piperidines and Aortic-Aneurysm--Abdominal

Endovascular abdominal aortic aneurysm (AAA) repair was performed with local anaesthesia and intravenous analgesia. The objective of the study was to evaluate how two analgesia protocols affected stress response, measured as cortisol, 17-OH progesterone (17OHP) and prolactin (PRL) concentration during the procedure.. 44 patients undergoing elective AAA endovascular repair were included to either receive regular boluses of fentanyl midazolam or remifentanil continuous infusion, analgesia was monitored by Visual Analogue Scale (VAS) measurement; cortisol, 17OHP and PRL were sampled preoperatively, at skin incision, endovascular prosthesis release and skin suture.. 42 patients were included. Mean VAS values were lower in the remifentanil group 0.50±0.68 vs 1.48±1.20, p=0.002 at incision, 0.24±0.58 vs 1.45±1.18, p<0.001 prosthesis release, 0.51±0.90 vs 1.73±1.45, p=0.002 suture. No statistically significant difference was found among cortisol and 17OHP levels; PRL was significantly lower in the fentanyl-midazolam group (23.83±16.92 ng/ml vs 40.81±22.45 p=0.009 at prosthesis release and 28.23±15.05 vs 41.37±14.54, p=0.007 at suture).. Although statistically significant VAS difference had a limited clinical impact due to its small entity. The group that experienced less pain showed a more intense PRL response, while cortisol and 17OHP did not reach statistical significance.

Topics: 17-alpha-Hydroxyprogesterone; Aged; Aged, 80 and over; Analgesics, Opioid; Aortic Aneurysm, Abdominal; Endovascular Procedures; Fentanyl; Humans; Hydrocortisone; Hypnotics and Sedatives; Intraoperative Period; Male; Midazolam; Middle Aged; Pain; Piperidines; Prolactin; Remifentanil; Stress, Physiological

Endovascular repair offers a less surgically invasive procedure for abdominal aortic aneurysms but nevertheless, still requires analgesic sedative cover to ensure an acceptable level of patient comfort and cardiorespiratory stability. The peculiarity of this kind of operation is that painful stimuli are concentrated in specific moments separated by intervals devoid of pain, so the insurgence of pain can be predicted and prevented with a bolus of analgesic, making a continuous infusion not essential, but potentially useful in achieving a better analgesic stability. The primary objective of the study was pain control measured by Visual Analogue Scale; secondary endpoints were cardiorespiratory stability and an acceptable level of sedation.. The sedative analgesic protocols of two groups of randomly allocated patients, undergoing abdominal aortic aneurysm endovascular repair, were compared. The experimental group received remifentanil infusion (0.03-0.1 microg kg min) and the control group received intravenous doses of fentanyl and midazolam (1-3 microg kg and 0.05-0.1 mg kg, respectively).. Fifty patients were investigated out of 60 enrolled. There were no relevant differences concerning cardiorespiratory stability and level of sedation, but pain levels were significantly lower in the experimental group: mean Visual Analogue Scale 0.35+/-0.40 vs. 1.49+/-0.62 (P<0.001) and area under the curve 17.48+/-5.09 vs. 33.05+/-8.19 (P<0.001).. Both techniques were shown to be safe and most importantly effective in offering cardiovascular stability and analgesia for American Society of Anaesthesiologists III-IV patients undergoing endovascular abdominal aortic aneurysm repair. However, remifentanil continuous infusion proved to offer significantly more stable pain control compared with the currently used combination fentanyl-midazolam.

Topics: Aged; Analgesia; Analgesics, Opioid; Aortic Aneurysm, Abdominal; Area Under Curve; Blood Pressure; Conscious Sedation; Female; Fentanyl; Heart Rate; Humans; Hypnotics and Sedatives; Intraoperative Care; Male; Midazolam; Oxygen; Pain; Pain Measurement; Piperidines; Remifentanil; Stents; Treatment Outcome

Inflammation, oxidative stress, matrix degradation, medial calcification and vascular smooth muscle cell (VSMC) loss are prominent features in abdominal aortic aneurysm (AAA). VSMC phenotypic switch to a proinflammatory state and VSMC apoptosis could be targetable mechanisms implicated in the pathogenesis of AAA formation. Herein, we investigated the hypothesis that a xanthine derivative (KMUP-3) might suppress AAA through inhibition of VSMC phenotypic switch and apoptosis.. In vitro, VSMC calcification was induced using β-glycerophosphate. In vivo, AAA was induced using angiotensin II (1000 ng/kg per minute) infusion for 4 weeks in apolipoprotein E-deficient mice.. As determined by alizarin red S staining and calcium content measurements, KMUP-3 suppressed VSMC calcification. During VSMC calcification, KMUP-3 inhibited mTOR and β-catenin upregulation, essential for VSMC phenotypic switch, while it enhanced AMP-activated protein kinase (AMPK) activation that protects against VSMC phenotypic switch. Moreover, KMUP-3 attenuated VSMC apoptosis with an increased Bcl-2/Bax ratio and reduced activated caspase-3 expression. During AAA formation, treatment with KMUP-3 inhibited phosphorylated mTOR expression and increased phosphorylated AMPK expression in the medial layer. In addition, KMUP-3 treatment suppressed aortic dilatation together with reduction in proinflammatory cytokines and infiltrating macrophages, attenuation of medial VSMC apoptosis and mitigation of reactive oxygen species generation, matrix-degrading proteinase activities, elastin breakdown and vascular calcification.. Treatment with KMUP-3 inhibits aneurysm growth possibly through its interference with signaling pathways involved in VSMC phenotypic switch and apoptosis. These findings provide a proof-of-concept validation for VSMC dysfunction as a potential therapeutic target in AAA.

