scholarly journals Alterations in Endothelin Receptors Following Hemorrhage and Resuscitation by Centhaquin

2018 ◽  
pp. S199-S214
Author(s):  
S. BRIYAL ◽  
R. GANDHAKWALA ◽  
M. KHAN ◽  
M. S. LAVHALE ◽  
A. GULATI

Endothelin-1 (ET-1) acts on ETA and ETB receptors and has been implicated in hemorrhagic shock (shock). We determined effect of shock and resuscitation by hypertonic saline (saline) or centhaquin on ETA and ETB receptor expression. Rats were anesthetized, a pressure catheter was placed in the left femoral artery; blood was withdrawn from the right femoral artery to bring mean arterial pressure (MAP) to 35 mm Hg for 30 min, resuscitation was performed and 90 min later sacrificed to collect samples for biochemical estimations. Resuscitation with centhaquin decreased blood lactate and increased MAP. Protein levels of ETA or ETB receptor were unaltered in the brain, heart, lung and liver following shock or resuscitation. In the abdominal aorta, shock produced an increase (140 %) in ETA expression which was attenuated by saline and centhaquin; ETB expression was unaltered following shock but was increased (79 %) by centhaquin. In renal medulla, ETA expression was unaltered following shock, but was decreased (-61 %) by centhaquin; shock produced a decrease (-34 %) in ETB expression which was completely attenuated by centhaquin and not saline. Shock induced changes in ETA and ETB receptors in the aorta and renal medulla are reversed by centhaquin and may be contributing to its efficacy.

1992 ◽  
Vol 68 (05) ◽  
pp. 500-505 ◽  
Author(s):  
Ch M Samama ◽  
Ph Bonnin ◽  
M Bonneau ◽  
G Pignaud ◽  
E Mazoyer ◽  
...  

SummaryWe investigated the comparative antithrombotic properties of clopidogrel, an analogue of ticlopidine, and aspirin, using the Folts' model on femoral arteries in 22 pigs. On each animal, clopidogrel or aspirin were used to treat the thrombotic process on the left femoral artery and to prevent this process on the right femoral artery. Sequentially: an injury and stenosis were carried out on the left femoral artery; the thrombotic process was monitored with a Doppler during a 30-min observation period for cyclic flow reductions or permanent cessation of flow; after the first cyclic flow reduction occurred, clopidogrel (5 mg kg-1) or aspirin (2.5, 5, 100 mg kg-1) were injected intravenously; if cyclic flow reductions were abolished, epinephrine (0.4 µg kg-1 min-1) was injected to try to restore cyclic flow reductions and/or permanent cessation of flow; then injury and stenosis were applied on the right femoral artery. Before and after injection of clopidogrel or aspirin, ear immersion bleeding times and ex-vivo platelet aggregation were performed. Clopidogrel (n = 7) abolished cyclic flow reductions in all animals and epinephrine did not restore any cyclic flow reduction. On the right femoral artery, cyclic flow reductions were efficiently prevented, even for two injuries. Basal bleeding time (5 min 28) was lengthened (>15 min, 30 min after clopidogrel and remained prolonged even after 24 h). ADP-induced platelet aggregation was inhibited (more than 78%). Comparatively, aspirin had a moderate and no dose-dependent effect. Aspirin 2.5 mg kg-1 (n = 6) abolished cyclic flow reductions in 2 animals, CFR reoccurred spontaneously in one animal and epinephrine restored it in a second animal. Aspirin 5 mg kg-1 (n = 6) abolished cyclic flow reductions in only 3 animals and epinephrine always restored it. Aspirin 100 mg kg-1 (n = 3) was unable to abolish cyclic flow reductions. On the right femoral artery, aspirin did not significantly prevent cyclic flow reductions which occurred in all animals after one (n = 14) or two injuries (n = 1), except for one animal. Basal bleeding time was lengthened but it shortened rapidly, reaching its basal value after 24 h. ADP-induced aggregation was not significantly inhibited, whereas arachidonic acid induced aggregation was always inhibited. Clopidogrel appears as a more potent antithrombotic drug than aspirin in this model, in treating and preventing spontaneous or epinephrine-induced cyclic flow reductions and lengthening bleeding time.


