The effect of thalidomide on spinal cord ischemia/reperfusion injury in a rabbit model.

PubMed

Lee, C-J; Kim, K-W; Lee, H-M; Nahm, F S; Lim, Y-J; Park, J-H; Kim, C-S

2007-02-01

Randomized study. To evaluate the effects of thalidomide on spinal cord ischemia/reperfusion injury via reduced TNF-alpha production. Animal experimental laboratory, Clinical Research Institute of Seoul National University Hospital, Seoul, Korea. Spinal cord ischemia was induced in rabbits by occluding the infrarenal aorta. Rabbits in group N did not undergo ischemic insult, but rabbits in groups C (the untreated group), THA, and THB underwent ischemic insult for 15 min. The THA and THB groups received thalidomide (20 mg/kg) intraperitoneally (i.p.) before ischemia, but only the THB group received thalidomide (i.p., 20 mg/kg) after 24 and 48 h of reperfusion. After evaluating neurologic functions at 1.5 h, 3, and 5 days of reperfusion, rabbits were killed for histopathologic examination and Western blot analysis of TNF-alpha. The THA and THB groups showed significantly less neurologic dysfunction than the C group at 1.5 h, 3, and 5 days of reperfusion. The number of normal spinal motor neurons in ventral gray matter was higher in THA and THB than in C, but no difference was observed between THA and THB. Western blot analysis showed a significantly higher level of TNF-alpha in C than in THA and THB at 1.5 h of reperfusion, but no difference was observed between C, THA, or THB at 3 or 5 days of reperfusion. Thalidomide treatment before ischemic insult reduces early phase ischemia/reperfusion injury of the spinal cord in rabbits.

The effect of repeated diazepam administration on myocardial function in the ischemia-reperfused isolated rat heart.

PubMed

Shackebaei, Dareuosh; Kayhani, Bijan; Godini, Aliashraf; Pourshanazari, Aliasghar; Reshadat, Sohyla

2009-06-01

To evaluate whether repeated diazepam administration affects the heart in ischemia-reperfusion. This study was performed at the Medical Biology Research Center, Kermanshah, Iran, from March to September 2008. Four groups of rats were subjected to a daily injection of diazepam (group 1 [0.5 mg/kg for 21 days], group II [2.5 mg/kg for 5 days], and group III [5 mg/kg for 5 days] intraperitoneally), and saline solution (21 days) in the control groups. Isolated, perfused hearts were subjected to 40 minutes global ischemia, and 45 minutes reperfusion. The left ventricular developed pressure (LVDP), heart rate, and coronary flow were measured. Rate pressure product (RPP) was calculated. In reperfusion, released lactate dehydrogenase (LDH) enzyme in effluent was measured. It was observed that the recovery of the RPP and LVDP in reperfusion significantly decreased in the test group III (n=9) in comparison to the control (n=8). During the reperfusion period, the released LDH significantly increased in test group II (n=8) and group III in comparison with the control. The results show that repeated administration of diazepam (5 mg/kg for 5 days) reduced the cardiac performance in reperfusion, and significantly exacerbated the ischemia-reperfusion injury. It is probably mediated by the changing of cardiac susceptibility in ischemia due to repeated administration of diazepam.

A nationwide analysis of 30-day readmissions related to critical limb ischemia.

PubMed

Masoomi, Reza; Shah, Zubair; Quint, Clay; Hance, Kirk; Vamanan, Karthik; Prasad, Anand; Hoel, Andrew; Dawn, Buddhadeb; Gupta, Kamal

2018-06-01

Objectives There is paucity of information regarding critical limb ischemia-related readmission rates in patients admitted with critical limb ischemia. We studied 30-day critical limb ischemia-related readmission rate, its predictors, and clinical outcomes using a nationwide real-world dataset. Methods We did a secondary analysis of the 2013 Nationwide Readmissions Database. We included all patients with a primary diagnosis of extremity rest pain, ulceration, and gangrene secondary to peripheral arterial disease. From this group, all patients readmitted with similar diagnosis within 30 days were recorded. Results Of the total 25,111 index hospitalization for critical limb ischemia, 1270 (5%) were readmitted with a primary diagnosis of critical limb ischemia within 30 days. The readmission rate was highest (9.5%) for the group that did not have any intervention (revascularization or major amputation) and was lowest for surgical revascularization and major amputation groups (2.6% and 1.3%, P value <0.001 for all groups). Severity of critical limb ischemia at index admission was associated with a significantly higher rate of 30-day readmission. Critical limb ischemia-related readmission was associated with a higher rate of major amputation (29.6% vs. 16.2%, P<0.001), a lower rate of any revascularization procedure (46% vs. 62.6%, P<0.001), and a higher likelihood of discharge to a skilled nursing facility (43.2% vs. 32.2%, P<0.001) compared to index hospitalization. Conclusions In patients with primary diagnosis of critical limb ischemia, 30-day critical limb ischemia-related readmission rate was affected by initial management strategy and the severity of critical limb ischemia. Readmission was associated with a significantly higher rate of amputation, increased length of stay, and a more frequent discharge to an alternate care facility than index admission and thus may serve as a useful quality of care metric in critical limb ischemia patients.

The effect of thalidomide on vascular endothelial growth factor and tumor necrosis factor-alpha levels in retinal ischemia/reperfusion injury.

PubMed

Aydoğan, Semih; Celiker, Ulkü; Türkçüoğlu, Peykan; Ilhan, Nevin; Akpolat, Nusret

2008-03-01

To evaluate the effects of thalidomide treatment on the temporal course of TNF-alpha, VEGF production and the histopathological changes in ischemia/reperfusion (I/R) injured guinea pigs retina. Control, ischemia, and thalidomide/ischemia groups including seven animals each were formed. Retinal ischemia was induced in male guinea pigs by cannulating anterior chambers and lifting the bottle to a height of 205 cm for 90 min in the ischemia and thalidomide/ischemia groups. The thalidomide/ischemia group received thalidomide (300 mg/kg/day) via nasogastric tube 24 h before ischemia and during 7 days of reperfusion. Guinea pigs were sacrificed for histopathological examination to evaluate the mean thickness of the inner plexiform layer (IPL), polymorphonuclear leukocyte (PMNL) infiltration, and biochemical analysis of retinal VEGF and TNF-alpha levels by ELISA. The mean retinal VEGF and TNF-alpha levels of the control, ischemia, and thalidomide/ischemia groups were 10.22 +/- 2.58 and 270.41 +/- 69.77 pg/ml; 35.80 +/- 5.97 and 629.93 +/- 146.41 pg/ml; 19.01 +/- 3.01 and 340.93 +/- 158.26 pg/ml, respectively. The retinal VEGF levels were significantly higher in I/R injured groups. The thalidomide/ischemia group retinal VEGF level was significantly lower versus the ischemia group. The retinal TNF-alpha levels were significantly elevated in the ischemia group, but no difference was observed between the thalidomide/ischemia and control groups. Also, the retinal TNF-alpha level was significantly lower in the thalidomide/ischemia group versus the ischemia group. The mean thickness of IPL and PMNL infiltration showed no difference between the control and thalidomide/ischemia groups. However, there was a significant difference between the control and ischemia groups. Thalidomide treatment decreases PMNL infiltration, retinal edema, VEGF, and TNF-alpha synthesis following I/R injury to the guinea pig retina.

Effects of various timings and concentrations of inhaled nitric oxide in lung ischemia-reperfusion. The Paris-Sud University Lung Transplantation Group.

PubMed

Murakami, S; Bacha, E A; Mazmanian, G M; Détruit, H; Chapelier, A; Dartevelle, P; Hervé, P

1997-08-01

Experimental studies reveal that inhaled nitric oxide (NO) can prevent, worsen, or have no effect on lung injury in the setting of ischemia-reperfusion (I-R). We tested the hypothesis that these disparate effects could be related to differences in the timing of administration and/or concentration of inhaled NO during I-R. Isolated rat lungs were subjected to 1-h periods of ischemia followed by 1-h periods of blood reperfusion. We investigated the effects of NO (30 ppm) given during ischemia, NO (30 or 80 ppm) begun immediately at reperfusion, or NO (30 ppm) given 15 min after the beginning of reperfusion, on total pulmonary vascular resistance (PVR), the coefficient of filtration (Kfc), the lung wet/dry weight ratio (W/D) of lung tissue, and lung myeloperoxidase activity (MPO). A control group did not receive NO. NO given during ischemia had no effect on Kfc or MPO, but decreased PVR. NO (30 ppm) during reperfusion (early or delayed) decreased PVR, W/D, Kfc and MPO. NO at 80 ppm decreased PVR and MPO but not W/D or Kfc. In conclusion, NO at 30 ppm, given immediately or in a delayed fashion during reperfusion, attenuates I-R-induced lung injury. NO at 30 ppm given during ischemia or at 80 ppm during reperfusion is not protective.

Quercetin dose affects the fate of hepatic ischemia and reperfusion injury in rats: An experimental research.

PubMed

Uylaş, Mustafa Ufuk; Şahin, Adnan; Şahintürk, Varol; Alataş, İbrahim Özkan

2018-05-01

Quercetin found in fruits and vegetables has an antioxidative effect. We aimed to investigate the protective effects of quercetin according to different doses on hepatic and ischemia-reperfusion (I/R) injury. Fifty mature male Sprague-Dawley rats were randomly divided into five groups (n = 10 for each). All the animal groups underwent laparotomy. Group 1 rats served as a sham-operated group. Groups 2-5 underwent 1 h hepatic ischemia and were followed by 2 h reperfusion. Group 3-5 animals received an additional intraperitoneal dose of 25, 50 or 100 mg/kg quercetin respectively before I/R operation. Blood samples were collected for determining serum aspartate transaminase (AST), alanine transaminase (ALT) and malondialdehyde (MDA) levels. Also, liver tissue samples were taken for measuring of liver MDA concentration and for histopathology assessment. The highest levels of biochemical parameters were observed in group 2. In quercetin-treated groups, serum AST, ALT, MDA levels, and tissue MDA concentration were decreased as inversely with increasing quercetin dose. Microscopic evaluation revealed that most conspicuous histological improvement was observed in 50 mg/kg quercetin co-treated rats. 25 and 100 mg/kg quercetin co-treatment could not protect completely against hepatic I/R injury. Quercetin can be effective in preventing of hepatic I/R injury when the correct dose was used. Copyright © 2018. Published by Elsevier Ltd.

Increased E-selectin in hepatic ischemia-reperfusion injury mediates liver metastasis of pancreatic cancer

PubMed Central

YOSHIMOTO, KATSUHIRO; TAJIMA, HIDEHIRO; OHTA, TETSUO; OKAMOTO, KOICHI; SAKAI, SEISHO; KINOSHITA, JUN; FURUKAWA, HIROYUKI; MAKINO, ISAMU; HAYASHI, HIRONORI; NAKAMURA, KEISHI; OYAMA, KATSUNOBU; INOKUCHI, MASAFUMI; NAKAGAWARA, HISATOSHI; ITOH, HIROSHI; FUJITA, HIDETO; TAKAMURA, HIROYUKI; NINOMIYA, ITASU; KITAGAWA, HIROHISA; FUSHIDA, SACHIO; FUJIMURA, TAKASHI; WAKAYAMA, TOMOHIKO; ISEKI, SHOICHI; SHIMIZU, KOICHI

2012-01-01

Several recent studies have reported that selectins are produced during ischemia-reperfusion injury, and that selectin ligands play an important role in cell binding to the endothelium and in liver metastasis. Portal clamping during pancreaticoduodenectomy with vessel resection for pancreatic head cancer causes hepatic ischemia-reperfusion injury, which might promote liver metastasis. We investigated the liver colonization of pancreatic cancer cells under hepatic ischemia-reperfusion and examined the involvement of E-selectin and its ligands. A human pancreatic cancer cell line (Capan-1) was injected into the spleen of mice after hepatic ischemia-reperfusion (I/R group). In addition, to investigate the effect of an anti-E-selectin antibody on liver colonization in the IR group, mice received an intraperitoneal injection of the anti-E-selectin antibody following hepatic ischemia-reperfusion and tumor inoculation (IR+Ab group). Four weeks later, mice were sacrificed and the number of tumor nodules on the liver was compared to mice without hepatic ischemia-reperfusion (control group). The incidence of liver metastasis in the I/R group was significantly higher (16 of 20, 80%) than that in the control group (6 of 20, 30%) (P<0.01). Moreover, mice in the I/R group had significantly more tumor nodules compared to those in the control group (median, 9.9 vs. 2.7 nodules) (P<0.01). In the I/R+Ab group, only 2 of 5 (40%) mice developed liver metastases. RT-PCR and southern blotting of the liver extracts showed that the expression of IL-1 and E-selectin mRNA after hepatic ischemia-reperfusion was significantly higher than the basal levels. Hepatic ischemia-reperfusion increases liver metastases and E-selectin expression in pancreatic cancer. These results suggest that E-selectin produced due to hepatic ischemia-reperfusion is involved in liver metastasis. PMID:22766603

The relation between persistent coma and brain ischemia after severe brain injury.

PubMed

Cheng, Quan; Jiang, Bing; Xi, Jian; Li, Zhen Yan; Liu, Jin Fang; Wang, Jun Yu

2013-12-01

To investigate the relation between brain ischemia and persistent vegetative state after severe traumatic brain injury. The 66 patients with severe brain injury were divided into two groups: The persistent coma group (coma duration ≥10 d) included 51 patients who had an admission Glasgow Coma Scale (GCS) of 5-8 and were unconscious for more than 10 d. There were 15 patients in the control group, their admission GCS was 5-8, and were unconscious for less than 10 d. The brain areas, including frontal, parietal, temporal, occipital lobes and thalamus, were measured by Single Photon Emission Computed Tomography (SPECT). In the first SPECT scan, multiple areas of cerebral ischemia were documented in all patients in both groups, whereas bilateral thalamic ischemia were presented in all patients in the persistent coma group and were absented in the control group. In the second SPECT scan taken during the period of analepsia, with an indication that unilateral thalamic ischemia were persisted in 28 of 41 patients in persistent coma group(28/41,68.29%). Persistent coma after severe brain injury is associated with bilateral thalamic ischemia.

The effect of captopril and losartan on the electrophysiology of myocardial cells of myocardial ischemia rats.

PubMed

Shi, Xiangmin; Shan, Zhaoling; Yuan, Hongtao; Guo, Hongyang; Wang, Yutang

2014-01-01

This study aims to investigate the effect of captopril and losartan on the electrophysiology of myocardial cells parameters in ventricular vulnerable period and effective refractory period of myocardial ischemia rats. 96 wistar rats were enrolled in the study and divided into six groups: Captopril myocardial ischemia group, losartan myocardial ischemia group, myocardial ischemia control group, captopril normal group, losartan normal group and normal control group (n=16). We observed morphological changes of myocardial tissue in each group. The cardiac electrophysiological parameters in effective refractory period of each group were measured. Creatine kinase (CK), alanine aminotransferase (GOT), lactate dehydrogenase (LDH), the expression of Cardiotrophin 1 (CT-1) and malonaldehyde (MDA) were detected. Compared the losartan and captopril group with the control group, (P<0.05). Losartan and captopril can shorten the ventricular vulnerable period of the normal group and ischemic group. There was no interaction effect between losartan and captopril group and the acute myocardial ischemia group. The effect of losartan and captopril on time window in ventricular vulnerable period showed that compared with the control group (P<0.05). Losartan and captopril had a significant effect on prolonged effective refractory period of normal and ischemic rats. There was no interaction effect between losartan and captopril group and the acute myocardial ischemia group. Compared with the myocardial ischemia control group, CK, GOT, LDH and MDA decreased in captopril and losartan myocardial ischemia groups (P<0.05). Losartan and captopril had a significant effect on prolonged effective refractory period and shorten ventricular vulnerable period, they can also effectively prevent arrhythmias.

Renoprotective Effect of Humic Acid on Renal Ischemia-Reperfusion Injury: An Experimental Study in Rats.

PubMed

Akbas, Alpaslan; Silan, Coskun; Gulpinar, Murat Tolga; Sancak, Eyup Burak; Ozkanli, Sidika Seyma; Cakir, Dilek Ulker

2015-12-01

Humic acid is an antioxidant molecule used in agriculture and livestock breeding, as well as in medicine. Our aim was to investigate the potential renoprotective effects of humic acid in a renal ischemia reperfusion model. Twenty-one rats were randomly divided into three equal groups. Intraperitoneal serum or humic acid was injected at 1, 12, and 24 h. Non-ischemic group I was evaluated as sham. The left renal artery was clamped in serum (group II) and intraperitoneal humic acid (group III) to subject to left renal ischemic reperfusion procedure. Ischemia and reperfusion time was 60 min for each. Total antioxidant status, total oxidative status, oxidative stress index, and ischemia-modified albumin levels were analyzed biochemically from the serum samples. Kidneys were evaluated histopatologically and immunohistochemically. Biochemical results showed that total oxidative status, ischemia-modified albumin, and oxidative stress index levels were significantly decreased, but total antioxidant status was increased in the humic acid group (III) compared with the ischemia group (II) On histopathological examination, renal tubular dilatation, tubular cell damage and necrosis, dilatation of Bowman's capsule, hyaline casts, and tubular cell spillage were decreased in the humic acid group (III) compared with the ischemia group (II). Immunohistochemical results showed that apoptosis was deteriorated in group III. Renal ischemia reperfusion injury was attenuated by humic acid administration. These observations indicate that humic acid may have a potential therapeutic effect on renal ischemia reperfusion injury by preventing oxidative stress.

Protective effect of dexpanthenol on ischemia-reperfusion-induced renal injury in rats.

PubMed

Altintas, Ramazan; Parlakpinar, Hakan; Beytur, Ali; Vardi, Nigar; Polat, Alaadin; Sagir, Mustafa; Odabas, Gul Pelin

2012-01-01

This experimental study was designed to investigate protective and therapeutic effects of Dexpanthenol (Dxp), an alcoholic analogue of pantothenic acid, on kidney damage induced by ischemia-reperfusion (I/R) in rats. Forty rats were randomly divided into a control group and 4 I/R groups (1 h ischemia followed by 23 h reperfusion). Three I/R groups were treated by Dxp (500 mg/kg, i.p.) at 3 different time points (before ischemia, during ischemia and late reperfusion). The histopathological findings including apoptotic changes, and also tissue malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPX), blood urea nitrogen (BUN), serum creatinine (Cr) and albumin (Alb) levels were determined. Kidney tissue MDA levels were found to be significantly higher in the I/R group, whereas the values of GPX were lower when compared to the control group. The levels of SOD and CAT did not reach to statistical meaning level in I/R group. Dxp given during ischemia reduced the elevated MDA levels to the nearly control levels and this ameliorating effect was found as parallel to the result of GPX. Serum levels of BUN and Cr were significantly higher in I/R group. Dxp given during ischemia significantly reduced the elevated BUN and Cr levels when compared to I/R group. Renal I/R injury also induced extensive tubular necrosis, glomerular damage and apoptosis in the histological evaluation. Dxp ameliorated these histological damages in different amounts in all treatment groups. In this study the protective effects of Dxp against renal I/R injury has been evaluated for the first time. Copyright © 2012 S. Karger AG, Basel.

Desflurane inhalation before ischemia increases ischemia-reperfusion-induced vascular leakage in isolated rabbit lungs.

