OBJECTIVETo investigate the pharmacokinetics of Danshensu with in vivo microdialysis in freely moving rat's jugular vein.

METHODthree days after a microdialysis probe introducer was implanted into the jugular vein, a microdialysis probe was introduced to the blood vessel, and began to sample following a single intravenous injection (40 mg x kg(-1)) or a single oral dose (40 mg x kg(-1)) of Danshensu. All the samples were analyzed with HPLC. The concentration of Danshensu in blood were calculated according to the recovery of microdialysis probe and the concentration in dialysates. Pharmacokinetic parameters were than calculated with the concentration-time curve.

RESULTFor intravenous administration, t(1/2 zeta) = (69.62 +/- 33.42) min, AUC(0-infinity) = (3416.24 +/- 779.80) min x mg x L(-1), MRT(0-infinity) = (38.15 +/- 8.61) min, and for oral administration, Cmax = (7.42 +/- 3.08) mg x L(-1), tmax = (31.50 +/- 8.57) min, t(1/2 zeta) = (83.25 +/- 37.35) min, AUC(0-infinity) = (793.19 +/- 101.32) min x mg x L(-1), MRT(0-infinity) = (125.89 +/- 58.27) min. The oral bioavailability of Danshensu F = 22.56%.

CONCLUSIONIn vivo microdialysis in freely moving rat's jugular vein is a useful tool to obtain a complete set of free drug concentrations to determine reliable pharmacokinetic parameters.

Animals ; Area Under Curve ; Jugular Veins ; cytology ; metabolism ; Lactates ; pharmacokinetics ; Male ; Microdialysis ; Motor Activity ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo investigate the cerebral uptake and regional distribution of propofol when plasma propofol concentration reaches equilibrium in the internal carotid artery and internal jugular vein in dogs.

METHODSEight male hybrid dogs aged 12-18 months weighing 10-12 kg were anesthetized with propofol at a single bolus (7 mg/kg) in 15 s followed by propofol infusion at a constant rate of 70 mg.kg(-1).h(-1) via the great saphenous vein of the right posterior limb. Blood samples were taken from the internal carotid artery and internal jugular vein at 30 min (T30) after propofol infusion for measurement of plasma propofol concentrations by high-pressure liquid chromatography (HPLC). The thalamus, epithalamus, metathalamus, hypothalamus, subthalamus, frontal lobe, parietal lobe, temporal lobe, hippocampus, cingulate gyrus, cerebellum, midbrain, pons, medulla oblongata and cervical cord were then dissected to determine propofol concentrations in these tissues by HPLC.

RESULTSThe propofol concentrations in the internal carotid artery and internal jugular vein blood plasma were comparable at T30 (6.16-/+1.02 vs 6.17-/+1.00 microg/ml, P>0.05). The propofol concentration was 6.11-/+1.07 microg/g in the epithalamus, 6.14-/+0.98 microg/g in the metathalamus, 6.12-/+1.02 microg/g in the hypothalamus, 6.15-/+1.00 microg/g in the subthalamus, 6.20-/+1.03 microg/g in the frontal lobe, 6.18-/+1.02 microg/g in the parietal lobe, 6.13-/+1.00 microg/g in the temporal lobe, 6.07-/+0.99 microg/g in the hippocampus, 6.14-/+1.06 microg/g in the cingulate gyrus, 6.15-/+1.00 microg/g in the cerebellum, 6.13-/+1.05 microg/g in the midbrain, 6.18-/+1.01 microg/g in the pons, 6.15-/+0.93 microg/g in the medulla oblongata, and 6.13-/+1.00 microg/g in the cervical cord, showing no significant differences in the distributions (P>0.05). Propofol concentration in the thalamus (8.68-/+0.88 microg/g) was significantly higher than those in the other brain tissues (P<0.05).

CONCLUSIONSAt the constant intravenous propofol injection rate of 70 mg.kg(-1).h(-1), plasma propofol concentration reaches equilibrium 30 min after the injection in the internal carotid artery and internal jugular vein with even distribution in the cerebral tissues in dogs, but the thalamus contains high propofol concentration.

