Transcranial Doppler (TCD) was carried out to determine the resistive index (RI) values of normal canine cerebral arteries and its reproducibility and to evaluate the change of cerebral vascular resistance following diuretics administration. RI values of rostral cerebral artery (RCA) were compared between fontanelle window and temporal window. Normal ranges and reproducibility of the RI values were examined in the rostal cerebral artery (RCA) and caudal cerebral artery (CCA). And after administration of diuretics, TCD-derived RI values were measured at RCA and CCA. Cerebral vascular RI values of RCA and CCA were 0.55 +/- 0.05 and 0.55 +/- 0.03 in the normal dogs, respectively. There was no significant difference of RI between male and female; between fontanelle window and temporal window. Reproducibility of RI measurements between intraobserver and interobserver were relatively high. The RI of RCA and CCA were significantly increased 15 minutes after mannitol administration (p<0.01) and returned to baseline values by 30 minutes, but it did not significantly change after furosemide and saline administration. The results suggest that TCD is a useful test which can obtain reproducible results from any window and has the advantage of detecting subtle changes in cerebral vascular resistance.
Animals ; Cerebral Arteries/drug effects/*ultrasonography ; Diuretics/pharmacology ; Dogs/*physiology ; Feasibility Studies ; Furosemide/pharmacology ; Mannitol/pharmacology ; Reference Values ; Reproducibility of Results ; Ultrasonography, Doppler/*veterinary ; Vascular Resistance/drug effects/*physiology

OBJECTIVETo observe the effect of polyethylene oxide (PEO) solution at different concentrations on abdominal aortic blood flow and vascular resistance in rats and evaluate the safety and drag-reducing effect of PEO solution.

METHODSThirty-two rats were anesthetized and randomly divided into 4 groups. An ultrasonic flow probe was deployed on the abdominal aorta (5 mm above the common iliac artery) to measure the blood flow. The carotid artery pressure, iliac artery pressure, iliac vein pressure, central venous pressure (CVP) and ECG were also monitored. Saline or different concentrations of PEO [(1x10(-6)(low), 1x10(-5)(middle) and 5x10(-5)(high) g/ml)] were injected in the 4 groups of rats through the caudal vein at a constant rate of 5 ml/h for 20 min, and the changes of the vascular resistance was observed. RESULTS After injections of 1x10(-6) and 1x10(-5) g/ml PEO, the abdominal aortic flow increased significantly (P<0.05) while the vascular resistance was reduced (P(low)=0.052, P(middle)<0.001) as compared to those in the saline control group. Following the injection with 5x10(-5) g/ml PEO, the abdominal aortic flow increased to a threshold in the initial 4 min, after which it rapidly decreased to approach the baseline levels despite continuous infusion. Blood pressure remained stable after the injections except for 5x10(-5) g/mlPEO injection, which resulted in a reduction of the blood pressure by about 10 mmHg (P=0.014). The heart rate and CVP both underwent no significant changes following the injections.

CONCLUSIONThe drag-reducing effect of PEO is closely related to its concentration, and compared with 1x10(-6) g/ml, 1x10(-5) g/ml PEO more effectively increases the blood flow and decreases the resistance. The effectiveness and safety of EPO are attenuated at a concentration higher than 5x10(-5) g/ml.

Animals ; Aorta, Abdominal ; physiology ; Blood Flow Velocity ; drug effects ; Dose-Response Relationship, Drug ; Male ; Polyethylene Glycols ; pharmacology ; Random Allocation ; Rats ; Rats, Wistar ; Vascular Resistance ; drug effects

BACKGROUNDUnder an insulin resistance (IR) state, overproduction of reactive oxygen species (ROS) may be playing a major role in the pathogenesis of endothelial dysfunction, hypertension and atherosclerosis. Recently, increasing attention has been drawn to the beneficial effects of heme oxygenase-1 (HO-1) in the cardiovascular system. This study aimed to investigate the effects of HO-1 on vascular function of thoracic aorta in IR rats and demonstrate the probable mechanisms of HO-1 against endothelial dysfunction in IR states.

