Penehyclidine Hydrochloride Group Research Articles

Protective effect of penehyclidine hydrochloride on lipopolysaccharide-induced acute kidney injury in rat.

We aimed to observe the effect of penehyclidine hydrochloride (PHC) on lipopolysaccharide (LPS)-induced acute kidney injury in rats and expression of tight junction proteins ZO-1 and occludin. Adult male Sprague-Dawley (SD) rats were divided randomly (N = 10) into control group (C), LPS group (LPS), low-dose PHC group (L-PHC), and high-dose PHC group (H-PHC). All rats, except C group, received a vena caudalis injection of 5.0 mg/kg LPS; after 30 min, rats in L-PHC and H-PHC groups received a vena caudalis injection of 0.3 and 0.9 mg/kg PHC. After 24 h, tumor necrosis factor (TNF)-α, interleukin (IL)-1β, serum creatinine (Scr), and blood urea nitrogen (BUN) were detected. Histopathological changes and expression of ZO-1 and occludin were observed in renal tissues. Versus levels of TNF-α (38.5 ± 9.0), IL-1β (46.3 ± 12.7), Scr (37.2 ± 9.3), and BUN (6.5 ± 1.1) in control group, those in LPS group, TNF-α (159.0 ± 21.3), IL-1β (130.8 ± 18.7), Scr (98.5 ± 18.2), and BUN (12.8 ± 1.8), increased obviously (P < 0.05), with significantly structural changes and decreases of ZO-1 and occludin. However, TNF-α (111.3 ± 11.6), IL-1β (78.4 ± 14.3), Scr (51.3 ± 12.5), BUN (8.1 ± 1.2) in H-PHC group, and TNF-α (120.8 ± 14.3), IL-1β (92.5 ± 19.0), Scr (56.7 ± 14.7), BUN (9.7 ± 1.6) in L-PHC group were obviously decreased (P < 0.05). PHC has protective effects on acute kidney injury in sepsis, including abatement of renal tissue inflammation and functional improvement, potentially by upregulating ZO-1 and occludin.

Protective effects of penehyclidine hydrochloride on acute lung injury caused by severe dichlorvos poisoning in swine

Background Organophosphate poisoning is an important health problem in developing countries which causes death mainly by inducing acute lung injury. In this study, we examined the effects of penehyclidine hydrochloride (PHC), a selective M-receptor inhibitor, on dichlorvos-induced acute lung injury in swine. Methods Twenty-two female swines were randomly divided into control (n=5), dichlorvos (n=6), atropine (n=6), and PHC (n=5) groups. Hemodynamic data, extravascular lung water index (EVLWI), and pulmonary vascular permeability index (PVPI) were monitored; blood gas analysis and acetylcholinesterase (AchE) levels were measured. PaO2/FiO2, cardiac index (CI), and pulmonary vascular resistance indices (PVRI) were calculated. At termination of the study, pulmonary tissue was collected for ATPase activity determination and wet to dry weight ratio (W/D) testing 6 hours post-poisoning. TUNEL assay, and Bax, Bcl-2, and caspase-3 expression were applied to pulmonary tissue, and histopathology was observed. Results After poisoning, PHC markedly decreased PVRI, increased CI more effectively than atropine. Anticholinergic treatment reduced W/D, apoptosis index (AI), and mitigated injury to the structure of lung; however, PHC reduced AI and caspase-3 expression and improved Bcl-2/Bax more effectively than atropine. Atropine and PHC improved ATPase activities; a significant difference between groups was observed in Ca2+-ATPase activity, but not Na+-K+-ATPase activity. Conclusions The PHC group showed mild impairment in pathology, less apoptotic cells, and little impact on cardiac function compared with the atropine group in dichlorvos-induced acute lung injury.

Effects of penehyclidine hydrochloride on expression of Toll like receptor-4 and nuclear factor kappa B in a rat model of sepsis-induced acute lung injury

Objective To evaluate the effects of penehyclidine hydrochloride (PHC) on the expression of Toll like receptor-4 (TLR4) and nuclear factor kappa B (NF-κcB) in a rat model of sepsis-induced acute lung injury (ALI).Methods Seventy-two adult male Sprague-Dawley rats,weighing 180-220 g,were randomly divided into 3 groups (n =24 each) using a random number table:shame operation group (group S),ALI group and PHC group.Sepsis-induced ALl was induced by cecal ligation and puncture in anesthetized rats.In group PHC,PHC 0.45 mg/kg was intramuscularly injected immediately after cecal ligation and puncture.At 6,12,24 and 36 h after ligation,the broncho-alveolar lavage fluid (BALF) was collected for detection of TNF-α and IL-6 concentrations and the lungs were removed for determination of the expression of TLR4 (using RT-PCR and Western blot) and NF-κBp65 (using Western blot) in lung tissues and for microscopic examination.The pathological changes of lungs were scored.The wet to dry lung weight (W/D) ratio was calculated and the activity of myeloperoxidase (MPO) in lung tissues was measured.Results As compared with S group,the IL-6 concentrations in BALF at 6,12 and 24 h after ligation,TNF-α concentration in BALF at 6 and 12 h after ligation,and the expression of TLR4 and NF-κBp65,pathological scores,W/D ratio and MPO activity at each time point were significantly increased in ALI group (P ＜ 0.05).Compared with ALI group,the TNF-α concentration in BALF at 6 and 12 h after ligation,and IL-6 concentrations in BALF,the expression of TLR4 and NF-κBp65,pathological scores,W/D ratio and MPO activity at each time point were significantly decreased in group PHC (P ＜ 0.05).Conclusion PHC inhibits NF-κB activation and decreases inflammatory responses through blocking TLR4 expression in lung tissues,thus attenuating sepsis-induced ALI in rats. Key words: Cholinergic antagonists; Sepsis; Respiratory distress syndrome, adult ; Toll-like receptor 4; NF-kappa B

