that safflower injection could activate endoplasmic reticulum stress-induced apoptosis and especially promote apoptosis in pulmonary vascular smooth muscle cells.</p>

Effect of apelin on vasodilatation of isolated pulmonary arteries in rats is concerned with the nitric oxide pathway / 中国应用生理学杂志

<p><b>OBJECTIVE</b>To investigate the effect of apelin on vasodilatation of isolated pulmonary arterial rings in rats and its relationship to the nitric oxide (NO) pathway, and to observe the difference of vasodilatation between hypoxic rats and normoxic rats.</p><p><b>METHODS</b>Thirty-six male Sprague-Dawley (SD) rats were randomly divided into hypoxic group and normoxic group. The effects of accumulated apelin on pulmonary arterial rings preconstricted with norepinephrine (NE) were observed by using tissue organ bath system. After pulmonary arterial rings were pretreated with three methods: removing the endothelium, pretreating with nitric oxide synthase inhibitor L-NAME or soluble guanylatecyclase inhibitor ODQ, the different effect of apelin was observed. In addition, the difference of vasodilatation between hypoxic rats and normal rats were observed.</p><p><b>RESULTS</b>(1) Exposure of intact endothelium pulmonary arterial rings preconstricted by NE to apelin at concentration (0.01 - 100 nmol/L) induced a significant concentration dependent relaxation. The maximal vasorelaxant effect of apelin was 10.62% +/- 2.60%, which was inhibited by removal of the endothelium (P < 0.01), pretreatment with L-NAME (P < 0.01) or ODQ (P < 0.01). (2) Response of pulmonary arterial rings from hypoxic pulmonary hypertension rats was decreased (P < 0.05). Compared to normal rats, at a concentration of 100 nmol/L, the response to apelin on arteries from hypoxic rats decreased 60.45% (P < 0.01). But the values of EC50 were not significantly different (P > 0.05).</p><p><b>CONCLUSION</b>These results indicate that apelin relaxes the pulmonary arterial rings of rats in an endothelium dependent manner, which may have a relationship to NO signaling pathway. The response of vasodilatation is decreased in the pulmonary arterial rings from the hypoxic rats.</p>

Changes of endoplasmic reticulum stress-induced apoptosis in pulmonary tissue of rats with hypoxic pulmonary hypertension / 中国应用生理学杂志

<p><b>OBJECTIVE</b>To investigate the changes of endoplasmic reticulum stress-induced apoptosis in pulmonary tissue of rats with hypoxic pulmonary hypertension.</p><p><b>METHODS</b>Twenty two male SD rats were randomly divided into control group and 4-week hypoxia-hypercapnia group (n=11). The mean pulmonary arterial pressure (mPAP) and the mean carotid arterial pressure (mCAP) were monitored, and the weight ratio of right ventricle (RV) to left ventricle plus septum (LV + S) were measured. The rattish pathological model were assessed by mPAP, mCAP, RV/(LV+ S), vessel wall area/total area (WA/TA), vessel cavity area/total area (CA/TA) and media thickness of pulmonary arteriole (PAMT). The pulmonary apoptotic cells were detected by Hoechst staining. RT-PCR was used to study the genetic expression of caspasel2, glucose regulated protein 78 (GRP78) and GRP94 in pulmonary tissue. The expression of GRP94 and GRP78 proteins in pulmonary tissue were determined by using immunohistochemistry.</p><p><b>RESULTS</b>(1) (The mPAP, RV/(LV + S), WA/TA and PAMT were respectively higher by 50.5%, 37.3%, 72.5% and 137% in hypoxic group than those in control group, while CA/TA was lower by 41.9% (all P < 0.01). There was not significant difference of mCAP between the two groups. (2) Hoechst staining showed that the pulmonary apoptotic cells in hypoxic group outnumbered markedly than those in control group, and the apoptotic cells were mainly in pulmonary tissue, while they were rare in pulmonary vascular smooth muscle cell. (3) Compared with control group, the expression of pulmonary caspasel2, GRP78 and GRP94 mRNA in hypoxic group were higher by 144%, 137% and 80.7% (all P < 0.05), respectively. (4) The expression of pulmonary GRP78 and GRP94 proteins were up-regulated in hypoxic group, and these proteins mainly localized in pulmonary vascular endothelial cell.</p><p><b>CONCLUSION</b>The endoplasmic reticulum stress-induced apoptosis may be one of the mechanism of hypoxic pulmonary hypertension and pulmonary vascular wall remodeling.</p>