PubMed

Oshima, Yoshiaki; Sakamoto, Seiji; Yamasaki, Kazumasa; Mochida, Shinsuke; Funaki, Kazumi; Moriyama, Naoki; Otsuki, Akihiro; Endo, Ryo; Nakasone, Masato; Takahashi, Shunsaku; Harada, Tomomi; Minami, Yukari; Inagaki, Yoshimi

2016-01-01

Isoflurane and sevoflurane protect lungs with ischemia-reperfusion (IR) injury. We examined the influence of desflurane on IR lung injury using isolated rabbit lungs perfused with a physiological salt solution. The isolated lungs were divided into three groups: IR, desflurane-treated ischemia-reperfusion (DES-IR), and ventilation/perfusion-continued control (Cont) groups (n = 6 per group). In the DES-IR group, inhalation of desflurane at 1 minimum alveolar concentration (MAC) was conducted in a stable 30-min phase. In the IR and DES-IR groups, ventilation/perfusion was stopped for 75 min after the stable phase. Subsequently, they were resumed. Each lung was placed on a balance, and weighed. Weight changes were measured serially throughout this experiment. The coefficient of filtration (K fc ) was determined immediately before ischemia and 60 min after reperfusion. Furthermore, bronchoalveolar lavage fluid (BALF) was collected from the right bronchus at the completion of the experiment. After the completion of the experiment, the left lung was dried, and the lung wet-to-dry weight ratio (W/D) was calculated. The K fc values at 60 min after perfusion were 0.40 ± 0.13 ml/min/mmHg/100 g in the DES-IR group, 0.26 ± 0.07 ml/min/mmHg/100 g in the IR group, and 0.22 ± 0.08 (mean ± SD) ml/mmHg/100 g in the Cont group. In the DES-IR group, the K fc at 60 min after the start of reperfusion was significantly higher than in the other groups. In the DES-IR group, W/D was significantly higher than in the Cont group. In the DES-IR group, the BALF concentrations of nitric oxide metabolites were significantly higher than in the other groups. In the DES-IR group, the total amount of vascular endothelial growth factor in BALF was significantly higher than in the Cont group. The pre-inhalation of desflurane at 1 MAC exacerbates pulmonary IR injury in isolated/perfused rabbit lungs.

Functional Recovery From Extended Warm Ischemia Associated With Partial Nephrectomy.

PubMed

Zhang, Zhiling; Zhao, Juping; Velet, Lily; Ercole, Cesar E; Remer, Erick M; Mir, Carme M; Li, Jianbo; Takagi, Toshio; Demirjian, Sevag; Campbell, Steven C

2016-01-01

To evaluate the impact of extended warm ischemia on incidence of acute kidney injury (AKI) and ultimate functional recovery after partial nephrectomy (PN), incorporating rigorous control for loss of parenchymal mass, and embedded within comparison to cohorts of patients managed with hypothermia or limited warm ischemia. From 2007 to 2014, 277 patients managed with PN had appropriate studies to evaluate changes in function/mass specifically within the operated kidney. Recovery from ischemia was defined as %function saved/%parenchymal mass saved. AKI was based on global renal function and defined as a ≥1.5-fold increase in serum creatinine above the preoperative level. Hypothermia was utilized in 112 patients (median = 27 minutes) and warm ischemia in 165 (median = 21 minutes). AKI strongly correlated with solitary kidney (P < .001) and duration (P < .001) but not type (P = .49) of ischemia. Median recovery from ischemia in the operated kidney was 100% (interquartile range [IQR] = 88%-109%) for cold ischemia, with 6 (5%) noted to have <80% recovery from ischemia. For the warm ischemia group, median recovery from ischemia was 91% (IQR = 82%-101%, P < .001 compared with hypothermia), and 34 (21%) had recovery from ischemia <80% (P < .001). For warm ischemia subgrouped by duration <25 minutes (n = 114), 25-35 minutes (n = 35), and >35 minutes (n = 16), median recovery from ischemia was 92% (IQR = 86%-100%), 90% (IQR = 78%-104%), and 91% (IQR = 80%-96%), respectively (P = .77). Our results suggest that AKI after PN correlates with duration but not with type of ischemia. However, subsequent recovery, which ultimately defines the new baseline glomerular filtration rate, is most reliable with hypothermia. However, most patients undergoing PN with warm ischemia still recover relatively strongly from ischemia, even if extended to 35-45 minutes. Copyright © 2015 Elsevier Inc. All rights reserved.

Sildenafil Attenuates Hepatocellular Injury after Liver Ischemia Reperfusion in Rats: A Preliminary Study

PubMed Central

Savvanis, Spyridon; Nastos, Constantinos; Tasoulis, Marios-Konstantinos; Papoutsidakis, Nikolaos; Demonakou, Maria; Karmaniolou, Iosifina; Arkadopoulos, Nikolaos; Smyrniotis, Vassilios; Theodoraki, Kassiani

2014-01-01

We evaluated the role of sildenafil in a rat liver ischemia-reperfusion model. Forty male rats were randomly allocated in four groups. The sham group underwent midline laparotomy only. In the sildenafil group, sildenafil was administered intraperitoneally 60 minutes before sham laparotomy. In the ischemia-reperfusion (I/R) group, rats were subjected to 45 minutes of hepatic ischemia followed by 120 minutes of reperfusion, while in the sild+I/R group rats were subjected to a similar pattern of I/R after the administration of sildenafil, 60 minutes before ischemia. Two hours after reperfusion, serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were measured and histopathological examination of the lobes subjected to ischemia as well as TUNEL staining for apoptotic bodies was performed. Additionally, myeloperoxidase (MPO) activity and the expression of intercellular adhesion molecule-1 (ICAM-1) were analyzed. Serum markers of hepatocellular injury were significantly lower in the sild+I/R group, which also exhibited lower severity of histopathological lesions and fewer apoptotic bodies, as compared to the I/R group. The I/R group showed significantly higher MPO activity and higher expression of ICAM-1, as compared to the sild+I/R group. Use of sildenafil as a preconditioning agent in a rat model of liver I/R exerted a protective effect. PMID:24999378

[Application of Ischemia Modified Albumin for Acute Ischemic Heart Disease in Forensic Science].

PubMed

Wang, P; Zhu, Z L; Zhu, N; Yu, H; Yue, Q; Wang, X L; Feng, C M; Wang, C L; Zhang, G H

2017-10-01

To explore the application value and forensic significance of ischemia modified albumin （IMA） in pericardial fluid to diagnose sudden cardiac death. IMA level in pericardial fluid was detected in acute ischemic heart disease group （ n =36）, acute myocardial infarction group （ n =6）, cardiomyopathy group （ n =4） and control group （ n =15） by albumin cobalt binding method. The levels of IMA were compared among these groups. The best cut-off IMA value was estimated and the sensitivity and specificity of acute myocardial ischemia group was distinguished from control group by receiver operating characteristics （ROC） curve. The IMA level in acute ischemic heart disease group was significantly higher than that of control group （ P <0.05）. Compared with acute myocardial infarction group and cardiomyopathy group, the IMA level in acute ischemic heart disease group had no significant difference （ P >0.05）. The cut-off value for the identification of acute myocardial ischemia which obtained by ROC analysis was 40.65 U/mL. And the sensitivity and specificity for distinguishing acute ischemia cardiac disease was 60.0% and 80.5%, respectively. The IMA value in pericardial fluid can be a reference marker for the diagnosis of acute myocardial ischemia, which also can provide objective basis for the forensic identification of sudden cardiac death. Copyright© by the Editorial Department of Journal of Forensic Medicine

Expression of Bcl-2 and NF-κB in brain tissue after acute renal ischemia-reperfusion in rats.

PubMed

Zhang, Na; Cheng, Gen-Yang; Liu, Xian-Zhi; Zhang, Feng-Jiang

2014-05-01

To investigate the effect of acute renal ischemia reperfusion on brain tissue. Fourty eight rats were randomly divided into four groups (n=12): sham operation group, 30 min ischemia 60 min reperfusion group, 60 min ischemia 60 min reperfusion group, and 120 min ischemia 60 min reperfusion group. The brain tissues were taken after the experiment. TUNEL assay was used to detect the brain cell apoptosis, and western blot was used to detect the expression of apoptosis-related proteins and inflammatory factors. Renal ischemia-reperfusion induced apoptosis of brain tissues, and the apoptosis increased with prolongation of ischemia time. The detection at the molecular level showed decreased Bcl-2 expression, increased Bax expression, upregulated expression of NF-κB and its downstream factor COX-2/PGE2. Acute renal ischemia-reperfusion can cause brain tissue damage, manifested as induced brain tissues apoptosis and inflammation activation. Copyright © 2014 Hainan Medical College. Published by Elsevier B.V. All rights reserved.

Cerebral ischemia and neuroregeneration

PubMed Central

Lee, Reggie H. C.; Lee, Michelle H. H.; Wu, Celeste Y. C.; Couto e Silva, Alexandre; Possoit, Harlee E.; Hsieh, Tsung-Han; Minagar, Alireza; Lin, Hung Wen

2018-01-01

Cerebral ischemia is one of the leading causes of morbidity and mortality worldwide. Although stroke (a form of cerebral ischemia)-related costs are expected to reach 240.67 billion dollars by 2030, options for treatment against cerebral ischemia/stroke are limited. All therapies except anti-thrombolytics (i.e., tissue plasminogen activator) and hypothermia have failed to reduce neuronal injury, neurological deficits, and mortality rates following cerebral ischemia, which suggests that development of novel therapies against stroke/cerebral ischemia are urgently needed. Here, we discuss the possible mechanism(s) underlying cerebral ischemia-induced brain injury, as well as current and future novel therapies (i.e., growth factors, nicotinamide adenine dinucleotide, melatonin, resveratrol, protein kinase C isozymes, pifithrin, hypothermia, fatty acids, sympathoplegic drugs, and stem cells) as it relates to cerebral ischemia. PMID:29623912

[Effect and mechanism of icariin on myocardial ischemia-reperfusion injury model in diabetes rats].

PubMed

Hu, Yan-wu; Liu, Kai; Yan, Meng-tong

2015-11-01

To study the therapeutic effect and possible mechanism of icariin on myocardial ischemia-reperfusion injury ( MIRI) model in diabetes rats. The model of diabetic rats were induced by Streptozotocin (STZ), then the model of MIRI was established by ligating the reversible left anterior descending coronary artery for 30 min, and then reperfusing for 120 min. totally 40 male SD were randomly divided into five groups: the control group (NS), the ischemia reperfusion group (NIR), the diabetes control group (MS), the diabetic ischemia reperfusion group (MIR) and the diabetic ischemia reperfusion with icariin group (MIRI). The changes in blood glucose, body weight and living status were observed; the enzyme activity of serum CK-MB, LDH, GSH-Px and myocardium SOD and the content MDA and NO in myocardium were detected; the myocardial pathological changes were observed by HE staining; the myocardial Caspase-3, the Bcl-2, Bax protein expressions were detected by Western blot. The result showed that the diabetes model was successfully replicated; myocardial ischemia-reperfusion injury was more serious in diabetes rats; icariin can increase NO, SOD, GSH-Px, Bcl-2 protein expression, decrease MDA formation, CK-MB and LDH activities and Caspase-3 and Bcl-2 protein expressions and myocardial damage. The result suggested that icariin may play a protective role against ischemia reperfusion myocardial injury in diabetes rats by resisting oxidative stress and inhibiting cell apoptosis.

Thromboxane A2 moderates permeability after limb ischemia.

PubMed Central

Lelcuk, S; Alexander, F; Valeri, C R; Shepro, D; Hechtman, H B

1985-01-01

Reperfusion after limb ischemia results in muscle edema as well as excess secretion of thromboxane A2 (TxA2), an agent associated with permeability increase in other settings. This study tests whether TxA2 moderates the permeability following limb ischemia. A tourniquet inflated to 300 mmHg was applied for 2 hours around the hind limb of four groups of dogs. In untreated animals (N = 25), 2 hours following tourniquet release, plasma TxB2 values rose from 320 pg/ml to 2416 pg/ml (p less than 0.001), and popliteal lymph values rose from 378 pg/ml to 1046 pg/ml (p less than 0.001). Platelet TxB2 was unaltered and plasma 6-keto-PGF1 alpha levels did not vary. Following ischemia, lymph flow (QL) increased from 0.07 to 0.37 ml/h (p less than 0.05), while the lymph/plasma (L/P) protein ratio was unchanged at 0.41. These measurements indicate increased permeability since increase in hydrostatic pressure in a second group by tourniquet inflation to 50 mmHg (N = 7) led to a rise in QL from 0.07 to 0.22 ml/h, but a fall in the L/P ratio to 0.32, a value lower than the ischemic group (p less than 0.05). Pretreatment with the imidazole derivative ketoconazole (N = 11) reduced platelet Tx synthesis from 42 ng to 2 ng/10(9) platelets, but lymph TxB2 levels rose to 1703 pg/ml after ischemia, indicating an extravascular or vessel wall site of synthesis not inhibited by ketoconazole. Pretreatment with a lower molecular weight imidazole derivative OKY 046 (N = 9) inhibited all Tx synthesis after ischemia. Prior to tourniquet inflation, both OKY 046 and ketoconazole lowered plasma TxB2 levels as well as the L/P ratio (p less than 0.05). After ischemia, OKY 046, but not ketoconazole, maintained the L/P ratio at 0.33, a value below that of untreated animals (p less than 0.05). These results indicate that nonplatelet-derived TxA2 modulates both baseline and ischemia-induced increases in microvascular permeability in the dog hind limb. PMID:3840349

Nigella sativa relieves the deleterious effects of ischemia reperfusion injury on liver

PubMed Central

Yildiz, Fahrettin; Coban, Sacit; Terzi, Alpaslan; Ates, Mustafa; Aksoy, Nurten; Cakir, Hale; Ocak, Ali Riza; Bitiren, Muharrem

2008-01-01

AIM: To determine whether Nigella sativa prevents hepatic ischemia-reperfusion injury to the liver. METHODS: Thirty rats were divided into three groups as sham (Group 1), control (Group 2), and Nigella sativa (NS) treatment group (Group 3). All rats underwent hepatic ischemia for 45 min followed by 60 min period of reperfusion. Rats were intraperitoneally infused with only 0.9% saline solution in group 2. Rats in group 3 received NS (0.2 mL/kg) intraperitoneally, before ischemia and before reperfusion. Blood samples and liver tissues were harvested from the rats, and then the rats were sacrificed. Serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), and lactate dehydrogenase (LDH) levels were determined. Total antioxidant capacity (TAC), catalase (CAT), total oxidative status (TOS), oxidative stress index (OSI) and myeloperoxidase (MPO) in hepatic tissue were measured. Also liver tissue histopathology was evaluated by light microscopy. RESULTS: The levels of liver enzymes in group 3 were significantly lower than those in the group 2. TAC in liver tissue was significantly higher in group 3 than in group 2. TOS, OSI and MPO in hepatic tissue were significantly lower in group 3 than the group 2. Histological tissue damage was milder in the NS treatment group than that in the control group. CONCLUSION: Our results suggest that Nigella sativa treatment protects the rat liver against to hepatic ischemia-reperfusion injury. PMID:18777598

Hepatic ischemia

MedlinePlus

... artery to the liver (hepatic artery) after a liver transplant Swelling of blood vessels leading to reduced blood ... the illness causing hepatic ischemia can be treated. Death from liver failure due to hepatic ischemia is ...

The effects of Y-27632 on pial microvessels during global brain ischemia and reperfusion in rabbits.

PubMed

Shintani, Noriyuki; Ishiyama, Tadahiko; Kotoda, Masakazu; Asano, Nobumasa; Sessler, Daniel I; Matsukawa, Takashi

2017-03-07

Global brain ischemia-reperfusion during propofol anesthesia provokes persistent cerebral pial constriction. Constriction is likely mediated by Rho-kinase. Cerebral vasoconstriction possibly exacerbates ischemic brain injury. Because Y-27632 is a potent Rho-kinase inhibitor, it should be necessary to evaluate its effects on cerebral pial vessels during ischemia-reperfusion period. We therefore tested the hypotheses that Y-27632 dilates cerebral pial arterioles after the ischemia-reperfusion injury, and evaluated the time-course of cerebral pial arteriolar status after the ischemia-reperfusion. Japanese white rabbits were anesthetized with propofol, and a closed cranial window inserted over the left hemisphere. Global brain ischemia was produced by clamping the brachiocephalic, left common carotid, and left subclavian arteries for 15 min. Rabbits were assigned to cranial window perfusion with: (1) artificial cerebrospinal fluid (Control group, n = 7); (2) topical infusion of Y-27632 10 -6 mol · L -1 for 30 min before the initiation of global brain ischemia (Pre group, n = 7); (3) topical infusion of Y-27632 10 -6 mol · L -1 starting 30 min before ischemia and continuing throughout the study period (Continuous group, n = 7); and, (4) topical infusion of Y-27632 10 -6 mol · L -1 starting 10 min after the ischemia and continuing until the end of the study (Post group, n = 7). Cerebral pial arterial and venule diameters were recorded 30 min before ischemia, just before arterial clamping, 10 min after clamping, and 5, 10, 20, 40, 60, 80, 100, and 120 min after unclamping. Mean arterial blood pressure and blood glucose concentration increased significantly after global brain ischemia except in the Continuous group. In the Pre and Continuous groups, topical application of Y-27632 produced dilation of large (mean 18-19%) and small (mean; 25-29%) pial arteries, without apparent effect on venules. Compared with the Control and Pre groups

DIFFERENT PROTOCOLS OF POSTCONDITIONING DOES NOT ATTENUATE MESENTERIC ISCHEMIA-REPERFUSION INJURY AFTER SHORT-TERM REPERFUSION

PubMed Central

BRITO, Marcus Vinicius Henriques; YASOJIMA, Edson Yuzur; MACHADO, Andressa Abnader; SILVEIRA, Matheus Paiva Pacheco Reis; TEIXEIRA, Renan Kleber Costa; YAMAKI, Vitor Nagai; COSTA, Felipe Lobato da Silva

2017-01-01

ABSTRACT Background: Mesenteric ischemia is a challenging diagnosis. Delay in diagnosis can lead to extent bowel necrosis and poor outcomes. Ischemia and reperfusion syndrome plays an important role in this scenario. Aim: To access effects of different post-conditioning cycles on mesenteric ischemia-reperfusion syndrome. Method: Twenty-five rats were assigned into five groups: Sham, used to establish normal parameters; control group, submitted to mesenteric ischemia for 30 min; in groups GP3, GP1 and GP30, ischemia was followed by post-conditioning protocol, which consisted of 1 cycle of 3 min (GP3), 3 cycles of 1 min (GP1) or 6 cycles of 30 s (GP30), respectively. Ileum samples were harvested after one hour of reperfusion. Intestinal mucosal injury was evaluated through histopathological analysis. Results: The average of mesenteric injury degree was 0 in the sham group, 3.6 in the control group, 3.4 in GP3, 3.2 in GP1, and 3.0 in GP30; villous length average was 161.59 in sham group, 136.27 in control group, 135.89 in GP3, 129.46 in GP1, and 135.18 in GP30. Was found significant difference between sham and other groups (p<0.05); however, there was no difference among post-conditioning groups. Conclusion: Post-conditioning adopted protocols were not able to protect intestinal mucosa integrity after mesenteric ischemia and short term reperfusion. PMID:28489164

Ischemia-modified albumin levels in cerebrovascular accidents.

PubMed

Gunduz, Abdulkadir; Turedi, Suleyman; Mentese, Ahmet; Altunayoglu, Vildan; Turan, Ibrahim; Karahan, Suleyman Caner; Topbas, Murat; Aydin, Murat; Eraydin, Ismet; Akcan, Buket

2008-10-01

Previous studies have demonstrated that ischemia-modified albumin (IMA) is a useful marker for the diagnosis of ischemic events. It was also recently demonstrated that IMA levels increase in the acute phase of cerebrovascular diseases. Yet the data regarding IMA levels in various types of cerebrovascular events are insufficient. The aim of this study was to evaluate IMA levels in various types of cerebrovascular events such as ischemic stroke, subarachnoid hemorrhage (SAH), and intracranial hemorrhage. This case-controlled study consisted of 106 consecutive patients, 43 with brain infarction (BI), 11 with brain hemorrhage (ICH), 52 with SAH, and a 43-member control group. We investigated whether there was a statistical correlation between these 3 groups and the control group. The relations among the 3 groups were also examined. Comparisons among groups were done with analysis of variance. Mean serum IMA levels were 0.280 +/- 0.045 absorbance units (ABSU) for BI patients, 0.259 +/- 0.053 ABSU for ICH patients, 0.243 +/- 0.061 ABSU for SAH patients, and 0.172 +/- 0.045 ABSU for the control group.There was a statistically significant difference between the mean IMA levels of BI, ICH, and SAH patients and the mean control patient IMA levels (P b .0001). Ischemia-modified albumin levels are high in cerebrovascular diseases. Ischemia-modified albumin measurement can also be used to distinguish SAH from BI during the acute phase of cerebrovascular event in the emergency department.

