Myointimale Hyperplasie und sympathische Reinervation der Ohrarterie des Kaninchens nach lokalem Kälteschaden und schneller Wiedererwärmung

VASA ◽  
2001 ◽  
Vol 30 (3) ◽  
pp. 176-183 ◽  
Author(s):  
A. Arvesen ◽  
J. Mæhlen ◽  
L. Rosén ◽  
Pål Aas
Keyword(s):  
Vascular Ring ◽  
Control Level ◽  
Glyoxylic Acid ◽  
Sympathetic Nerves ◽  
Vascular Wall ◽  
Spontaneous Release ◽  
Subsequent Increase ◽  
Total Uptake

Background: Functional and pathological improvements following rapid rewarming in 42°C water was compared with alterations following slow thawing at room temperature (22°C) after frostbite (–9°C, 15 minutes) in vivo of the rabbit central ear artery. Methods: Following two to ten weeks of in vivo regeneration, vascular segments were tested in vitro. Maximal and dose-dependent isometric contractions were induced by exogenous noradrenaline. Sympathetic nerves in the vascular wall were stained with glyoxylic acid. Vascular ring segments were stained with haematoxylin and eosin. Results: Following slow thawing, the total uptake, the K+ evoked and the spontaneous release of [3H]noradrenaline in the sympathetic nervous system were strongly reduced two weeks after freezing, with a subsequent increase to control level within 3–4 weeks. After rapid rewarming the total uptake, the spontaneous release and the K+ evoked release of [3H]noradrenaline commenced earlier such that after ten weeks the level was twice as high as following slow rewarming. The glyoxylic acid induced catecholamine fluorescence in sympathetic nerves, revealed an earlier regeneration after rapid rewarming. Haematoxylin and eosin-stained segments revealed less intimal hyperplasia three to 20 weeks after rapid rewarming than after slow thawing. Conclusion: Rapid rewarming of in vivo frozen arteries in warm water (42°C) did not prevent immediate vasoparalysis and degeneration of sympathetic nerves. However, nerve regeneration occurred earlier and with higher tissue nerve densities as compared to tissue that had been slowly rewarmed. Myointimal hyperplasia was less pronounced after rapid rewarming. Abnormal sympathetic nerve function and myointimal hyperplasia, as observed in this study, may contribute to a greater understanding of sequelae in the human body following frostbite.

Frühe und späte funktionelle und histopathologische Störungen nach Kälteschaden im Tierexperiment

VASA ◽  
1999 ◽  
Vol 28 (2) ◽  
pp. 85-94 ◽  
Author(s):  
Arvesen ◽  
Mæhlen ◽  
Rosén ◽  
Aas
Keyword(s):  
Electrical Stimulation ◽  
Vascular Ring ◽  
Glyoxylic Acid ◽  
Sympathetic Nerves ◽  
Isometric Tension ◽  
Autonomic Nerve ◽  
Nerve Function ◽  
Autonomic Nerve Function

Background: These experiments aimed to study the in vivo short and long term neurovascular regeneration after frostbite. Methods: The rabbit central ear-artery was used as the experimental model. The effects on the noradrenergic innervation of the artery were measured in isolated vascular ring segments the first day and 2, 3–4, and 8–10 or 10–20 weeks following freezing at –9°C or –18°C for 15 min with slow rewarming for 7 min at room temperature. Results: Two days after freezing the sympathetic nerves were completely degenerated, as observed with glyoxylic acid-induced fluorescence. The vascular isometric tension responses to exogenous noradrenaline and endogenously released noradrenaline by electrical stimulation in vitro were abolished. A varying degree of necrosis of the vascular wall was observed. Two weeks after freezing at –18°C in vitro responses to exogenous noradrenaline and electrical stimulation were still abolished, then gradually approaching control levels after 10–20 weeks of in vivo regeneration. Eight and 10 weeks after injury at –9°C increased vascular tension responses to exogenous noradrenaline was found. In spite of a long regeneration period the total uptake and the spontaneous and K+ (75 mM) evoked releases of [3H]noradrenaline were persistently decreased after frostbite at –18°C, but they were regenerated to control levels already 10–20 weeks after –9°C. Regeneration of noradrenergic nerve function, expressed as [3H]noradrenaline uptake and release and responsiveness to electrical stimulation, expressed as vascular contraction, was slower than the regeneration of the vascular smooth muscle. Myointimal hyperplasia developed in response to –9°C and –18°C frostbite. The uptake and the K+ evoked release of [3H]noradrenaline were particularly sensitive parameters for autonomic nerve function. Conclusions: The present findings may demonstrate important neurovascular reactions to local frostbite and may explain human sequelae following frostbite