Effect of penehyclidine hydrochloride on level of angiopoietin-1 and tyrosine kinase receptor-2 during endotoxin-induced acute lung injury in rats

Objective To evaluate the effect of penehyclidine hydrochloride (PHC) on the level of angiopoietin-1 (Ang-1) and tyrosine kinase receptor-2 (Tie-2) during endotoxin-induced acute lung injury (ALI) in rats.Methods Forty adult male Sprague-Dawley rats,weighing 180-220 g,were randomly divided into 4 groups using a random number table (n =10 each):control group (group C),ALI group,low-dose PHC group (group L-PHC) and high-dose PHC group (group H-PHC).ALI was induced with iv injection of lipopolysaccharide 5.0 mg/kg via the tail vein.In L-PHC and H-PHC groups,PHC 0.6 and 2 mg/kg were injected,respectively,via the tail vein at 1 and 24 h after lipopolysaccharide injection.The rats were sacrificed at 48 h after the initial injection of PHC to measure the lung water content,protein concentration in bronchoalveolar lavage fluid (BALF),and the expression of Ang-1,Tie-2 and phosphorylated Tie-2 in lung tissues.The morphological changes of lung tissues were observed under light microscope and the ultrastructural changes of alveolar epithelial barrier under transmission electron microscope.Results Compared with group C,the lung water content and protein concentrations in BALF were significantly increased,and the expression of Ang-1 and phosphorylated Tie-2 was down-regulated in the other three groups (P ＜ 0.05).Compared with group ALI,the lung water content and protein concentrations in BALF were significantly decreased,and the expression of Ang-1 and phosphorylated Tie-2 was up-regulated in H-PHC group (P ＜ 0.05),and no significant changes were found in the parameters mentioned above in group L-PHC (P ＞0.05).The damage to lung tissues was significantly reduced in group H-PHC as compared with group ALI.Conclusion PHC can improve the permeability of pulmonary microvascular and reduce injury to alveolar epithelial barrier,thus ameliorating endotoxin-induced ALI in rats,and the effect is dose-related and up-regulation of Ang-1 expression and inhancement of Tie-2 activity are involved in the mechanism. Key words: Cholinergic antagonist ; Respiratory distress syndrome, adult ; Endotoxemia; Angiopoietin-1 ; Receptor, protein-tyrosine kinases

Effects of penehyclidine hydrochloride pretreatment on expression of β-arrestin-1 during sepsis-induced acute lung injury in mice

Objective To investigate the effects of penehyclidine hydrochloride (PHCD) pretreatment on β-arrestin-1 expression during sepsis-induced acute lung injury in mice.Methods Thirty female Kunming mice,weighing 18-20 g,were randomly divided into 3 groups (n =10 each):sham operation group (S group),sepsis group (CLP group) and PHCD group.Sepsis was induced by cecal ligation and puncture (CLP).In PHCD group,PHCD 0.45 mg/kg was injected intraperitoneally 1 h before CLP.The equal volume of normal saline was given instead in groups S and CLP.The mice were sacrificed at 12 h after CLP,bronchoalveolar lavage fluid (BALF) was collected for measurement of the total protein concentration,and the lungs were removed for determination of wet/dry lung weight ratio and expression of myosin light chain kinase (MLCK),vascular endothelial cadherin (VE-cad-herin) and β-arrestin-1 in lung tissues.The pathological changes of the lung were scored.Results Compared with group S,the lung injury score,wet/dry lung weight ratio and total protein concentration in BALF were significantly increased,MLCK expression was up-regulated and VE-cadherin expression was down-regulated in groups CLP and PHCD,β-arrestin-1 expression was down-regulated in group CLP and β-arrestin-1 expression was up-regulated in group PHCD (P ＜ 0.05 or 0.01).The lung injury score,wet/dry lung weight ratio,total protein concentration in BALF,and MLCK expression were significantly lower,while the expression of VE-cadherin and β-arrestin-1 was higher in PHCD group than in CLP group (P ＜ 0.05 or 0.01).Conclusion PHCD pretreatment can ameliorate acute lung injury through up-regulating β-arrestin-1 expression and reducing microvascular permeability in septic mice. Key words: Cholinergic antagonists ; Arrestins ; ; Respiratory distress syndrome, adult ; Sepsis

Penehyclidine hydrochloride preserves the intestinal barrier function in patients undergoing cardiopulmonary bypass