METHODSSprague-Dawley (SD) rats fed with high-fat diet for 6 weeks and the IR models were validated with hyperinsulinemic-euglycemic clamp test. Then the IR rat models (n = 44) were further randomized into 3 subgroups, namely, the IR control group (n = 26, in which 12 were sacrificed immediately and evaluated for all study measures), a hemin treated IR group (n = 10) and a zinc protoporphyrin-IX (ZnPP-IX) treated IR group (n = 8) that were fed with a high-fat diet. Rats with standardized chow diet were used as the normal control group (n = 12). The rats in IR control group, hemin treated IR group and ZnPP-IX treated IR group were subsequently treated every other day with an intraperitoneal injection of normal saline, hemin (inducer of HO-1, 30 micromol/kg) or ZnPP-IX (inhibitor of HO-1, 10 micromol/kg) for 4 weeks. Rats in the normal control group remained on a standardized chow diet and were treated with intraperitoneal injections of normal saline every other day for 4 weeks. Systolic arterial blood pressure (SABP) was measured by tail-cuffed microphotoelectric plethysmography. The blood carbon monoxide (CO) was measured by blood gas analysis. The levels of nitric oxide (NO), inducible nitric oxide synthase (iNOS), endothelial nitric oxide synthase (eNOS), blood glucose (BG), insulin, total cholesterol (TC) and triglyceride (TG) in serum, and the levels of total antioxidant capacity (TAOC), malondialdehyde (MDA) and superoxide dismutase (SOD) in the aorta were measured. The expression of HO-1 mRNA and HO-1 protein in aortal tissue were detected by semi-quantitative RT-PCR and Western blot. The vasoreactive tensometry was performed with thoracic aortic rings (TARs).

RESULTSCompared with the normal control group, the levels of SABP, BG, insulin, TC, TG, NO, iNOS and MDA were higher, while the levels of CO, TAOC, SOD and eNOS were lower in IR control rats. After treatment of IR rats for 4 weeks a more intensive expression of HO-1 mRNA and HO-1 protein were observed in hemin treated IR group compared with the normal control group. And compared with 4-week IR control rats, the levels of CO, TAOC, SOD and eNOS were increased, while the levels of SABP and iNOS activity were lower in the hemin treated IR group. Administration of hemin in IR rats appeared to improve the disordered vasorelaxation of TARs to acetylcholine (ACh). Alternatively, the reverse results of SABP, CO, TAOC, SOD, iNOS and vasorelaxation responses to ACh were observed in IR rats with administration of ZnPP-IX.

CONCLUSIONSThe endothelial dysfunction in the aorta is present in the IR state. The protective effects of HO-1 against aortic endothelial dysfunction may be due to its antioxidation and regulative effect of vasoactive substances. It is proposed that hemin, inducer of HO-1, could be a potential therapeutic option for vascular dysfunction in IR states.

Animals ; Aorta ; drug effects ; physiology ; Carbon Monoxide ; blood ; Endothelium, Vascular ; drug effects ; physiology ; Enzyme Induction ; drug effects ; Heme Oxygenase-1 ; analysis ; biosynthesis ; genetics ; Hemin ; pharmacology ; Insulin Resistance ; Male ; Nitric Oxide ; blood ; Oxidative Stress ; Rats ; Rats, Sprague-Dawley ; Systole ; drug effects

OBJECTIVETo observe the effects of series of Muskone (the muskone includes Slender Dutchmanspipe Root, Inula Root and neither kind of Common Aucklandia Root) on the heart hemodynamics and myocardial consumption of oxygen in experimental dogs, and to explain its pharmacological action on cardiovascular system.

METHODArterial blood pressure, coronary blood flow, resistance in coronary artery, total peripheral resistance, work of left artrium and oxygen consumption index of the cardiac muscles were observed in anaesthetic dogs.

RESULTThe series of Muskone decreased arterial blood pressure significantly, dilated coronary artery and peripheral arteries significantly, increased coronary blood flow, decreased resistance in coronary artery, improved the work of left artrium, the oxygen availability of cardiac muscles and the complaisance of arteries in cardiac muscles.

Animals ; Aristolochia ; chemistry ; Asteraceae ; chemistry ; Blood Pressure ; drug effects ; Coronary Circulation ; drug effects ; Cycloparaffins ; isolation & purification ; pharmacology ; Dogs ; Drug Combinations ; Female ; Heart ; drug effects ; physiology ; Hemodynamics ; drug effects ; Inula ; chemistry ; Male ; Myocardium ; metabolism ; Oxygen Consumption ; drug effects ; Plant Roots ; chemistry ; Plants, Medicinal ; chemistry ; Vascular Resistance ; drug effects