Absorption ; Anesthetics, Intravenous ; blood ; pharmacokinetics ; Animals ; Brain ; metabolism ; Carotid Artery, Internal ; metabolism ; Dogs ; Jugular Veins ; metabolism ; Male ; Propofol ; blood ; pharmacokinetics ; Thalamus ; metabolism

PURPOSE: We hypothesized that regional cerebral oxygen saturation (rSO2) could replace jugular bulb oxygen saturation (SjvO2) in the steep Trendelenburg position under pneumoperitoneum. Therefore, we evaluated the relationship between SjvO2 and rSO2 during laparoscopic surgery. MATERIALS AND METHODS: After induction of anesthesia, mechanical ventilation was controlled to increase PaCO2 from 35 to 45 mm Hg in the supine position, and the changes in SjvO2 and rSO2 were measured. Then, after establishment of pneumoperitoneum and Trendelenburg position, ventilation was controlled to maintain a PaCO2 at 35 mm Hg and the CO2 step and measurements were repeated. The changes in SjvO2 (rSO2) -CO2 reactivity were compared in the supine position and Trendelenburg-pneumoperitoneum condition, respectively. RESULTS: There was little correlation between SjvO2 and rSO2 in the supine position (concordance correlation coefficient=0.2819). Bland-Altman plots showed a mean bias of 8.4% with a limit of agreement of 21.6% and -4.7%. SjvO2 and rSO2 were not correlated during Trendelenburg-pneumoperitoneum condition (concordance correlation coefficient=0.3657). Bland-Altman plots showed a mean bias of 10.6% with a limit of agreement of 23.6% and -2.4%. The SjvO2-CO2 reactivity was higher than rSO2-CO2 reactivity in the supine position and Trendelenburg-pneumoperitoneum condition, respectively (0.9+/-1.1 vs. 0.4+/-1.2% mm Hg-1, p=0.04; 1.7+/-1.3 vs. 0.5+/-1.1% mm Hg-1, p<0.001). CONCLUSION: There is little correlation between SjvO2 and rSO2 in the supine position and Trendelenburg-pneumoperitoneum condition during laparoscopic surgery.
Adult ; Aged ; Anesthesia, General ; Brain/*metabolism ; Carbon Dioxide/chemistry ; Cerebrovascular Circulation ; Head-Down Tilt ; Humans ; Jugular Veins/*metabolism ; Laparoscopy/*methods ; Male ; Middle Aged ; Oxygen/*metabolism ; Pneumoperitoneum, Artificial ; Pressure ; Respiration

OBJECTIVETo investigate the cerebral distribution of propofol during continued infusion at a constant rate when the cerebral propofol uptake reaches equilibrium in dogs.

METHODSSix healthy 1-year-old male dogs were used in this study. The venous channel was established in the great saphenous vein of the right posterior limb. Anesthesia was induced with a single bolus injection of propofol (7 mg/kg), followed by propofol infusion at a constant rate of 70 mg/(kg.h) using a microinfusion pump. The blood samples were taken from the right internal carotid and internal jugular vein at 30 min (T30) and 50 min (T50) during propofol infusion for measurement of plasma propofol concentrations with high performance liquid chromatography (HPLC). At T50, the frontal lobe, parietal lobe, temporal lobe, hippocampus, cingulate gyrus, thalamus, midbrain, pons, and cerebellum were dissected respectively for determination of propofol concentrations.

RESULTSPropofol concentrations in the internal carotid artery and internal jugular vein blood plasma were 3.107-/+1.067, 3.095-/+1.085 microg/ml at T30 and 3.091-/+1.101, 3.117-/+1.091 microg/ml at T50, respectively, showing no significant differences (P>0.05). Propofol concentrations in the frontal lobe, parietal lobe, temporal lobe, hippocampus, cingulate gyrus, thalamus, midbrain, pons, cerebellum at T50 were 3.085-/+1.123, 3.116-/+1.125, 3.073-/+1.159, 3.117-/+1.090, 3.075-/+1.178, 3.073-/+1.146, 3.075-/+1.151, 3.102-/+1.174, and 3.072-/+1.192 microg/g respectively, suggesting homogeneous propofol distribution in these cerebral tissues (P>0.05).