The study objective was to investigate the protective effect of penehyclidine hydrochloride on intestinal barrier function integrity and its therapeutic potential on endotoxemia and systemic inflammatory response in patients undergoing cardiopulmonary bypass. Forty patients undergoing cardiac valve replacement with cardiopulmonary bypass were enrolled in the study. All patients were randomly divided into the penehyclidine hydrochloride or control group (20 patients in each group). Patients in the penehyclidine hydrochloride group received an intravenous injection of 0.05 mg/kg penehyclidine hydrochloride 10 minutes before cardiopulmonary bypass, and those in the control group were given the same volume of saline. Blood samples for blood glucose, lactic acid, intestinal fatty acid binding protein, D-lactate, serum endotoxin (lipopolysaccharide), interleukin-6, and interleukin-10 measurements were collected during the following time points: immediately after anesthesia induction (T0), 10 minutes after the release of aortic-clamping (T1), immediately after weaning from cardiopulmonary bypass (T2), 2 hours postoperatively (T3), 6 hours postoperatively (T4), and 18 hours postoperatively (T5). Blood glucose, lactic acid, intestinal fatty acid binding protein, D-lactate, lipopolysaccharide, interleukin-6, and interleukin-10 were significantly increased at all postoperative time points. At specific postoperative time points, blood glucose, lactic acid, intestinal fatty acid binding protein, D-lactate, lipopolysaccharide, and interleukin-6 were statistically lower in the penehyclidine hydrochloride group than in the control group. Postoperatively, interleukin-10 did not differ between the penehyclidine hydrochloride and control groups. Penehyclidine hydrochloride preserves intestinal barrier function integrity, attenuates endotoxemia, and inhibits systemic inflammatory response in patients undergoing cardiopulmonary bypass, possibly by improving intestinal microcirculation and depressing stress response.

Protective effect of penehyclidine hydrochloride on secondary lung injury after traumatic shock in rats

Objective To observe the interfering effect of different doses of penehyclidine hydrochloride (PHC) on the mRNA expressions of nuclear factor kappa B (NF-κB) and inducible nitric oxide synthase (iNOS) in the lung tissue of rats with traumatic shock so as to investigate the protective role of PHC in secondary long injury following traumatic shock and the underlying mechanism.Methods The traumatic shock model was established.A total of 104 Wistar rats were randomly divided into four groups:control group,shock group,low dose PHC group ( P1 group) and high dose PHC group ( P2 group).At the beginning of resuscitation,the rats in P1 and P2 groups were given transjugular intravenous injection of 2 ml/kg isotonic saline containing 0.15 mg/kg and 0- 45 mg/kg PHC respectively,while the rats in shock and control groups were injected only isometric isotonic saline.The rats in the four groups were killed at 2 h,6 h,12 h and 24 h after resuscitation respectively to detect the mRNA expressions of NF-κB and iNOS by using RT-PCR and determine the lung wet/dry weight (W/D) ratio,lung permeability index (LPI) and lung injury score (LIS).Results The mRNA expressions of NF-κB and iNOS,lung W/D ratio,LPI and LIS at all the time intervals in the shock,P1 and P2 groups were all significantly increased as compared with those in the control group (P＜0.05).Howerver,the P2 group showed significant reduction in aspects of the mRNA expressions of NF- κB and iNOS,lung W/D ratio,LPI and LIS at all time points and P1 group also had significant decrease regarding the mRNA expressions of NF-κB and iNOS,lung W/D ratio at2 h,6 h,and LPI and LIS at 2 h,6 h,12 h,as compared with the shock group.Meanwhile,P2 group showed evident decrease at 6 h concerning the mRNA expressions of NF-κB and iNOS,lung W/D ratio,LPI and LIS as compared with P1 group (P ＜ 0.05 ).Conclusions PHC,especially at a large dosage,can significantly mitigate the long injury secondary to traumatic shock,and the mechanism may be associated with the inhibition of mRNA expressions of NF-κB and iNOS. Key words: Shock, traumatic; Nuclear factor kappa B; Nitric oxide synthase; Acute lung injury; Penehyclidine hydrochloride

Clinical study of effect of penehyclidine hydrochloride and atropine sequential therapy in the treatment of severe acute organophosphorus pesticide poisoning