BACKGROUND: Endogenous nitric oxide (NO) induces the peripheral vasodilation via the activation of guanylate cyclase in patients with septic shock. The purpose of this study was to assess the acute effects of methylene blue (MB), which is an inhibitor of guanylate cyclase, on the hemodynamics and on the production of pro-inflammatory cytokines and nitric oxide (NO) in patients with refractory septic shock. METHODS: Twenty consecutive patients with refractory septic shock, which was defined as shock refractory to a dopamine infusion of more than 20 microgram/kg/min with the appropriate use of antibiotics and adequate volume replacement, received MB infusion of 1 mg/kg intravenously. The hemodynamic and respiratory variables were measured at baseline, 30, 60 and 120 min after an infusion of MB (1 mg/kg). The blood levels of NO, IL-1, IL-10 and TNF-alpha were measured at baseline, 30 and 120 min after MB infusion. RESULTS: The administration of MB induced an increase in the systemic vascular resistance (SVR) that resulted in an increase of the mean arterial pressure (MAP) in patients with refractory septic shock, and this was without a decrease in cardiac output. The administered MB induced an increase in pulmonary vascular resistance (PVR) that resulted in an increase of pulmonary arterial pressure (PAP), without any deterioration of gas exchange. However, the increases in SVR and PVR were not associated with the alteration of endogenous production of NO, IL-1, IL-10 and TNF-alpha. CONCLUSION: MB transiently elevated the MAP by increasing the SVR without altering the endogenous productions of NO, IL-1, IL-10 and TNF-alpha during the study period in patients with refractory septic shock.
Anti-Infective Agents, Urinary/administration & dosage/*therapeutic use ; Blood Pressure/*drug effects/physiology ; Comparative Study ; Cytokines/*blood ; Enzyme-Linked Immunosorbent Assay ; Female ; Humans ; Infusions, Intravenous ; Male ; Methylene Blue/administration & dosage/*therapeutic use ; Middle Aged ; Pulmonary Circulation/drug effects/physiology ; Research Support, Non-U.S. Gov't ; Retrospective Studies ; Shock, Septic/blood/*drug therapy/physiopathology ; Treatment Outcome ; Vascular Resistance/*drug effects/physiology

The effects of electroacupuncture (EA) on the minimum alveolar concentration (MAC) and on the cardiovascular system were evaluated with dogs under isoflurane anesthesia. Eight healthy male beagles were randomly assigned to six study groups (five heads/group) with washout intervals of 7 ~ 31 days between experiments for recovery and anesthetic clearance. MAC of isoflurane and cardiovascular parameters were determined after EA at nonacupoint and and at acupoints LI-4, SP-6, ST-36 and TH-8. Electroacupuncture for 30 minutes at LI-4, SP-6, ST-36 and TH-8 acupoints lowered the MAC of isoflurane by 17.5 +/- 3.1%, 21.3 +/- 8.0%, 20.5 +/- 8.2% and 15.6 +/- 3.1%, respectively (p < 0.05). However, electrical stimulation of nonacupoint did not induce a significant change in MAC of isoflurane. In the cardiovascular system, the ST-36 group did not induce any significant change in cardiovascular parameters. In the TH-8 group, the mean and diastolic arterial pressure and the systemic vascular resistance were decreased. In the LI-4 group, cardiac output and cardiac index decreased after EA. These results indicate that EA at LI-4, SP-6 and ST-36 have advantages in isoflurane anesthesia in terms of reducing the dose of anesthetics and minimizing cardiovascular side effects.
Anesthesia, Inhalation/adverse effects/*veterinary ; Anesthetics, Inhalation/*pharmacokinetics/pharmacology ; Animals ; Blood Pressure/drug effects ; Cardiac Output ; Dogs/*metabolism/physiology ; Electroacupuncture/*veterinary ; Heart Rate/drug effects ; Isoflurane/*pharmacokinetics/pharmacology ; Male ; Pulmonary Alveoli/*metabolism ; Pulmonary Wedge Pressure/drug effects ; Random Allocation ; Vascular Resistance/drug effects

OBJECTIVETo explore the biological effect on NB4 cells proliferation, all-trans retinoic acid (ATRA) inducing differentiation and resistance to apoptosis by vascular endothelial growth factor (VEGF)-C cDNA transfection.

METHODSThe recombinant eukaryotic expression plasmid pcDNA3.1-VEGF-C and the vacant pcDNA3.1 vector were introduced separately into NB4 cells by lipofectamine mediation. The positive clones were screened by G418 and identified by reverse transcriptase-PCR (RT-PCR) and Western blotting. The proliferation capacity of NB4/VEGF-C cells was analysed by MTT assay and colony forming assay in vitro. After NB4/VEGF-C cells were induced by ATRA, the expression level of C/EBPalpha gene, CD11b on cells surface and morphological alteration were analysed by real-time quantitative PCR (RQ-PCR), flow cytometry (FCM), and Wright-Giemsa staining, respectively. FCM Annexin V-FITC/PI dual labeling technique was performed to investigate the etoposide (Vp16) induced NB4/VEGF-C cells apoptosis and bcl-2 gene expression level in these cells was analysed by RQ-PCR. The NB4/pcDNA3.1 cells was used as control in the above experiments.