Protective and therapeutic effect of apelin on chronic hypoxic pulmonary hypertension in rats / 中国应用生理学杂志

<p><b>OBJECTIVE</b>To study the role of apelin in the prevention of pulmonary hypertension induced by hypoxia in rats.</p><p><b>METHODS</b>The animal model of hypoxic pulmonary hypertension was established by exposing the rats to isobaric hypoxic chamber for 4 weeks (8 h/d, 6 d/ w). Forty male Sprague-Dawley rats were randomly divided into control group (NC), hypoxic group(HH), hypoxic with low-dose apelin (5 nmol/(kg x d) group(LA) and high-dose apelin (10 nmol/(kg x d) (HA). [pGlu]apelin-13 was administered into the rats of apelin groups by mini-osmotic pump subcutaneously. The mean pulmonary arterial pressure(mPAP) and the mean carotid arterial pressure (mCAP) were measured by either right or left cardiac catheterization, and the weight ratio of right ventricule/left ventricule plus septum (RV/(LV + S)) were calculated. The Masson's trichrome stained lung specimens were examined by light microscope to examine the vessel wall area/total area (WA/TA), vessel cavity area/total area (CA/TA) and media thickness of pulmonary arterioles (PAMT). Meanwhile, the lung homogenates were assayed for the activity of supeeroxide dismutase (SOD) and the content of malondialdehyde (MDA).</p><p><b>RESULTS</b>(1) mPAP and RV/(LV + S) of HH group were significantly higher than those of NC group. mPAP of LA and HA groups were lower than those of HH group. The RV/(LV + S) of HA group was significantly lower than that of HH group, but there was no significant difference between HH group and LA group. (2) Masson's trichrome staining revealed that WA/TA and PAMT of HH group were higher than those of NC group. Administration of apelin significantly eliminated WA/TA and PAMT in LA and HA groups. (3) CA/TA of HH group was lower than that of NC group. Administration of apelin significantly elevated CA/TA in LA and HA groups. (4) The activity of SOD and content of MDA in HH group was, respectively, lower and higher than those in NC group. Apelin treatment increased the activity of SOD in LA and HA groups while decreased the content of MDA.</p><p><b>CONCLUSIONS</b>Apelin could play an important role in treatment of hypoxic pulmonary hypertension of rats and the mechanisms of protection were associated with vasodilation of pulmonary artery and inhibition of oxidative stress.</p>

Effect of apelin on hypoxic pulmonary hypertension in rats: role of the NO pathway / 生理学报

To investigate the effectiveness and mechanism of apelin against pulmonary hypertension and pulmonary vascular remodeling induced by hypoxia in rats, 24 male Sprague-Dawley rats were randomly divided into normal control (NC) group, 4-week hypoxia (HH) group and 4-week hypoxia with apelin (HA) group (each n=8). The rats of hypoxic group were placed in an isobaric hypoxic chamber, in which O₂ and CO₂ content was maintained at 9%-11% and <3%, respectively, for 4 weeks (8 h/d, 6 d/week). [pGlu]apelin-13 (10 nmol/kg per day, 28 d) was administered subcutaneously by osmotic mini-pump before hypoxia treatment in HA group. L-arginine (L-Arg) uptake of pulmonary artery was assay by [³H]-L-Arg, while nitric oxide synthase (NOS) activity of pulmonary tissue, and nitrate/nitrite (NO₂(-)/NO₃(-)) concentrations in pulmonary tissue and plasma were detected by colorimetric technique and nitrate reductase method, respectively. The results showed that mean pulmonary arterial pressure, the ratio value of right ventricle weight to left ventricle plus septum weight, the relative medial thickness, and the relative medial area of pulmonary arterioles were higher in HH group than those in NC group (all P<0.01), while these indices were lower in HA group than those in HH group (P<0.05 or P<0.01). Compared with those in HH group, the uptake of 0.5, 5 and 10 nmol/L [³H]-L-Arg in pulmonary artery in HA group increased by 121.4% (P<0.01), 85.0% (P<0.05) and 61.5% (P<0.05), respectively; cNOS activity of pulmonary tissue increased by 74.3%, while iNOS activity decreased by 25.0% (all P<0.01); and NO₂(-)/NO₃(-) concentrations in pulmonary tissue and plasma increased by 97.6% and 48.0% (all P<0.05), respectively. Taken together, our results suggest that apelin has a prophylactic effect against hypoxic pulmonary hypertension in rats, and that the mechanism of this effect is possibly associated with activation of the L-Arg/NOS /NO pathway.