Effectiveness of sugammadex for cerebral ischemia/reperfusion injury.

PubMed

Ozbilgin, Sule; Yılmaz, Osman; Ergur, Bekir Ugur; Hancı, Volkan; Ozbal, Seda; Yurtlu, Serhan; Gunenc, Sakize Ferim; Kuvaki, Bahar; Kucuk, Burcu Ataseven; Sisman, Ali Rıza

2016-06-01

Cerebral ischemia may cause permanent brain damage and behavioral dysfunction. The efficacy and mechanisms of pharmacological treatments administered immediately after cerebral damage are not fully known. Sugammadex is a licensed medication. As other cyclodextrins have not passed the necessary phase tests, trade preparations are not available, whereas sugammadex is frequently used in clinical anesthetic practice. Previous studies have not clearly described the effects of the cyclodextrin family on cerebral ischemia/reperfusion (I/R) damage. The aim of this study was to determine whether sugammadex had a neuroprotective effect against transient global cerebral ischemia. Animals were assigned to control, sham-operated, S 16 and S 100 groups. Transient global cerebral ischemia was induced by 10-minute occlusion of the bilateral common carotid artery, followed by 24-hour reperfusion. At the end of the experiment, neurological behavior scoring was performed on the rats, followed by evaluation of histomorphological and biochemical measurements. Sugammadex 16 mg/kg and 100 mg/kg improved neurological outcome, which was associated with reductions in both histological and neurological scores. The hippocampus TUNEL (terminal deoxynucleotidyl transferase dUTP nick end labeling) and caspase results in the S 16 and S 100 treatment groups were significantly lower than those of the I/R group. Neurological scores in the treated groups were significantly higher than those of the I/R group. The study showed that treatment with 16 mg/kg and 100 mg/kg sugammadex had a neuroprotective effect in a transient global cerebral I/R rat model. However, 100 mg/kg sugammadex was more neuroprotective in rats. Copyright © 2016. Published by Elsevier Taiwan.

The relationship between renal warm ischemia time and glomerular loss. An experimental study in a pig model.

PubMed

Damasceno-Ferreira, José Aurelino; Bechara, Gustavo Ruschi; Costa, Waldemar Silva; Pereira-Sampaio, Marco Aurélio; Sampaio, Francisco José Barcellos; Souza, Diogo Benchimol De

2017-05-01

To investigate the glomerular number after different warm ischemia times. Thirty two pigs were assigned into four groups. Three groups (G10, G20, and G30) were treated with 10, 20, and 30 minutes of left renal warm ischemia. The sham group underwent the same surgery without renal ischemia. The animals were euthanized after 3 weeks, and the kidneys were collected. Right kidneys were used as controls. The kidney weight, volume, cortical-medullar ratio, glomerular volumetric density, volume-weighted mean glomerular volume, and the total number of glomeruli per kidney were obtained. Serum creatinine levels were assessed pre and postoperatively. Serum creatinine levels did not differ among the groups. All parameters were similar for the sham, G10, and G20 groups upon comparison of the right and left organs. The G30 group pigs' left kidneys had lower weight, volume, and cortical-medullar ratio and 24.6% less glomeruli compared to the right kidney. A negative correlation was found between warm ischemia time and glomerular number. About one quarter of glomeruli was lost after 30 minutes of renal warm ischemia. No glomeruli loss was detected before 20 minutes of warm ischemia. However, progressive glomerular loss was associated with increasing warm ischemia time.

Mesenchymal Stem Cell-Based Therapy Improves Lower Limb Movement After Spinal Cord Ischemia in Rats.

PubMed

Takahashi, Shinya; Nakagawa, Kei; Tomiyasu, Mayumi; Nakashima, Ayumu; Katayama, Keijiro; Imura, Takeshi; Herlambang, Bagus; Okubo, Tomoe; Arihiro, Koji; Kawahara, Yumi; Yuge, Louis; Sueda, Taijiro

2018-05-01

Spinal cord ischemia is a devastating complication after thoracic and thoracoabdominal aortic operations. In this study, we aimed to investigate the effects of mesenchymal stem cells (MSCs), which have regenerative capability and exert paracrine actions on damaged tissues, injected into rat models of spinal cord ischemia-reperfusion injury. Forty-five Sprague-Dawley rats were divided into sham, phosphate-buffered saline (PBS), and MSC groups. Spinal cord ischemia was induced in the latter two groups by balloon occlusion of the thoracic aorta. MSCs and PBS were then immediately injected into the left carotid artery of the MSC and PBS groups, respectively. Hindlimb motor function was evaluated at 6 and 24 hours. The spinal cord was removed at 24 hours after ischemia-reperfusion injury, and histologic and immunohistochemical analyses and real-time polymerase chain reaction assessments were performed. Rats in the MSC and PBS groups showed flaccid paraparesis/paraplegia postoperatively. Hindlimb function was significantly better at 6 and 24 hours after ischemia-reperfusion injury in the MSC group than in the PBS group (p < 0.05). The number of terminal deoxynucleotidyl transferase dUTP nick end labeling-positive neuron cells in the spinal cord and the ratio of Bax to Bcl2 were significantly larger (p < 0.05) in the PBS group than in the MSC group. The injected MSCs were observed in the spinal cord 24 hours after ischemia-reperfusion injury. The MSC therapy by transarterial injection immediately after spinal cord ischemia-reperfusion injury may improve lower limb function by preventing apoptosis of neuron cells in the spinal cord. Copyright © 2018 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

Effects of ischemic preconditioning and iloprost on myocardial ischemia-reperfusion damage in rats.

PubMed

Ay, Yasin; Kara, Ibrahim; Aydin, Cemalettin; Ay, Nuray Kahraman; Teker, Melike Elif; Senol, Serkan; Inan, Bekir; Basel, Halil; Uysal, Omer; Zeybek, Rahmi

2013-01-01

This study investigates the effects of cardiac ischemic preconditioning and iloprost on reperfusion damage in rats with myocardial ischemia/reperfusion. 38 male Wistar Albino rats used in this study were divided into 5 groups. The control group (Group 1) (n=6), ischemia/reperfusion (IR) group (Group 2) (n=8), cardiac ischemic preconditioning (CIP) group (Group 3) (n=8), iloprost (ILO) group (Group 4) (n=8), and cardiac ischemic preconditioning + iloprost (CIP+ILO) group (Group 5) (n=8). Pre-ischemia, 15 minutes post-ischemia, 45 minutes post-reperfusion, mean blood pressure (MBP), and heart rates (HR) were recorded. The rate-pressure product (RPP) was calculated. Post-reperfusion plasma creatine kinase-MB (CK-MB), lactate dehydrogenase (LDH), troponin (cTn) vlaues, and infarct size/area at risk (IS/AAR) were calculated from myocardial tissue samples. Arrhythmia and ST segment elevations were evaluated during the ischemia and reperfusion stages. Although the MBP, HR, RPP values, biochemical parameters of CK-MB and LDH levels, IS/AAR rates, ST segment elevation values were found to be similar in CIP and CIP+ILO groups and the IR and ILO groups (p>0.05), CIP-containing group values had a positively meaningful difference (p<0.05) compared with the IR and ILO group. While mild-moderate findings of damage were observed in Group 3 and Group 5, severely findings of damage were releaved in Group 2 and Group 4. The arrhythmia score of the ILO group was meaningfully lower (F: 41.4, p<0.001) than the IR group. We can conclude that the effects of myocardial reperfusion damage can be reduced by cardiac ischemic preconditioning, intravenous iloprost reduced the incidence of ventricular arrhythmia associated with reperfusion, and its use with CIP caused no additional changes.

Renal ischemia induces an increase in nitric oxide levels from tissue stores.

PubMed

Salom, Miguel G; Arregui, Begoña; Carbonell, Luis F; Ruiz, Fernando; González-Mora, José Luis; Fenoy, Francisco J

2005-11-01

Tissue nitric oxide (NO) levels increase dramatically during ischemia, an effect that has been shown to be partially independent from NO synthases. Because NO is stored in tissues as S-nitrosothiols and because these compounds could release NO during ischemia, we evaluated the effects of buthionine sulfoximine (BSO; an intracellular glutathione depletor), light stimulation (which releases NO, decomposing S-nitrosothiols), and N-acetyl-L-cysteine (a sulfhydryl group donor that repletes S-nitrosothiols stores) on the changes in outer medullary NO concentration produced during 45 min of renal artery occlusion in anesthetized rats. Renal ischemia increased renal tissue NO concentration (+223%), and this effect was maintained along 45 min of renal arterial blockade. After reperfusion, NO concentration fell below preischemic values and remained stable for the remainder of the experiment. Pretreatment with 10 mg/kg nitro-L-arginine methyl ester (L-NAME) decreased significantly basal NO concentration before ischemia, but it did not modify the rise in NO levels observed during ischemia. In rats pretreated with 4 mmol/kg BSO and L-NAME, ischemia was followed by a transient increase in renal NO concentration that fell to preischemic values 20 min before reperfusion. A similar response was observed when the kidney was illuminated 40 min before the ischemia. The coadministration of 10 mg/kg iv N-acetyl-L-cysteine with BSO + L-NAME restored the increase in NO levels observed during renal ischemia and prevented the depletion of renal thiol groups. These results demonstrate that the increase in renal NO concentration observed during ischemia originates from thiol-dependent tissue stores.

Effects of Aloe Vera on Spinal Cord Ischemia-Reperfusion Injury of Rats.

PubMed

Yuksel, Yasemin; Guven, Mustafa; Kaymaz, Burak; Sehitoglu, Muserref Hilal; Aras, Adem Bozkurt; Akman, Tarik; Tosun, Murat; Cosar, Murat

2016-12-01

The purpose of this study was to evaluate the possible protective/therapeutic effects of aloe vera (AV) on ischemia-reperfusion injury (I/R) of spinal cord in rats. A total of 28 Wistar Albino rats were divided into four random groups of equal number (n = 7). Group I (control) had no medication or surgery; Group II underwent spinal cord ischemia and was given no medication; Group III was administered AV by gastric gavage for 30 days as pre-treatment; Group IV was administered single dose intraperitoneal methylprednisolone (MP) after the ischemia. Nuclear respiratory factor-1 (NRF1), malondialdehyde (MDA) and superoxide dismutase (SOD) levels were evaluated. Tissue samples were examined histopathologically and neuronal nitric oxide synthase (nNOS) and nuclear factor-kappa B (NF-κB) protein expressions were assessed by immunohistochemical staining. NRF1 and SOD levels of ischemia group were found to be lower compared to the other groups. MDA levels significantly increased after I/R. Treatment with AV and MP resulted in reduced MDA levels and also alleviated hemorrhage, edema, inflammatory cell migration and neurons were partially protected from ischemic injury. When AV treatment was compared with MP, there was no statistical difference between them in terms of reduction of neuronal damage. I/R injury increased NF-κB and nNOS expressions. AV and MP treatments decreased NF-κB and nNOS expressions. It was observed that aloe vera attenuated neuronal damage histopathologically and biochemically as pretreatment. Further studies may provide more evidence to determine the additional role of aloe vera in spinal cord ischemia reperfusion injury.

The Protective Effects of Lycium Barbarum Polysaccharides on Transient Retinal Ischemia

PubMed Central

Yang, Di; Li, Suk-Yee; Yeung, Chung-Man; Yu, Wing-Yan; Chang, Raymond Chuen-Chung; So, Kwok-Fai; Wong, David; Lo, Amy C. Y.

2011-01-01

Retinal ischemia/reperfusion (I/R) injury leads to irreversible neuronal death, glial activation, retinal swelling and oxidative stress. It is a common feature in various ocular diseases, such as glaucoma, diabetic retinopathy and amaurosis fugax. In the present study, we aimed to evaluate the effects of Lycium Barbarum Polysaccharides (LBP) in a murine retinal I/R model. Mice were orally treated with either vehicle (PBS) or LBP (1mg/kg) daily for 1 week before induction of retinal ischemia. Retinae were collected after 2 hours ischemia and 22 hours reperfusion. Paraffin-embedded sections were prepared for immunohistochemical analyses. Significantly fewer viable cells were found in vehicle-treated retinae comparing to LBP group. This finding was further confirmed by TUNEL assay where significantly fewer apoptotic cells were identified in LBP-treated retinae. Additionally, retinal swelling induced by retinal I/R injury in the vehicle-treated group was not observed in LBP-treated group. Moreover, intense GFAP immunoreactivity and IgG extravasation were observed in vehicle-treated group but not in LBP treated group. The results showed that pre-treatment with LBP was protective in retinal I/R injury via reducing neuronal death, apoptosis, retinal swelling, GFAP activation and blood vessel leakage. LBP may be used as a preventive agent for retinal ischemia diseases.

Protective effect of remote ischemic per-conditioning in the ischemia and reperfusion-induce renal injury in rats.

PubMed

Yamaki, Vitor Nagai; Gonçalves, Thiago Barbosa; Coelho, João Vitor Baia; Pontes, Ruy Victor Simões; Costa, Felipe Lobato da Silva; Brito, Marcus Vinicius Henriques

2012-12-01

To evaluate the protective effect of remote ischemic per-conditioning in ischemia and reperfusion-induced renal injury. Fifteen rats (Rattus norvegicus) were randomized into three groups (n = 5): Group Normality (GN), Control Ischemia and Reperfusion (GIR) and Group remote ischemic per-conditioning (GPER). With the exception of the GN group, all others underwent renal ischemia for 30 minutes. In group GPER we performed the ischemic remote per-conditioning, consisting of three cycles of ischemia and reperfusion applied every five minutes during the ischemic period, to the left hindlimb of the rats by means of a tourniquet. To quantify the lesions we measured serum levels of creatinine and urea, as well as analyzed renal histopathology. The GPER group presented with better levels of urea (83.74 ± 14.58%) and creatinine (0.72 ± 26.14%) when compared to GIR group, approaching the GN group. Histopathologically, the lower levels of medullary congestion and hydropic degeneration were found in group GPER. The remote ischemic per-conditioning had a significant protective effect on renal ischemia and reperfusion.

Forearm ischemia decreases endothelial colony-forming cell angiogenic potential.

PubMed

Mauge, Laetitia; Sabatier, Florence; Boutouyrie, Pierre; D'Audigier, Clément; Peyrard, Séverine; Bozec, Erwan; Blanchard, Anne; Azizi, Michel; Dizier, Blandine; Dignat-George, Françoise; Gaussem, Pascale; Smadja, David M

2014-02-01

Circulating endothelial progenitor cells and especially endothelial colony-forming cells (ECFCs) are promising candidate cells for endothelial regenerative medicine of ischemic diseases, but the conditions for an optimal collection from adult blood must be improved. On the basis of a recently reported vascular niche of ECFCs, we hypothesized that a local ischemia could trigger ECFC mobilization from the vascular wall into peripheral blood to optimize their collection for autologous implantation in critical leg ischemia. Because the target population with critical leg ischemia is composed of elderly patients in whom a vascular impairment has been documented, we also analyzed the impact of aging on ECFC mobilization and vascular integrity. After having defined optimized ECFC culture conditions, we studied the effect of forearm ischemia on ECFC numbers and functions in 26 healthy volunteers (13 volunteers ages 20-30-years old versus 13 volunteers ages 60-70 years old). The results show that forearm ischemia induced an efficient local ischemia and a normal endothelial response but did not mobilize ECFCs regardless of the age group. Moreover, we report an alteration of angiogenic properties of ECFCs obtained after forearm ischemia, in vitro as well as in vivo in a hindlimb ischemia murine model. This impaired ECFC angiogenic potential was not associated with a quantitative modification of the circulating endothelial compartment. The procedure of local ischemia, although reulting in a preserved endothelial reactivity, did not mobilize ECFCs but altered their angiogenic potential. Copyright © 2014 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

The protective effect of diosmin on hepatic ischemia reperfusion injury: an experimental study

PubMed Central

Tanrikulu, Yusuf; Şahin, Mefaret; Kismet, Kemal; Kilicoglu, Sibel Serin; Devrim, Erdinc; Tanrikulu, Ceren Sen; Erdemli, Esra; Erel, Serap; Bayraktar, Kenan; Akkus, Mehmet Ali

2013-01-01

Liver ischemia reperfusion injury (IRI) is an important pathologic process leading to bodily systemic effects and liver injury. Our study aimed to investigate the protective effects of diosmin, a phlebotrophic drug with antioxidant and anti-inflammatory effects, in a liver IRI model. Forty rats were divided into 4 groups. Sham group, control group (ischemia-reperfusion), intraoperative treatment group, and preoperative treatment group. Ischemia reperfusion model was formed by clamping hepatic pedicle for a 60 minute of ischemia followed by liver reperfusion for another 90 minutes. Superoxide dismutase (SOD) and catalase (CAT) were measured as antioaxidant enzymes in the liver tissues, and malondialdehyde (MDA) as oxidative stress marker, xanthine oxidase (XO) as an oxidant enzyme and glutathione peroxidase (GSH-Px) as antioaxidant enzyme were measured in the liver tissues and the plasma samples. Hepatic function tests were lower in treatment groups than control group (p<0.001 for ALT and AST). Plasma XO and MDA levels were lower in treatment groups than control group, but plasma GSH-Px levels were higher (p<0.05 for all). Tissue MDA levels were lower in treatment groups than control group, but tissue GSH-Px, SOD, CAT and XO levels were higher (p<0.05 for MDA and p<0.001 for others). Samples in control group histopathologically showed morphologic abnormalities specific to ischemia reperfusion. It has been found that both preoperative and intraoperative diosmin treatment decreases cellular damage and protects cells from toxic effects in liver IRI. As a conclusion, diosmin may be used as a protective agent against IRI in elective and emergent liver surgical operations. PMID:24289756

[Effect of progesterone on the expression of GLUT in the brain following hypoxic-ischemia in newborn rats].

PubMed

Li, Dong-Liang; Han, Hua

2008-08-01

To investigate the expression of GLUT1 and GLUT3 in the hippocampus after cerebral hypoxic-ischemia (HI) in newborn rats and the effect of progesterone (PROG) on them. Forty newborn SD rats were randomly divided into four groups: normal group, sham-operated group, hypoxic-ischemic group and progesterone group. Model of hypoxic-ischemia encephalopathy (HIE) was established in the 7-day-old newborn SD rats. Immunohistochemical method was applied to detect the expression of GLUT1 and GLUT3 in hippocampus. GLUT1 and GLUT3 were slightly seen in normal and sham operation group, there was no obviously difference between the two groups (P > 0.05). The expression of GLUT1 and GLUT3 in hypoxic-ischemia group were all higher than that in sham operated group (P < 0.05). Not only the expression of GLUT in progesterone group were significantly higher than that in sham operated group (P < 0.01), but also than that in hypoxic-ischemia group (P < 0.05). PROG could increase the tolerance of neuron to hypoxic-ischemia with maintaining the energy supply in the brain by up-regulating GLUT expression.

Effect of flaxseed supplementation and exercise training on lipid profile, oxidative stress and inflammation in rats with myocardial ischemia.

