scholarly journals The effect of aerosolized indomethacin on lung inflammation and injury in a rat model of blunt chest trauma

2018 ◽  
pp. S208-S218
Author(s):  
Raymond L. Kao ◽  
Weixiong Huang ◽  
Claudio M. Martin ◽  
Tao Rui

Background: Acute lung contusion from blunt chest trauma (BCT) is characterized by an intense inflammatory response in the pulmonary parenchyma, which is associated with acute lung injury (ALI), acute respiratory distress syndrome and ventilator-associated pneumonia. We hypothesized that aerosolized indomethacin may reduce pulmonary inflammation and ALI in a rat model of BCT. Methods: Sprague-Dawley rats were anesthetized and received a tracheotomy for administration of aerosolized medication through a catheter. The BCT procedure involved free-dropping a hollow metal weight (200 g) from a height of 25.5, 38.3 or 51.2 cm onto the right thorax. We administered 1 mg/kg of indomethacin or 1 mL/kg of saline intratracheally 15 minutes after BCT. The sham group had a similar procedure without the exposure to BCT and treatment. Three hours postimpact, we obtained arterial blood gas and analyzed bronchoalveolar lavage for protein concentration, polymorphonuclear leukocytes (PMN) and cytokine levels, and lung tissue samples were taken for histopathological analysis. Results: The rats’ mean arterial pressure and heart rate dropped immediately postimpact but recovered close to that of the sham group after 30 minutes in both control and treatment groups. Compared to BCT alone, indomethacin significantly reduced the total protein level in the lungs (1.06 ± 0.39 mg/mL v. 3.75 ± 1.95 mg/mL, p = 0.006) and alveolar FD-70 leak (0.23 ± 0.19 μg/mL v. 0.53 ± 0.19 μg/mL, p = 0.02). Indomethacin also significantly attenuated the acute inflammatory response in percent PMN (13.33 ±7.5% v. 28.0 ± 12.96%, p = 0.04). Tumour necrosis factor-α and interleukin-6 decreased in the indomethacin group, but the decreases were not significant compared with other groups. Conclusion: Aerosolized indomethacin has a protective effect against alveloar tissue permeability and inflammatory response induced by BCT.

2020 ◽  
Vol 274 ◽  
pp. 103363
Author(s):  
Maria Viviana Carlino ◽  
Mario Guarino ◽  
Arturo Izzo ◽  
Daniele Carbone ◽  
Maria Immacolata Arnone ◽  
...  

Circulation ◽  
2019 ◽  
Vol 140 (Suppl_2) ◽  
Author(s):  
Claudius Balzer ◽  
Franz J Baudenbacher ◽  
Susan S Eagle ◽  
Michele M Salzman ◽  
William J Cleveland ◽  
...  

Introduction: Experimental models of hemorrhagic shock (HS) in rats are important to test new treatments that may improve outcomes in humans, and general anesthesia is required during these experiments. The volatile anesthetic Isoflurane is known for its beneficial effects in rat HS models. Focusing on cardiovascular compensatory mechanisms, we wanted to evaluate Isoflurane versus the injectable anesthetic Pentobarbital in our rat model of mild HS (class 2). We hypothesize that Isoflurane during development of HS improves hemodynamics compared to Pentobarbital. Methods: Twelve Sprague-Dawley rats were initially anesthetized with an intraperitoneal (IP) injection of Pentobarbital (45 mg/kg) and intubated (1 L/min, FiO 2 0.25); heart rate (HR) was monitored by subcutaneous ECG needles. Femoral artery and vein were cannulated for continuous blood pressure measurement and delivery of fluids, respectively. In one group (n=7), anesthesia was continued with repeated IP injections of Pentobarbital (dose mg/kg), the other group (n=5) received continuous Isoflurane (1%). After 30 min of stabilization and administration of Heparin (100 IU/kg), HS was induced by removal of 1 ml of blood over 1 min via the femoral vein, repeated every 3 min until a volume of 5 ml of blood was removed. Mean arterial blood pressure (MAP) and HR were recorded and analyzed in LabChart. Results: During baseline, rats showed no significant differences in HR and MAP between both groups. After 5 ml of hemorrhage, both groups showed significant changes compared to baseline, with significantly higher MAP and HR in rats given only Pentobarbital. Conclusions: In our rat model of HS, Isoflurane dampens the physiologic response to compensate for mild hemorrhage. The cardiovascular response of rats in the Isoflurane group was a decrease of HR and MAP to every ml of hemorrhage, while rats given only Pentobarbital were able to maintain their MAP by raising their HR until decompensation.