Effect of hypoxia on the expressions of intermedin/ adrenomedullin2 in plasma and the tissues of heart and lung in rats / 中国应用生理学杂志

<p><b>AIM</b>To study the effect and significances of two-week hypoxia on the expression of intermedin/adrenomedullin2 (IMD/ADM2) in plasma and the tissues of heart and lung in rats.</p><p><b>METHODS</b>Twenty male SD rats were randomly divided into normal control group and hypoxia group. The concentrations of IMD/ADM2 and adrenomedullin (ADM) in plasma, right ventricle and lung tissue were measured by radioimmunoassay. RT-PCR was used to detect the mRNA levels of IMD/ADM2 and ADM in right ventricle and lung tissue.</p><p><b>RESULTS</b>(1) The mean pulmonary arterial pressure (mPAP) and the weight ratio of right ventricle (RV) to left ventricle plus septum (LV + S) of hypoxia group were significantly higher than those of normal control group (P < 0.01). (2) The concentrations of IMD/ADM2 and ADM in plasma were significantly higher in hypoxia group, compared with normal control group (P < 0.01). (3) The concentration of ADM in right ventricle and lung tissue in hypoxia group was significantly higher than that in normal control group (P < 0.01), while there was no significant difference in IMD/ADM2 between the two groups. (4) The mRNA levels of IMD/ADM2 and ADM in right ventricle and lung tissues were significantly up-regulated in hypoxia group (P < 0.05).</p><p><b>CONCLUSION</b>The expressions of IMD/ADM2 peptides and gene in plasma, right ventricular and pulmonary tissues are different in the early-middle pathological proceeding of pulmonary hypertension induced by two-week hypoxia in rats.</p>

Changes of intermedin/adrenomedullin 2 and its receptors in the right ventricle of rats with chronic hypoxic pulmonary hypertension / 生理学报

The purpose of the present study was to explore the expression changes of intermedin/adrenomedullin 2 (IMD/ADM2), a novel small molecular bioactive peptide, and its receptors, calcitonin receptor-like receptor (CRLR) and receptor activity modifying proteins (RAMP1, RAMP2, RAMP3) in the right ventricle of rats with chronic hypoxia-induced pulmonary hypertension. Twenty male Sprague-Dawley rats were randomly divided into 4-week hypoxia group and normal control group (each n=10). The rats in hypoxia group were placed in an isobaric hypoxic chamber, in which O(2) content was maintained at 9%-11% by delivering N(2), and CO(2) content was maintained at <3% for 4 weeks (8 h/d, 6 d/week). The rats in the control group were housed in room air. The protein levels of IMD/ADM2 and adrenomedullin (ADM) in blood plasma and right ventricular tissue were measured by radioimmunoassay. The mRNA expressions of IMD/ADM2, ADM and their receptors CRLR, RAMP1, RAMP2, RAMP3 in right ventricular tissue were determined by reverse transcription-polymerase chain reaction (RT-PCR). The results showed that the ratio of right ventricle weight to left ventricle plus septum weight [RV/(LV+S)] and mean pulmonary arterial pressure (mPAP) were higher in hypoxia group than those in the control group (all P<0.01), suggesting that the rat model of pulmonary hypertension was successfully established. However, the mean carotid arterial pressure (mCAP) between the two groups had no significant difference. Compared with that in the control group, ADM contents in plasma and right ventricular tissue in hypoxia group increased by 1.26 and 1.68 folds (all P<0.01), respectively. Likewise, IMD/ADM2 contents in blood plasma and right ventricular tissue in hypoxia group increased by 0.90 and 1.19 folds (P<0.01), respectively, compared with that in the control group. The data of RT-PCR showed that mRNA levels of ADM, IMD/ADM2 and RAMP2 in hypoxia group increased by 155.1% (P<0.01), 80.9% (P<0.01) and 52.9% (P<0.05), respectively, compared with those in the control group. There were no significant differences in mRNA expressions of CRLR, RAMP1 and RAMP3 between the two groups (all P>0.05). Taken together, the results show that the level of IMD/ADM2 increases in the rats with chronic hypoxia-induced pulmonary hypertension.