β-blockade abolishes the augmented cardiac tPA release induced by transactivation of heterodimerised bradykinin receptor-2 and β2-adrenergic receptor in vivo

2014 ◽  
Vol 112 (11) ◽  
pp. 951-959 ◽  
Author(s):  
Morten Eriksen ◽  
Arnfinn Ilebekk ◽  
Alessandro Cataliotti ◽  
Cathrine Rein Carlson ◽  
Torstein Lyberg ◽  
...  
Keyword(s):  
Adrenergic Receptor ◽  
Sympathetic Nerves ◽  
Ventricular Myocardium ◽  
Left Ventricular ◽  
Left Ventricular Myocardium ◽  
Adrenergic Stimulation ◽  
Β2 Adrenergic Receptor ◽  
Β Blocker

SummaryBradykinin (BK) receptor-2 (B2R) and β2-adrenergic receptor (β2AR) have been shown to form heterodimers in vitro. However, in vivo proofs of the functional effects of B2R-β2AR heterodimerisation are missing. Both BK and adrenergic stimulation are known inducers of tPA release. Our goal was to demonstrate the existence of B2R-β2AR heterodimerisation in myocardium and to define its functional effect on cardiac release of tPA in vivo. We further investigated the effects of a non-selective β-blocker on this receptor interplay. To investigate functional effects of B2R-β2AR heterodimerisation (i. e. BK transactivation of β2AR) in vivo, we induced serial electrical stimulation of cardiac sympathetic nerves (SS) in normal pigs that underwent concomitant BK infusion. Both SS and BK alone induced increases in cardiac tPA release. Importantly, despite B2R desensitisation, simultaneous BK infusion and SS (BK+SS) was characterised by 2.3 ± 0.3-fold enhanced tPA release compared to SS alone. When β-blockade (propranolol) was introduced prior to BK+SS, tPA release was inhibited. A persistent B2R-β2AR heterodimer was confirmed in BK-stimulated and nonstimulated left ventricular myocardium by immunoprecipitation studies and under non-reducing gel conditions. All together, these results strongly suggest BK transactivation of β2AR leading to enhanced β2AR-mediated release of tPA. Importantly, non-selective β-blockade inhibits both SS-induced release of tPA and the functional effects of B2R-β2AR heterodimerisation in vivo, which may have important clinical implications.

scholarly journals Evaluation of a Novel Therapeutic Approach to Treating Severe Pneumococcal Infection Using a Mouse Model

2009 ◽  
Vol 16 (6) ◽  
pp. 806-810 ◽  
Author(s):  
Nikkol Melnick ◽  
Gowrisankar Rajam ◽  
George M. Carlone ◽  
Jacquelyn S. Sampson ◽  
Edwin W. Ades
Keyword(s):  
Single Dose ◽  
Combination Therapy ◽  
Polymorphonuclear Leukocytes ◽  
Low Dose ◽  
Control Level ◽  
Pneumococcal Infection ◽  
Amino Acid Peptide ◽  
Opsonophagocytic Killing