To investigate the clinical efficacy of penehyclidine hydrochloride sequential to atropine in severe acute organophosphorus pesticide poisoning (AOPP). A retrospective analysis of the clinical data of 180 patients with severe AOPP admitted to the Emergency Center of Wuwei City People's Hospital from January 2007 to August 2011 was conducted. The patients were divided into penehyclidine hydrochloride sequential to atropine group, atropine group and penehyclidine hydrochloride group according to difference of anti-choline drugs using, with 60 cases in each group. The complication rate, time of recovery of cholinesterase (ChE) activity to 70％, hospital stay time and cost, the cure rate, mortality rate in three groups were analyzed. In penehyclidine hydrochloride sequential to atropine group, except for 1 case of cancer of gastric cardia with poisoning after operation showing intermediate syndrome of poisoning, the remaining patients did not have any complication, and the incidence of complications was 1.67％.No death occurred in all the patients, and the cure rate was 100.00％.Time of recovery from ChE activity to 70％ was (4.0 ± 1.1 ) days; hospital stay was (7.0 + 2.2) days; hospital expenses were (6268 ± 238 ) yuan. In atropine group, 3 patients were found to have atropine resistance, 3 patients showed intermediate syndrome, rebound was observed in 2 cases, atropine poisoning in 2 patients, and the incidence of complications was 16.67％.Three patients died of respiratory or circulatory failure, and the mortality rate was 5.00％.Fifty-seven patients were cured, the cure rate was 95.00％.The time of ChE activity recovery to 70％ was (8.0 ± 0.9) days. Hospital stay was (12.0 ± 2.1) days. Hospital expenses were (7160 ± 110) yuan. In penehyclidine hydrochloride group, 1 patient was found to have respiratory failure, 1 case suffered from pulmonary edema, and the complication rate was 3.33％.Two patients died, the mortality rate wan 3.33％.Fifty-eight patients were cured, the cure rate was 96.67％.The time of ChE activity recovery to 70％ was (6.0 ± 0.7) days, hospital stay was (9.0 ± 1.5) days, and hospital expenses were (7921 ± 230) yuan. Compared with atropine group, penehyclidine hydrochloride sequential to atropine group had a low death rate, high cure rate, less complications, ChE activity recover fast, short hospital days, and the hospitalization expenses were lower than that of the single use of atropine or single use of penehyclidine hydrochloride group, and the differences were statistically significant (all P＜0.01). In treatment of severe AOPP by penehyclidine hydrochloride sequential to atropine, curative effect was more significant, with fewer adverse reactions, short hospital stay, and lower cost.

Effect of penehyclidine hydrochloride on acute lung injury induced by cardiopuimonary bypass in rats

Objective To investigate the effect of penehyclidine hydrochloride on acute lung injury induced by cardiopulmonary bypass (CPB) in rats.Methods Forty adult male SD rats aged 4-6 months weighing 330-420 g were randomly divided into4 groups ( n =10 each): sham operation group (group S),acute lung injury group (group ALI) and low and high dose of penehyclidine hydrochloride groups (groups PL and PH ).Penehyclidine hydrochloride 0.6 and 2.0 mg/kg were added to the priming solution in groups PL and PH,while the equal volume of normal saline was added in group ALI instead.The rats of groups ALI,PL and PH were underwent 1 h of CPB.Arterial blood samples were collected before CPB and at 2 h after CPB for blood gas analysis.The superior vera cava blood samples and lung tissues were collected at 2 h after CPB for determination of concentrations of TNF-α and IL-6,lung tissue contents of water and malondialdehyde (MDA) and activity of glutathione peroxidase (GSH-px).The pathological change of lung tissue was also examined.Results Compared with group S,PaO2 was significantly decreased at 2 h after CPB,plasma concentrations of TNF-α and IL-6 and contents of water and MDA in lung tissues were increased,while activity of GSH-px in lung tissues was decreased in groups ALI,PL and PH ( R ＜ 0.05).Compared with group ALI,PaO2 was significantly increased at 2 h after CPB,plasma concentrations of TNF-α and IL-6 and contents of water and MDA in lung tissues were decreased,activity of GSH-px in lung tissues was increased (P ＜ 0.05),and the pathological change was reduced in groups PL and PH.Compared with group PL,PaO2 was significantly increased at 2 h after CPB,plasma concentrations of TNF-α and IL-6 and contents of water and MDA in lung tissues were decreased,activity of GSH-px in lung tissues was increased ( P ＜0.05),and the pathological change was reduced more obviously in group PH.Conclusion Penehyclidine hydrochloride 0.6 or 2.0 mg/kg can reduce the CPB-induced lung injury in a dose-dependent manner by antioxidant and anti-inflammatory mechanism in rats. Key words: Cholinergic antagonists; Cardiopulmonary bypass; Respiratory distress syndrome, adult

Effect of penehyclidine hydrochloride on tramadol dependence and c-fos, △FosB and M5 receptor expression in relevant brain regions in rats

Objective To investigate the effect of penehyclidine hydrochloride (PHCD) on tramadol dependence and c-fos,△ FosB and M5 receptor expression in relevant brain regions in rats.Methods Thirty male adult SD rats weighing 180-220 g were randomly assigned to 3 groups (n =10 each):control group (group C),tramadol dependence group (group T) and PHCD group (group P).Tramadol dependence was induced by subcutaneous 10 mg/kg once a day for 7 consecutive days in groups T and P.PHCD 1.5 mg/kg was injected intraperitoneally on day 8 in group P,while in groups C and T the equal volume of normal saline was injected intraperitoneally instead of PHCD.The rats underwent conditioned place perference test at 30 min after intraperitoneal injection.The time spent in drug-paired side (gray area) was recorded.The rats were sacrificed after the conditioned place perference testand the brain was removed.The relevant brain regions (ventral tegmental area,prefrontal cortex,nucleus accumbens )were separated for determination of c-fos,△ FosB expression by Western blot and M5 receptor mRNA expression by RT-PCR.Results Compared with group C,the time spent in the drug-paired side (gray area) was significantly prolonged,and c-fos,△FosB and M5 receptor mRNA expressions were up-regulated in group T,△FosB and Ms receptor mRNA expressions were down-regulated in group P ( P ＜ 0.05 or 0.01 ).There was no significant difference in time spent in the drug-paired side (gray area) and c-fos expression between groups C and P( P ＞ 0.05).Compared with group T,the time spent in the drug-paired side (gray area) was significantly shortened,and c-fos,△ FosB and M5 receptor mRNA expressions were down-regulated in group P (P ＜0.01).Conclusion PHCD can significantly inhibit tramadol dependence by down-regulating c-fos,△FosB and M5 receptor expression in relevant brain regions. Key words: Cholinergic antagonists; Tramadol; Substance-related disorders ; Proto-oncogene proteins c-fos ; Receptors, cholinergic