RESULTSA stable NB4 cell line that secrets VEGF-C and its control lines were established. The proliferation capacity of the former was stronger than that of the latter. The expression level of C/EBPalpha gene of NB4/VEGF-C cells on ATRA treatment was only 1/32 that of NB4/pcDNA3.1 cells. The CD11b level and the degree of differentiation of NB4/VEGF-C were weaker than that of NB4/pcDNA3.1 cells. The percentage of apoptotic NB4/VEGF-C cells induced by Vp16 [(7.20 +/- 2.52)%] was significantly lower than that of NB4/pcDNA3.1 cells [(16.07 +/- 3.58)%] (P = 0.005), but the bcl-2 gene expression level of NB4/VEGF-C cells is 2.28-fold that of NB4/pcDNA3.1 cells.

CONCLUSIONThe VEGF-C via VEGFR-3 signaling pathway could promote the proliferation of leukemic cells by autocrine pathway and inhibit the cell differentiation mediated by ATRA and chemotherapy-induced apoptosis. VEGF-C/VEGFR-3 signaling loops might play an important role in disease progression and be potential therapeutic target for the treatment of leukemias.

Apoptosis ; drug effects ; genetics ; physiology ; Blotting, Western ; CCAAT-Enhancer-Binding Protein-alpha ; genetics ; metabolism ; CD11b Antigen ; genetics ; metabolism ; Cell Differentiation ; genetics ; physiology ; Cell Line, Tumor ; Cell Proliferation ; DNA, Complementary ; genetics ; Drug Resistance, Neoplasm ; Flow Cytometry ; Genetic Vectors ; Humans ; Leukemia, Promyelocytic, Acute ; genetics ; metabolism ; pathology ; Reverse Transcriptase Polymerase Chain Reaction ; Transfection ; Tretinoin ; pharmacology ; Vascular Endothelial Growth Factor C ; genetics ; metabolism ; physiology

OBJECTIVETo study the protective effects and the possible mechanism of shengmai for injection(SM) against the experimental acute cardiogenic shock.

METHODThe experimental acute cardiogenic shock model was established by ligating the anterior descending cornonary in dogs. The effects of SM on cardiogenic shock were investigated by measuring the hemodynamics parameter, the activity of LDH, CK, SOD and the contents of MDA in blood serum.

RESULTIn the dogs treated with SM, the mean arterial pressure (MAP), heart rate (HR), left ventricular pressure (LVP), the maximum of its first derivative (+/- dp/dtmax), the cardiac output (CO) and the cardiac index (CI) were increased significantly. The left ventricular end diastolic pressure (LVEDP) and the peripheral vascular resistance (TPVR) were decreased significantly, the myocardial infarct size was redused observely. In addition, the activity of LDH, CK and the contents of MDA in serum were decreased significantly, however the activity of SOD was increased observely.

CONCLUSIONThe results indicate that SM has the protective effects on cardiogenic shock.

Animals ; Cardiac Output ; drug effects ; Cardiotonic Agents ; administration & dosage ; pharmacology ; therapeutic use ; Creatine Kinase ; blood ; Dogs ; Drug Combinations ; Drugs, Chinese Herbal ; administration & dosage ; pharmacology ; therapeutic use ; Female ; Heart Rate ; drug effects ; Hemodynamics ; drug effects ; physiology ; Injections, Intravenous ; L-Lactate Dehydrogenase ; blood ; Male ; Malondialdehyde ; blood ; Myocardial Infarction ; pathology ; prevention & control ; Ophiopogon ; chemistry ; Panax ; chemistry ; Phytotherapy ; Plants, Medicinal ; chemistry ; Random Allocation ; Schisandra ; chemistry ; Shock, Cardiogenic ; blood ; physiopathology ; prevention & control ; Vascular Resistance ; drug effects

