Inflation-associated increases in lung polyamine uptake: role of altered pulmonary vascular flow

1989 ◽  
Vol 257 (5) ◽  
pp. E729-E735 ◽  
Author(s):  
H. W. Karl ◽  
L. A. Russo ◽  
D. E. Rannels
Keyword(s):  
Flow Rate ◽  
Metabolic Response ◽  
Left Lung ◽  
Pulmonary Flow ◽  
Vascular Flow ◽  
Isolated Lung ◽  
Wide Range ◽  
Camp Metabolism ◽  
The Right

Unilateral pneumonectomy in rats leads to rapid compensatory growth of the remaining lung. Previous studies showed that postoperative increases in lung mass are preceded by enhanced uptake of exogenous polyamines and by alterations in adenosine 3',5'-cyclic monophosphate (cAMP) metabolism. These effects are both mimicked in lungs of intact animals subjected to increased inflation in vitro. Partial pneumonectomy also leads to increased flow to the contralateral lung associated with reduced pulmonary vascular resistance. This raises the possibility that the postoperative metabolic response is initiated by changes in pulmonary artery pressure (Pa) or flow, rather than altered inflation. The present studies were designed to investigate this issue. Uptake of exogenous [14C]spermidine by isolated perfused rat lungs was examined over a wide range (greater than 4-fold) of pulmonary flow and ventilation at fixed PaS. Assessment of tissue metabolism from rates of protein synthesis suggested stability of the isolated lung preparations. Apnea (0 ventilation) had no effect on spermidine uptake or flow rate, compared with lungs evaluated under normal conditions of ventilation (inspiratory pressure, 15 cmH2O; positive end expiratory pressure, 2 cmH2O; rate, 70 breaths/min). At both high and low Pa (at a flow rate of 37 +/- 1 and 11 +/- 2 ml/min, respectively, with 0 ventilation), removal of the left lung from the perfusion circuit increased specific right lung flow rate greater than 30% but had no effect on spermidine uptake. Similar alterations in flow rate to the right or both apneic lungs had no effect on the tissue content of cAMP.(ABSTRACT TRUNCATED AT 250 WORDS)

Evaluation of 99mTc-Label led Vitamin K4 as an Agent for Testicular Imaging

1991 ◽  
Vol 30 (01) ◽  
pp. 35-39 ◽  
Author(s):  
H. S. Durak ◽  
M. Kitapgi ◽  
B. E. Caner ◽  
R. Senekowitsch ◽  
M. T. Ercan
Keyword(s):  
Soft Tissue ◽  
Room Temperature ◽  
Normal Subjects ◽  
Left Testis ◽  
Wide Range ◽  
Activity Ratios ◽  
The Right ◽  
Radioactivity Levels

Vitamin K4 was labelled with 99mTc with an efficiency higher than 97%. The compound was stable up to 24 h at room temperature, and its biodistribution in NMRI mice indicated its in vivo stability. Blood radioactivity levels were high over a wide range. 10% of the injected activity remained in blood after 24 h. Excretion was mostly via kidneys. Only the liver and kidneys concentrated appreciable amounts of radioactivity. Testis/soft tissue ratios were 1.4 and 1.57 at 6 and 24 h, respectively. Testis/blood ratios were lower than 1. In vitro studies with mouse blood indicated that 33.9 ±9.6% of the radioactivity was associated with RBCs; it was washed out almost completely with saline. Protein binding was 28.7 ±6.3% as determined by TCA precipitation. Blood clearance of 99mTc-l<4 in normal subjects showed a slow decrease of radioactivity, reaching a plateau after 16 h at 20% of the injected activity. In scintigraphic images in men the testes could be well visualized. The right/left testis ratio was 1.08 ±0.13. Testis/soft tissue and testis/blood activity ratios were highest at 3 h. These ratios were higher than those obtained with pertechnetate at 20 min post injection.99mTc-l<4 appears to be a promising radiopharmaceutical for the scintigraphic visualization of testes.

scholarly journals The Xenobiotic Compound 1,4-Bis[2-(3,5-Dichloropyridyloxy)]Benzene Is an Agonist Ligand for the Nuclear Receptor CAR