CONCLUSIONAt T50, the cerebral uptake of propofol reached equilibrium when propofol is distributed homogeneously in the cerebral tissues in dogs.

Anesthetics, Intravenous ; administration & dosage ; blood ; pharmacokinetics ; Animals ; Brain ; metabolism ; Carotid Artery, Internal ; metabolism ; Chromatography, High Pressure Liquid ; Dogs ; Infusions, Intravenous ; Jugular Veins ; metabolism ; Male ; Propofol ; administration & dosage ; blood ; pharmacokinetics ; Tissue Distribution

OBJECTIVETo investigate the effects of Shenfu Injection (, SFI) on cerebral metabolism in a porcine model of cardiac arrest (CA).

METHODSThirty Wuzhishan minipigs were randomly assigned to the control group (n=6), epinephrine group (EP group, n=12) and Sfigroup (n=12). After 8 min of untreated ventricular fifibrillation (VF), pigs in the EP group or Sfigroup were administered with either EP (0.02 mg/kg) or Sfi(1.0 mL/kg), respectively. After successful resuscitation, cerebrospinal fluid (CSF) levels of glucose, pyruvate, lactate, glutamate and glycerol were measured at 1, 6, 12 and 24 h after recover from spontaneous circulation (ROSC). In addition, neurologic defificit score (NDS) was calculated at 24 h after ROSC. Surviving pigs were killed at 24 h after ROSC, and the brain tissue was obtained for ultra-microstructure examination.

RESULTSCompared with the EP group, CSF glucose and pyruvate levels were higher (all P<0.01), and lactate levels were lower in the Sfigroup (P<0.01). Meanwhile, CSF glutamate and glycerol levels in the Sfigroup were lower in comparison to the EP group (all P<0.05). In addition, Sfidecreased NDS at 24 h after ROSC (P<0.01), and alleviated the histopathological damage of the brain.

CONCLUSIONSSficould alleviate brain injury after CA, which may be associated with improving cerebral metabolism.

Animals ; Blood Circulation ; Blood Gas Analysis ; Brain ; drug effects ; metabolism ; ultrastructure ; Cardiopulmonary Resuscitation ; Disease Models, Animal ; Drugs, Chinese Herbal ; administration & dosage ; pharmacology ; therapeutic use ; Heart Arrest ; cerebrospinal fluid ; drug therapy ; physiopathology ; Injections ; Jugular Veins ; drug effects ; metabolism ; Perfusion ; Sus scrofa

Central venous catheterization (CVC)-related venous thrombosis is a common but serious clinical complication, thus prevention and treatment on this problem should be extensively investigated. In this research, we aimed to investigate the incidence rate of CVC-related venous thrombosis in senile patients and give a further discussion on the related risk factors and predictors. A total of 324 hospitalized senile male patients subjected to CVC were selected. Retrospective investigation and analysis were conducted on age, underlying diseases, clinical medications, catheterization position and side, catheter retention time, and incidence of CVC-related venous thrombosis complications. Basic laboratory test results during catheterization and thrombogenesis were also collected and analyzed. Among the 324 patients, 20 cases (6.17%) of CVC-related venous thrombosis were diagnoseds. The incidence rate of CVC-related venous thrombosis in subclavian vein catheterization was significantly lower than that in femoral vein catheterization (P<0.01) and that in internal jugular vein catheterization (P<0.05). No statistically significant difference was found between femoral vein catheterization and internal jugular vein catheterization (P<0.05). Previous venous thrombosis history (P<0.01), high lactate dehydrogenase level (P<0.01), low high-density lipoprotein (HDL) level (P<0.05), and low albumin level (P<0.05) were found as risk factors or predictors of CVC-related venous thrombosis in senile male patients. Subclavian vein catheterization was the most appropriate choice among senile patients to decrease the incidence of CVC-related venous thrombosis. Previous venous thrombosis history, high lactate dehydrogenase level, low HDL level, and low albumin level were important risk factors in predicting CVC-related venous thrombosis.
Aged ; Aged, 80 and over ; Biomarkers ; metabolism ; Central Venous Catheters ; adverse effects ; Femoral Vein ; pathology ; Humans ; Incidence ; Jugular Veins ; pathology ; Male ; Retrospective Studies ; Risk Factors ; Subclavian Vein ; pathology ; Venous Thrombosis ; epidemiology ; etiology