PURPOSE: Hypoxia-inducible factor-1alpha (HIF-1alpha) increases transcription of the vascular endothelial growth factor (VEGF) gene. Inhibition of VEGF abolishes VEGF mediated induction of HIF-1alpha. Recent reports suggested that HIF-1alpha also mediated the induction of class III beta-tubulin (TUBB3) in hypoxia. TUBB3 confers resistance to taxanes. Inhibition of VEGF may decrease the expression of HIF-1alpha and TUBB3. This study was undertaken to investigate the roles of vascular endothelial growth factor receptor (VEGFR) in gastric cancer cell behavior and to identify methods to overcome paclitaxel resistance in vitro. MATERIALS AND METHODS: The protein expression levels of HIF-1alpha and TUBB3 were measured in human gastric cancer cell lines (AGS) under normoxic and hypoxic conditions. The relationship between TUBB3 and paclitaxel resistance was assessed with small interfering TUBB3 RNA. AGS cells were treated with anti-VEGFR-1, anti-VEGFR-2, placental growth factor (PlGF), bevacizuamb, and paclitaxel. RESULTS: Hypoxia induced paclitaxel resistance was decreased by knockdown of TUBB3. Induction of HIF-1alpha and TUBB3 in AGS is VEGFR-1 mediated and PlGF dependent. Hypoxia-dependent upregulation of HIF-1alpha and TUBB3 was reduced in response to paclitaxel treatment. Expressions of HIF-1alpha and TUBB3 were most decreased when AGS cells were treated with a combination of paclitaxel and anti-VEGFR-1. AGS cell cytotoxicity was most increased in response to paclitaxel, anti-VEGFR-1, and anti-VEGFR-2. CONCLUSION: We suggest that blockade of VEGFR-1 and VEGFR-2 enhances paclitaxel sensitivity in TUBB3-expressing gastric cancer cells.
Angiogenesis Inhibitors/pharmacology ; Antibodies, Monoclonal, Humanized/pharmacology ; Antineoplastic Agents, Phytogenic/*pharmacology ; Cell Hypoxia ; Cell Line, Tumor ; *Drug Resistance, Neoplasm ; Gene Expression Regulation, Neoplastic/drug effects ; Gene Knockdown Techniques ; Humans ; Hypoxia-Inducible Factor 1, alpha Subunit/metabolism ; Paclitaxel/*pharmacology ; Pregnancy Proteins/pharmacology ; Stomach Neoplasms/drug therapy/genetics ; Tubulin/genetics/metabolism ; Vascular Endothelial Growth Factor Receptor-1/antagonists & inhibitors/*physiology ; Vascular Endothelial Growth Factor Receptor-2/antagonists & inhibitors/*physiology

OBJECTIVETo study the effects of inhaled nitric oxide (NO) on pulmonary vascular resistance in patients after total cavopulmonary connection (TCPC).

METHODSFifty-two patients after TCPC were evaluated, of them 24 patients were administered with inhaled nitric oxide in the early postoperative period. The cardiac index (CI) and pulmonary vascular resistance (PVR) were compared before and after inhaled NO.

RESULTSIn experimental group, after inhaled NO, partial pressure of oxygen in artery/fraction of inspired oxygen increased from 161 +/- 17 to 193 +/- 23 (t = 2.75, P < 0.01); CI from (2.86 +/- 0.24) L.min(-1).m(-2) to (3.13 +/- 0.22) L.min(-1).m(-2) (t = 2.25, P < 0.05); PVR decreased from (4.2 +/- 0.5) U/m(2) to (3.8 +/- 1.4) U/m(2) (t = 2.29, P < 0.05); central venous pressure (CVP) from (17.0 +/- 1.8) mm Hg to (15.0 +/- 1.1) mm Hg, decreased 11.7%. Compared with the control group, respirator time decreased from (86 +/- 27) h to (54 +/- 18) h (t = 2.29, P < 0.05); ICU time from (6 +/- 2) d to (4 +/- 2) d (t = 2.32, P < 0.05); But hydrothorax drainage and length of stay had no significant difference.

CONCLUSIONSThough inhaled NO, there is no significant long-term effects in patients after TCPC, but it may play an important role in the management of low cardiac output syndrome and high cava pressure caused by reactive elevated pulmonary vascular resistance in the early postoperative period of TCPC.

Administration, Inhalation ; Adolescent ; Adult ; Arteriovenous Shunt, Surgical ; methods ; Cardiac Output ; drug effects ; Child ; Child, Preschool ; Female ; Humans ; Male ; Nitric Oxide ; administration & dosage ; therapeutic use ; Postoperative Period ; Pulmonary Artery ; physiology ; surgery ; Time Factors ; Vascular Resistance ; drug effects ; Vasodilator Agents ; administration & dosage ; therapeutic use ; Venae Cavae ; surgery