PubMed

Nounou, Howaida A; Deif, Maha M; Shalaby, Manal A

2012-10-05

Flaxseed has recently gained attention in the area of cardiovascular disease primarily because of its rich contents of α-linolenic acid (ALA), lignans, and fiber. Although the benefits of exercise on any single risk factor are unquestionable, the effect of exercise on overall cardiovascular risk, when combined with other lifestyle modifications such as proper nutrition, can be dramatic.This study was carried out to evaluate the protective role of flaxseed and exercise on cardiac markers, lipids profile and inflammatory markers in isoproterenol (ISO)-induced myocardial ischemia in rats. The research was conducted on 40 male albino rats, divided into 4 groups (n=10): group I served as control, group II has acute myocardial ischemia induced by isoproterenol, groups III and IV have acute myocardial ischemia induced by isoproterenol pretreated with flaxseed supplementation orally for 6 weeks, additionally group IV practiced muscular exercise through swimming. Alterations of lipid profile, cardiac and inflammatory markers (Il-1β, PTX 3 and TNF- α) were observed in myocardial ischemia group. Flaxseed supplementation combined with exercise training showed significant increase of HDL and PON 1, on the other hand cardiac troponin, Il- 1β and TNF- α levels significantly decreased as compared to myocardial ischemic group. Receiver Operating Characteristics (ROC) analysis of cTnI, PTX 3, Il-1β and TNF- α revealed a satisfactory level of sensitivity and specificity. Regular exercise enhances the improvement in plasma lipoprotein levels and cardiovascular protection that results from flaxseed supplementation by mitigating the pathophysiology of atherosclerosis. Elevation of HDL, the antioxidant PON 1 and the cardioprotective marker PTX 3 emphasizes the protective effects of flaxseed and muscular exercise mutually against the harmful effects of acute myocardial ischemia.

Sevoflurane pretreatment enhance HIF-2α expression in mice after renal ischemia/reperfusion injury

PubMed Central

Zheng, Beijie; Zhan, Qionghui; Chen, Jue; Xu, Huan; He, Zhenzhou

2015-01-01

Ischemia/reperfusion (I/R) injury often occurs, which is one of the major causes of acute kidney injury, thus increasing in-hospital mortality. HIF-2α has a protective role against ischemia of the kidney. Renal ischemia/reperfusion under sevoflurane anesthesia resulted in drastic improvements in renal function. We hypothesized that underlying mechanism responsible for renal protection from sevoflurane pretreatment involves the upregulation of HIF-2α. Sevoflurane pretreatment were performed on WT and HIF-2α knockout mice before renal ischemia/reperfusion. Levels of blood urea nitrogen (BUN) and serum creatinine (Cr) were determined with a standard clinical automatic analyzer. The left kidneys were taken for morphological examination. Expression of HIF-2α in kidney tissue was examined by western blotting. In WT mice, group I/R injury had significantly higher BUN and Cr levels than group control, whereas group I/R + Sev had significantly lower BUN and Cr levels than group I/R injury. Renal HIF-2α expression levels were significantly higher in WT mice of group I/R + Sev than group control and group I/R. In HIF-2α-/- mice, group I/R + Sev showed much higher BUN and Cr levels and severer histological damage than group I/R and group control. Renal HIF-2α expression levels were significantly higher in WT mice of group I/R + Sev than group control and group I/R. Our findings suggested that HIF-2α might contribute to the beneficial effect of sevoflurane in renal ischemia/reperfusion injury. PMID:26722509

Definition of delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage as an outcome event in clinical trials and observational studies: proposal of a multidisciplinary research group.

PubMed

Vergouwen, Mervyn D I; Vermeulen, Marinus; van Gijn, Jan; Rinkel, Gabriel J E; Wijdicks, Eelco F; Muizelaar, J Paul; Mendelow, A David; Juvela, Seppo; Yonas, Howard; Terbrugge, Karel G; Macdonald, R Loch; Diringer, Michael N; Broderick, Joseph P; Dreier, Jens P; Roos, Yvo B W E M

2010-10-01

In clinical trials and observational studies there is considerable inconsistency in the use of definitions to describe delayed cerebral ischemia (DCI) after aneurysmal subarachnoid hemorrhage. A major cause for this inconsistency is the combining of radiographic evidence of vasospasm with clinical features of cerebral ischemia, although multiple factors may contribute to DCI. The second issue is the variability and overlap of terms used to describe each phenomenon. This makes comparisons among studies difficult. An international ad hoc panel of experts involved in subarachnoid hemorrhage research developed and proposed a definition of DCI to be used as an outcome measure in clinical trials and observational studies. We used a consensus-building approach. It is proposed that in observational studies and clinical trials aiming to investigate strategies to prevent DCI, the 2 main outcome measures should be: (1) cerebral infarction identified on CT or MRI or proven at autopsy, after exclusion of procedure-related infarctions; and (2) functional outcome. Secondary outcome measure should be clinical deterioration caused by DCI, after exclusion of other potential causes of clinical deterioration. Vasospasm on angiography or transcranial Doppler can also be used as an outcome measure to investigate proof of concept but should be interpreted in conjunction with DCI or functional outcome. The proposed measures reflect the most relevant morphological and clinical features of DCI without regard to pathogenesis to be used as an outcome measure in clinical trials and observational studies.

Is Chronic Curcumin Supplementation Neuroprotective Against Ischemia for Antioxidant Activity, Neurological Deficit, or Neuronal Apoptosis in an Experimental Stroke Model?

PubMed

Altinay, Serdar; Cabalar, Murat; Isler, Cihan; Yildirim, Funda; Celik, Duygu S; Zengi, Oguzhan; Tas, Abdurrahim; Gulcubuk, Ahmet

2017-01-01

To investigate the neuroprotective effect of chronic curcumin supplementation on the rat forebrain prior to ischemia and reperfusion. Forebrain ischemia was induced by bilateral common carotid artery occlusion for 1/2 hour, followed by reperfusion for 72 hours. Older rats were divided into five groups: Group I received 300 mg/kg oral curcumin for 21 days before ischemia and 300 mg/kg intraperitoneal curcumin after ischemia; Group II received 300 mg/kg intraperitoneal curcumin after ischemia; Group III received 300 mg/kg oral curcumin for 21 days before ischemia; Group IV had only ischemia; Group V was the sham-operated group. The forebrain was rapidly dissected for biochemical parameter assessment and histopathological examination. In forebrain tissue, enzyme activities of superoxide dismutase, glutathione peroxidase, and catalase were significantly higher in Group I than Groups II or III (p < 0.05) while xanthine dehydrogenase and malondialdehyde enzyme activities and concentrations of interleukin-6 and TNF-alpha were significantly lower in Group I when compared to Groups II and III (p < 0.05). A significant reduction in neurological score was observed after 24 and 72 hours in the curcumin-treated groups compared with the ischemic group. We also found a marked reduction in apoptotic index after 72 hours in the groups receiving curcumin. Significantly more TUNEL-positive cells were observed in the ischemic group compared to those treated with curcumin. We demonstrated the neuroprotective effect of chronic curcumin supplement on biochemical parameters, neurological scores and apoptosis following ischemia and reperfusion injury in rats.

Pharmacological postconditioning with atorvastatin calcium attenuates myocardial ischemia/reperfusion injury in diabetic rats by phosphorylating GSK3β.

PubMed

Chen, Linyan; Cai, Ping; Cheng, Zhendong; Zhang, Zaibao; Fang, Jun

2017-07-01

Diabetes is an independent risk factor for myocardial ischemia, and many epidemiological data and laboratory studies have revealed that diabetes significantly exacerbated myocardial ischemia/reperfusion injury and ameliorated protective effects. The present study aimed to determine whether pharmacological postconditioning with atorvastatin calcium lessened diabetic myocardial ischemia/reperfusion injury, and investigated the role of glycogen synthase kinase (GSK3β) in this. A total of 72 streptozotocin-induced diabetic rats were randomly divided into six groups, and 24 age-matched male non-diabetic Sprague-Dawley rats were randomly divided into two groups. Rats all received 40 min myocardial ischemia followed by 180 min reperfusion, except sham-operated groups. Compared with the non-diabetic ischemia/reperfusion model group, the diabetic ischemia/reperfusion group had a comparable myocardial infarct size, but a higher level of serum cardiac troponin I (cTnI) and morphological alterations to their myocardial cells. Compared with the diabetic ischemia/reperfusion group, the group that received pharmacological postconditioning with atorvastatin calcium had smaller myocardial infarct sizes, lower levels of cTnI, reduced morphological alterations to myocardial cells, higher levels of p-GSK3β, heat shock factor (HSF)-1 and heat shock protein (HSP)70. The cardioprotective effect conferred by atorvastatin calcium did not attenuate myocardial ischemia/reperfusion injury following application of TDZD-8, which phosphorylates and inactivates GSK3β. Pharmacological postconditioning with atorvastatin calcium may attenuate diabetic heart ischemia/reperfusion injury in the current context. The phosphorylation of GSK3β serves a critical role during the cardioprotection in diabetic rats, and p-GSK3β may accelerate HSP70 production partially by activating HSF-1 during myocardial ischemic/reperfusion injury.

Preconditioning of intravenous parecoxib attenuates focal cerebral ischemia/reperfusion injury in rats.

PubMed

Wang, Na; Guo, Qu-lian; Ye, Zhi; Xia, Ping-ping; Wang, E; Yuan, Ya-jing

2011-07-05

Several studies suggest that cyclooxygenase-2 (COX-2) contributes to the delayed progression of ischemic brain damage. This study was designed to investigate whether COX-2 inhibition with parecoxib reduces focal cerebral ischemia/reperfusion injury in rats. Ninety male Sprague-Dawley rats were randomly assigned to three groups: the sham group, ischemia/reperfusion (I/R) group and parecoxib group. The parecoxib group received 4 mg/kg of parecoxib intravenously via the vena dorsalis penis 15 minutes before ischemia and again at 12 hours after ischemia. The neurological deficit scores (NDSs) were evaluated at 24 and 72 hours after reperfusion. The rats then were euthanized. Brains were removed and processed for hematoxylin and eosin staining, Nissl staining, and measurements of high mobility group Box 1 protein (HMGB1) and tumor necrosis factor-α (TNF-α) levels. Infarct volume was assessed with 2,3,5-triphenyltetrazolium chloride (TTC) staining. The rats in the I/R group had lower NDSs (P < 0.05), larger infarct volume (P < 0.05), lower HMGB1 levels (P < 0.05), and higher TNF-α levels (P < 0.05) compared with those in the sham group. Parecoxib administration significantly improved NDSs, reduced infarct volume, and decreased HMGB1 and TNF-α levels (P < 0.05). Pretreatment with intravenous parecoxib was neuroprotective. Its effects may be associated with the attenuation of inflammatory reaction and the inhibition of inflammatory mediators.

The Effect of Pentoxifylline on bcl-2 Gene Expression Changes in Hippocampus after Ischemia-Reperfusion in Wistar Rats by a Quatitative RT-PCR Method

PubMed Central

Sari, Soyar; Hashemi, Mehrdad; Mahdian, Reza; Parivar, Kazem; Rezayat, Mehdi

2013-01-01

Ischemia-reperfusion injury is the tissue damage caused when blood supply returns to the tissue after a period of ischemia or lack of oxygen. Ischemia-reperfusion brain injury initiates an inflammatory response involving the expression of adhesion molecules and cytokines. Twenty–four male Wistar rats (250-300 g body wt) were used in this study. The animals were divided into four groups of 6 rats each: I: Control group that was subjected to ischemia-reperfusion, II: Ischemia-reperfusion group that was subjected to all surgical procedures, III: Drug group that received pentoxifylline (200, 400 and 600 mg/kg) 60 min before and after ischemia and IV: Vehicle group that received saline. Seventy two h after ischemia-reperfusion, the hippocampus was taken for studying the changes in bcl-2 gene expression. We used quantitative real-time PCR for the detection of bcl-2 gene expression in ischemia and drug groups and then compared them to normal samples. The results showed the gene dosage ratio of 0.66 and 1.5 for ischemia group and the drug groups, respectively. The results also showed the bcl-2 gene expression declined in ischemia group as compared to the drug group. Furthermore, we observed a significant difference in the bcl-2 gene expression between ischemia and drug groups. These findings are consistent with anti-apoptotic properties of bcl-2 gene. Furthermore this method provides a powerful tool for the investigators to study brain ischemia and respond to the treatment drugs with anti-apoptotic agents. PMID:24250655

Ischemic preconditioning protects neurons from damage and maintains the immunoreactivity of kynurenic acid in the gerbil hippocampal CA1 region following transient cerebral ischemia

PubMed Central

LEE, JAE-CHUL; TAE, HYUN-JIN; CHO, GEUM-SIL; KIM, IN HYE; AHN, JI HYEON; PARK, JOON HA; CHEN, BAI HUI; CHO, JEONG-HWI; SHIN, BICH NA; CHO, JUN HWI; BAE, EUN JOO; PARK, JINSEU; KIM, YOUNG-MYEONG; CHOI, SOO YOUNG; WON, MOO-HO

2015-01-01

Pyramidal neurons in region I of hippocampus proper (CA1) are particularly vulnerable to excitotoxic processes following transient forebrain ischemia. Kynurenic acid (KYNA) is a small molecule derived from tryptophan when this amino acid is metabolized through the kynurenine pathway. In the present study, we examined the effects of ischemic preconditioning (IPC) on the immunoreactivity and protein levels of KYNA following 5 min of transient forebrain ischemia in gerbils. The animals were randomly assigned to 4 groups (sham-operated group, ischemia-operated group, IPC + sham-operated group and IPC + ischemia-operated group). IPC was induced by subjecting the gerbils to 2 min of ischemia followed by 1 day of recovery. In the ischemia-operated group, we observed a significant loss of pyramidal neurons in the CA1 stratum pyramidale (SP) at 5 days post-ischemia; however, in the IPC + ischemia-operated group, the pyramidal neurons were well protected. KYNA immunoreactivity in the SP of the ischemia-operated group was significantly altered following ischemia-reperfusion and was very low 5 days following ischemia-reperfusion. In the IPC + ischemia-operated group, however, KYNA immunoreactivity was constitutively detected in the SP of the CA1 region after the ischemic insult. We also found that the alteration pattern of the KYNA protein level in the CA1 region following ischemia was generally similar to the immunohistochemical changes observed. In brief, our findings demonstrated that IPC maintained and even increased KYNA immunoreactivity in the SP of the CA1 region following ischemia-reperfusion. The data from the present study thus indicate that the enhancement of KYNA expression by IPC may be necessary for neuronal survival following transient ischemic injury. PMID:25872573

Pretreatment of parecoxib attenuates hepatic ischemia/reperfusion injury in rats.

PubMed

Zhang, Tao; Ma, Yi; Xu, Kang-Qing; Huang, Wen-Qi

2015-11-17

Previous studies showed that cyclooxygenase(COX) was involved in ischemia/reperfusion (I/R) injuries. Parecoxib, a selective inhibitor for COX -2, has been shown to have protective properties in reducing I/R injury in the heart, kidney and brain. The aim of this study was to investigate the effects of parecoxib on hepatic I/R and to explore the underlying mechanisms. Fifty-two Sprague-Dawley rats were randomly divided into three groups: the sham-operation (Sham) group, the hepatic ischemia/reperfusion (I/R) group, and the parecoxib pretreated I/R (I/R + Pare) group. Partial warm ischemia was produced in the left and middle hepatic lobes of Sprague-Dawley rats for 60 min, followed by 6 h of reperfusion. Rats in the I/R + Pare group received parecoxib (10 mg/kg) intraperitoneally twice a day for three consecutive days prior to ischemia. Blood and tissue samples from the groups were collected 6 h after reperfusion, and a survival study was performed. Pretreatment with parecoxib prior to I/R insult significantly reduced I/R-induced elevations of aminotransferases, and significantly improved the histological status of the liver. Parecoxib significantly suppressed inflammatory cascades, as demonstrated by attenuations in TNF-α and IL-6. Parecoxib significantly inhibited iNOS and nitrotyrosine expression after I/R and significantly attenuated I/R-induced apoptosis. The 7-day survival rate was increased by pre-administration of parecoxib. Administration of parecoxib prior to hepatic I/R attenuates hepatic injury through inhibition of inflammatory response and nitrosative stress.

Effects of angiotensin-converting enzyme inhibition on transient ischemia: the Quinapril Anti-Ischemia and Symptoms of Angina Reduction (QUASAR) trial.

PubMed

Pepine, Carl J; Rouleau, Jean-Lucien; Annis, Karen; Ducharme, Anique; Ma, Patrick; Lenis, Jacques; Davies, Richard; Thadani, Udho; Chaitman, Bernard; Haber, Harry E; Freedman, S Ben; Pressler, Milton L; Pitt, Bertram

2003-12-17

We sought to determine whether angiotensin-converting enzyme inhibition (ACE-I) (i.e., quinapril) prevents transient ischemia (exertional and spontaneous) in patients with coronary artery disease (CAD). It is known that ACE-I reduces the risk of death, myocardial infarction (MI), and other CAD-related outcomes in high-risk patients. Numerous studies have confirmed that ACE-I improves coronary flow and endothelial function. Whether ACE-I also decreases transient ischemia is unclear, because no studies have been adequately designed or sufficiently powered to evaluate this issue. Using a randomized, double-blinded, placebo-controlled, multicenter design, we enrolled 336 CAD patients with stable angina. None had uncontrolled hypertension, left ventricular (LV) dysfunction, or recent MI, and all developed electrocardiographic (ECG) evidence of ischemia during exercise. They were randomly assigned to one of two groups: 40 mg/day quinapril (n = 177) or placebo (n = 159) for 8 weeks. Patients then entered an additional eight-week treatment phase to examine the full dose range. Those assigned to 40 mg quinapril continued that dose and those assigned to placebo were titrated to 80 mg/day. Treadmill testing, the Seattle Angina Questionnaire, and ambulatory ECG monitoring were used to assess responses at baseline and at 8 and 16 weeks. The groups did not differ significantly at entry or in terms of indexes assessing myocardial ischemia at 8 or 16 weeks of treatment. In this low-risk population, ACE-I was not associated with serious adverse events. Our findings suggest short-term ACE-I in CAD patients without hypertension, LV dysfunction, or acute MI is not associated with significant effects on transient ischemia.

Vagal modulation of high mobility group box-1 protein mediates electroacupuncture-induced cardioprotection in ischemia-reperfusion injury.

PubMed

Zhang, Juan; Yong, Yue; Li, Xing; Hu, Yu; Wang, Jian; Wang, Yong-qiang; Song, Wei; Chen, Wen-ting; Xie, Jian; Chen, Xue-mei; Lv, Xin; Hou, Li-li; Wang, Ke; Zhou, Jia; Wang, Xiang-rui; Song, Jian-gang

2015-10-26

Excessive release of high mobility group box-1 (HMGB1) protein from ischemic cardiomyocytes activates inflammatory cascades and enhances myocardial injury after reperfusion. Here we report evidence that electroacupuncture of mice at Neiguan acupoints can inhibit the up-regulation of cardiac HMGB1 following myocardial ischemia and attenuate the associated inflammatory responses and myocardial injury during reperfusion. These benefits of electroacupuncture were partially reversed by administering recombinant HMGB1 to the mice, and further potentiated by administering anti-HMGB1 antibody. Electroacupuncture-induced inhibition of HMGB1 release was markedly reduced by unilateral vagotomy or administration of nicotinic receptor antagonist, but not by chemical sympathectomy. The cholinesterase inhibitor neostigmine mimicked the effects of electroacupuncture on HMGB1 release and myocardial ischemia reperfusion injury. Culture experiments with isolated neonatal cardiomyocytes showed that acetylcholine, but not noradrenaline, inhibited hypoxia-induced release of HMGB1 via a α7nAchR-dependent pathway. These results suggest that electroacupuncture acts via the vagal nerve and its nicotinic receptor-mediated signaling to inhibit HMGB1 release from ischemic cardiomyocytes. This helps attenuate pro-inflammatory responses and myocardial injury during reperfusion.