2000 ◽  
Vol 20 (9) ◽  
pp. 2951-2958 ◽  
Author(s):  
Iphigenia Tzameli ◽  
Pavlos Pissios ◽  
Erin G. Schuetz ◽  
David D. Moore
Keyword(s):  
Ligand Binding ◽  
Nuclear Receptor ◽  
Metabolic Response ◽  
Inhibitory Effect ◽  
Dependent Manner ◽  
Inverse Agonists ◽  
Wide Range ◽  
Xenobiotic Compound

ABSTRACT A wide range of xenobiotic compounds are metabolized by cytochrome P450 (CYP) enzymes, and the genes that encode these enzymes are often induced in the presence of such compounds. Here, we show that the nuclear receptor CAR can recognize response elements present in the promoters of xenobiotic-responsive CYP genes, as well as other novel sites. CAR has previously been shown to be an apparently constitutive transactivator, and this constitutive activity is inhibited by androstanes acting as inverse agonists. As expected, the ability of CAR to transactivate the CYP promoter elements is blocked by the inhibitory inverse agonists. However, CAR transactivation is increased in the presence of 1,4-bis[2-(3,5-dichloropyridyloxy)]benzene (TCPOBOP), the most potent known member of the phenobarbital-like class of CYP-inducing agents. Three independent lines of evidence demonstrate that TCPOBOP is an agonist ligand for CAR. The first is that TCPOBOP acts in a dose-dependent manner as a direct agonist to compete with the inhibitory effect of the inverse agonists. The second is that TCPOBOP acts directly to stimulate coactivator interaction with the CAR ligand binding domain, both in vitro and in vivo. The third is that mutations designed to block ligand binding block not only the inhibitory effect of the androstanes but also the stimulatory effect of TCPOBOP. Importantly, these mutations do not block the apparently constitutive transactivation by CAR, suggesting that this activity is truly ligand independent. Both its ability to target CYP genes and its activation by TCPOBOP demonstrate that CAR is a novel xenobiotic receptor that may contribute to the metabolic response to such compounds.

A Comparative Study of the Effects of Adrenoceptor Antagonists on Platelet Aggregation and Thromboxane Generation

1985 ◽  
Vol 54 (02) ◽  
pp. 480-484 ◽  
Author(s):  
I A Greer ◽  
J J Walker ◽  
M McLaren ◽  
A A Calder ◽  
C D Forbes
Keyword(s):  
Platelet Aggregation ◽  
Vascular Disease ◽  
Platelet Rich Plasma ◽  
Thromboxane A2 ◽  
Inhibitory Effect ◽  
Dependent Manner ◽  
Wide Range ◽  
The Right

SummaryPlatelet aggregation and thromboxane A2 have been implicated in the pathogenesis of several forms of vascular disease. The aim of this study was to determine the effect of a wide range of adrenoceptor antagonists on platelet aggregation, and thromboxane A2 production, from normal human platelet rich plasma in vitro. Labetalol, pindolol and propranolol inhibited platelet aggregation to collagen in a dose dependent manner. Increasing the concentration of collagen “shifted” the dose response curve to the right. These 3 drugs also significantly inhibited thromboxane A2 generation in response to collagen but not to arachidonic acid. This effect was independent of any inhibitory effect of these drugs on platelet aggregation, and occurred at a drug concentration close to that obtained in vivo. Atenolol, metoprolol, prazosin and timolol were similarly assessed but had no effect on either platelet aggregation or thromboxane A2 generation. This ability of labetalol, pindolol, and propranolol to inhibit platelet aggregation and thromboxane generation, may be of clinical benefit in view of the increasing evidence implicating thromboxane A2 in the pathogenesis of vascular disease.

scholarly journals In-Vitro Validation of Self-Powered Fontan Circulation for Treatment of Single Ventricle Anomaly

Fluids ◽  
2021 ◽  
Vol 6 (11) ◽  
pp. 401
Author(s):  
Arka Das ◽  
Ray Prather ◽  
Eduardo Divo ◽  
Michael Farias ◽  
Alain Kassab ◽  
...  
Keyword(s):  
Flow Rate ◽  
Experimental Testing ◽  
Fontan Operation ◽  
Fontan Circulation ◽  
Lumped Parameter Model ◽  
Pressure Reduction ◽  
Flow Loop ◽  
Pulmonary Flow ◽  
Self Powered