OBJECTIVETo evaluate the efficacy of using small interfering RNA targeting TF as a therapy for vein graft failure.

METHODSExternal jugular vein to carotid artery interposition vein grafts, which were applied to a low flow condition, were made in 120 Sprague-Dawley rats weighing 260 to 300 g. These rats were randomly divided into 4 groups, 30 rats each group. Group A was atelocollagen-TF Stealth Select RNAi group. Group B was atelocollagen-TF Stealth RNAi group. Group C was atelocollagen group. Group D was control group. Small interfering RNA mixed with atelocollagen was administrated to the external wall of grafted veins. The TF protein expression of vein grafts was analyzed by Western blot at 1, 3, 7, 14, and 28 d postoperatively, and by immunochemistry at 3 d postoperatively. The proliferation index was determined at 14 d postoperatively. Neointimal hyperplasia was evaluated at 28 d postoperatively. BLOCK-iT fluorescent oligo was used to confirm its stability and successful transfer into the vein graft wall at 3 and 7 d postoperatively for another group (n=12).

RESULTSFluorescence of BLOCK-iT fluorescent oligo could be detected in the graft wall even at 7 d postoperatively. Knockdown of the TF expression was achieved by perivascular application of siRNA using atelocollagen. Compared with control group, the intima thickness at 28 d after grafting was significantly reduced (P < 0.05). This phenomenon was preceded by significant reduction of cell proliferation in siRNA-treated grafts at 14 d postoperatively (P < 0.05).

CONCLUSIONThe expression of TF in vein grafts can be effectively inhibited by specific siRNAs using a atelocollagen-based nonviral delivery approach in vivo, so that the neointimal thickening can be prevented. Transplants;

Animals ; Collagen ; pharmacology ; Drug Carriers ; pharmacology ; Female ; Hyperplasia ; prevention & control ; Jugular Veins ; pathology ; transplantation ; Male ; RNA Interference ; RNA, Small Interfering ; pharmacology ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Thromboplastin ; genetics ; metabolism ; Tunica Intima ; pathology

OBJECTIVE: To investigate the adenovirus-mediated LacZ gene expression and the destination in different organs of SD rats after the intravenous injection in rats. METHODS: Recombinant adenovirus vector containing LacZ was transferred to SD rats by injecting into the internal jugular vein. To identify the sites and periods of LacZ gene expression, X-gal staining was used to detect beta-gal level and period of LacZ gene expression of different organs in the transfected and non-transfected rats at different time intervals. RESULTS: On the 1st day after the injection, the lung, liver, kidney, and spleen expressed some beta-gal; on the 3rd day after the injection, the lung, liver, kidney, and spleen expressed beta-gal obviously; their peak levels were on the 7th day; the beta-gal level decreased on the 14th day; beta-gal expression disappeared in the most organs except the lungs on the 28th day. In all animals, the brain did not express any beta-gal. CONCLUSION The adenovirus-mediated exogenous gene transfer in the internal jugular vein may be an effective approach of gene therapy in some diseases in the lung, liver, and kidney.
Adenoviridae ; genetics ; Animals ; Female ; Gene Transfer Techniques ; Genetic Therapy ; Injections, Intravenous ; Jugular Veins ; Lac Operon ; genetics ; Lung ; metabolism ; Male ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Recombinant Proteins ; genetics ; Transfection

OBJECTIVETo investigate the expression of mammalian target of rapamycin (mTOR) and its substrates including p70s6k and 4E-BP1 in autogenous vein graft.