Vagal modulation of high mobility group box-1 protein mediates electroacupuncture-induced cardioprotection in ischemia-reperfusion injury

PubMed Central

Zhang, Juan; Yong, Yue; Li, Xing; Hu, Yu; Wang, Jian; Wang, Yong-qiang; Song, Wei; Chen, Wen-ting; Xie, Jian; Chen, Xue-mei; Lv, Xin; Hou, Li-li; Wang, Ke; Zhou, Jia; Wang, Xiang-rui; Song, Jian-gang

2015-01-01

Excessive release of high mobility group box-1 (HMGB1) protein from ischemic cardiomyocytes activates inflammatory cascades and enhances myocardial injury after reperfusion. Here we report evidence that electroacupuncture of mice at Neiguan acupoints can inhibit the up-regulation of cardiac HMGB1 following myocardial ischemia and attenuate the associated inflammatory responses and myocardial injury during reperfusion. These benefits of electroacupuncture were partially reversed by administering recombinant HMGB1 to the mice, and further potentiated by administering anti-HMGB1 antibody. Electroacupuncture-induced inhibition of HMGB1 release was markedly reduced by unilateral vagotomy or administration of nicotinic receptor antagonist, but not by chemical sympathectomy. The cholinesterase inhibitor neostigmine mimicked the effects of electroacupuncture on HMGB1 release and myocardial ischemia reperfusion injury. Culture experiments with isolated neonatal cardiomyocytes showed that acetylcholine, but not noradrenaline, inhibited hypoxia-induced release of HMGB1 via a α7nAchR-dependent pathway. These results suggest that electroacupuncture acts via the vagal nerve and its nicotinic receptor-mediated signaling to inhibit HMGB1 release from ischemic cardiomyocytes. This helps attenuate pro-inflammatory responses and myocardial injury during reperfusion. PMID:26499847

Glomerular loss after arteriovenous and arterial clamping for renal warm ischemia in a swine model.

PubMed

Bechara, Gustavo Ruschi; Damasceno-Ferreira, José Aurelino; Abreu, Leonardo Albuquerque Dos Santos; Costa, Waldemar Silva; Sampaio, Francisco José Barcellos; Pereira-Sampaio, Marco Aurélio; Souza, Diogo Benchimol De

2016-11-01

To evaluate the glomerular loss after arteriovenous or arterial warm ischemia in a swine model. Twenty four pigs were divided into Group Sham (submitted to all surgical steps except the renal ischemia), Group AV (submitted to 30 minutes of warm ischemia by arteriovenous clamping of left kidney vessels), and Group A (submitted to 30 minutes of ischemia by arterial clamping). Right kidneys were used as controls. Weigh, volume, cortical volume, glomerular volumetric density (Vv[Glom]), volume-weighted glomerular volume (VWGV), and the total number of glomeruli were measured for each organ. Group AV showed a 24.5% reduction in its left kidney Vv[Glom] and a 25.4% reduction in the VWGV, when compared to the right kidney. Reductions were also observed when compared to kidneys of sham group. There was a reduction of 19.2% in the total number of glomeruli in AV kidneys. No difference was observed in any parameters analyzed on the left kidneys from group A. Renal warm ischemia of 30 minutes by arterial clamping did not caused significant glomerular damage, but arteriovenous clamping caused significant glomerular loss in a swine model. Clamping only the renal artery should be considered to minimize renal injury after partial nephrectomies.

Ischemic preconditioning maintains the immunoreactivities of glucokinase and glucokinase regulatory protein in neurons of the gerbil hippocampal CA1 region following transient cerebral ischemia

PubMed Central

CHO, YOUNG SHIN; CHO, JUN HWI; SHIN, BICH-NA; CHO, GEUM-SIL; KIM, IN HYE; PARK, JOON HA; AHN, JI HYEON; OHK, TAEK GEUN; CHO, BYUNG-RYUL; KIM, YOUNG-MYEONG; HONG, SEONGKWEON; WON, MOO-HO; LEE, JAE-CHUL

2015-01-01

Glucokinase (GK) is involved in the control of blood glucose homeostasis. In the present study, the effect of ischemic preconditioning (IPC) on the immunoreactivities of GK and its regulatory protein (GKRP) following 5 min of transient cerebral ischemia was investigated in gerbils. The gerbils were randomly assigned to four groups (sham-operated group, ischemia-operated group, IPC + sham-operated group and IPC + ischemia-operated group). IPC was induced by subjecting the gerbils to 2 min of ischemia, followed by 1 day of recovery. In the ischemia-operated group, a significant loss of neurons was observed in the stratum pyramidale (SP) of the hippocampal CA1 region (CA1) at 5 days post-ischemia; however, in the IPC+ischemia-operated group, the neurons in the SP were well protected. Following immunohistochemical investigation, the immunoreactivities of GK and GKRP in the neurons of the SP were markedly decreased in the CA1, but not the CA2/3, from 2 days post-ischemia, and were almost undetectable in the SP 5 days post-ischemia. In the IPC + ischemia-operated group, the immunoreactivities of GK and GKRP in the SP of the CA1 were similar to those in the sham-group. In brief, the findings of the present study demonstrated that IPC notably maintained the immunoreactivities of GK and GKRP in the neurons of the SP of CA1 following ischemia-reperfusion. This indicated that GK and GKRP may be necessary for neuron survival against transient cerebral ischemia. PMID:26134272

Effects of Chronic and Acute Zinc Supplementation on Myocardial Ischemia-Reperfusion Injury in Rats.

PubMed

Ozyıldırım, Serhan; Baltaci, Abdulkerim Kasim; Sahna, Engin; Mogulkoc, Rasim

2017-07-01

The present study aims to explore the effects of chronic and acute zinc sulfate supplementation on myocardial ischemia-reperfusion injury in rats. The study registered 50 adult male rats which were divided into five groups in equal numbers as follows: group 1, normal control; group 2, sham; group 3, myocardial ischemia reperfusion (My/IR): the group which was fed on a normal diet and in which myocardial I/R was induced; group 4, myocardial ischemia reperfusion + chronic zinc: (5 mg/kg i.p. zinc sulfate for 15 days); and group 5, myocardial ischemia reperfusion + acute zinc: the group which was administered 15 mg/kg i.p. zinc sulfate an hour before the operation and in which myocardial I/R was induced. The collected blood and cardiac tissue samples were analyzed using spectrophotometric method to determine levels of MDA, as an indicator of tissue injury, and GSH, as an indicator of antioxidant activity. The highest plasma and heart tissue MDA levels were measured in group 3 (p < 0.05). Group 5 had lower MDA values than group 3, while group 4 had significantly lower MDA values than groups 3 and 5 (p < 0.05). The highest erythrocyte GSH values were found in group 4 (p < 0.05). Erythrocyte GSH values in group 5 were higher than those in group 3 (p < 0.05). The highest GSH values in heart tissue were measured in group 4 (p < 0.05). The results of the study reveal that the antioxidant activity inhibited by elevated oxidative stress in heart ischemia reperfusion in rats is restored partially by acute zinc administration and markedly by chronic zinc supplementation.

Transient ischemia reduces norepinephrine release during sustained ischemia. Neural preconditioning in isolated rat heart.

PubMed

Seyfarth, M; Richardt, G; Mizsnyak, A; Kurz, T; Schömig, A

1996-04-01

Endogenous catecholamine release may play a role in ischemic preconditioning either as a trigger or as a target within the process of myocardial preconditioning. Therefore, we investigated the effect of transient ischemia (TI) on norepinephrine release during sustained ischemia in isolated rat hearts. TI was induced by multiple cycles of global ischemia followed by reperfusion with a duration of 5 minutes each, comparable to ischemic preconditioning protocols. After TI, norepinephrine release was evoked by either sustained global ischemia, anoxia, cyanide intoxication, tyramine, or electrical stimulation. During TI, no washout of norepinephrine was observed, and tissue concentrations of norepinephrine were not changed. TI, however, reduced norepinephrine overflow after 20 minutes of sustained ischemia from 239 +/- 26 pmol/g (control) to 79+/-8 pmol/g (67% reduction, P <.01 ). A similar reduction of ischemia-induced norepinephrine release from 192 +/- 22 pmol/g (control) to 90 +/- 15 pmol/g was observed when hearts underwent transient anoxia without glucose (P < .05). When reperfusion between TI and sustained ischemia was prolonged from 5 to 90 minutes, the inhibitory effect of TI on norepinephrine release was gradually lost. Susceptibility to TI was a unique feature of norepinephrine release induced by sustained ischemia, since release of norepinephrine evoked by anoxia, cyanide intoxication, tyramine, or electrical stimulation remained unaffected by TI. We propose a protective effect of TI on neural tissue, which may reduce norepinephrine-induced damage during prolonged myocardial ischemia.

Augmentation of systemic blood pressure during spinal cord ischemia to prevent postoperative paraplegia after aortic surgery in a rabbit model.

PubMed

Izumi, So; Okada, Kenji; Hasegawa, Tomomi; Omura, Atsushi; Munakata, Hiroshi; Matsumori, Masamichi; Okita, Yutaka

2010-05-01

Paraplegia from spinal cord ischemia remains an unresolved complication in thoracoabdominal aortic surgery, with high morbidity and mortality. This study investigated postoperative effects of systemic blood pressure augmentation during ischemia. Spinal cord ischemia was induced in rabbits by infrarenal aortic occlusion for 15 minutes with infused phenylephrine (high blood pressure group, n = 8) or nitroprusside (low blood pressure group, n = 8) or without vasoactive agent (control, n = 8). Spinal cord blood flow, transcranial motor evoked potentials, neurologic outcome, and motor neuron cell damage (apoptosis, necrosis, superoxide generation, myeloperoxidase activity) were evaluated. Mean arterial pressures during ischemia were controlled at 121.9 +/- 2.8, 50.8 +/- 4.3, and 82.3 +/- 10.7 mm Hg in high blood pressure, low blood pressure, and control groups, respectively. In high blood pressure group, high spinal cord blood flow (P < .01), fast recovery of transcranial motor evoked potentials (P < .01), and high neurologic score (P < .05) were observed after ischemia relative to low blood pressure and control groups. At 48 hours after ischemia, there were significantly more viable neurons, fewer terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling-positive neurons, and less alpha-fodrin expression in high blood pressure group than low blood pressure and control groups. Superoxide generation and myeloperoxidase activity at 3 hours after ischemia were suppressed in high blood pressure group relative to low blood pressure group. Augmentation of systemic blood pressure during spinal cord ischemia can reduce ischemic insult and postoperative neurologic adverse events. 2010 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.

Physical exercise prevents motor disorders and striatal oxidative imbalance after cerebral ischemia-reperfusion.

PubMed

Sosa, P M; Schimidt, H L; Altermann, C; Vieira, A S; Cibin, F W S; Carpes, F P; Mello-Carpes, P B

2015-09-01

Stroke is the third most common cause of death worldwide, and most stroke survivors present some functional impairment. We assessed the striatal oxidative balance and motor alterations resulting from stroke in a rat model to investigate the neuroprotective role of physical exercise. Forty male Wistar rats were assigned to 4 groups: a) control, b) ischemia, c) physical exercise, and d) physical exercise and ischemia. Physical exercise was conducted using a treadmill for 8 weeks. Ischemia-reperfusion surgery involved transient bilateral occlusion of the common carotid arteries for 30 min. Neuromotor performance (open-field and rotarod performance tests) and pain sensitivity were evaluated beginning at 24 h after the surgery. Rats were euthanized and the corpora striata was removed for assay of reactive oxygen species, lipoperoxidation activity, and antioxidant markers. Ischemia-reperfusion caused changes in motor activity. The ischemia-induced alterations observed in the open-field test were fully reversed, and those observed in the rotarod test were partially reversed, by physical exercise. Pain sensitivity was similar among all groups. Levels of reactive oxygen species and lipoperoxidation increased after ischemia; physical exercise decreased reactive oxygen species levels. None of the treatments altered the levels of antioxidant markers. In summary, ischemia-reperfusion resulted in motor impairment and altered striatal oxidative balance in this animal model, but those changes were moderated by physical exercise.

Kidney ischemia and reperfunsion syndrome: effect of lidocaine and local postconditioning.

PubMed

Yamaki, Igor Nagai; Pontes, Ruy Victor Simões; Costa, Felipe Lobato DA Silva; Yamaki, Vitor Nagai; Teixeira, Renan Kleber Costa; Yasojima, Edson Yuzur; Brito, Marcus Vinicius Henriques

2016-01-01

to evaluate the effects of blocking the regulation of vascular tone on the ischemia and reperfusion syndrome in rats through the use of lidocaine in the postconditioning technique. we randomized 35 rats into seven groups of five animals: Group 1- Control; Group 2- Ischemia and Reperfusion; Group 3- Ischemia, Reperfusion and Saline; Group 4- Ischemic Postconditioning; Group 5- Ischemic Postconditioning and Saline; Group 6- Lidocaine; Group 7- Ischemic Postconditioning and Lidocaine. Except for the control group, all the others were submitted to renal ischemia for 30 minutes. In postconditioning groups, we performed ischemia and reperfusion cycles of five minutes each, applied right after the main ischemia. In saline and lidocaine groups, we instilled the substances at a rate of two drops per minute. To compare the groups, we measured serum levels of urea and creatinine and also held renal histopathology. The postconditioning and postconditioning + lidocaine groups showed a decrease in urea and creatinine values. The lidocaine group showed only a reduction in creatinine values. In histopathology, only the groups submitted to ischemic postconditioning had decreased degree of tubular necrosis. Lidocaine did not block the effects of postconditioning on renal ischemia reperfusion syndrome, and conferred better glomerular protection when applied in conjunction with ischemic postconditioning. avaliar os efeitos do bloqueio da regulação do tônus vascular por meio do uso da lidocaína na técnica de pós-condicionamento isquêmico na síndrome de isquemia e reperfusão renal em ratos. trinta e cinco ratos foram randomizados em sete grupos de cinco animais: Grupo 1- Controle; Grupo 2- Isquemia e Reperfusão; Grupo 3- Isquemia, Reperfusão e Solução Salina; Grupo 4- Pós-condicionamento Isquêmico; Grupo 5- Pós-condicionamento Isquêmico e Solução Salina; Grupo 6- Lidocaína; Grupo 7- Pós-condicionamento Isquêmico e lidocaína. Com exceção do grupo controle, todos

Hemin offers neuroprotection through inducing exogenous neuroglobin in focal cerebral hypoxic-ischemia in rats

PubMed Central

Song, Xue; Xu, Rui; Xie, Fei; Zhu, Haiyuan; Zhu, Ji; Wang, Xin

2014-01-01

Objective: To investigate the inducible effect of hemin on exogenous neuroglobin (Ngb) in focal cerebral hypoxic-ischemia in rats. Methods: 125 healthy SD rats were randomly divided into five groups: sham-operation control group, operation group, hemin treatment group, exogenous Ngb treatment group, and hemin and exogenous Ngb joint treatment group. Twenty-four hours after focal cerebral hypoxic-ischemia, Ngb expression was evaluated by immunocytochemistry, RT-PCR, and western blot analyses, while the brain water content and infarct volume were examined. Results: Immunocytochemistry, RT-PCR, and western blot analyses showed more pronounced Ngb expression in the hemin and exogenous Ngb joint operation group than in the hemin or exogenous Ngb individual treatment groups, thus producing significant differences in brain water content and infarct volume (p < 0.05). Conclusions: Hemin may be beneficial in protecting against focal cerebral hypoxic-ischemia through inducing the expression of exogenous Ngb. PMID:24966924

Influence of remote ischemic conditioning and tramadol hydrochloride on oxidative stress in kidney ischemia/reperfusion injury in rats.

PubMed

Oliveira, Rita de Cássia Silva de; Brito, Marcus Vinicius Henriques; Ribeiro, Rubens Fernando Gonçalves; Oliveira, Leonam Oliver Durval; Monteiro, Andrew Moraes; Brandão, Fernando Mateus Viegas; Cavalcante, Lainy Carollyne da Costa; Gouveia, Eduardo Henrique Herbster; Henriques, Higor Yuri Bezerra

2017-03-01

To evaluate the effects of tramadol hydrochloride associated to remote ischemic perconditioning on oxidative stress. Twenty five male rats (Wistar) underwent right nephrectomy and were distributed into five groups: Sham group (S); Ischemia/Reperfusion group (I/R) with 30 minutes of renal ischemia; Remote ischemic perconditioning group (Per) with three cycles of 10 minutes of I/R performed during kidney ischemia; Tramadol group (T) treated with tramadol hydrochloride (40mg/kg); remote ischemic perconditioning + Tramadol group (Per+T) with both treatments. Oxidative stress was assessed after 24 hours of reperfusion. Statistical differences were observed in MDA levels between I/R group with all groups (p<0.01), in addition there was difference between Tramadol with Sham, Per and Per+T groups (p<0.05), both in plasma and renal tissue. Remote ischemic perconditioning was more effective reducing renal ischemia-reperfusion injury than administration of tramadol or association of both treatments.

Thymoquinone protects end organs from abdominal aorta ischemia/reperfusion injury in a rat model.

PubMed

Aydin, Mehmet Salih; Kocarslan, Aydemir; Kocarslan, Sezen; Kucuk, Ahmet; Eser, İrfan; Sezen, Hatice; Buyukfirat, Evren; Hazar, Abdussemet

2015-01-01

Previous studies have demonstrated that thymoquinone has protective effects against ischemia reperfusion injury to various organs like lungs, kidneys and liver in different experimental models. We aimed to determine whether thymoquinone has favorable effects on lung, renal, heart tissues and oxidative stress in abdominal aorta ischemia-reperfusion injury. Thirty rats were divided into three groups as sham (n=10), control (n=10) and thymoquinone (TQ) treatment group (n=10). Control and TQ-treatment groups underwent abdominal aorta ischemia for 45 minutes followed by a 120-min period of reperfusion. In the TQ-treatment group, thymoquinone was given 5 minutes. before reperfusion at a dose of 20 mg/kg via an intraperitoneal route. Total antioxidant capacity, total oxidative status (TOS), and oxidative stress index (OSI) in blood serum were measured and lung, kidney, and heart tissue histopathology were evaluated with light microscopy. Total oxidative status and oxidative stress index activity in blood samples were statistically higher in the control group compared to the sham and TQ-treatment groups (P<0.001 for TOS and OSI). Control group injury scores were statistically higher compared to sham and TQ-treatment groups (P<0.001 for all comparisons). Thymoquinone administered intraperitoneally was effective in reducing oxidative stress and histopathologic injury in an acute abdominal aorta ischemia-reperfusion rat model.

Valeriana officinalis Extracts Ameliorate Neuronal Damage by Suppressing Lipid Peroxidation in the Gerbil Hippocampus Following Transient Cerebral Ischemia

PubMed Central

Yoo, Dae Young; Jung, Hyo Young; Nam, Sung Min; Kim, Jong Whi; Choi, Jung Hoon; Kwak, Youn-Gil; Yoo, Miyoung; Lee, Sanghee; Yoon, Yeo Sung

2015-01-01

Abstract As a medicinal plant, the roots of Valeriana officinalis have been used as a sedative and tranquilizer. In the present study, we evaluated the neuroprotective effects of valerian root extracts (VE) on the hippocampal CA1 region of gerbils after 5 min of transient cerebral ischemia. Gerbils were administered VE orally once a day for 3 weeks, subjected to ischemia/reperfusion injury, and continued on VE for 3 weeks. The administration of 100 mg/kg VE (VE100 group) significantly reduced the ischemia-induced spontaneous motor hyperactivity 1 day after ischemia/reperfusion. Four days after ischemia/reperfusion, animals treated with VE showed abundant cresyl violet-positive neurons in the hippocampal CA1 region when compared to the vehicle or 25 mg/kg VE-treated groups. In addition, the VE treatment markedly decreased microglial activation in the hippocampal CA1 region 4 days after ischemia. Compared to the other groups, the VE100 group showed the lowest level of lipid peroxidation during the first 24 h after ischemia/reperfusion. In summary, the findings in this study suggest that pretreatment with VE has protective effects against ischemic injury in the hippocampal pyramidal neurons by decreasing microglial activation and lipid peroxidation. PMID:25785762

Valeriana officinalis Extracts Ameliorate Neuronal Damage by Suppressing Lipid Peroxidation in the Gerbil Hippocampus Following Transient Cerebral Ischemia.