ABSTRACT P4, a 28-amino-acid peptide, is a eukaryotic cellular activator that enhances specific in vitro opsonophagocytic killing of multiple bacterial pathogens. In a previous study, we successfully recreated this phenomenon in mice in vivo by using a two-dose regimen of P4 and pathogen-specific antibodies, which significantly reduced moribundity in mice. For the present study, we hypothesized that the inclusion of a low-dose antibiotic would make it possible to treat the infected mice with a single dose containing a mixture of P4 and a pathogen-specific antibody. A single dose consisting of P4, intravenous immunoglobulin (IVIG), and ceftriaxone effectively reduced moribundity compared to that of untreated controls (n = 10) by 75% (P < 0.05) and rescued all (10 of 10) infected animals (P < 0.05). If rescued animals were reinfected with Streptococcus pneumoniae and treated with a single dose containing P4, IVIG, and ceftriaxone, they could be rerescued. This observation of the repeated successful use of P4 combination therapy demonstrates a low risk of tolerance development. Additionally, we examined the polymorphonuclear leukocytes (PMN) derived from infected mice and observed that P4 enhanced in vitro opsonophagocytic killing (by >80% over the control level; P < 0.05). This finding supports our hypothesis that PMN are activated by P4 during opsonophagocytosis and the recovery of mice from pneumococcal infection. P4 peptide-based combination therapy may offer an alternative and rapid immunotherapy to treat fulminant pneumococcal infection.

Effects of Cyclic Stress on the Mechanical Properties of Cultured Collagen Fascicles from the Rabbit Patellar Tendon

2003 ◽  
Vol 125 (6) ◽  
pp. 893-901 ◽  
Author(s):  
Ei Yamamoto ◽  
Susumu Tokura ◽  
Kozaburo Hayashi
Keyword(s):  
Mechanical Properties ◽  
Tensile Strength ◽  
Patellar Tendon ◽  
Control Level ◽  
Quadratic Function ◽  
Peak Stress ◽  
Cyclic Stress ◽  
Original Strength

Effects of cyclic stress on the mechanical properties of collagen fascicles were studied by in vitro tissue culture experiments. Collagen fascicles (approximately 300 μm in diameter) obtained from the rabbit patellar tendon were applied cyclic load at 4 Hz for one hour per day during culture period for one or two weeks, and then their mechanical properties were determined using a micro-tensile tester. There was a statistically significant correlation between tensile strength and applied peak stress in the range of 0 to 5 MPa, and the relation was expressed by a quadratic function. The maximum strength (19.4 MPa) was obtained at the applied peak stress of 1.8 MPa. The tensile strength of fascicles were within a range of control values, if they were cultured under peak stresses between 1.1 and 2.6 MPa. Similar results were also observed in the tangent modulus, which was maintained at control level under applied peak stresses between 0.9 and 2.8 MPa. The stress of 0.9 to 1.1 MPa is equivalent to approximately 40% of the in vivo peak stress which is developed in the intact rabbit patellar tendon by running, whereas that of 2.6 to 2.8 MPa corresponds to approximately 120% of the in vivo peak stress. Therefore, the fascicles cultured under applied peak stresses of lower than 40% and higher than 120% of the in vivo peak stress do not keep the original strength and modulus. These results indicate that the mechanical properties of cultured collagen fascicles strongly depend upon the magnitude of the stress applied during culture, which are similar to our previous results observed in stress-shielded and overstressed patellar tendons in vivo.

scholarly journals Effect of Lactic Acid Bacteria on the Pharmacokinetics and Metabolism of Ginsenosides in Mice

Pharmaceutics ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 1496
Author(s):  
Ji-Hyeon Jeon ◽  
Jaehyeok Lee ◽  
Jin-Hyang Park ◽  
Chul-Haeng Lee ◽  
Min-Koo Choi ◽  
...  
Keyword(s):  
Lactic Acid ◽  
Lactic Acid Bacteria ◽  
Formation Rate ◽  
Plasma Concentrations ◽  
Control Level ◽  
In Vitro Fermentation ◽  
Fecal Recovery ◽  
Fermentation Test