PEDIATRICS ◽  
1985 ◽  
Vol 75 (4) ◽  
pp. 741-744
Author(s):  
Harry Schanzer ◽  
Julius H. Jacobson

In order to elucidate whether tissue damage produced on occasion by intramuscular injection of longacting penicillin is due to accidental intra-arterial injection or vasospasm, two types of experiments were carried out in rabbits. In the first set of experiments, six New Zealand White rabbits were given intra-arterial injections of 0.4 mL of a mixture containing 300,000 U of penicillin G benzathine and 300,000 units of penicillin procaine per milliliter (Bicillin C-R) into the left femoral artery and 0.4 mL of normal saline into the right femoral artery as autocontrol. In a second set of experiments, 0.4 mL of the same penicillin preparation was injected in the space surrounding the left femoral artery in five New Zealand rabbits, and 0.4 mL of normal saline was injected in a similar fashion around the right femotal artery as control. The legs of the rabbits that received the intra-arterial injection of penicillin invariably developed ischemic manifestations. None of the legs of rabbits given intra-arterial injections of normal saline had pathologic manifestations. None of the rabbits that received the periarterial penicillin preparation or normal saline developed abnormalities. These results strongly suggest that the tissue damage produced by penicillin is secondary to the intra-arterial administration of the drug.


2002 ◽  
Vol 10 (3) ◽  
pp. 05-08
Author(s):  
Fábio Richieri Hanania ◽  
Maurício Masasi Iamaguchi ◽  
Marcelo Rosa de Rezende

The purpose of our research consists of studying a new dye which, besides allowing the macroscopic study of small vessels <FONT FACE=Symbol>¾</FONT> following the pioneer research of Salmon(3) <FONT FACE=Symbol>¾</FONT>, permits the radiographic study due to its radiopacity. To do so, ten rats were utilized and their abdominal aorta was catheterized for the injection of the dye towards the periphery, being the flow of the dye observed along the left femoral artery (the right one was cauterized for occlusion). The results of this injection revealed that the dye penetrates well in extremely small vessels and allows dissection without extravasations. Thus, we believe that this dye has the necessary requirements for the study of details of the vascular anatomy.


1994 ◽  
Vol 19 (4) ◽  
pp. 461-465 ◽  
Author(s):  
S. SAITOH ◽  
Y. NAKATSUCHI

An arterial graft was taken from the left femoral artery of the rat and grafted into the right femoral artery using the telescoping anastomotic technique at both the proximal and distal anastomoses to compare the patency rate with that of the vein grafts interposed into the arterial defect with the same telescoping technique. The time required for each anastomosis was about 10 minutes and all of the 31 grafts remained patent without application of xylocaine, yielding a higher patency rate than the vein grafts interposed in an arterial defect. The telescoping technique proved to be so dependable that it could be used at least twice in an artery. Inserting one vessel stump into another using the telescoping technique may not itself be responsible for the failure of vein grafts interposed in an arterial defect, but distortion of the slack venous wall of the graft by high arterial blood pressure is.


2018 ◽  
pp. S175-S184 ◽  
Author(s):  
J. HONDA ◽  
T. KIMURA ◽  
S. SAKAI ◽  
H. MARUYAMA ◽  
K. TAJIRI ◽  
...  

The glucagon-like peptide-1 receptor (GLP-1R) agonist liraglutide is an incretin hormone mimetic used in the treatment of diabetes. However, the effects of liraglutide on pulmonary hypertension (PH) and pulmonary endothelin (ET) system are unknown. Eight-week-old C57BL6/J mice were injected liraglutide or vehicle for 5 weeks. One week after injection, the mice were exposed to either room air (normoxia) or chronic hypoxia (10 % O2) for 4 weeks. The right ventricular systolic pressure (RVSP) was significantly higher in hypoxia + vehicle group than in normoxia + vehicle group. ET-1 mRNA expression in the lungs was comparable among all the groups. ETB mRNA and protein expression in the lungs was significantly lower in hypoxia + vehicle group than in normoxia + vehicle group. The above changes were normalized by liraglutide treatment. The expression of phospho-eNOS and phospho-AMPK proteins in the lungs was significantly higher in hypoxia + liraglutide group than in normoxia + vehicle group. We demonstrated for the first time that liraglutide effectively improved RVSP and RV hypertrophy in hypoxia-induced PH mice by activating eNOS through normalization of impaired ETB pathway and augmentation of AMPK pathway. Therefore, GLP-1R agonists can be promising therapeutic agents for PH.


Perfusion ◽  
2017 ◽  
Vol 33 (4) ◽  
pp. 297-302 ◽  
Author(s):  
Xuan Jiang ◽  
Tianxiang Gu ◽  
Yu Liu ◽  
Chun Wang ◽  
Enyi Shi ◽  
...  