PubMed

Yoo, Dae Young; Jung, Hyo Young; Nam, Sung Min; Kim, Jong Whi; Choi, Jung Hoon; Kwak, Youn-Gil; Yoo, Miyoung; Lee, Sanghee; Yoon, Yeo Sung; Hwang, In Koo

2015-06-01

As a medicinal plant, the roots of Valeriana officinalis have been used as a sedative and tranquilizer. In the present study, we evaluated the neuroprotective effects of valerian root extracts (VE) on the hippocampal CA1 region of gerbils after 5 min of transient cerebral ischemia. Gerbils were administered VE orally once a day for 3 weeks, subjected to ischemia/reperfusion injury, and continued on VE for 3 weeks. The administration of 100 mg/kg VE (VE100 group) significantly reduced the ischemia-induced spontaneous motor hyperactivity 1 day after ischemia/reperfusion. Four days after ischemia/reperfusion, animals treated with VE showed abundant cresyl violet-positive neurons in the hippocampal CA1 region when compared to the vehicle or 25 mg/kg VE-treated groups. In addition, the VE treatment markedly decreased microglial activation in the hippocampal CA1 region 4 days after ischemia. Compared to the other groups, the VE100 group showed the lowest level of lipid peroxidation during the first 24 h after ischemia/reperfusion. In summary, the findings in this study suggest that pretreatment with VE has protective effects against ischemic injury in the hippocampal pyramidal neurons by decreasing microglial activation and lipid peroxidation.

Effects of Sildenafil and Tadalafil on Edema and Reactive Oxygen Species Production in an Experimental Model of Lung Ischemia-Reperfusion Injury.

PubMed

Guerra-Mora, J R; Perales-Caldera, E; Aguilar-León, D; Nava-Sanchez, C; Díaz-Cruz, A; Díaz-Martínez, N E; Santillán-Doherty, P; Torres-Villalobos, G; Bravo-Reyna, C C

Lung ischemia-reperfusion injury is characterized by formation of reactive oxygen species and cellular swelling leading to pulmonary edema and primary graft dysfunction. Phosphodiesterase 5 inhibitors could ameliorate lung ischemia-reperfusion injury by interfering in many molecular pathways. The aim of this work was to evaluate and compare the effects of sildenafil and tadalafil on edema and reactive oxygen species formation in an ex vivo nonhuman animal model of lung ischemia-reperfusion injury. Thirty-two Wistar rats were distributed, treated, perfused and the cardiopulmonary blocks were managed as follows: control group: immediate excision and reperfusion without pretreatment; ischemia reperfusion group: treatment with dimethylsulfoxide 0.9% and excision 1 hour later; sildenafil group: treatment with sildenafil (0.7 mg/kg) and excision 1 hour later; and tadalafil group: treatment with tadalafil (0.15 mg/kg) and excision 2 hours later. All cardiopulmonary blocks except control group were preserved for 8 hours and then reperfused. Pulmonary arterial pressure, pulmonary venous pressure, and capillary filtration coefficient were measured. Reactive oxygen species were measured. Edema was similar between control and sildenafil groups, but significantly greater in the ischemia-reperfusion (P ≤ .04) and tadalafil (P ≤ .003) groups compared with the sildenafil group. The malondialdehyde levels were significantly lower in the sildenafil (P ≤ .001) and tadalafil (P ≤ .001) groups than the ischemia-reperfusion group. Administration of sildenafil, but not tadalafil, decreased edema in lung ischemia-reperfusion injury. Both drugs decreased reactive oxygen species formation in a lung ischemia-reperfusion injury model. Copyright © 2017 Elsevier Inc. All rights reserved.

Cardioprotective effect of resistance training and Crataegus oxyacantha extract on ischemia reperfusion-induced oxidative stress in diabetic rats.

PubMed

Ranjbar, Kamal; Zarrinkalam, Ebrahim; Salehi, Iraj; Komaki, Alireza; Fayazi, Bayan

2018-04-01

Discovering an effective approach to limit infarction size after ischemia-reperfusion has a clinical importance in diabetics. We investigated the anti-myocardial ischemia-reperfusion injury effect of resistance training and Crataegus oxyacantha extract on diabetic rats. To this end, 50 male Wistar rats were randomly divided into 5 groups: the sedentary control (SC), sedentary diabetic (SD), resistance trained diabetic (RD), diabetic plus C. oxyacantha extract treatment (CD) and resistance trained diabetic plus C. oxyacantha extract treatment (RCD) groups. Animals in trained groups were subjected to progressive resistance training program with the use of a ladder (5 days/week, for 10 weeks). C. oxyacantha extract rats were treated with 100 mg/kg body weight of the extract using a gavage every day for 10 weeks. After treatments, rats were subjected to ischemia via LAD artery ligation for 30 min followed by 90 min reperfusion. The heart was collected following the ischemia-reperfusion and analyzed for oxidative stress and ischemia-reperfusion injury. Compared to the SC group, LDH, CK-MB and infarction size in the SD group were significantly higher, whereas injury indices in the RCD group were significantly lower than those in the SD group. GPx and MPO levels after reperfusion increased and decreased, respectively in response to training and C. oxyacantha. These findings suggest that 10 weeks resistance training and C. oxyacantha can synergistically decrease ischemia-reperfusion injury, and this mechanism may be related to a reduction in oxidative stress which is normally associated with ischemia-reperfusion. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Selenium effect on ischemia-reperfusion injury of gastrocnemius muscle in adult rats.

PubMed

Gholami, Mohammadreza; Zendedel, Abolfazl; Khanipour khayat, Zahra; Ghanad, Kourosh; Nazari, Afshin; Pirhadi, Atieh

2015-04-01

Selenium is a trace element that has antioxidant and neuroprotective effects. The aim of this study is to investigate the effects of selenium in reducing ischemia-reperfusion injury of the gastrocnemius muscle. In this experimental study, 80 adult male Wistar rats weighing 250-300 g were divided into ten groups (N = 8 per group). Group 1 is control group (without ischemia-reperfusion). Group 2 received 0.2 mg/kg selenium. Group 3 received ischemia + 3 d reperfusion + 0.2 mg/kg selenium, group 4 received ischemia + 3 d reperfusion + 0.2 mg/kg placebo, group 5 received ischemia + 7 d reperfusion + 0.2 mg/kg selenium, group 6 received ischemia + 7 d reperfusion + 0.2 mg/kg placebo, group 7 received ischemia + 14 d reperfusion + 0.2 mg/kg selenium, group 8 received ischemia + 14 d reperfusion + 0.2 mg/kg placebo, group 9 received ischemia + 28 d reperfusion + 0.2 mg/kg selenium and group 10 received ischemia + 3 d reperfusion + 0.2 mg/kg placebo. External iliac artery blocked for 3 h. After reperfusion, rats killed and gastrocnemius muscle removed, fixed, and tissue processing performed. Samples stained with hematoxylin-eosin for edema evaluation, toluidine blue for mast cell infiltration evaluation and immunohistochemistry for detection TNF-alpha and NF-kappa B proteins. Comparison of mast cell infiltration, edema of the interstitial fluid on the tissue, expression of TNF-alpha protein, and expression of NF-kappa B protein in the groups that received selenium with corresponding placebo group showed that selenium can reduce edema, mast cell infiltration, and TNF-alpha expression and inactivated NF-kappa B. The use of selenium simultaneously with creating ischemia can reduce ischemia-reperfusion injury of the gastrocnemius muscle.

Effects of Urtica dioica on hepatic ischemia-reperfusion injury in rats.

PubMed

Kandis, Hayati; Karapolat, Sami; Yildirim, Umran; Saritas, Ayhan; Gezer, Suat; Memisogullari, Ramazan

2010-01-01

To evaluate the effects of Urtica dioica on hepatic ischemia-reperfusion injury. Thirty adult male Wistar albino rats were divided into three groups: sham group (group 1), control group (group 2), and Urtica dioica group (group 3). All the rats were exposed to hepatic ischemia for 60 min, followed by 60 min of reperfusion. In group 2, a total of 2 ml/kg 0.9% saline solution was given intraperitoneally. In group 3, a total of 2 ml/kg Urtica dioica was given intraperitoneally. At the end of the procedure, liver tissue and blood samples were taken from all rats. Serum aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase, ceruloplasmin, catalase, paraoxonase, arylesterase, and lipid hydroperoxide levels were measured. Liver tissue histopathologies were also evaluated by light microscopy. Serum aspartate aminotransferase, alanine aminotransferase and lactate dehydrogenase levels were significantly higher in group 2 than in group 1, and significantly lower in group 3 than in group 2. Also, group 2 had higher serum lipid hydroperoxides and ceruloplasmin levels but lower catalase, paraoxonase, and arylesterase levels than group 1. In group 3, serum lipid hydroperoxides and ceruloplasmin levels were significantly lower, and catalase, paraoxonase, and arylesterase levels were higher than those in group 2. Histopathological examination showed that liver tissue damage was significantly decreased in group 3 compared with group 2. Urtica dioica has a protective effect on the liver in hepatic ischemia-reperfusion-injured rats.

[Transfection of hBcl-2 gene protects the liver against ischemia/reperfusion injury in rats during liver transplantation].

PubMed

Liu, Ji-tong; Liu, Jing-shi; Jiang, Jin-yu; Zhou, Li-xue; Liang, Gang; Li, Yan-chun

2010-12-01

To study the effect of hBcl-2 gene transfer on rat liver against ischemia-reperfusion injury, and explore the feasibility of this approach to reduce ischemia-reperfusion injury in liver transplantation. We constructed the replication-deficient recombinant adenoviruses Adv-EGFP and Adv-Bcl-2 and transfected them into 293 cells and packaged into adenovirus particles for amplification and purification. The empty plasmid vector virus was constructed similarly. Male SD rats were randomized into Adv-Bcl-2-transfected group, Adv-EGFP-transfected group, ischemia-reperfusion group, and sham-operated group, and liver allograft transplantation model was established by sleeve method. In the transfected groups, the recombinant viruses were administered by perfusion through the portal vein, and the ischemia-reperfusion and sham-operated groups received no treatment. Real-time quantitative PCR and Western blotting were used to detect the mRNA and protein expressions of bcl-2 in the liver tissue of each group, and at 0, 60 and 180 min after reperfusion, serum AST, LDH, and MDA levels were measured. Histological changes of the liver cells were evaluated by HE staining. Bcl-2 mRNA and protein expressions in Adv-Bcl-2-transfected group, as compared with those in Adv-EGFP-transfected group and control group, were significantly increased (P<0.01); the serum levels of AST, LDH and MDA in Adv-Bcl-2-transfected group were significantly lower than those of Adv-EGFP-transfected group and ischemia-reperfusion group (P<0.05 or 0.01). Compared with the sham-operated group, Adv-Bcl-2 treatment group showed lessened edema and vacuolar degeneration of the liver cells without patches or spots of necrosis. In ischemia-reperfusion and Adv-EGFP group, HE staining revealed hepatic lobular destruction and extensive liver cell swelling, enlargement, vacuolar degeneration, edema and occasional focal necrosis. Adv-Bcl-2 transfection can induce the expression of bcl-2 gene to reduce ischemia

Abate Cytochrome C induced apoptosome to protect donor liver against ischemia reperfusion injury on rat liver transplantation model.

PubMed

Zhuang, Zhuonan; Lian, Peilong; Wu, Xiaojuan; Shi, Baoxu; Zhuang, Maoyou; Zhou, Ruiling; Zhao, Rui; Zhao, Zhen; Guo, Sen; Ji, Zhipeng; Xu, Kesen

2016-01-01

Aim of this study is to protect donor liver against ischemia-reperfusion injury by abating Cytochrome C induced apoptosome on rat model. A total of 25 clean SD inbred male rats were used in this research. The rats in ischemia-reperfusion injury group (I/R group, n=5) were under liver transplantation operation; rats in dichloroacetate diisopropylamine group (DADA group, n=5) were treated DADA before liver transplantation; control group (Ctrl group, n=5); other 10 rats were used to offer donor livers. In DADA therapy group, Cytochrome C expression in donor hepatocellular cytoplasm was detected lower than that in I/R group. And the Cytochrome C induced apoptosome was also decreased in according to the lower expressions of Apaf-1 and Caspase3. Low level of cleaved PARP expression revealed less apoptosis in liver tissue. The morphology of donor liver mitochondria in DADA group was observed to be slightly edema but less than I/R group after operation 12 h. The liver function indexes of ALT and AST in serum were tested, and the results in DADA group showed it is significantly lower than I/R group after operation 12 h. The inflammation indexes of IL-6 and TNF-α expressions in DADA group were significantly lower than that in I/R group after operation 24 h. The dichloroacetate diisopropylamine treatment could protect the hepatocellular mitochondria in case of the spillage of Cytochrome C induced apoptosome, and protect the liver against ischemia-reperfusion injury. Thus, it may be a method to promote the recovery of donor liver function after transplantation.

Chronotropic incompetence and a higher frequency of myocardial ischemia in exercise echocardiography

PubMed Central

Oliveira, Joselina LM; Góes, Thiago JS; Santana, Thaiana A; Travassos, Thiago F; Teles, Lívia D; Anjos-Andrade, Fernando D; Nascimento-Júnior, Adão C; Alves, Érica O; Barreto, Martha A; Barreto-Filho, José A; D'Oliveira, Argemiro; Sousa, Antônio CS

2007-01-01

Background Exercise echocardiography (EE) is an established method to diagnose coronary artery disease (CAD). Chronotropic incompetence (CI) during the EE may be a marker of myocardial ischemia. The purpose of this investigation was to evaluate the additive value of CI during EE in CAD diagnosis. Methods Between 2000 and 2006, 4042 patients (1900 men with a mean age of 56 ± 11 years) were evaluated by EE. Based on the heart rate (HR) reached during the exercise test, the subjects were divided into two groups: G1 group – 490 patients who failed to achieve 85% of the maximal age-predicted HR, and G2 group – 3552 patients who were able to achieve 85% of the maximal age-predicted HR. Clinical characteristics, left ventricular wall motion abnormalities – wall motion score index (WMSI) – and coronary angiography (CA) were the parameters compared between the two groups. Results The left ventricular wall motion abnormalities were more frequent in G1 group than in G2 group (54% versus 26%; P < 0.00001). WMSI was higher in G1 group than in G2 group, both at rest (1.06 ± 0.17 versus 1.02 ± 0.09; P < 0.0001) and after exercise (1.12 ± 0.23 versus 1.04 ± 0.21; P < 0.0001). In G1 group, 82% of the patients with positive EE for myocardial ischemia presented obstructive coronary, compared to 71% (P = 0.03) in G2 group. Conclusion CI is associated with a higher frequency of myocardial ischemia during EE, reinforcing the concept that CI is a marker of the severity of myocardial ischemia. PMID:17980022

N-acetylcysteine ameliorates liver injury in a rat model of intestinal ischemia reperfusion.

PubMed

Kalimeris, Konstantinos; Briassoulis, Panagiotis; Ntzouvani, Agathi; Nomikos, Tzortzis; Papaparaskeva, Kleio; Politi, Aikaterini; Batistaki, Chrysanthi; Kostopanagiotou, Georgia

2016-12-01

N-acetylcysteine (NAC) is an antioxidant with direct and indirect antioxidant actions used in the clinical setting. Oxidative stress is known to play a pivotal role in the intestinal ischemia reperfusion (IIR). Therefore, we studied the effect of different pretreatment regimens with NAC on the IIR injury in rats. Thirty-five male Wistar rats were randomly assigned to five groups. In group sham, only laparotomy was performed. Group control underwent IIR without NAC. In the other groups, NAC was administered intraperitoneally with different regimens: 150 mg/kg before ischemia (NAC 150), 300 mg/kg before ischemia (NAC 300), and 150 mg/kg before ischemia plus 150 mg/kg 5 min before reperfusion (NAC 150 + 150). Measurements in tissues and blood were conducted at 4 h of reperfusion following exsanguination. Histological score of the liver was significantly improved in NAC 300 compared with control (1.7 ± 0.5 versus 2.9 ± 1.1, respectively, P = 0.05). In addition, NAC treatment significantly reduced liver transaminases in all groups of treatment, mostly in group NAC 300. Plasma malondialdehyde levels were lower with NAC treatment, although not statistically significant. Lung glutathione peroxidase was significantly increased in group NAC 300 (P = 0.04), while the other oxidation biomarkers showed no significant differences. NAC exerts a significant protective role in liver injury following IIR, which seems to be independent of an intestinal protective effect. Additional administration of NAC before reperfusion was of no further benefit. The most effective regimen among the compared regimens was that of 300 mg/kg before ischemia. Copyright © 2016 Elsevier Inc. All rights reserved.

Biological and histopathological investigations of moclobemide on injured ovarian tissue following induction of ischemia-reperfusion in rats.

PubMed

Ingec, Metin; Calik, Muhammet; Gundogdu, Cemal; Kurt, Ali; Yilmaz, Mehmet; Isaoglu, Unal; Salman, Suleyman; Akcay, Fatih; Suleyman, Halis

2012-04-01

The effects of moclobemide on damaged ovarian tissue induced by ischemia- reperfusion and damaged contralateral ovarian tissue were investigated in rats, biochemically and histologically. In this experimental study, 40 rats were equally divided into four groups: 10 mg/kg moclobemide, 20 mg/kg moclobemide, ischemia/reperfusion control, and intact control groups. A 2-2.5-cm-long vertical incision was made in the lower abdomen of each rat in order to reach the ovaries, after which a vascular clip was placed on the lower side of the right ovary of each animal in the two treatment groups and the ischemia-reperfusion control group, but not in the healthy (intact control) animal group. The purpose of this procedure was to create ischemia over the course of three hours, then the clips were unclamped to provide reperfusion for the next two hours. At the end of the two hours of reperfusion, all the animals were killed by high-dose anaesthesia and their ovaries were taken and subjected to histological and biochemical (malondialdehyde, nitric oxide, glutathione) studies. The obtained results showed that moclobemide suppressed nitric oxide and malondialdehyde production in the ischemia-reperfusion damage area, and prevented the decrease in endogenous antioxidant levels (glutathione) in the rat ovarian tissue. Moclobemide also prevented infiltration of leukocytes to the ovarian tissue. These results showed that moclobemide protected ovarian tissue against ischemiareperfusion injury. This study shows that moclobemide represses malondialdehyde and nitric oxide production in the rat ovarian tissue subjected to ischemia-reperfusion injury and keeps the endogenous antioxidant glutathione level from decreasing. Moclobemide also inhibits leukocytic migration into ovarian tissue following ischemia-reperfusion injury. From these results, it is suggested that moclobemide can be used in the treatment of ovarian ischemia-reperfusion injury.

Suppressing Receptor-Interacting Protein 140: a New Sight for Salidroside to Treat Cerebral Ischemia.

PubMed

Chen, Tong; Ma, Zhanqiang; Zhu, Lingpeng; Jiang, Wenjiao; Wei, Tingting; Zhou, Rui; Luo, Fen; Zhang, Kai; Fu, Qiang; Ma, Chunhua; Yan, Tianhua

2016-11-01

The purpose of the current study was to detect the effect of salidroside (Sal) on cerebral ischemia and explore its potential mechanism. Middle cerebral artery occlusion (MCAO) was performed to investigate the effects of Sal on cerebral ischemia. The rats were randomly divided into five groups: sham group, vehicle group, clopidogrel (7.5 mg/kg) group, Sal (20 mg/kg) group, and Sal (40 mg/kg) group. SH-SY5Y cells were exposed to ischemia-reperfusion (I/R) injury to verify the protective effect of Sal in vitro. We also built the stable receptor-interacting protein 140 (RIP140)-overexpressing SH-SY5Y cells. The results showed that Sal significantly reduces brain infarct size and cerebral edema. Sal could effectively decrease the levels of interleukin-6 (IL-6), interleukin-1β (IL-1β), and tumor necrosis factor-α (TNF-α) in serum of the MCAO rats and supernatant of I/R-induced SH-SY5Y cells. Immunohistochemical and Western blot results demonstrated that Sal inhibited RIP140-mediated inflammation and apoptosis in the MCAO rats and SH-SY5Y cells. In addition, we further confirmed that RIP140/NF-κB signaling plays a crucial role by evaluating the protein expression in RIP140-overexpressing SH-SY5Y cells. Our findings suggested that Sal could be used as an effective neuroprotective agent for cerebral ischemia due to its significant effect on preventing neuronal cell injury after cerebral ischemia both in vivo and in vitro by the inhibitions of RIP140-mediated inflammation and apoptosis.