Changes of adrenomedullin 2/intermedin in the lung of rats with chronic hypoxic pulmonary hypertension / 中国应用生理学杂志

<p><b>AIM</b>To investigate the changes and probable roles of adrenomedullin2/intermedin (AIDM2/IMD), a novel micromolecular bioactive peptide, in the lungs of rats with chronic hypoxic pulmonary hypertension.</p><p><b>METHODS</b>Twenty male SD rats were randomly divided into normal control group (NC) and normobaric hypoxia group (4H). The protein levels of ADM and ADM2/IMD) in the plasma and lung were measured by radioimmunoassay and immunohistochemistry. The mRNA expressions of ADM, ADM2/IMD and their receptors C (RLR, RAMP1, RAMP2 and RAMP3 in the lung tissue were determined by reverse transcription-polymerase chain reaction (RT-PCR).</p><p><b>RESULTS</b>(1) The rat model of chronic pulmonary hypertension was confirmed by the increased mean pulmonary arterial pressure (mPAP) and weight ratio of right ventricle to left ventricle plus septum [RV/(LV + S)] in 4H group compared to NC group. (2) The concentrations of ADM in the plasma and lung homogenate of 4H group were 2.3 and 3.2 folds of NC group, respectively (all P < 0.01). The levels of ADM2/IMD were higher 89.6% and 45.0% in the plasma and lung homogenate of 4H group than those of NC group (respectively, P < 0.01, P < 0.05). (3) The mRNA expressions of ADM2/IMD and ADM in the lung of 4H group were up-regulated (respectively, P < 0.01, P < 0.05 vs. NC group). The expressions of CRLR and RAMP1 mRNAs were down-regulated (all P < 0.01 vs. NC group), while the levels of RAMP2 and RAMP3 mRNAs were no significant difference between the two groups. (4) The strong ADM2/IMD immunostaining was detected in the endothelial and adventitial cells of the rat pulmonary arteriole.</p><p><b>CONCLUSION</b>ADM2/IMD, like its paralog ADM, might be closely related to the chronic hypoxic pulmonary hypertension in rats. The disorders of the gene expression and/or the synthesis and metabolism of ADM2/IMD and its receptor CRLR/RAMP1 possibly take part in the pathogenesis of chronic hypoxic pulmonary hypertension in rats.</p>

Expression of Urotensin II and its receptor on right ventricle in rats of pulmonary hypertension / 中国应用生理学杂志

<p><b>AIM</b>To observe the expression of Urotensin II (U II) and its receptor (UT) on right ventricle in rats with chronic pulmonary hypertension induced by hypoxia and hypercapnia.</p><p><b>METHODS</b>Twenty male SD rats were randomly divided into normal control group (NC) and hypoxia-hypercapnia 4-week group(HH). Mean pulmonary arterial pressure(MPAP) and the weight ratio of right ventricle (RV) to left ventricle plus septum (LV+ S) were calculated separately. U II in plasma was measured using radioimmunoassay. The expression of U II was observed in right ventricle myocytes and right ventricle arteries by immunohistochemistry. The expression of U II mRNA and UT mRNA were observed in right ventricle myocytes and right ventricle arteries by in situ hybridization.</p><p><b>RESULTS</b>(1) The MPAP and RV/LV + S of HH group were higher respectively than those of NC group (P < 0.01, respectively). (2) The plasma U II content of HH group did not increased obviously than that of NC group. (3) The expression score of U II, U II mRNA, UT mRNA by right ventricle myocytes in HH group were higher significantly than those of NC group (P < 0.01 respectively). (4) The average value of integral light density (LD) of U II, U II mRNA, UT mRNA by right cardial arteries in HH group were higher significantly than those of NC group (P < 0.01, respectively).</p><p><b>CONCLUSION</b>The expression of U II in right ventricle arteries and right ventricle myocytes increase significantly during the formation of pulmonary hypertension and right ventricle hypertrophy in rats chronically exposed to hypoxia-hypercapnia. These changes indicate that U II might be involved in right ventricle remodeling, which promotes proliferation of cardiac muscle cells.</p>