1986 ◽  
Vol 61 (3) ◽  
pp. 1192-1194 ◽  
Author(s):  
J. D. Wood ◽  
N. L. Herman ◽  
D. R. Kostreva

Rats were effectively ventilated with 100% O2 mixed with room air utilizing a modified tracheostomy tube and a Bird Mark 7 respirator to maintain arterial blood gases within normal limits. A 3-cm segment of rubber pilot tubing was attached to a 15-mm respiratory connector and a 3-cm piece of polyethylene catheter tubing was fitted snugly into the other end. The catheter was inserted and secured into the trachea of 250- to 500-g Sprague-Dawley rats with the adaptor hose of the respirator fitted onto the 15-mm connector following tracheostomy. Manometer and inspiratory flow rate controls of the respirator were set to their minimum operating position. Appropriate rate control adjustments were made when necessary as determined by arterial blood gas measurements. By use of the above ventilation system, adequate arterial blood gases of anesthesized rats can be maintained for greater than 3 h.


Shock ◽  
2006 ◽  
Vol 26 (Supplement 1) ◽  
pp. 10
Author(s):  
M.W. Kn??ferl ◽  
F. Gebhard ◽  
D.H. Seitz ◽  
U.C. Liener ◽  
L. Kinzl ◽  
...  

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Daesung Lim ◽  
Soo Hoon Lee ◽  
Dong Hoon Kim ◽  
Changwoo Kang ◽  
Jin Hee Jeong ◽  
...  

Abstract Background Obtaining vascular access can be challenging during resuscitation following cardiac arrest, and it is particularly difficult and time-consuming in paediatric patients. We aimed to compare the efficacy of high-dose intramuscular (IM) versus intravascular (IV) epinephrine administration with regard to the return of spontaneous circulation (ROSC) in an asphyxia-induced cardiac arrest rat model. Methods Forty-five male Sprague-Dawley rats were used for these experiments. Cardiac arrest was induced by asphyxia, and defined as a decline in mean arterial pressure (MAP) to 20 mmHg. After asphyxia-induced cardiac arrest, the rats were randomly allocated into one of 3 groups (control saline group, IV epinephrine group, and IM epinephrine group). After 540 s of cardiac arrest, cardiopulmonary resuscitation was performed, and IV saline (0.01 cc/kg), IV (0.01 mg/kg, 1:100,000) epinephrine or IM (0.05 mg/kg, 1:100,000) epinephrine was administered. ROSC was defined as the achievement of an MAP above 40 mmHg for more than 1 minute. Rates of ROSC, haemodynamics, and arterial blood gas analysis were serially observed. Results The ROSC rate (61.5%) of the IM epinephrine group was less than that in the IV epinephrine group (100%) but was higher than that of the control saline group (15.4%) (log-rank test). There were no differences in MAP between the two groups, but HR in the IM epinephrine group (beta coefficient = 1.02) decreased to a lesser extent than that in the IV epinephrine group with time. Conclusions IM epinephrine induced better ROSC rates compared to the control saline group in asphyxia-induced cardiac arrest, but not compared to IV epinephrine. The IM route of epinephrine administration may be a promising option in an asphyxia-induced cardiac arrest.


Author(s):  
Tian Li ◽  
Xiaojun Ji ◽  
Jingfeng Liu ◽  
Xinjie Guo ◽  
Ran Pang ◽  
...  