Neuroprotective effects of pretreatment with minocycline on memory impairment following cerebral ischemia in rats.

PubMed

Naderi, Yazdan; Sabetkasaei, Masoumeh; Parvardeh, Siavash; Moini Zanjani, Taraneh

2017-04-01

Cerebral ischemia leads to memory impairment that is associated with loss of hippocampal CA1 pyramidal neurons. Neuroinflammation and oxidative stress may be implicated in the pathogenesis of ischemia/reperfusion damage. Minocycline has anti-inflammatory and antioxidant properties. We investigated the neuroprotective effects of minocycline in rats subjected to cerebral ischemia/reperfusion injury. Thirty male rats were divided into three groups: control, sham, and minocycline-pretreated group. Minocycline (40 mg/kg) was injected intraperitoneally immediately before surgery, and then ischemia was induced by occlusion of common carotid arteries for 20 min. Seven days after reperfusion, the Morris water-maze task was used to evaluate memory. Nissl staining was also performed to analyze pyramidal cell damage. We measured the contents of malondialdehyde and proinflammatory cytokines in the hippocampus by the thiobarbituric acid method and enzyme-linked immunosorbent assay, respectively. Microglial activation was also investigated by Iba1 immunostaining. The results showed that pretreatment with minocycline prevented memory impairment induced by cerebral ischemia/reperfusion. Minocycline pretreatment also significantly attenuated ischemia-induced pyramidal cell death and microglial activation in the CA1 region and reduced the levels of malondialdehyde and proinflammatory cytokines (interleukin-1β and tumor necrosis factor-α) in the hippocampus of ischemic rats. Minocycline showed neuroprotective effects on cerebral ischemia-induced memory deficit probably through its anti-inflammatory and antioxidant activities.

The effects of sildenafil and n-acetylcysteine on ischemia and reperfusion injury in gastrocnemius muscle and femoral artery endothelium.

PubMed

Aksu, Volkan; Yüksel, Volkan; Chousein, Serchat; Taştekin, Ebru; İşcan, Şahin; Sağiroğlu, Gönül; Canbaz, Suat; Sunar, Hasan

2015-02-01

We aimed to examine the effects of sildenafil and n-acetylcystein on ischemia/reperfusion injury in femoral artery endothelium and gastrocnemius muscle. 32 rats of Sprague-Dawley breed were randomly divided into four groups (n=8). Median laparotomy was performed, then a 120-minute ischemia was created by microvascular clamping of infrarenal aorta, followed by the release of clamping. In sildenafil group, 1 mg/kg of sildenafil infusion and in the n-acetylcystein group, 100 mg/kg of n-acetylcystein infusion was administered after release of clamps. Blood samples and tissue samples of femoral artery and gastrocnemius muscle were extracted for a histopathological evaluation. Serum levels of malondialdehyde in ischemia/reperfusion group (6.16±0.79) were higher compared to the control group (4.69±0.33), whereas a significant decrease was detected in sildenafil (5.17±0.50) and n-acetylcystein (4.96±0.49) groups. Femoral artery tissue sections of the control group, mean tumor necrosis factor alpha and hypoxy-induced factor-1 alpha immunoreactivity were found to be negative. In the ischemia/reperfusion group, mean tumor necrosis factor α immunoreactivity was intense and mean hypoxy-induced factor-1 alpha immunoreactivity was 51-75%. In the ischemia/reperfusion+Sildenafil and ischemia/reperfusion+NAS groups, mean tumor necrosis factor α immunoreactivity was slight and mean hypoxy-induced factor-1 alpha immunoreactivity was 26-50%. In conclusion, sildenafil and n-acetylcystein may reduce femoral artery endothelium and gastrocnemius muscle injury following lower extremity ischemia/reperfusion. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

Upregulation of heme oxygenase-1 protected against brain damage induced by transient cerebral ischemia-reperfusion injury in rats.

PubMed

Lu, Xiufang; Gu, Renjun; Hu, Weimin; Sun, Zhitang; Wang, Gaiqing; Wang, Li; Xu, Yuming

2018-06-01

The aim of the present study was to identify the effect of heme oxygenase (HO)-1 gene on cerebral ischemia-reperfusion injury. Sprague-Dawley rats were divided randomly into four groups: Sham group, vehicle group, empty adenovirus vector (Ad) group and recombinant HO-1 adenovirus (Ad-HO-1) transfection group. Rats in the vehicle, Ad and Ad-HO-1 groups were respectively injected with saline, Ad or Ad-HO-1 for 3 days prior to cerebral ischemia-reperfusion injury. Subsequently, the middle cerebral artery occlusion method was used to establish the model of cerebral ischemia-reperfusion injury. Following the assessment of neurological function, rats were sacrificed, and the infarction volume and apoptotic index in rat brains were measured. Furthermore, the protein expression levels of HO-1 in brain tissues were detected using western blot analysis. Results indicated that the neurological score of the Ad-HO-1 group was significantly increased compared with the Ad or vehicle groups, respectively (P<0.001). The volume of cerebral infarction and the index score of neuronal apoptosis in the vehicle and Ad groups was significantly increased compared with the Ad-HO-1 group (P<0.01). The death of neuronal cells following cerebral ischemia-reperfusion injury reduced remarkably induced by over-expression of HO-1. These findings suggest a neuroprotective role of HO-1 against brain injury induced by transient cerebral ischemia-reperfusion injury.

Dragon's blood dropping pills have protective effects on focal cerebral ischemia rats model.

PubMed

Xin, Nian; Yang, Fang-Ju; Li, Yan; Li, Yu-Juan; Dai, Rong-Ji; Meng, Wei-Wei; Chen, Yan; Deng, Yu-Lin

2013-12-15

Dragon's blood is a bright red resin obtained from Dracaena cochinchinensis (Lour.) S.C.Chen (Yunnan, China). As a traditional Chinese medicinal herb, it has great traditional medicinal value and is used for wound healing and to stop bleeding. Its main biological activity comes from phenolic compounds. In this study, phenolic compounds were made into dropping pills and their protective effects were examined by establishing focal cerebral ischemia rats model used method of Middle Cerebral Artery Occlusion (MCAO), and by investigating indexes of neurological scores, infarct volume, cerebral index, cerebral water content and oxidation stress. Compared to model group, high, middle and low groups of Dragon's blood dropping pills could improve the neurological function significantly (p<0.01) and reduce cerebral infarct volume of focal cerebral ischemia rats remarkably (p<0.05-0.01). Meanwhile, each group could alleviate cerebral water content and cerebral index (p<0.05-0.01) and regulate oxidative stress of focal cerebral ischemia rats obviously (p<0.05-0.01). Activities of middle group corresponded with that treated with positive control drug. The results obtained here showed that Dragon's blood dropping pills had protective effects on focal cerebral ischemia rats. Copyright © 2013 Elsevier GmbH. All rights reserved.

Neuronal cell reconstruction with umbilical cord blood cells in the brain hypoxia-ischemia.

PubMed

Ghaffaripour, Hossein Ali; Jalali, Mehdi; Nikravesh, Mohammad Reza; Seghatoleslam, Masoumeh; Sanchooli, Javad

2015-01-01

Brain hypoxia-ischemia is a human neonatal injury that is considered a candidate for stem cell therapy. The possible therapeutic potential of human umbilical cord blood (HUCB) stem cells was evaluated in 14-day-old rats subjected to the right common carotid occlusion, a model of neonatal brain hypoxia-ischemia. Seven days after hypoxia-ischemia, rats received either saline solution or 4 × 105 HUCB cells i.v. Rats in control group did not receive any injection. After two weeks, rats were assessed using two motor tests. Subsequently, rats were scarified for histological and immunohistochemical analyses. Our immunohistochemical findings demonstrated selective migration of the injected HUCB cells to the ischemic area as well as reduction in infarct volume. Seven days after surgery, we found significant recovery in the behavioral performance in the test group (12.7 +/- 0.3) compared to the sham group (10.0 +/-0.05), a trend which continued to day 14 (15.3 ± 0.3 vs. 11.9 ± 0.5, P<0.05). Postural and motor asymmetries at days 7 and 14 in the test group showed a significant decrease in the percentage of right turns in comparison to the sham group (75% and 59% vs. 97% and 96%, P<0.05). The results show the potential of HUCB stem cells in reduction of neurologic deficits associated with neonatal hypoxia-ischemia.

Silent ischemia: silent after all?

PubMed

D'Antono, Bianca; Dupuis, Gilles; Arsenault, André; Burelle, Denis

2008-04-01

To examine the association of nonpain symptoms in men and women with exercise-related silent ischemia, as well as the independence of these findings from other clinical factors. A prospective study of 482 women and 425 men (mean age 58 years) undergoing exercise stress testing with myocardial perfusion imaging. Analyses were performed on 60 women and 155 men with no angina but medical perfusion imaging evidence of ischemia during exercise. The presence of various non-pain-related symptoms. Ischemia is indicated by myocardial perfusion defects on exercise stress testing with single photon emission computed tomography. Women reported more nonangina symptoms than men (P<0.05). They experienced fatigue, hot flushes, tense muscles, shortness of breath and headaches more frequently (P<0.05). Symptoms relating to muscle tension and diaphoresis were associated with ischemia after controlling for pertinent clinical covariates. However, the direction of association differed according to sex and history of coronary artery disease events or procedures. Sensitivity of the detection models showed modest improvements with the addition of these symptoms. While patients who experience silent ischemia experience a number of nonpain symptoms, those symptoms may not be sufficiently specific to ischemia, nor sensitive in detecting ischemia, to be of particular help to physicians in the absence of other clinical information.

Collateral circulation of the rat lower limb and its significance in ischemia-reperfusion studies.

PubMed

Rosero, Olivér; Németh, Károly; Turóczi, Zsolt; Fülöp, András; Garbaisz, Dávid; Győrffy, András; Szuák, András; Dorogi, Bence; Kiss, Mátyás; Nemeskéri, Ágnes; Harsányi, László; Szijártó, Attila

2014-12-01

Rats are the most commonly used animal model for studies of acute lower limb ischemia-reperfusion. The ischemia induced by arterial clamping may cause milder damage than the application of a tourniquet if the presence of a possible collateral system is considered. Male Wistar rats were randomized into three groups: in group A, the muscle weight affected by ischemia was measured; in group B, the severity of muscle damage caused by the application of a tourniquet and by infrarenal aortic occlusion was examined. Blood and muscle samples were taken from group B to assess the serum necroenzyme, potassium and TNF-α levels, as well as the muscle fiber viability and for histological examinations. In group C, the identification of the lower limb collateral system was performed using corrosion casting. Tourniquet application affected the lower muscle mass and resulted in significantly more severe injury compared to infrarenal aortic occlusion. This difference was reflected in the serum necroenzyme, potassium and TNF-α levels. The histological examination and viability assay confirmed these findings. The corrosion casts showed several anastomoses capable of supplying the lower limb. Tourniquet application proved to be capable of inducing absolute lower limb ischemia, in contrast to infrarenal aortic ligation, where a rich collateral system is considered to help mitigate the injury.

[Anti-apoptosis and expression of microRNA-21 in rat myocardium during early ischemia-reperfusion injury].

PubMed

Yang, Qiong; Yang, Kan; Li, Anying; Tan, Wenpeng

2013-05-01

To observe the expression and anti-apoptosis of microRNA-21(miR-21) in rat myocardium during early ischemia-reperfusion injury (I/R). Sprague-Dawley rats were randomly divided into 5 groups: a control group (transfected with rAAV9-ZsGreen by coronary injection), a miR-21group (transfected rAAV9-ZsGreen-premiR- 21 by coronary injection), a sham group (open-chest only), an I/R group (I/R), and an I/ R+miR-21 (I/R after transfected rAAV9-ZsGreen-pre-miR-21 by coronary injection). Realtime PCR was used to assess the expression level of miR-21. Immunohistochemistry and Western blot were used to determine the expression of Bcl-2, Bax, caspase-3 and Bcl-2/Bax. MiR-21 was increased by 4.43 times in the miR-21 group (P<0.001). MiR-21 was downregulated in the ischemia zone after I/R compared with the sham group (P<0.05), but that in the non-ischemia zone was significantly increased compared with the sham group (P<0.01). MiR- 21 expression was decreased in the I/R group compared with that in the sham group at 1 h, 2 h and 6 h after I/R (P<0.05), and it was up-regulated in the I/R+miR-21 group at the same time point compared with the I/R group (P<0.01). The expression of Bcl-2, Bax, and caspase-3 was upregulated and Bcl-2/Bax was decreased in the ischemia zone in the I/R group and I/R+miR-21 group than the sham group(P<0.05). Compared with the I/R group, the expression of Bcl-2 and caspase-3 was down-regulated and Bcl-2/Bax was increased in the ischemia zone in the I/ R+miR-21 group (P<0.05). MiR-21 expression is down-regulated and cell apoptosis is increased in rat myocardium during early ischemia-reperfusion injury. Myocardial cell apoptosis may be alleviated by miR-21 over-expression.

Protection of Hippocampal CA1 Neurons Against Ischemia/Reperfusion Injury by Exercise Preconditioning via Modulation of Bax/Bcl-2 Ratio and Prevention of Caspase-3 Activation.

PubMed

Aboutaleb, Nahid; Shamsaei, Nabi; Rajabi, Hamid; Khaksari, Mehdi; Erfani, Sohaila; Nikbakht, Farnaz; Motamedi, Pezhman; Shahbazi, Ali

2016-01-01

Ischemia leads to loss of neurons by apoptosis in specific brain regions, especially in the hippocampus. The purpose of this study was investigating the effects of exercise preconditioning on expression of Bax, Bcl-2, and caspase-3 proteins in hippocampal CA1 neurons after induction of cerebral ischemia. Male rats weighing 260-300 g were randomly allocated into three groups (sham, exercise, and ischemia). The rats in exercise group were trained to run on a treadmill 5 days a week for 4 weeks. Ischemia was induced by the occlusion of both common carotid arteries (CCAs) for 20 min. Levels of expression of Bax, Bcl-2, and caspase-3 proteins in CA1 area of hippocampus were determined by immunohistochemical staining . The number of active caspase-3-positive neurons in CA1 area were significantly increased in ischemia group, compared to sham-operated group (P<0.001), and exercise preconditioning significantly reduced the ischemia/reperfusion-induced caspase-3 activation, compared to the ischemia group (P<0.05). Also, results indicated a significant increase in Bax/Bcl-2 ratio in ischemia group, compared to sham-operated group (P<0.001). This study indicated that exercise has a neuroprotective effects against cerebral ischemia when used as preconditioning stimuli.

Poloxamer 188 protects against ischemia-reperfusion injury in a murine hind-limb model.

PubMed

Murphy, Adrian D; McCormack, Michael C; Bichara, David A; Nguyen, John T; Randolph, Mark A; Watkins, Michael T; Lee, Raphael C; Austen, William G

2010-06-01

Ischemia-reperfusion injury can activate pathways generating reactive oxygen species, which can injure cells by creating holes in the cell membranes. Copolymer surfactants such as poloxamer 188 are capable of sealing defects in cell membranes. The authors postulated that a single-dose administration of poloxamer 188 would decrease skeletal myocyte injury and mortality following ischemia-reperfusion injury. Mice underwent normothermic hind-limb ischemia for 2 hours. Animals were treated with 150 microl of poloxamer 188 or dextran at three time points: (1) 10 minutes before ischemia; (2) 10 minutes before reperfusion; and (3) 2 or 4 hours after reperfusion. After 24 hours of reperfusion, tissues were analyzed for myocyte injury (histology) and metabolic dysfunction (muscle adenosine 5'-triphosphate). Additional groups of mice were followed for 7 days to assess mortality. When poloxamer 188 treatment was administered 10 minutes before ischemia, injury was reduced by 84 percent, from 50 percent injury in the dextran group to 8 percent injury in the poloxamer 188 group (p < 0.001). When administered 10 minutes before reperfusion, poloxamer 188 animals demonstrated a 60 percent reduction in injury compared with dextran controls (12 percent versus 29 percent). Treatment at 2 hours, but not at 4 hours, postinjury prevented substantial myocyte injury. Preservation of muscle adenosine 5'-triphosphate paralleled the decrease in myocyte injury in poloxamer 188-treated animals. Poloxamer 188 treatment significantly reduced mortality following injury (10 minutes before, 75 percent versus 25 percent survival, p = 0.0077; 2 hours after, 50 percent versus 8 percent survival, p = 0.032). Poloxamer 188 administered to animals decreased myocyte injury, preserved tissue adenosine 5'-triphosphate levels, and improved survival following hind-limb ischemia-reperfusion injury.

Prophylactic Treatment with Cerium Oxide Nanoparticles Attenuate Hepatic Ischemia Reperfusion Injury in Sprague Dawley Rats.

PubMed

Manne, Nandini D P K; Arvapalli, Ravikumar; Graffeo, Vincent A; Bandarupalli, Venkata V K; Shokuhfar, Tolou; Patel, Sweetu; Rice, Kevin M; Ginjupalli, Gautam Kumar; Blough, Eric R

2017-01-01

Hepatic ischemia reperfusion is one the main causes for graft failure following transplantation. Although, the molecular events that lead to hepatic failure following ischemia reperfusion (IR) are diverse and complex, previous studies have shown that excessive formation of reactive oxygen species (ROS) are responsible for hepatic IR injury. Cerium oxide (CeO2) nanoparticles have been previously shown to act as an anti-oxidant and anti-inflammatory agent. Here, we evaluated the protective effects of CeO2 nanoparticles on hepatic ischemia reperfusion injury. Male Sprague Dawley rats were randomly assigned to one of the four groups: Control, CeO2 nanoparticle only, hepatic ischemia reperfusion (IR) group and hepatic ischemia reperfusion (IR) plus CeO2 nanoparticle group (IR+ CeO2). Partial warm hepatic ischemia was induced in left lateral and median lobes for 1h, followed by 6h of reperfusion. Animals were sacrificed after 6h of reperfusion and blood and tissue samples were collected and processed for various biochemical experiments. Prophylactic treatment with CeO2 nanoparticles (0.5mg/kg i.v (IR+CeO2 group)) 1 hour prior to hepatic ischemia and subsequent reperfusion injury lead to a decrease in serum levels of alanine aminotransaminase and lactate dehydrogenase at 6 hours after reperfusion. These changes were accompanied by significant decrease in hepatocyte necrosis along with reduction in several serum inflammatory markers such as macrophage derived chemokine, macrophage inflammatory protein-2, KC/GRO, myoglobin and plasminogen activator inhibitor-1. However, immunoblotting demonstrated no significant changes in the levels of apoptosis related protein markers such as bax, bcl2 and caspase 3 in IR and IR+ CeO2 groups at 6 hours suggesting necrosis as the main pathway for hepatocyte death. Taken together, these data suggest that CeO2 nanoparticles attenuate IR induced cell death and can be used as a prophylactic agent to prevent hepatic injury associated with graft

Neutralizing anti-interleukin-1β antibodies modulate fetal blood-brain barrier function after ischemia.