Effects of intravenous penehyclidine hydrochloride or doxofylline on respiratory mechanics during non-thoracotomy in patients with chronic obstructive pulmonary disease

Objective To investigate the effects of intravenous penehyclidine hydrochloride or doxofylline on respiratory mechanics during non-thoracotomy in patients with chronic obstructive pulmonary disease (COPD).Methods One hundred and thirty-five ASA Ⅱ or Ⅲ patients with COPD, aged 55-86 yr, weighing 44-78 kg,scheduled for elective non-thoracotomy under general anesthesia, were randomly divided into 3 groups ( n = 45 each): control group (group C), penehyclidine hydrochloride group (group P) and doxofylline group (group D).Anesthesia was induced with fentanyl 4 μg/kg, propofol 1.5 rg/kg and cis-atracurium 0.2 mg/kg. The patients were tracheal intubated and mechanically ventilated. PETCO2 was maintained at 40 mm Hg. At 5 rin after tracheal intubation, penehyclidine hydrochloride 0.01 mg/kg was injected intravenously in group P, and doxofylline 4 mg/kg was injected intravenously in group D. The equal volume of normal saline was injected intravenously in group C. Anesthesia was maintained with propofol 5 mg· kg- 1 · h- 1, eis-atracurium 0.2 mg· kg- 1 · h- 1, and intermittent iv boluses of fentsnyl. The auditory evoked potential index was maintained at 15-20 during operation. The peak airway pressure, airway plateau pressure, lung compliance and airway resistance were recorded immediately before administration, and at 30, 45 and 60 rin after administration. Results Compared with group C, the peak airway pressure, airway plateau pressure and airway resistance were significantly decreased, while the lung compliance was significantly increased at each time point after administration in groups P and D ( P ＜ 0.05 ). There was no significant difference in the parameters of respiratory mechanics at each time point between group P and group D ( P ＞ 0.05). Conclusion Both intravenous penehyclidine hydrochloride and doxofylline can improve respiratory mechanics during non-thoracotomy in patients with COPD. Key words: Cholinergic antagonists; Bronchodilator agents; Respiratory mechanics; Pulmonary disease, chronic obstructive

Protective effects of penehyclidine hydrochloride on lipopolysaccharide-induced endothelial cells injury

Objective To investigate the effects of penehyclidine hydrochloride ( PHC) on lipopolysaccharide (LPS) -induced endothelial cells injury and its mechanism. Methods ECV-304 was cultured in RPMI1640 in a 5% humidified CO2 atmosphere at 37 ℃. Then cultured cells were used to assess the following treatments: control group, LPS group (1 μg/mL) and PHC group(2 μg/mL). At the end of the experiments, supernatant was collected for determination of lactate dehydrogenase ( LDH), and cells were collected for determination of malondialdehyde (MDA), superoxide dismutase (SOD), and nitric oxide (NO) levels. And extracellular regulated kinasel/2( ERKl/2)and JNK MAPK (mitogen-activated protein kinases, MAPK) protein expressions were determined using Western blot technique. Analysis of variance (ANOVA) was used for statistical analysis to compare values among all groups. A significant difference was presumed for a probability value < 0.05. Results Compared with control group, LDH leakage [(1642 ± 367) U/L vs (169±33)U/L], the contents of MDA[(13. 2 ± 1. 2) nmol/L vs (7. 2 ±0. 8)nmol/mL] and NO levels [(143.2 ± 10.3) μmol/L vs(85.5 ±4.1) μmol/L], expressions of ERK1/2 and JNK were remarkably increased and SOD activities[(41.2 ±2.7) U/mL vs (61. 1 ±2.8) U/mL] were obviously decreased in LPS group. PHC markedly decreased LDH leakage [(392 ±90) U/L], MDA contents [(8. 6 ± 1. 3) nmol/ mL] and NO levels [(92.1 ±6.6) μmol/L], ERK1/2 activation and enhanced SOD activities [(58.0± 3.0) U/mL]. Conclusions PHC could protect endothelial cells against LPS-induced cell injury. The effect of PHC is likely mediated through inhibition of ERK1/2 MAPK activation. Key words: Penehyclidine hydrochloride; Lipopolysaccharide; Endothelial cell; MDA; SOD; NO; ERK1/2; JNK

Effects of penehyclidine hydrochloride on rat intestinal barrier function during cardiopulmonary bypass