Objective: Cardiopulmonary bypass (CPB) and deep hypothermic circulatory arrest (DHCA) are commonly used in cardiac surgery. However, the mortality and morbidity are still high in practice. Developing novel protective stategies and elucidating the underlying mechanisms for the pathophysiological consequences of DHCA have been hampered because of the absence of a satisfactory recovery animal model. The aim of this study was to establish a novel and safe DHCA model without blood priming in rats to study the pathophysiology of potential complications. Methods: Ten adult male Sprague-Dawley rats (age, 14-16 weeks; weight, 200-300g) were used. The entire CPB circuit consisted of a modified reservoir, a custom-designed small-volume membrane oxygenator, a roller pump and a home-made heat exchanger, all of which were connected via silicon tubing. The volume of the priming solution was less than 10 ml. The right jugular vein, right carotid artery and left femoral artery were cannulated. The blood was drained from the right atrium through the right jugular vein and fed back to the rat via the left femoral artery. CPB was commenced at a full flow rate. The animals were cooled to a pericranial temperature of 18°C and then subjected to 45 minutes of DHCA with global ischemia. Circulatory arrest was followed by rewarming and over 60 minutes of reperfusion. CPB was terminated carefully. Blood in the circuit was centrifuged and slowly transfused to achieve optimal hematocrit. Blood gas and hemodynamic parameters were recorded at each time point before CPB, during CPB and after CPB. Results: All CPB and DHCA processes were achieved successfully. No rat died in our research. Blood gas analyses at different times were normal. Cardiac function and blood pressure were stable after the operation. The vital signs of all the rats were stable. Conclusion: The novel augmented venous-drainage CPB and DHCA model in rats could be established successfully without blood priming.


Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Wei-Tien Chang ◽  
Woan-Yi Wang ◽  
Chun-Pei Lee ◽  
Hsiao-Ching Wei ◽  
Sung-Chun Tang ◽  
...  

Introduction: Cerebrovascular circulation is usually compromised after cardiac arrest and CPR. Remote limb ischemic post-conditioning (RLIP) is clinically feasible and can potentially mitigate post-resuscitation neurological deficits. Since nitric oxide (NO) is implicated in post-conditioning protection, we aim to investigate if RLIP impacts post-resuscitation cerebral perfusion and prognosis via NO-related mechanism. Hypothesis: RLIP improves post-CPR cerebral perfusion and prognosis through in situ and remote activation of Akt-eNOS-NO signaling. Methods: Using an established rat model of asphyxia cardiac arrest and CPR, we randomized the rats to the following groups: (1) sham, (2) standard CPR, (3) RLIP 5 min after return of spontaneous circulation (ROSC). RLIP was done by 3 cycles of 5 min of left hind limb ischemia followed by 5 min of reperfusion. Arterial blood was sampled for colorimetric determination of nitrate/nitrite. The cerebral perfusion was continuously recorded by OxyFLO probe. Two hours after ROSC, the brain and left femoral artery were harvested for measuring phosphorylated endothelial NO synthase (p-eNOS at Ser1177) and protein kinase B (p-Akt at Ser473). In a subgroup the survival and neurological outcomes were monitored up to 3 days. Results: The cerebral perfusion was significantly decreased (0.6-0.8 folds that of baseline) after ROSC in standard CPR group. If RLIP was employed, the cerebral perfusion was significantly augmented (up to 1.6 folds, P < 0.001) in the post-resuscitation phase. This was associated with improved survival (log-rank P < 0.05) and neurological scores at 6, 24, 48 and 72 h (all P < 0.05). Plasma NO as indicated by nitrate/nitrite was significantly increased in the RLIP group ( P < 0.05). Most of all, p-eNOS and p-Akt were significantly increased not only in left femoral artery but also in brain. If NOS inhibitor N ω -nitro-L-arginine methyl ester (10 mg/kg) was used, not only the NO increase was reversed, the improvement in survival and neurological outcomes were also abrogated. Conclusions: RLIP enhances post-resuscitation cerebral perfusion and improves survival and neurological prognoses not only via in situ limb artery derived NO but remote activation of Akt-eNOS signaling in the brain.


2014 ◽  
Vol 307 (8) ◽  
pp. F962-F970 ◽  
Author(s):  
Alexis A. Gonzalez ◽  
Torrance Green ◽  
Christina Luffman ◽  
Camille R. T. Bourgeois ◽  
L. Gabriel Navar ◽  
...  