Effects and relationship between NO and HIF-1alpha in rats with pulmonary hypertension induced by hypoxia / 中国应用生理学杂志

<p><b>AIM</b>To investigate the expression of hypoxia-inducible factor-1 alpha (HIF-1alpha) in rats with chronic pulmonary hypertension induced by hypoxia and hypercapnia and its relationship with nitric oxide(NO).</p><p><b>METHODS</b>Fourty male Sprague-Dawley rats were randomly divided into four groups, normal control group (NC), hypoxia-hypercapnia group (HH), hypoxia - hypercapnia + L-arginine liposome group(HP) and hypoxia-hypercapnia+ N-nitro-L-arginine methylester group (HM). Colorimetric analysis, immunohistochemistry and in situ hybridization were used for detection of NO, HIF-1alpha and constitutive nitric oxide synthase (ecNOS).</p><p><b>RESULTS</b>(1) The mean pulmonary arterial pressure (mPAP) and the weight ratio of right ventricular to left ventricle plus septum (RV/(LV + S)) of HH group were higher than those of NC group (P < 0.05), HP group much lower than HH group (P < 0.01), mPAP of HM higher than HH group ( P < 0.05). 2)0 Contents of NO in plasma and pulmonary tissue homogenates of HH group were much lower than those of NC group (P < 0.01), HP group higher than HH group (P < 0.01). There were no difference between HM group and HH group. (Expression of HIF-1alpha and HIF-1alpha mRNA in pulmonary arterioles of HH group were significantly higher than those of NC group( P < 0.01), HP group lower than HH group (P < 0.01) ,HM group higher than HH group (P < 0.01); Whereas expression of ecNOS and ecNOS mRNA in pulmonary arterioles of HH were lower than those of NC group( P < 0.05, IP group higher than HH group (P < 0.01), HM group lower than HH group (P < 0.05).</p><p><b>CONCLUSION</b>HIF-1alpha is involved in the pathogenesis of chronic pulmonary hypertension induced by hypoxia and hypercapnia. The protective function of NO in the pathogenesis might be partly depended on its effects on the expression/activity of HIF-1alpha in lung.</p>

Dynamic changes of urotensin II receptor in pulmonary artery and arterioles of rats chronically exposed to hypoxia-hypercapnia / 中国应用生理学杂志

<p><b>AIM</b>To investigate the dynamic changes and functions of urotensin II (U lI) receptor (UT) in pulmonary arteries of rats chronically exposed to hypoxia-hypercapnia.</p><p><b>METHODS</b>In rats with hypoxia-hypercapnia at 1, 2 and 4 weeks U II receptor binding of pulmonary arteries sarcolemma was determined by radioligand assay. U II mRNA and UTmRNA in various grades of pulmonary arterioles were measured by in situ hybridization.</p><p><b>RESULTS</b>(1) Mean pulmonary pressure (mPAP) and weight ratio of right ventricle to left ventricle and septum (RV/LV + S) of 1-week group were higher than those of normal control (NC) group by 26.2% and 21.6% (P < 0.01), respectively, and 2-week group higher than 1-week group by 22.5% and 14.1% (respectively, P < 0.01). However, no significant changes were found between 4-week and 2-week group. (2) U Il receptor (Bmax) of 1-week group was higher than NC group by 38.8%, 2-week group higher than 1-week group by 23.2%, and 4-week group increased 7.3% compared with 2-week group (respectively, P < 0.01). The UT changes were time-dependent, while the affinity to U II (Kd) was no different among each group. (3) UII mRNA in each grade of pulmonary arterioles of 2-week group and 4-week group were higher than NC group (respectively, P < 0.01), and those of 2-week group were higher than 1-week group by 5.9% (P > 0.05), 16.4% and 9.1% (respectively, P < 0.01), while no differences existed between 2-week group and 4-week group. (4) UT mRNA in each grade of pulmonary arterioles of all hypoxia-hypercapnia groups was higher than NC group (respectively, P < 0.01), and those of two abaxial grade vessels in 1-week group were the highest. No differences existed between 2-week group and 4-week group. (5) The pulmonary vessels remodeling were time-dependently aggravated by hypoxia-hypercapnia.</p><p><b>CONCLUSION</b>The dynamic changes of UT in pulmonary arterioles might have important contribution to the development of pulmonary hypertension and pulmonary arteriole remodeling induced by chronic hypoxia-hypercapnia in rats.</p>