To test the ability of penehyclidine hydrochloride (PHC) to attenuate intestinal injury in a rat cardiopulmonary bypass (CPB) model. Male Sprague-Dawley rats were randomly divided into six groups (eight each): sham-operated control; sham-operated low-dose PHC control (0.6 mg/kg); sham-operated high-dose PHC control (2.0 mg/kg); CPB vehicle control; CPB low-dose PHC (0.6 mg/kg); and CPB high-dose PHC (2.0 mg/kg). Blood samples were collected from the femoral artery 2 h after CPB for determination of plasma diamine oxidase (DAO), D-lactate and endotoxin levels. Spleen, liver, mesenteric lymph nodes and lung were removed for biochemical analyses. Intestinal tissue ultrastructure was examined by electron microscopy. In the sham-operated groups, high- and low-dose-PHC had no significant impact on the levels of DAO, D-lactate and endotoxin, or the incidence of intestinal bacterial translocation (BT). Serum levels of DAO, D-lactate, endotoxin and the incidence of intestinal BT were significantly increased in the surgical groups, compared with the sham-operated groups (0.543 ± 0.061, 5.697 ± 0.272, 14.75 ± 2.46, and 0/40 vs 1.038 ± 0.252, 9.377 ± 0.769, 60.37 ± 5.63, and 30/40, respectively, all P < 0.05). PHC alleviated the biochemical and histopathological changes in a dose-dependent manner. Serum levels of DAO, D-lactate, and endotoxin and the incidence of intestinal BT in the high-dose PHC group were significantly lower than in the low-dose PHC group (0.637 ± 0.064, 6.972 ± 0.349, 29.64 ± 5.49, and 14/40 vs 0.998 ± 0.062, 7.835 ± 0.330, 38.56 ± 4.28, and 6/40, respectively, all P < 0.05). PHC protects the structure and function of the intestinal mucosa from injury after CPB in rats.

Effects of penehyclidine hydrochloride combined with ulinastatin on lung injury in patients undergoing cardiac valve replacement with cardiopulmonary bypass

Objective To investigate the effects of penehyclidine hydrochloride combined with ulinastatin on lung injury in patients undergoing cardiac valve replacement with cardiopulmonary bypass(CPB).Methods Sixty ASA Ⅱ or Ⅲ patients of both sexes,aged 33-64,weighing 47-81 kg,NYHA class Ⅱ or Ⅲ ,scheduled for cardiac valve replacement,were randomly divided into 4 groups(n = 15 each): control group(group C),ulinastatin group(group U),penehyclidine hydrochloride group(group P)and penehyclidine hydrochloride + ulinastatin group(group PU).Group U,P and PU received iv injection of ulinastatin 20 000 U/kg,penehyclidine hydrochloride 0.05 mg/kg and ulinastatin 20 000 U/kg + penehyclidine hydrochloride 0.05 mg/kg 30 min after the end of CPB,respectively,while group C received equal volume of normal saline.Then PEEP was increased to 8 cm H2O in all groups.Blood samples were taken at 30 min,3 and 6 h after the end of CPB and 12 and 24 h after operation for determination of PaO2 and serum concentrations of TNF-α,IL-6,IL-8 and IL-10.Airway peak pressure and airway plateau pressure were recorded at the corresponding time points.Oxygen index(OI)and pulmonary compliance(CL)were calculated.Lung injury was scored at 6 h after the end of CPB and 12 and 24 h after operation.Results OI and CL were significantly increased and lung injury score was significantly decreased in group U,P and PU compared with group C(P ＜ 0.05 or 0.01),and in group PU compared with group U and P (P ＜ 0.05).Serum concentrations of TNF-α,IL-6 and IL-8 were significantly lower and the serum IL-10 concentration was significantly higher in group U,P and PU than in group C(P ＜ 0.05 or 0.01),and in group PU than in group U and P(P ＜ 0.05).There was no significant difference in the indices mentioned above between group U and P(P ＞ 0.05).Conclusion Penehyclidine hydrochloride combined with ulinastatin can attenuate lung injury by inhibiting inflammatory response in patients undergoing cardiac valve replacement with CPB. Key words: Quinuclidines; Trypsin inhibitors; Respiratory distress syndrome,adult; Cardiopulmonary bypass

Effect of penehyclidine hydrochloride on brain injury induced by cardiopulmonary bypass in rats

Objective To investigate the effect of penehyclidine hydrochloride on brain injury induced by cardiopulmonary bypass (CPB) in rats. Methods Thirty adult male SD rats were randomly divided into 5 groups ( n = 6 each): sham operation group (group S), CPB group, and low, median and high dose penehyclidine hydrochloride groups (group PL, PM , PH). Penehyclidine hydrochloride 0.2, 0.6 and 2.0 mg/kg were added to the priming solution in group PL, PM and PH respectively, while the equal volume of normal saline was added instead in group S. Blood samples were obtained at 2 h after termination of CPB to determine the plasma concentrations of neuron specific enolase (NSE) and S-100β protein. The brain tissues were taken to observe the ultrastructure of hippocampal neurons with electron microscope. Results The concentrations of NSE and S-100β protein were significantly higher in the other groups than in group S, while lower in group PM and PH than in group CPB and PL( P＜ 0.05). The S-100β protein concentration was significantly lower in group PH than in group PM( P ＜ 0.05). The damage to hippocampal neurons was significantly attenuated in group PM and Ps. Conclusion Penehyclidine hydrochloride 0.6 or 2.0 mg/kg can reduce the CPB-induced brain injury in a dose-dependent manner in rats. Key words: Cholinergic antagonists; Cardiopulmonary bypass; Brain