Around 8% of all newborns with a Congenital Heart Defect (CHD) have only a single functioning ventricle. The Fontan operation has served as palliation for this anomaly for decades, but the surgery entails multiple complications, and the survival rate is less than 50% by adulthood. A rapidly testable novel alternative is proposed by creating a bifurcating graft, or Injection Jet Shunt (IJS), used to “entrain” the pulmonary flow and thus provide assistance while reducing the caval pressure. A dynamically scaled Mock Flow Loop (MFL) has been configured to validate this hypothesis. Three IJS nozzles of varying diameters 2, 3, and 4 mm with three aortic anastomosis angles and pulmonary vascular resistance (PVR) reduction have been tested to validate the hypothesis and optimize the caval pressure reduction. The MFL is based on a Lumped-Parameter Model (LPM) of a non-fenestrated Fontan circulation. The best outcome was achieved with the experimental testing of a 3 mm IJS by producing an average caval pressure reduction of more than 5 mmHg while maintaining the clinically acceptable pulmonary flow rate (Qp) to systemic flow rate (Qs) ratio of ~1.5. Furthermore, alteration of the PVR helped in achieving higher caval pressure reduction with the 3 mm IJS at the expense of an increase in Qp/Qs ratio.

Effect of Vascular Stiffness on Pulmonary Flow in Normotensive and Hypertensive States: Numerical Study With Fluid Structure Interaction

2008 ◽  
Author(s):  
Zhenbi Su ◽  
Kendall Hunter ◽  
Robin Shandas
Keyword(s):  
Numerical Study ◽  
Vascular Stiffness ◽  
Mean Flow ◽  
Pulmonary Flow ◽  
Vascular Flow ◽  
Primary Determinant ◽  
Mean Pressure ◽  
Pulmonary Arterial ◽  
The Mean ◽  
The Right

Invasive measurement of pulmonary vascular flow and pressure provides the hemodynamic status of the pulmonary circulation for children with pulmonary arterial hypertension (PAH). Clinicians are primarily interested in pulmonary vascular resistance, which is the mean pressure of the circuit divided by the mean flow through it [1], in that it is believed to well-quantify the right ventricular (RV) afterload, the primary determinant of mortality. However, previous and current investigations on the pulmonary vascular stiffness (PVS), input impedance and RV power [2–4] have found PVS to be an important contributor to power, and thus, afterload. These previous and current investigations focus on the analysis of clinical data, which is limited by the clinical equipment and techniques.

Results of bench tests of hydraulic dynamometer of type CFT-9.0 manufactured by Fuchino Co Ltd

2019 ◽  
Vol 12 (3) ◽  
pp. 200-205
Author(s):  
V. E. Mikhailov ◽  
S. P. Kolpakov ◽  
L. A. Khomenok
Keyword(s):  
Flow Rate ◽  
Water Flow Rate ◽  
Cooling Water ◽  
Rotation Frequency ◽  
High Precision Measurement ◽  
Experimental Development ◽  
Domestic Industry ◽  
Cooling Water Flow Rate ◽  
Wide Range ◽  
The Right

Topical issues of creating test benches for power drive units are considered. The results of testing a hydraulic dynamometer with the aim of clarifying its characteristics are presented. When creating test benches, it is important to choose the right power damping system with its accurate measurement. For these purposes hydraulic dynamometers (HD) are used. The domestic industry has not yet mass-produced them, experimental development is underway. In this regard, it seems appropriate to use imported diesel engines, for example, Japanese-made, of type CFT-9.0 manufactured by Fuchino Co Ltd. This equipment has a commercial preference over other foreign manufacturers. This article discusses the principle of HD operation, its design features, the identified shortcomings and ways to address them, the results of tests of the gas engine on a special bench of JSC «NPO CKTI».The tests carried out made it possible to verify the operability of the acquired HD, to determine the dependence of the HD power on the rotation frequency, the dependence of the cooling water flow rate on the HD power and the dependence of the HD power on the steam flow rate to the steam turbine drive.The results obtained indicate that the HD of type CFT-9.0 manufactured by «Fuchino Co Ltd» can be recommended as a hydrodynamic power absorber with its high-precision measurement in a wide range of rotation speed, modes and power consumption up to 8.5 MW.