Effect of L-arginine liposome on nitric oxide content and nitric oxide synthase gene expression in rats chronically exposed to hypoxia and hypercapnia / 中国应用生理学杂志

<p><b>AIM</b>To investigate the effects of L-arginine liposome on nitric oxide(NO) and nitric oxide synthase gene (NOS mRNA) in rats chronically exposed to hypoxia-hypercapnia.</p><p><b>METHODS</b>Fourty male SD rats were randomly divided into four groups (n=10): normal control group(NC), hypoxia-hypercapnia group (HH), hypoxia-hypercapnia + L-arginine group(HL) and hypoxia-hypercapnia + L-arginine liposome group (HP). Contents of NO in plasma were measured using colorimetric analysis. Expression of nitric oxide synthase gene were measured with situ hybridization.</p><p><b>RESULTS</b>(1) The mean pulmonary artery pressure(mPAP) and weight ratio of right ventricle to left ventricle and septum(RV/LV + S) of HP group were obviously lower than those of HH group and HL group. (2) The NO contents in plasma of HP group were obviously higher than those of HH group and HL group (P < 0.01). (3) Situ hybridization showed the average value of integral light density(LD) of ecNOS mRNA in pulmonary arterioles was significantly higher in rats of HP group than that of HH group and HL group (P < 0.01). (4) Light microscopy showed WA/TA (vessel wall area/total area) and PAMT (media thickness ratio of pulmonary arterioles) were significantly lower in rats of HP group than those of HH group (P < 0.01).</p><p><b>CONCLUSION</b>L-arginine liposome could lower the mPAP and lighten the remodeling of pulmonary arterioles of the rats chronically exposed to hypoxia-hypercapnia than L-arginine does. It suggests that L-arginine liposome significantly promotes the membrane transportin of L-arginine.</p>