The effects of penehyclidine hydrochloride on the withdrawal syndrome and conditioned place preference of morphine dependent rats

Objective To explore the effects of penehyclidine hydrochloride (PHC) on the withdrawal syndrome and conditioned place preference(CPP) of morphine dependent rats. Methods ( 1 ) Forty-eight male SD rats were randomly assigned to 6 groups with one of 8 rats:morphine dependent group (MOR group) ,naloxone precipitated withdrawal group ( NAL group) ,PHC treatment groups ( PHC1,2,3 ) ,normal saline control group ( NS group). Subcutaneous injection of morphine in gradually increasing doses for 5 days (from 10 to 50 mg/kg ,two times daily) to establish the model of morphine physical dependent rats. The withdrawal syndrome was precipitated by naloxone (5 mg/kg,sc) and treated with PHC in various doses (0.5,1.0,1.5 mg/kg ,ip ) 30 min before haloxone-precipitated withdrawal. The body weight loss and withdrawal syndrome were observed respectively in 20 minutes. (2) 40 male SD rats were randomly assigned to 5 groups with one of 8 rats: morphine dependent group (MOR group) ,PHC treatment groups (PHC1 ,2,3 ) ,normal saline control group (NS group). The morphine conditioned place preference was induced by alternate subcutaneous injection of morphine for 7 days in rats ( 10mg/kg,once daily,8:00 AM) and saline( 16:00 PM). At d8,the rats were received the CPP test. The rats of PHC groups were treated with PHC (0.5,1.0,1.5 mg/kg , ip) prior to the CPP test, whereas the rats were treated with saline in MOR and NS group. Results (1) Theweight loss((8.53 ±l.20)g,(7.36±l.06)g,(5.40±1.79 ) g vs ( 12.63 ± 2.22 ) g, F = 83.16, P ＜ 0.01 ) and score precipitated withdrawal symptoms ( 25.36 ± 3.11,21.38±3.50,17.06±1.78 vs 31.69 ±2.76, F=256.56, P＜0.01)of morphine withdrawal rats was obviously alleviated by ip PHC in dose-related manner before naloxone-precipitated withdrawal. (2) There were significant differences in the times spent in the drug-paired side (gray area) between MOR and PHC groups( (529 ± 83 )s,(460 ± 107 ) s, (418 ± 97 ) s vs ( 643 ± 111 ) s, F = 13.22, P ＜ 0.01 ), and also in dose-related manner. Conclusion PHC could significantly inhibit the withdrawal syndrome and the expression of CPP on morphine dependent rats in a dose-dependent manner. Key words: Penehyclidine hydrochloride; Morphine dependent; Withdrawal syndrome

Effect of penehyclidine hydrochloride pretreatment on NF-κB mRNA expression and SOD activity in lung tissues in rats with acute lung injury induced by LPS

Objective To investigate the effects of penehyclidine hydrochloride (PHCD) pretreatment on NF-κB mRNA expression and SOD activity in lung tissues in rats with acute lung injury (ALI) induced by LPS.Methods Thirty-two male SD rats, 2 months old, weighing 230-280 g, were randomly divided into 4 groups (n=8 each): control group (group C), ALI group, low dose PHCD group (group LP) and high dose PHCD group (group HP). ALI was induced by intravenous LPS 5 mg/kg via tail vein. Group LP and HP received intraperitoneal PHCD 0. 3 and 1 mg/kg respectively 30 min before LPS administration. The rats were killed at 6 h after LPS administration. The lungs were removed immediately for determination of W/D lung weight ratio, lung water content, NF-κB mRNA expression, TNF-α and MDA content, and SOD activity and microscopic examination. Results NF-κB mRNA expression, TNF-α and MDA content, W/D lung weight ratio and lung water content were significantly higher, while SOD activity was significantly lower in group ALI, LP and HP than in group C (P ＜ 0.05). NF-κB mRNA expression, TNF-α and MDA content, W/D lung weight ratio and lung water content were significantly lower, while SOD activity was significantly higher in group LP and HP than in group ALI and HP than in group LP (P ＜ 0.05). The LPS-induced changes were mitigated by pretreatment with low and high doses of PHCD in group LP and HP.Conclusion Pretreatment with PHCD attenuates LPS-induced ALI by downregulating NF-κB mRNA expression, decreasing local inflammatory response and enhancing anti-oxidant activity. Key words: Cholinergic antagonists; NF-κB; Superoxide dismutase; Respiratory distress syndrome,adult; Endotoxemia

Effect of penehyclidine hydrochloride on the reinstatement of conditioned place preference in morphine dependent rats