Effect of ageing on cyclic AMP output by renal medullary cells in response to arginine vasopressin in vitro in C57BL/Icrfat mice

1984 ◽  
Vol 103 (2) ◽  
pp. 133-139 ◽  
Author(s):  
C. Goddard ◽  
Y. S. Davidson ◽  
B. B. Moser ◽  
I. Davies ◽  
E. B. Faragher
Keyword(s):  
Cyclic Amp ◽  
Arginine Vasopressin ◽  
Age Related ◽  
Camp Metabolism ◽  
The Right ◽  
Old Mice ◽  
Effect Of Age ◽  
Urine Concentrating Ability ◽  
Medullary Cells

ABSTRACT The effect of age on the cyclic AMP (cAMP) response to increases in the concentration of arginine vasopressin in the presence of isobutyl methylxanthine (100 μmol/l) was studied in an in-vitro renal cell suspension prepared from C57BL/Icrfat mice at 6, 12, 18, 24, 29 and 35 months of age. Comparison of the response of the preparation to vasopressin, calcitonin and parathyroid hormone suggested that it was enriched with renal medullary cells. Basal cAMP output was similar throughout but the threshold dose of vasopressin increased from 1 × 10−11 mol/l (6, 12 and 18 months of age) to 1 × 10−10 mol/l (24, 29 and 35 months of age). The dose–response curve in 35-month-old mice was shifted to the right with the concentration of vasopressin required to give half maximal cAMP increased from 9·4 ± 0·37 × 10−11 mol/l (6 months) to 3·5±1·6 × 10−10 mol/l (35 months). Maximum cAMP output at 1 × 10 −9 mol/l was also reduced in the same animals (stimulated:basal ratio, 51·22±19·12 at 6 months; 11·50 ± 6·02 at 35 months). The results suggest that the lack of renal response to vasopressin in terms of cAMP metabolism may play a role in the well-documented age-related decline in urine-concentrating ability in experimental animals and elderly people. J. Endocr. (1984) 103, 133–139

Maximum Flow Rates Possible During Power Injection Through Currently Available PICCs: An In-Vitro Study

2004 ◽  
Vol 9 (3) ◽  
pp. 150-154
Author(s):  
Ari I. Salis ◽  
Anthony Eclavea ◽  
Matthew S. Johnson ◽  
Nilesh H. Patel ◽  
Debie G. Wong ◽  
...  
Keyword(s):  
Flow Rate ◽  
Superior Vena ◽  
Vena Cava ◽  
In Vitro Study ◽  
Maximum Flow ◽  
Intravenous Contrast ◽  
Flow Rates ◽  
Wide Range ◽  
Polyurethane Catheters

ABSTRACT Purpose Currently available 4 French and 5 French PICCs were investigated to evaluate their possible application for contrast injection using power injectors. The study was performed using an in-vitro model to demonstrate the feasibility of using PICCs for contrast enhanced studies. Materials and Methods An evaluation of 24 catheter versions consisting of 4 French single lumen and 5 French dual lumen PICCs from 13 different manufacturers was conducted. Six of the catheter types were silicone and 18 catheter types were polyurethane. Ten catheters of each type were evaluated with five at full length and five trimmed to 40cm. Using a silicone-based simulated superior vena cava model, the catheters were infused with 50cc of intravenous contrast at each flow rate increment. Catheters were tested at increasing flow rates from 0.5cc/second to 5cc/second in 0.5cc/second increments using a Percupump CT injector. Catheters that failed to rupture were then infused at 1 cc/second increments at flow rates from 5cc/second to 17cc/second using a MedRad Mark VTM power injector. Tolerated and bursting pressures were recorded. Results Polyurethane catheters ruptured at flow rates between 4–15.4cc/second, with one catheter not rupturing at the maximum flow rate (l7cc/second). Silicone catheters ruptured at flow rates between 0.5–3.5cc/second. Average rupture locations by type and length were at the extension leg/hub connection area on 5 of the PICCs, on the extension legs on 21 of the PICCs, on the catheter/hub connection on 4 PICCs, and on the proximal catheter on 16 of the PICCs. Conclusion The low burst rates at which all silicone catheters ruptured suggest those catheters are not able to withstand typical flow rates used for CTA. Conversely, although a wide range of discrepancy is found in the polyurethane catheter burst pressures, many polyurethane catheters can tolerate relatively high flow rates without rupture. This suggests that they may be safely used for CTA with appropriate precautions and protocols in place.