This study aims to investigate the effect of lactic acid bacteria (LAB) on in vitro and in vivo metabolism and the pharmacokinetics of ginsenosides in mice. When the in vitro fermentation test of RGE with LAB was carried out, protopanaxadiol (PPD) and protopanaxadiol (PPD), which are final metabolites of ginsenosides but not contained in RGE, were greatly increased. Compound K (CK), ginsenoside Rh1 (GRh1), and GRg3 also increased by about 30%. Other ginsenosides with a sugar number of more than 2 showed a gradual decrease by fermentation with LAB for 7 days, suggesting the involvement of LAB in the deglycosylation of ginsenosides. Incubation of single ginsenoside with LAB produced GRg3, CK, and PPD with the highest formation rate and GRd, GRh2, and GF with the lower rate among PPD-type ginsenosides. Among PPT-type ginsenosides, GRh1 and PPT had the highest formation rate. The amoxicillin pretreatment (20 mg/kg/day, twice a day for 3 days) resulted in a significant decrease in the fecal recovery of CK, PPD, and PPT through the blockade of deglycosylation of ginsenosides after single oral administrations of RGE (2 g/kg) in mice. The plasma concentrations of CK, PPD, and PPT were not detectable without change in GRb1, GRb2, and GRc in this group. LAB supplementation (1 billion CFU/2 g/kg/day for 1 week) after the amoxicillin treatment in mice restored the ginsenoside metabolism and the plasma concentrations of ginsenosides to the control level. In conclusion, the alterations in the gut microbiota environment could change the ginsenoside metabolism and plasma concentrations of ginsenosides. Therefore, the supplementation of LAB with oral administrations of RGE would help increase plasma concentrations of deglycosylated ginsenosides such as CK, PPD, and PPT.

scholarly journals Vascular-dependent effects of elevated glucose on postganglionic sympathetic neurons

2011 ◽  
Vol 300 (4) ◽  
pp. H1386-H1392 ◽  
Author(s):  
Deborah H. Damon
Keyword(s):  
Vascular Function ◽  
Sympathetic Neurons ◽  
Vascular Complications ◽  
Sympathetic Nerves ◽  
T Test ◽  
Neuronal Cultures ◽  
Elevated Glucose ◽  
Low Glucose

Perivascular sympathetic nerves are important determinants of vascular function that are likely to contribute to vascular complications associated with hyperglycemia and diabetes. The present study tested the hypothesis that glucose modulates perivascular sympathetic nerves by studying the effects of 7 days of hyperglycemia on norepinephrine (NE) synthesis [tyrosine hydroxylase (TH)], release, and uptake. Direct and vascular-dependent effects were studied in vitro in neuronal and neurovascular cultures. Effects were also studied in vivo in rats made hyperglycemic (blood glucose >296 mg/dl) with streptozotocin (50 mg/kg). In neuronal cultures, TH and NE uptake measured in neurons grown in high glucose (HG; 25 mM) were less than that in neurons grown in low glucose (LG; 5 mM) ( P < 0.05; n = 4 and 6, respectively). In neurovascular cultures, elevated glucose did not affect TH or NE uptake, but it increased NE release. Release from neurovascular cultures grown in HG (1.8 ± 0.2%; n = 5) was greater than that from cultures grown in LG (0.37 ± 0.28%; n = 5; P < 0.05; unpaired t-test). In vivo, elevated glucose did not affect TH or NE uptake, but it increased NE release. Release in hyperglycemic animals (9.4 + 1.1%; n = 6) was greater than that in control animals (5.39 + 1.1%; n = 6; P < 0.05; unpaired t-test). These data identify a novel vascular-dependent effect of elevated glucose on postganglionic sympathetic neurons that is likely to affect the function of perivascular sympathetic nerves and thereby affect vascular function.

Dogfish pressor response to potassium blocked by magnesium and phentolamine

1982 ◽  
Vol 242 (3) ◽  
pp. R185-R188
Author(s):  
R. G. Carroll ◽  
D. F. Opdyke ◽  
N. E. Keller
Keyword(s):  
Adrenergic Receptor ◽  
Pressor Response ◽  
In Vitro Experiments ◽  
Spontaneous Release ◽  
Alpha Adrenergic Receptor ◽  
Receptor Sites ◽  
Catecholamine Levels ◽  
Chromaffin Tissue