Introduction: Increased permeability of the renal capillaries is a common consequence of sepsis-associated acute kidney injury. Vascular endothelial (VE)-cadherin is a strictly endothelial-specific adhesion molecule that can control the permeability of the blood vessel wall. Additionally, autophagy plays an important role in maintaining cell stability. Ulinastatin, a urinary trypsin inhibitor, attenuates the systemic inflammatory response and visceral vasopermeability. However, it is uncertain whether ulinastatin can improve renal microcirculation by acting on the endothelial adhesion junction. Methods: We observed the effect of ulinastatin in a septic rat model using contrast-enhanced ultrasonography (CEUS) to evaluate the perfusion of the renal cortex and medulla. Male adult Sprague-Dawley rats were subjected to cecal ligation and puncture and divided into the sham, sepsis, and ulinastatin groups. Ulinastatin (50,000 U/kg) was injected into the tail vein immediately after the operation. The CEUS was performed to evaluate the renal microcirculation perfusion at 3, 6, 12, and 24 hours after the operation. Histological staining was used to evaluate kidney injury scores. Western blot (WB) was used to quantify the expression of VE-cadherin, LC3II, and inflammatory factors [interleukin -1β (IL-1β), interleukin -6 (IL-6), and tumor necrosis factor-α (TNF-α)] in kidney tissue, and enzyme-linked immunosorbent assay (ELISA) detected serum inflammatory factors and kidney function and early kidney injury biomarker levels. Results: Compared with the sham group, ulinastatin reduced the inflammatory response, inhibited autophagy, maintained the expression of VE-cadherin, and meliorated cortical and medullary perfusion. Conclusion: Ulinastatin effectively protects the adhesion junction and helps ameliorate the perfusion of kidney capillaries during sepsis by the inhibition of autophagy and the expression of inflammatory factors.


2017 ◽  
Vol 66 (01) ◽  
pp. 099-108 ◽  
Author(s):  
Meng Wang ◽  
Rabea Verhaegh ◽  
Konstantinos Tsagakis ◽  
Lisa Brencher ◽  
Denise Zwanziger ◽  
...  

Background Acute mesenteric ischemia following cardiovascular surgery is a rare but fatal complication. We established a new rat model for hemodynamic monitoring during mesenteric ischemia/reperfusion (I/R) and evaluated the impact of mesenteric I/R on hemodynamics and remote organ injury. Methods Mesenteric I/R was induced in male Wistar rats by superior mesenteric artery occlusion for 90 minutes, followed by 120 minutes of reperfusion. Before I/R, ventilation and hemodynamic monitoring including mean arterial blood pressure (MAP) and cardiac output (CO) were established. During reperfusion Geloplasma (I/R + Geloplasma, N = 6) and Ringer's solution (I/R + Ringer, N = 6) were titrated according to CO and compared with I/R without volume resuscitation (I/R only, N = 6) and a sham group (sham, N = 6). Blood samples were regularly taken for serum marker measurements. After reperfusion organs were harvested for histology studies. Results After acute mesenteric I/R, MAP and CO decreased (p < 0.01) while systemic and pulmonary vascular resistance increased (p < 0.01) continuously in the I/R group. Volume substitution according to CO initially stabilized hemodynamic parameters, but CO declined independently in the late stage. Compared with the I/R + Ringer group, the I/R + Geloplasma group required less volume for resuscitation (p < 0.01), experienced less metabolic acidosis. I/R groups had more organ injuries, more neutrophils sequestration, and higher creatine phosphokinase-MB levels than sham group. Conclusion A new model for CO monitoring after mesenteric I/R injury demonstrated severe hypovolemic shock during reperfusion followed by remote myocardial and lung injury. Far less colloid volume is needed for hemodynamic stabilization after I/R compared with crystalloid volume.


Shock ◽  
2004 ◽  
Vol 21 ◽  
pp. 5-6
Author(s):  
M. W. Knöferl ◽  
M. Perl ◽  
U. C. Liener ◽  
J. Schneider ◽  
H. Begdeda ◽  
...  