Diagnostic study on children's diaphragmatic fatigue / 中华儿科杂志

<p><b>OBJECTIVE</b>In the recent twenty years, the diaphragmatic contraction, relaxation functions and electric activity have been explored through electromyography (EMG) and transdiaphragmatic pressure (Pdi) determination. But these techniques required some complex and expensive instruments, so the diagnosis and treatment of children's diaphragmatic fatigue have not been well evaluated. The present study explored the diagnosis of children's diaphragmatic fatigue through measuring ribcage-abdomen motion and analyzed its asynchrony.</p><p><b>METHODS</b>Fifty-three children (male 37, female 16, and age rage from 1 months to 9 years) with respiratory rate > 30 breaths/min, heart rate > 110 beats/min, and respiratory dysfunction had asynchronized ribcage-abdomen motion showed by impedance respirograph (IRG). The authors observed whether ribcage-abdomen motion was synchronic and calculated M levels (staggered peak time/total duration of the breathing cycle). The ribcage and abdomen outputs were displayed on vertical (for rib cage) and horizontal (for abdomen) axes of X-Y instrument. In addition, the change of respiratory frequency and heart rate was observed and arterial blood-gas analysis was also performed.</p><p><b>RESULTS</b>(1) M levels in one-dimensional IRG were positively correlated with alpha angle in two-dimensional IRG (r = 0.956, P < 0.001). Asynchronized respiratory motions could be divided into three types. type I showed completely contra-directional movements of respiration, M levels for (48.1 +/- 4.4)%, an irregularly clockwise loop in the two dimensional IRG, and alpha angle for (138.3 +/- 15.0) degrees. In type II, one dimensional IRG showed displaced peak of the chest and abdomen motion curves, M levels were (16.5 +/- 4.7)%, two dimensional IRG was displaced in a counterclockwise direction, and alpha angle was (55.3 +/- 10.8) degrees. In type III, abdominal motion curve of one dimensional IRG had double peaks, M levels were 0, two dimensional IRG was presented as 8-shaped double circles, alpha angle was (41.3 +/- 3.8) degrees; (2) pH levels in the patients with type I and type II diaphragmatic fatigue were significantly lower, and PCO(2) levels were significantly higher than those with type III or in the normal subjects (P < 0.001 for all), but there was no statistically significant difference between type III and the normal subjects (P > 0.05); (3) Both of respiratory rate and heart rate in type I, type II and type III were higher than those in the normal subjects (all P < 0.001), and the differences among the three types were significant (P < 0.001 for all); (4) Both M levels and alpha angle were negatively correlated with pH levels (r = -0.514, P < 0.001 and r = -0.497, P < 0.001), while positively correlated with PCO(2) levels (r = 0.672, P < 0.001 and r = 0.625, P = 0.01).</p><p><b>CONCLUSIONS</b>(1) IRG can be reliably used to diagnose children's diaphragmatic fatigue. This technique is simple and easy to perform and non-invasive. It is therefore worthy of recommending for further clinical investigations. (2) According to the characteristics of IRG, diaphragmatic fatigue can be divided into three types. (3) The development of children's diaphragmatic fatigue has a series of characteristic changes. (4) To avoid the patients suffering from respiratory failure, it is the key time to adopt the policies of prevention and treatment when IRG shows signs of type III diaphragmatic fatigue.</p>

Influences of perindopril on pulmonary vascular remodeling in normobaric hypoxia-hypercapnia rats / 中国临床药理学与治疗学

Aim To investigate the effects of perindopril, an angiotensin converting enzyme inhibitor, on mean pulmonary arterial pressure(mPAP) and pulmonary vascular remodeling.Methods Using the normobaric hypoxia-hypercapnia rat model,the changes of plasma angiotensin Ⅱ (Ang Ⅱ), mPAP and ultrastructure of pulmonary arteriolar wall were observed after administration of perindopril.Results The mPAP and AngⅡ were significantly greater and the ultrastructure of the small lung vessels had a more obvious change in the 4 weeks hypoxia-hypercapnia group than those in the control group.It was also found that perindopril decreased AngⅡ, declined mPAP and ameliorated vascular ultrastructure change.But the change of ultrastructure was similar in the 8 weeks hypoxia-hypercapnia group and perindopril treatment group.Conclusion It is suggested that chronic hypoxia-hypercapnia should induce the remodeling of pulmonary arteriolar structure via AngⅡ and that perindopril could ease pulmonary vascular remodeling in early stage.

Effect of puerain on Apelin/APJ system in right ventricle of pulmonary hypertensive rats induced by hypoxia-hypercapnia / 中草药

Objective To investigate whether the effect of puerarin on right ventricle hypertrophy of pulmonary hypertensive rats induced by chronic hypoxia-hypercapnia was related to new peptide Apelin or its receptor(APJ).Methods Thirty male Sprague-Dawley rats were randomly divided into three groups, they are control group,hypoxia-hypercapnia 4-week model group,and hypoxia-hypercapnia 4-week plus puerarin group.The concentrations of Apelin-36 protein in plasma and homogenate of right ventricular muscle were detected by radioimmunoassay.The mRNA expressions of Apelin and APJ in right ventricu- lar muscle were measured by semi-quantitive reverse transcription polymerase chain reaction(RT-PCR). Results The weight ratio of right ventricle to left ventricle plus septum[RV/(LV+S)] in model group was significantly higher than that in control group(P0.05).The plasma concen- tration of Apelin-36 protein in model group was significantly higher than that in control group(P