In vivo infusion of MgCl2 blocks the dogfish pressor response to K+. This action of Mg2+ was contrasted to phentolamine in in vivo and in vitro experiments. Mg2+ blocks the spontaneous release of catecholamines from dogfish chromaffin tissue but does not alter the norepinephrine-induced contraction of the isolated dogfish artery. In vivo infusion of Mg2+ causes a significant decrease in resting catecholamine levels and diminishes the catecholamine release caused by K+ challenge. Both Mg2+ and phentolamine block the pressor action of K+, Mg2+ by preventing the K+-induced release of catecholamines and phentolamine by preventing the circulating catecholamines from interacting with alpha-adrenergic receptor sites.

scholarly journals Mechanisms of zinc uptake in gills of freshwater rainbow trout: interplay with calcium transport

1996 ◽  
Vol 270 (5) ◽  
pp. R1141-R1147 ◽  
Author(s):  
C. Hogstrand ◽  
P. M. Verbost ◽  
S. E. Bonga ◽  
C. M. Wood
Keyword(s):  
Rainbow Trout ◽  
Control Level ◽  
Inhibitory Effect ◽  
Chloride Cells ◽  
Water Addition ◽  
Uptake Mechanism ◽  
Basolateral Membranes ◽  
Control Value

The uptake mechanism of Zn2+ through the gill epithelium of freshwater rainbow trout was investigated both in intact animals and in isolated basolateral membranes. Involvement of the apical Ca2+ uptake sites in Zn2+ uptake was examined in vivo by pharmacological manipulation of the apical Ca2+ permeability. The apical entries of Ca2+ and Zn2+, but not Na2+ and Cl-, were inhibited by addition of La to the water. Addition of 1.0 microM La reduced the influxes of Ca2+ and Zn2+ to 22 +/- 3 and 53 +/- 7% (mean +/- SE) of the control value, respectively. Injection of CaCl2 also reduced the branchial influxes of Ca2+ and Zn2+. This treatment decreased the influx of Ca2- to 45 +/- 4% of the control level and the Zn2+ influx to 68 +/- 5%. These results strongly imply that Zn2+ passes across the apical membrane of the chloride cells of the gills via the same pathway as Ca2+. The presence of an active basolateral transporter for Zn2+ was investigated in vitro on isolated basolateral membranes. There was no ATP-dependent or Na2+(-)gradient driven transport of Zn2+ at physiological Zn2+ activities. The same system was used to study potential effects of Zn2+ on the basolateral Ca2+(-)adenosinetri-phosphatase. Zn2+ was found to be a potent blocker of this transporter, causing a mixed inhibitory effect on the ATP driven Ca2+ transport at a free Zn2+ activity of 100 pM.

Macrovascular thrombosis is driven by tissue factor derived primarily from the blood vessel wall

Blood ◽  
2005 ◽  
Vol 105 (1) ◽  
pp. 192-198 ◽  
Author(s):  
Sharlene M. Day ◽  
Jennifer L. Reeve ◽  
Brian Pedersen ◽  
Diana M Farris ◽  
Daniel D. Myers ◽  
...  
Keyword(s):  
Blood Vessel ◽  
Tissue Factor ◽  
Vessel Wall ◽  
Thrombus Formation ◽  
Vena Cava ◽  
Vascular Wall ◽  
Blood Vessel Wall ◽  
Wild Type

Abstract Leukocytes and leukocyte-derived microparticles contain low levels of tissue factor (TF) and incorporate into forming thrombi. Although this circulating pool of TF has been proposed to play a key role in thrombosis, its functional significance relative to that of vascular wall TF is poorly defined. We tested the hypothesis that leukocyte-derived TF contributes to thrombus formation in vivo. Compared to wild-type mice, mice with severe TF deficiency (ie, TF–/–, hTF-Tg+, or “low-TF”) demonstrated markedly impaired thrombus formation after carotid artery injury or inferior vena cava ligation. A bone marrow transplantation strategy was used to modulate levels of leukocyte-derived TF. Transplantation of low-TF marrow into wild-type mice did not suppress arterial or venous thrombus formation. Similarly, transplantation of wild-type marrow into low-TF mice did not accelerate thrombosis. In vitro analyses revealed that TF activity in the blood was very low and was markedly exceeded by that present in the vessel wall. Therefore, our results suggest that thrombus formation in the arterial and venous macrovasculature is driven primarily by TF derived from the blood vessel wall as opposed to leukocytes.

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