METHODSAutogenous vein graft model was established in 64 Wistar rats by transplanting the right common jugular vein to infrarenal abdominal aorta. Vein graft samples were harvested 6 hours, 1 day, 3 days, 1 week, 2 weeks, 4 weeks, 6 weeks and 8 weeks after surgery. The mRNA expression of mTOR, p70s6k and 4E-BP1 were measured by RT-PCR and in situ hybridization. Western blot and immunohistochemistry methods also were used to detect the protein expression of mTOR, p70s6k and 4E-BP1. Proliferating cell nuclear antigen (PCNA) was also detected at the same time.

RESULTSThe mRNA expression of mTOR and p70s6k increased soon after vein graft transplanting, rose quickly and reached the peak 3 days to 2 weeks after surgery, which recovered 6 to 8 weeks after surgery. The expression of 4E-BP1 mRNA decreased soon after surgery and reached the lowest at 1 week, then rose to the peak 4 to 6 weeks after transplantation. Protein expression of mTOR and p70s6k reached the peak 2 to 4 weeks and recovered to normal level 8 weeks after surgery, but the expression of 4E-BP1 decreased to the lowest during 1 to 2 weeks and reached the peak 4 to 6 weeks after transplanting. The positive cells mostly located in vascular smooth muscle cell (VSMC) just like PCNA.

CONCLUSIONSThe expression of mTOR and its substrates were activated in vein graft soon after transplantation, which means that mTOR and its substrates might become new targets for the prevention and therapy of stenosis or obliteration after vein graft transplanting.

Animals ; Aorta, Abdominal ; surgery ; Carrier Proteins ; genetics ; metabolism ; Female ; Immunohistochemistry ; Jugular Veins ; transplantation ; Male ; Phosphoproteins ; genetics ; metabolism ; Protein Kinases ; genetics ; metabolism ; RNA, Messenger ; genetics ; Rats ; Rats, Wistar ; Ribosomal Protein S6 Kinases, 70-kDa ; genetics ; metabolism ; TOR Serine-Threonine Kinases ; Transplantation, Autologous

OBJECTIVETo observe the effect of perivenous support with autologous pericardium on neointimal thickening in canine vein grafts.

METHODSAn autologous pericardium graft of 7 cm x 4 cm was harvested in right anterolateral thoracotomy. Two equal segments of the jugular vein were transplanted to both sides of the femoral arteries in 12 dogs, and on one side of the vein graft, perivenous support with autologous pericardium was applied. The vein grafts were harvested 2 and 4 weeks after operation and the thickness and area of the neointima calculated using computerized image analysis system. Scanning electron microscopy and PCNA immunohistochemistry were also performed.

RESULTSThe thickness and area of the neointima were significantly greater in the control grafts than in the grafts with perivenous support (P<0.05), and the proliferation of vascular smooth muscle cells in the supported graft was less active (P<0.05). Electron microscopy showed extensive destruction of the endothelium in the control graft, but only slight damage was found in the graft with perivenous support.

CONCLUSIONPerivenous support of the vein graft with autologous pericardium can reduce intimal and medial hyperplasia in the graft.

Animals ; Dogs ; Femoral Artery ; surgery ; Graft Occlusion, Vascular ; prevention & control ; Hyperplasia ; Immunohistochemistry ; Jugular Veins ; pathology ; surgery ; transplantation ; Male ; Microscopy, Electron, Scanning ; Muscle, Smooth, Vascular ; metabolism ; pathology ; ultrastructure ; Pericardium ; transplantation ; Proliferating Cell Nuclear Antigen ; analysis ; Random Allocation ; Tunica Intima ; metabolism ; pathology ; ultrastructure