Topics: Angiotensin II; Animals; Aorta, Abdominal; Aortic Aneurysm, Abdominal; Apoptosis; Apoptosis Regulatory Proteins; Cells, Cultured; Disease Models, Animal; Male; Mice, Knockout, ApoE; Muscle, Smooth, Vascular; Myocytes, Smooth Muscle; Phenotype; Piperidines; Rats, Sprague-Dawley; Signal Transduction; Vascular Calcification; Xanthines

Abdominal aortic aneurysm (AAA) formation is characterized by inflammation, leukocyte infiltration, and vascular remodeling. This study investigates the role of TRPV4 channels, which are transmembrane calcium channels that can regulate vascular tone, in modulating AAA formation. The elastase-treatment model of AAA in C57BL6 (WT) mice and Angiotensin II treatment model in ApoE

Topics: Animals; Aortic Aneurysm, Abdominal; Inflammation; Macrophages; Male; Mice; Mice, Inbred C57BL; Mice, Knockout, ApoE; Pancreatic Elastase; Piperidines; Quinolines; TRPV Cation Channels

Dipeptidyl peptidase-4 (DPP-4) inhibitor, a novel antidiabetic drug, has a cardioprotective effect on ischemia-reperfusion injury through an antioxidant effect. However, the effect of DPP-4 inhibitor on aneurysm formation has not been investigated. We aimed to test the hypothesis that the DPP-4 inhibitor, alogliptin, attenuates vascular oxidative stress and thus inhibits abdominal aortic aneurysm (AAA) formation.. AAAs were created with intraluminal elastase and extraluminal calcium chloride in 36 male rats. Rats were divided into three groups: a low dose of alogliptin group (group LD; 1 mg/kg/d), a high-dose group (group HD; 3 mg/kg/d), and a control group (group C, water). Alogliptin was administered by gastric gavage once daily beginning 3 days before surgery. On day 7 after aneurysm preparation, reactive oxygen species (ROS) expression was semiquantified by dihydroethidium staining, and the oxidation product of DNA produced by ROS, 8-hydroxydeoxyguanosine (8-OHdG), was measured by immunohistochemical staining. Blood glucose concentrations were measured. Hematoxylin and eosin and elastica Van Gieson stainings were performed on day 28, and the AAA dilatation ratio was calculated.. On day 7 (six in each group), dihydroethidium staining of the aneurysm wall showed a reduced level of ROS expression (4.6 ± 0.6 in group C, 2.7 ± 0.3 in group LD, and 1.7 ± 0.5 in group HD; P < .0001) and showed fewer 8-OHdG-positive cells in alogliptin-treated samples (138.1 ± 7.4 cells in group C, 102.5 ± 4.5 cells in group LD, and 66.1 ± 4.5 cells in group HD; P < .0001) The treatment significantly reduced messenger RNA expression of matrix metalloproteinases (MMPs) in aneurysm walls (relative expression: MMP-2: 2.1 ± 0.4 in group C, 1.3 ± 0.3 in group LD, and 0.9 ± 0.2 in group HD; P < .001; MMP-9: 2.0 ± 0.5 in group C, 0.3 ± 0.3 in group LD, and 0.3 ± 0.2 in group HD; P < .001). On day 28 (six in each group), the aortic wall in groups LD and HD was less dilated (dilatation ratio: 199.2% ± 11.8% in group C, 159.6% ± 2.8% in group LD, and 147.1% ± 1.9% in group HD; P < .02 group C vs HD) and had higher elastin content than in group C. The difference in blood glucose levels among the three groups was not significant.. The DPP-4 inhibitor, alogliptin, attenuates aneurysm formation and expansion dose-dependently in a rat AAA model via an antioxidative action.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Administration, Oral; Animals; Antioxidants; Aorta, Abdominal; Aortic Aneurysm, Abdominal; Blood Glucose; Calcium Chloride; Deoxyguanosine; Dilatation, Pathologic; Dipeptidyl Peptidase 4; Dipeptidyl-Peptidase IV Inhibitors; Disease Models, Animal; DNA Damage; Dose-Response Relationship, Drug; Gene Expression Regulation, Enzymologic; Male; Matrix Metalloproteinase 2; Matrix Metalloproteinase 9; Oxidative Stress; Pancreatic Elastase; Piperidines; Rats; Rats, Sprague-Dawley; Reactive Oxygen Species; RNA, Messenger; Time Factors; Uracil

Topics: Acetaminophen; Analgesics; Anesthesia, General; Anesthesia, Local; Aortic Aneurysm, Abdominal; Aortic Rupture; Blood Vessel Prosthesis Implantation; Erythrocyte Transfusion; Fentanyl; Humans; Hypnotics and Sedatives; Male; Midazolam; Middle Aged; Morphine; Piperidines; Plasma; Pulmonary Disease, Chronic Obstructive; Radiography, Interventional; Remifentanil; Stents

Topics: Abdominal Pain; Aged; Anesthesia; Anesthetics, Inhalation; Anesthetics, Intravenous; Aortic Aneurysm, Abdominal; Atracurium; Desflurane; Fentanyl; Follow-Up Studies; Gait Disorders, Neurologic; Guillain-Barre Syndrome; Humans; Incidental Findings; Isoflurane; Male; Monitoring, Intraoperative; Muscle Weakness; Neuromuscular Nondepolarizing Agents; Piperidines; Propofol; Radiography, Abdominal; Remifentanil; Tomography, X-Ray Computed; Treatment Outcome