Stretch-related changes in lung cAMP after partial pneumonectomy

1989 ◽  
Vol 257 (2) ◽  
pp. E261-E268 ◽  
Author(s):  
L. A. Russo ◽  
S. R. Rannels ◽  
K. S. Laslow ◽  
D. E. Rannels
Keyword(s):  
Growth Response ◽  
Kinase Activity ◽  
Activity Ratio ◽  
Dependent Protein Kinase ◽  
Dependent Protein ◽  
Camp Metabolism ◽  
Polyamine Uptake ◽  
The Right

In rats, left pneumonectomy (PNX) initiates rapid compensatory hyperplastic growth of the right lung. Previous work indicated that increased polyamine uptake associated with post-PNX distortion or “stretch” of the remaining tissue and altered adenosine 3',5'-cyclic monophosphate (cAMP) metabolism may play a role in the early phase of the growth response. Evidence was sought to link these observations with the goal of understanding control of compensatory growth. At day 1 or 3 after left PNX in vivo, increased right lung cAMP was associated with activation of the cAMP-dependent protein kinase (PKa). Total PKa activity was unaffected, but the PKa activity ratio (-cAMP/+cAMP) doubled, providing evidence for PNX-associated activation of the kinase in vivo. Neither cAMP nor PKa was altered in sham-operated control lungs. To determine whether increased distension of the right lung after PNX might initiate these changes, lungs of unoperated animals were perfused 40 min in vitro, either without ventilation or with a distending constant positive airway pressure (CPAP) of 20 cmH2O. CPAP rapidly increased uptake of the polyamine spermidine (SPD; 1.5 microM), tissue cAMP, and the PKa activity ratio, in a manner similar to that observed after PNX. Both tissue cAMP and the kinase activity ratio increased with 1 microM forskolin (FSK), as expected, but SPD uptake was unaffected by FSK. FSK did not diminish the CPAP-associated elevations of SPD uptake (P less than 0.01) or cAMP (P less than 0.05), but the kinase was not further activated by CPAP with FSK present.(ABSTRACT TRUNCATED AT 250 WORDS)

In Vitro Clot Lysis as a Potential Indicator of Thrombus Resistance to Fibrinolysis – Study in Healthy Subjects and Correlation with Blood Fibrinolytic Parameters

1997 ◽  
Vol 77 (04) ◽  
pp. 725-729 ◽  
Author(s):  
Mario Colucci ◽  
Silvia Scopece ◽  
Antonio V Gelato ◽  
Donato Dimonte ◽  
Nicola Semeraro
Keyword(s):  
Plasminogen Activator ◽  
Clot Lysis ◽  
Individual Response ◽  
Plasminogen Activator Inhibitor 1 ◽  
Autologous Plasma ◽  
Wide Range ◽  
Blood Clots ◽  
Physiological Variations ◽  
Pai 1

SummaryUsing an in vitro model of clot lysis, the individual response to a pharmacological concentration of recombinant tissue plasminogen activator (rt-PA) and the influence on this response of the physiological variations of blood parameters known to interfere with the fibrinolytic/thrombolytic process were investigated in 103 healthy donors. 125I-fibrin labelled blood clots were submersed in autologous plasma, supplemented with 500 ng/ml of rt-PA or solvent, and the degree of lysis was determined after 3 h of incubation at 37° C. Baseline plasma levels of t-PA, plasminogen activator inhibitor 1 (PAI-1), plasminogen, α2-anti-plasmin, fibrinogen, lipoprotein (a), thrombomodulin and von Willebrand factor as well as platelet and leukocyte count and clot retraction were also determined in each donor. rt-PA-induced clot lysis varied over a wide range (28-75%) and was significantly related to endogenous t-PA, PAI-1, plasminogen (p <0.001) and age (p <0.01). Multivariate analysis indicated that both PAI-1 antigen and plasminogen independently predicted low response to rt-PA. Surprisingly, however, not only PAI-1 but also plasminogen was negatively correlated with rt-PA-ginduced clot lysis. The observation that neutralization of PAI-1 by specific antibodies, both in plasma and within the clot, did not potentiate clot lysis indicates that the inhibitor, including the platelet-derived form, is insufficient to attenuate the thrombolytic activity of a pharmacological concentration of rt-PA and that its elevation, similarly to the elevation of plasminogen, is not the cause of clot resistance but rather a coincident finding. It is concluded that the in vitro response of blood clots to rt-PA is poorly influenced by the physiological variations of the examined parameters and that factors other than those evaluated in this study interfere with clot dissolution by rt-PA. In vitro clot lysis test might help to identify patients who may be resistant to thrombolytic therapy.

Sign in / Sign up

Export Citation Format

Share Document