2019 ◽  
Vol 37 (1) ◽  
pp. 47-54
Author(s):  
Pei Pei ◽  
Lu Liu ◽  
Luo-Peng Zhao ◽  
Zheng-Yang Qu ◽  
Chu-Ying Tang ◽  
...  

Background: Acupuncture has been recommended as an alternative therapy for migraine. Emerging evidence suggests that the 5-HT7 receptor (5-HT7R) plays a significant facilitatory role in descending modulation in migraine pathophysiology, and that activation of 5-HT7R in the descending pathway is involved in migraine central sensitisation. Objective: To investigate the ability of electroacupuncture (EA) to ameliorate central sensitisation via modulation of 5-HT7R in the descending pain pathways using a rat model of migraine induced by repetitive dural electrical stimulation (DES). Design: 64 male Sprague-Dawley rats were randomly divided into four groups: Normal group; DES group (receiving dural electrical stimulation only); DES+GB20 group (DES model group treated with EA at GB20); and DES+Sham group (DES model group treated with EA at a non-traditional (sham) acupuncture point). The presence of cutaneous allodynia was determined by measuring facial and hind-paw withdrawal latencies to electronic von-Frey. The expression of 5-HT7R in the descending pathways (periaqueductal grey, raphe magnus nucleus, and trigeminal nucleus caudalis) was assessed using immunofluorescence and Western blotting. Results: Facial and hind-paw withdrawal thresholds were significantly increased in the DES+GB20 group compared with the untreated DES group. The expression of 5-HT7R was significantly decreased in the DES+GB20 group compared with the DES group (one-way analysis of variance (ANOVA), P<0.05). No significant differences in behaviour or expression were found between the rats in the DES+Sham group and the untreated DES group (one-way ANOVA, P>0.05). Conclusion: EA at GB20 may ameliorate central sensitisation in migraine by inhibiting the activation of 5-HT7 receptors in the descending pain pathway in a rat model of migraine.


2012 ◽  
Vol 303 (1) ◽  
pp. F56-F63 ◽  
Author(s):  
Anja Bienholz ◽  
Frank Petrat ◽  
Patricia Wenzel ◽  
Philipp Ickerott ◽  
Joel M. Weinberg ◽  
...  

Acute kidney injury (AKI) is the most common kidney disease in hospitalized patients with high mortality. Ischemia and reperfusion (I/R) is one of the major causes of AKI. The combination of α-ketoglutarate+malate (αKG/MAL) showed the ability to reduce hypoxia-induced damage to isolated proximal tubules. The present study utilizes a rat model of I/R-induced AKI accompanied by intensive biomonitoring to examine whether αKG/MAL provides protection in vivo. AKI was induced in male Sprague-Dawley rats by bilateral renal clamping (40 min) followed by reperfusion (240 min). αKG/MAL was infused continuously for 60 min before and 45 min after ischemia. Normoxic and I/R control groups received 0.9% NaCl solution. The effect of αKG/MAL was evaluated by biomonitoring, blood and plasma parameters, histopathology, and immunohistochemical staining for kidney injury molecule-1 (KIM-1) and neutrophil gelatinase-associated lipocalin (NGAL), as well as by determination of tissue ATP and nonesterified fatty acid concentrations. Intravenous infusion of αKG/MAL at a cumulative dose of 1 mmol/kg each (146 mg/kg αKG and 134 mg/kg MAL) did not prevent I/R-induced increases in plasma creatinine, histopathological alterations, or cortical ATP depletion. On the contrary, the most notable adverse affect in animals receiving αKG/MAL was the decrease in mean arterial blood pressure, which was also accompanied by a reduction in heart rate. Supplementation with αKG/MAL, which is very protective against hypoxia-induced injury in isolated proximal tubules, does not protect against I/R-induced renal injury in vivo, possibly due to cardiovascular depressive effects.


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