The (pro)renin receptor [(P)RR] upregulates cyclooxygenase-2 (COX-2) in inner medullary collecting duct (IMCD) cells through ERK1/2. Intrarenal COX-2 and (P)RR are upregulated during chronic ANG II infusion. However, the duration of COX-2 and (P)RR upregulation has not been determined. We hypothesized that during the early phase of ANG II-dependent hypertension, membrane-bound (P)RR and COX-2 are augmented in the renal medulla, serving to buffer the hypertensinogenic and vasoconstricting effects of ANG II. In Sprague-Dawley rats infused with ANG II (0.4 μg·min−1·kg−1), systolic blood pressure (BP) increased by day 7 (162 ± 5 vs. 114 ± 10 mmHg) and continued to increase by day 14 (198 ± 15 vs. 115 ± 13 mmHg). Membrane-bound (P)RR was augmented at day 3 coincident with phospho-ERK1/2 levels, COX-2 expression, and PGE2 in the renal medulla. In contrast, membrane-bound (P)RR was reduced and COX-2 protein levels were not different from controls by day 14. In cultured IMCD cells, ANG II increased secretion of the soluble (P)RR. In anesthetized rats, COX-2 inhibition decreased the glomerular filtration rate (GFR) and renal blood flow (RBF) during the early phase of ANG II infusion without altering BP. However, at 14 days of ANG II infusions, COX-2 inhibition decreased mean arterial BP (MABP), RBF, and GFR. Thus, during the early phase of ANG II-dependent hypertension, the increased (P)RR and COX-2 expression in the renal medulla may contribute to attenuate the vasoconstrictor effects of ANG II on renal hemodynamics. In contrast, at 14 days the reductions in RBF and GFR caused by COX-2 inhibition paralleled the reduced MABP, suggesting that vasoconstrictor COX-2 metabolites contribute to ANG II hypertension.


2014 ◽  
Vol 71 (10) ◽  
pp. 969-971 ◽  
Author(s):  
Miodrag Damjanovic ◽  
Sonja Salinger-Martinovic ◽  
Danijela Djordjevic-Radojkovic ◽  
Goran Koracevic ◽  
Vladimir Miloradovic

Introduction. Entrapment and fracture of diagnostic or therapeutic devices within the coronary circulatory system are a rare, but increasing problem. Case report. A 70-yearold man was admitted in our clinic for coronary angiography before the planned aortic valve replacement. An arterial sheath was inserted in the right common femoral artery. After introducing a J-tip diagnostic coronary guidewire into the aorta and advancing a left Judkins diagnostic catheter over it, suddenly occured peeling off of the wire?s hydrophilic coating at the aortic arch level. Very soon, this outer coating of guidewire carried by the blood stream was entered into the left femoral artery, then into the left popliteal artery. This stripped part of guidewire was successfully caught and extracted out by using a goose-neck snare catheter. Conclusion. A sudden stripping of outer coating of a J-tip diagnostic hydrophilic coronary guidewire during coronary angiography is possible to manage quickly and successfully by the use of a simple cathether.


2019 ◽  
Vol 25 (1) ◽  
pp. 1-5
Author(s):  
Prună Ion Irina ◽  
Ciufu Carmen ◽  
Bordei Petru

Abstract Common femoral arteries diameters (left and right) were studied, on a number of 60 cases (26 women and 34 men) with a General Electric – Voluson 730 Expert ultrasonograph. The diameters of the common femoral arteries, left and right, were measured in three points: proximal, middle and inferior, in 60 cases as it follows: 26 cases on women (43,33%) and 34 cases on men (56,70%). Regarding the proximal third of the right common femoral artery, the diameter range was found between 6,1 and 8,9mm, in women being between 6,2-7,9mm, and in men between 6,1-8,9mm. The diameter of the middle third had values between 5,8-9,7mm, in women ranging from 6,1 to 7,8mm, and in men from 5,8 to 9,7mm. At the level of the inferior third, the femoral artery had a diameter between 6,8-12,7mm, in women ranging from 6,5 to 9,8mm, and in men from 6,3 to 12,7mm. The common left femoral artery, in its proximal third had a diameter with values between 5,7 – 9,9mm, in women from 6,2 to 8,0mm, and in men being between 5,7-9,9mm. In the middle third the values were found between 6,1-9,8mm, in women being from 6,6 to 7,9mm, and in men from 6,1 to 9,8mm. Regarding the inferior third, the diameters had values between 7,0-12,5mm, in women ranging from 7,1 to 10,5mm, and in men, from 6,8 to 12,5mm.


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