Objective To investigate the effect of penehyclidine hydrochloride (PHCD) on the reinstatement of conditioned place preference (CPP) in morphine dependent rats. Methods Forty male adult SD rats weighing 180-220 g were randomly divided into 5 groups (n = 8 each): group control (group C); group morphine (group M) and 3 PHCD groups (group P1-3 ). Morphine 10 mg/kg was injected subcutaneously once a day for 8 days to induce morphine CPP. The rats were then subjected to extinction of CPP for 10 days with normal saline (NS) instead of morphine. After the extinction, the rats were put into the drug-paired side of the box. A single priming dose of morphine 4 mg/kg was injected to reinstate the morphine CPP. In group P1-3 the rats received PHCD 0.5, 1.0 and 1.5 mg/kg intraperitoneally 30 min prior to priming dose of morphine, whereas in group C and M the rats received NS. The second day the rats underwent CPP test. Results Compared with group M, the time spent in the drug-paired side (grey area) was significantly shortened in group P1-3 (P ＜ 0.05 or 0.01 ).Compared with group P1 ,no significant change in the time spent in the drug-paired side (grey area) was found in group P2(P ＞ 0.05), but the time spent in the drug-paired side (grey area) was significantly shortened in group P3 ( P ＜ 0.05). Conclusion PHCD could significantly inhibit the reinstatement of CPP induced by priming dose of morphine in morphine dependent rats and it is related to the dose. Key words: Cholinergic antagonists; Morphine dependence

Effect of intraoperative intravenous penehyclidine hydrochloride on pulmonary function in patients undergoning thoracotomy

Objective To investigate the effect of intmopemtive intravenous penehyclidine hydrochloride on pulmonary function in patients undergoning thoracotomy.Methods Sixty ASA Ⅰ or Ⅱ patients aged 30-64 yr scheduled for elective radical esophagectomy for cancer were randomly divided into 2 group(n=30 each):penehyclidinc hydrochloride group and control group.Penehychdine hydrochloride 0.01 mg/kg(in nolmal saline 2 ml)was injected iv 20 min after opening the thoracic cavity in penehyclidine hydrochloride group.The equal vohlme of normal saline was injected iv in control group.Anesthesia was induced with fentanyl 2μg/kg,propofol 0.4μG/ml and rocuronium 0.6 mg/kg.The patients were tracheal intubated and mechanically ventilated.Anesthesia was maintained with remlfentanyl 0.1μg·min-1,propofol 2.0-2.5 μg/ml and intermittent iv injecfion of rocuronium.The use of remifentanyl and pmpofol was stopped 5 min before operation.Dynamic lung compliance (Cd) and peak airway pressure were monitored and recorded immediately before penehychdine hydrechlofide administration (T0) and at 3 min(T1),5 min(T2),10 min(T3),30 min(T4),1 h(T5),2 h (T6)after penehyclidine hydrochloride administration.Results There was no significant difference in Cd and peak airway pressure among different time points in control group(P>0.05).Cd was significantly higher,while peak airway pressure lower at T1-6 than at T0 in penehychdine hydrochlofide group(P<0.05).Cd wag significantly higher,while peak airway pressure lower at T1-6 in penehyclidine hydrochloride group than in control group(P<0.05) .Conclusion Intraoperative intravenous penehyclidine hydrochloride can improve the pneumodynamics and is helpful for ventilation in patients undergoing thoracotomy. Key words: Cholinergic antagonists; Respiratory function tests

Effect of penehyclidine hydrochloride on gastric mucous membrane impairment during orthotopic liver transplantation

Objective To evaluate the effect of penehyclidine hydrochloride on gastric mucous membrane impairment during orthotopic liver transplantation (OLT) .Methods Thirty-eight ASA Ⅲ or Ⅳ patients aged 38-59 yr weighing 50-75 kg were randomly divided into 2 groups ( n = 19 each) : control group (C) and penehyclidine hydrochloride group (PH) . Penehyclidine hydrochloride 0.04 mg/kg in 50 ml of nomal saline (NS) was infused iv over 1 h after skin incision in group PH. Anesthesia was induced with midazolam, fentanyl, propofol and atracurium and maintained with isoflurane inhalation and infusion of propofol and atracurium. Radial artery was cannulated for blood sampling and BP monitoring. Swan-Ganz catheter was placed via right internal jugular vein. Gastric intramucosal tonometry catheter was inserted into the stomach. Gastric intramural pH and PCO_2 (pHi, PgCO_2) and arterial pH and PCO_2 ( pHa, PaCO_2 ) were measured immediately before operation (T_0, baseline) , 30 min before anhepatic phase (T_1 ) , 5, and 30 min of anhepatic phase (T_2 , T_3 ), 5, 30 and 60 min of neohepatic phase (T_4 , T_5 , T_6 ) and at the end of the operation (T_7 ) . Pg-aCO_2 was calculated. Results pHi and pHa significantly decreased while Pg-aCO_2 significantly increased at T_(2～5) as compared with the baseline values at T_0 in both groups. pHi and pHa values were significantly larger while Pg-aCO_2 was significantly smaller at T_(2～5) in group PH than in group C. Conclusion Intravenous penehyclidine hydrochloride 0.04 mg/kg can raise gastric intramural pH and protect gastric mucous membrane against injury. Key words: Cholinergic antagonists; liver transplantation; Gastric mucosa