PubMed

Chen, Xiaodi; Sadowska, Grazyna B; Zhang, Jiyong; Kim, Jeong-Eun; Cummings, Erin E; Bodge, Courtney A; Lim, Yow-Pin; Makeyev, Oleksandr; Besio, Walter G; Gaitanis, John; Threlkeld, Steven W; Banks, William A; Stonestreet, Barbara S

2015-01-01

We have previously shown that increases in blood-brain barrier permeability represent an important component of ischemia-reperfusion related brain injury in the fetus. Pro-inflammatory cytokines could contribute to these abnormalities in blood-brain barrier function. We have generated pharmacological quantities of mouse anti-ovine interleukin-1β monoclonal antibody and shown that this antibody has very high sensitivity and specificity for interleukin-1β protein. This antibody also neutralizes the effects of interleukin-1β protein in vitro. In the current study, we hypothesized that the neutralizing anti-interleukin-1β monoclonal antibody attenuates ischemia-reperfusion related fetal blood-brain barrier dysfunction. Instrumented ovine fetuses at 127 days of gestation were studied after 30 min of carotid occlusion and 24h of reperfusion. Groups were sham operated placebo-control- (n=5), ischemia-placebo- (n=6), ischemia-anti-IL-1β antibody- (n=7), and sham-control antibody- (n=2) treated animals. Systemic infusions of placebo (0.154M NaCl) or anti-interleukin-1β monoclonal antibody (5.1±0.6 mg/kg) were given intravenously to the same sham or ischemic group of fetuses at 15 min and 4h after ischemia. Concentrations of interleukin-1β protein and anti-interleukin-1β monoclonal antibody were measured by ELISA in fetal plasma, cerebrospinal fluid, and parietal cerebral cortex. Blood-brain barrier permeability was quantified using the blood-to-brain transfer constant (Ki) with α-aminoisobutyric acid in multiple brain regions. Interleukin-1β protein was also measured in parietal cerebral cortices and tight junction proteins in multiple brain regions by Western immunoblot. Cerebral cortical interleukin-1β protein increased (P<0.001) after ischemia-reperfusion. After anti-interleukin-1β monoclonal antibody infusions, plasma anti-interleukin-1β monoclonal antibody was elevated (P<0.001), brain anti-interleukin-1β monoclonal antibody levels were higher (P<0

Treatment with docosahexaenoic acid after hypoxia–ischemia improves forepaw placing in a rat model of perinatal hypoxia-ischemia

PubMed Central

Berman, Deborah R; Liu, YiQing; Barks, John; Mozurkewich, Ellen

2010-01-01

Objective Docosahexaenoic acid (DHA) is a dietary fatty acid with neuroprotective properties. We hypothesized that DHA treatment after hypoxia-ischemia (HI) would improve function and reduce brain volume loss in a perinatal rat model. Study design Seven-day-old Wistar rat pups from 7 litters (N=84) underwent right carotid ligation, followed by 8% O2 for 90 minutes. Fifteen minutes after HI, pups were divided into 3 treatment groups (intraperitoneal injections of DHA 1, 2.5 or 5 mg/kg) and 2 control groups (25% albumin or saline). At 14 days, rats underwent vibrissae-stimulated forepaw placing testing, and bilateral regional volumes were calculated for cortex, striatum, hippocampus, and hemisphere. Results Post HI treatment with DHA significantly improved vibrissae forepaw placing (complete responses: 8.5±2 treatment vs. 7.4±2 controls; normal=10; p = 0.032, t-test). Post injury DHA treatment did not attenuate brain volume loss in any region. Conclusion Post-hypoxia-ischemia DHA treatment significantly improves functional outcome. PMID:20691409

Use of the Wound, Ischemia, foot Infection classification system in hemodialysis patients after endovascular treatment for critical limb ischemia.

PubMed

Tokuda, Takahiro; Hirano, Keisuke; Sakamoto, Yasunari; Mori, Shisuke; Kobayashi, Norihiro; Araki, Motoharu; Yamawaki, Masahiro; Ito, Yoshiaki

2017-12-07

The Wound, Ischemia, foot Infection (WIfI) classification system is used to predict the amputation risk in patients with critical limb ischemia (CLI). The validity of the WIfI classification system for hemodialysis (HD) patients with CLI is still unknown. This single-center study evaluated the prognostic value of WIfI stages in HD patients with CLI who had been treated with endovascular therapy (EVT). A retrospective analysis was performed of collected data on CLI patients treated with EVT between April 2007 and December 2015. All patients were classified according to their wound status, ischemia index, and extent of foot infection into the following four groups: very low risk, low risk, moderate risk, and high risk. Comorbidities and vascular lesions in each group were analyzed. The prognostic value of the WIfI classification was analyzed on the basis of the wound healing rate and amputation-free survival at 1 year. This study included 163 consecutive CLI patients who underwent HD and successful endovascular intervention. The rate of the high-risk group (36%) was the highest among the four groups, and the proportions of very-low-risk, low-risk, and moderate-risk patients were 10%, 18%, and 34%, respectively. The mean follow-up duration was 784 ± 650 days. The wound healing rates at 1 year were 92%, 70%, 75%, and 42% in the very-low-risk, low-risk, moderate-risk, and high-risk groups, respectively (P <.01). A similar trend was observed for the 1-year amputation-free survival among the groups (76%, 58%, 61%, and 46%, respectively; P = .02). The WIfI classification system predicted the wound healing and amputation risks in a highly selected group of HD patients with CLI treated with EVT, with a statistically significant difference between high-risk patients and other patients. Copyright © 2017 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.

Effects of Platelet-Rich Plasma (PRP) on a Model of Renal Ischemia-Reperfusion in Rats.

PubMed

Martín-Solé, Oriol; Rodó, Joan; García-Aparicio, Lluís; Blanch, Josep; Cusí, Victoria; Albert, Asteria

2016-01-01

Renal ischemia-reperfusion injury is a major cause of acute renal failure, causing renal cell death, a permanent decrease of renal blood flow, organ dysfunction and chronic kidney disease. Platelet-rich plasma (PRP) is an autologous product rich in growth factors, and therefore able to promote tissue regeneration and angiogenesis. This product has proven its efficacy in multiple studies, but has not yet been tested on kidney tissue. The aim of this work is to evaluate whether the application of PRP to rat kidneys undergoing ischemia-reperfusion reduces mid-term kidney damage. A total of 30 monorrenal Sprague-Dawley male rats underwent renal ischemia-reperfusion for 45 minutes. During ischemia, PRP (PRP Group, n = 15) or saline solution (SALINE Group, n = 15) was administered by subcapsular renal injection. Control kidneys were the contralateral organs removed immediately before the start of ischemia in the remaining kidneys. Survival, body weight, renal blood flow on Doppler ultrasound, kidney weight, kidney volume, blood biochemistry and histopathology were determined for all subjects and kidneys, as applicable. Correlations between these variables were searched for. The PRP Group showed significantly worse kidney blood flow (p = 0.045) and more histopathological damage (p<0.0001). Correlations were found between body weight, kidney volume, kidney weight, renal blood flow, histology, and serum levels of creatinine and urea. Our study provides the first evidence that treatment with PRP results in the deterioration of the kidney's response to ischemia-reperfusion injury.

Effects of Platelet-Rich Plasma (PRP) on a Model of Renal Ischemia-Reperfusion in Rats

PubMed Central

Martín-Solé, Oriol; Rodó, Joan; García-Aparicio, Lluís; Blanch, Josep; Cusí, Victoria; Albert, Asteria

2016-01-01

Renal ischemia-reperfusion injury is a major cause of acute renal failure, causing renal cell death, a permanent decrease of renal blood flow, organ dysfunction and chronic kidney disease. Platelet-rich plasma (PRP) is an autologous product rich in growth factors, and therefore able to promote tissue regeneration and angiogenesis. This product has proven its efficacy in multiple studies, but has not yet been tested on kidney tissue. The aim of this work is to evaluate whether the application of PRP to rat kidneys undergoing ischemia-reperfusion reduces mid-term kidney damage. A total of 30 monorrenal Sprague-Dawley male rats underwent renal ischemia-reperfusion for 45 minutes. During ischemia, PRP (PRP Group, n = 15) or saline solution (SALINE Group, n = 15) was administered by subcapsular renal injection. Control kidneys were the contralateral organs removed immediately before the start of ischemia in the remaining kidneys. Survival, body weight, renal blood flow on Doppler ultrasound, kidney weight, kidney volume, blood biochemistry and histopathology were determined for all subjects and kidneys, as applicable. Correlations between these variables were searched for. The PRP Group showed significantly worse kidney blood flow (p = 0.045) and more histopathological damage (p<0.0001). Correlations were found between body weight, kidney volume, kidney weight, renal blood flow, histology, and serum levels of creatinine and urea. Our study provides the first evidence that treatment with PRP results in the deterioration of the kidney’s response to ischemia-reperfusion injury. PMID:27551718

Usefulness of automatic QT dispersion measurement for detecting exercise-induced myocardial ischemia.

PubMed

Takase, Bonpei; Masaki, Nobuyuki; Hattori, Hidemi; Ishihara, Masayuki; Kurita, Akira

2009-06-01

The electrocardiographic index of QT dispersion (QTd) is related to the occurrence of arrhythmia. In patients with suspected or known coronary artery disease, QTd may be affected by exercise. We investigated whether QTd that is automatically calculated by a newly developed computer system could be used as a marker of exercise-induced myocardial ischemia. The design of this study was prospective and observational. Eighty-three consecutive patients were enrolled in this study. Their QTd was measured at rest and after 3 min of exercise during exercise-stress Thallium-201 scintigraphy and compared with conventional ST-segment changes. The patients were classified into 4 groups (normal group, redistribution group, fixed defect group, redistribution with fixed defect group) based on the result of single photon emission computed tomography. As statistical analysis, one-way ANOVA with post-hoc Scheffe's method, receiver-operating characteristics (ROC) and multiple logistic regression analysis were performed. At rest, QTd was significantly greater (p<0.05) in the fixed defect group (52+/-21 ms) and the redistribution with fixed defect group (53+/-20 ms) than in the normal group (32+/-14 ms) and the redistribution group (31+/-16 ms). However, QTd tended to increase after exercise in the redistribution group, while QTd tended to decrease in the normal group, the fixed defect group, and the redistribution with fixed defect group (QTd after exercise, normal group, 28+/-17 ms, redistribution group, 35+/-19 ms, fixed defect group, 43+/-25 ms, redistribution with fixed defect group, 49+/-27 ms). Exercise significantly increased QTcd (RR interval-corrected QT dispersion) in the redistribution group. The best cut-off values of QTd and QTcd obtained from ROC curves for exercise-induced myocardial ischemia were 41.6 ms and 40.4 ms, respectively (Qtd--AUC 0.68, 95%CI 0.53- 0.83 and QTcd--AUC 0.67, 95%CI 0.55-0.80). Using these values as cut-off ones, QTd, QTcd, and conventional ST

Prevention of ischemia-induced myocardial platelet deposition by exogenous prostacyclin

DOE Office of Scientific and Technical Information (OSTI.GOV)

Aherne, T.; Price, D.C.; Yee, E.S.

1986-07-01

The antithrombotic effects of prostacyclin infusion on myocardial platelet deposition were studied in a canine model during and after global ischemia. Eleven isolated heart preparations were subjected to 1 hour of cardioplegic arrest under moderate hypothermia (27 to 28/sup 0/C), including a control group (n = 7) and a prostacyclin-treated group (n = 4). The hearts of four other dogs were continuously perfused for 180 minutes. Platelet deposition was measured at 15 minute intervals throughout the 3 hour study. Serial full-thickness myocardial biopsy specimens were analyzed for activity of /sup 111/In-labeled platelets with /sup 99m/Tc-labeled erythrocyte correction for tissue bloodmore » content. The pattern of platelet distribution was determined by scintiscans of each heart, taken with a gamma camera at the end of the 60 minute reperfusion period. Substantial myocardial platelet deposition was found in the control hearts after ischemia but not in the prostacyclin-treated group (p less than 0.05). Furthermore, prostacyclin infusion had a significant disaggregatory effect on intracoronary platelet deposits when the precardioplegic and postcardioplegic biopsy specimens were analyzed (p less than 0.05). Three hours of continuous perfusion did not increase tissue /sup 111/In-labeled platelet activity. Ex vivo images showed platelet deposition to be a diffuse patchy process with significantly more /sup 111/In activity in the endocardium than in the epicardium after global ischemia (p less than 0.05). These data show the potent antithrombotic properties of prostacyclin in preventing and disaggregating ischemia-induced intracoronary platelet deposition during and after cardioplegic arrest.« less

Nampt/PBEF/visfatin exerts neuroprotective effects against ischemia/reperfusion injury via modulation of Bax/Bcl-2 ratio and prevention of caspase-3 activation.

PubMed

Erfani, Sohaila; Khaksari, Mehdi; Oryan, Shahrbanoo; Shamsaei, Nabi; Aboutaleb, Nahid; Nikbakht, Farnaz

2015-05-01

Nicotinamide phosphoribosyl transferase/pre-B cell colony-enhancing factor/visfatin (Nampt/PBEF/visfatin) is an adipocytokine. By synthesizing nicotinamide adenine dinucleotide (NAD(+)), Nampt/PBEF/visfatin functions to maintain an energy supply that has critical roles in cell survival. Cerebral ischemia leads to energy depletion and eventually neuronal death by apoptosis in specific brain regions specially the hippocampus. However, the role of Nampt/PBEF/visfatin in brain and cerebral ischemia remains to be investigated. This study investigated the role of administration Nampt/PBEF/visfatin in hippocampal CA3 area using a transient global cerebral ischemia model. Both common carotid arteries were occluded for 20 min followed by reperfusion. Saline as a vehicle and Nampt/PBEF/visfatin at a dose of 100 ng were injected intracerebroventricularly (ICV) at the time of cerebral reperfusion. To investigate the underlying mechanisms of Nampt/PBEF/visfatin neuroprotection, levels of expression of apoptosis-related proteins (caspase-3 activation, Bax protein levels, and Bcl-2 protein levels) 96 h after ischemia were determined by immunohistochemical staining. The number of active caspase-3-positive neurons in CA3 was significantly increased in the ischemia group, compared with the sham group (P < 0.001), and treatment with Nampt/PBEF/visfatin significantly reduced the ischemia/reperfusion-induced caspase-3 activation, compared to the ischemia group (P < 0.05). Also, results indicated a significant increase in Bax/Bcl-2 ratio in the ischemia group, compared with the sham group (P < 0.01). However, treatment with Nampt/PBEF/visfatin significantly attenuated the ischemia/reperfusion-induced increase in Bax/Bcl-2 ratio, compared with the ischemia group (P < 0.05). This study has indicated that Nampt/PBEF/visfatin entails neuroprotective effects against ischemia injury when used at the time of cerebral reperfusion. These neuroprotective mechanisms of Nampt

Intraperitoneal Administration of Silymarin Protects End Organs from Multivisceral Ischemia/Reperfusion Injury in a Rat Model.

PubMed

Koçarslan, Aydemir; Koçarslan, Sezen; Aydin, Mehmet Salih; Gunay, Şamil; Karahan, Mahmut Alp; Taşkın, Abdullah; Üstunel, Murat; Aksoy, Nurten

2016-01-01

To determine whether intraperitoneal silymarin administration has favorable effects on the heart, lungs, kidney, and liver and on oxidative stress in a rat model of supraceliac aorta ischemia/reperfusion injury. Thirty male Wistar albino rats were divided equally into three groups: sham, control, and silymarin. The control and silymarin groups underwent supraceliac aortic occlusion for 45 min, followed by a 60 min period of reperfusion under terminal anesthesia. In the silymarin group, silymarin was administered intraperitoneally during ischemia at a dose of 200 mg/kg. Rats were euthanized using terminal anesthesia, and blood was collected from the inferior vena cava for total antioxidant capacity, total oxidative status, and oxidative stress index measurement. Lungs, heart, liver and kidney tissues were histologically examined. Ischemia/reperfusion injury significantly increased histopathological damage as well as the total oxidative status and oxidative stress index levels in the blood samples. The silymarin group incurred significantly lesser damage to the lungs, liver and kidneys than the control group, while no differences were observed in the myocardium. Furthermore, the silymarin group had significantly lower total oxidative status and oxidative stress index levels than the control group. Intraperitoneal administration of silymarin reduces oxidative stress and protects the liver, kidney, and lungs from acute supraceliac abdominal aorta ischemia/reperfusion injury in the rat model.

Inhibition of Angiotensin-II Production Increases Susceptibility to Acute Ischemia/Reperfusion Arrhythmia

PubMed Central

Taskin, Eylem; Tuncer, Kadir Ali; Guven, Celal; Kaya, Salih Tunc; Dursun, Nurcan

2016-01-01

Background Myocardial ischemia and reperfusion lead to impairment of electrolyte balance and, eventually, lethal arrhythmias. The aim of this study was to investigate the effects of pharmacological inhibition of angiotensin-II (Ang-II) production on heart tissue with ischemia-reperfusion damage, arrhythmia, and oxidative stress. Material/Methods Rats were divided into 4 groups: only ischemia/reperfusion (MI/R), captopril (CAP), aliskiren (AL), and CAP+AL. The drugs were given by gavage 30 min before anesthesia. Blood pressure and electrocardiography (ECG) were recorded during MI/R procedures. The heart tissue and plasma was kept so as to evaluate the total oxidant (TOS), antioxidant status (TAS), and creatine kinase-MB (CK-MB). Results Creatine kinase-MB was not different among the groups. Although TAS was not affected by inhibition of Ang-II production, TOS was significantly lower in the CAP and/or AL groups than in the MI/R group. Furthermore, oxidative stress index was significantly attenuated in the CAP and/or AL groups. Captopril significantly increased the duration of VT during ischemia; however, it did not have any effect on the incidence of arrhythmias. During reperfusion periods, aliskiren and its combinations with captopril significantly reduced the incidence of other types of arrhythmias. Captopril alone had no effect on the incidence of arrhythmias, but significantly increased arrhythmias score and durations of arrhythmias during reperfusion. MAP and heart rate did not show changes in any groups during ischemic and reperfusion periods. Conclusions Angiotensin-II production appears to be associated with elevated levels of reactive oxygen species, but Ang-II inhibitions increases arrhythmia, mainly by initiating ventricular ectopic beats. PMID:27889788

Dietary glutamine supplementation enhances endothelial progenitor cell mobilization in streptozotocin-induced diabetic mice subjected to limb ischemia.

PubMed

Su, Shiau-Tsz; Yeh, Chiu-Li; Hou, Yu-Chen; Pai, Man-Hui; Yeh, Sung-Ling

2017-02-01

Diabetes is a metabolic disorder with increased risk of vascular diseases. Tissue ischemia may occur with diabetic vascular complications. Bone marrow-derived endothelial progenitor cells (EPCs) constitute a reparative response to ischemic injury. This study investigated the effects of oral glutamine (GLN) supplementation on circulating EPC mobilization and expression of tissue EPC-releasing markers in diabetic mice subjected to limb ischemia. Diabetes was induced by a daily intraperitoneal injection of streptozotocin for 5 days. Diabetic mice were divided into 2 nonischemic groups and 6 ischemic groups. One of the nonischemic and 3 ischemic groups were fed the control diet, while the remaining 4 groups received diets with identical components except that part of the casein was replaced by GLN. The respective diets were fed to the mice for 3 weeks, and then the nonischemic mice were sacrificed. Unilateral hindlimb ischemia was created in the ischemic groups, and mice were sacrificed at 1, 7 or 21 days after ischemia. Their blood and ischemic muscle tissues were collected for further analyses. Results showed that plasma matrix metallopeptidase (MMP)-9 and the circulating EPC percentage increased after limb ischemia in a diabetic condition. Compared to groups without GLN, GLN supplementation up-regulated plasma stromal cell-derived factor (SDF)-1 and muscle MMP-9, SDF-1, hypoxia-inducible factor-1 and vascular endothelial growth factor gene expression. The CD31-immunoreactive intensities were also higher in the ischemic limb. These findings suggest that GLN supplementation enhanced circulating EPC mobilization that may promote endothelium repair at ischemic tissue in diabetic mice subjected to limb ischemia. Copyright © 2016 Elsevier Inc. All rights reserved.

Blockade of Central Angiotensin II AT1 Receptor Protects the Brain from Ischemia/Reperfusion Injury in Normotensive Rats.

PubMed

Panahpour, Hamdolah; Nekooeian, Ali Akbar; Dehghani, Gholam Abbas

2014-11-01

Stroke is the third leading cause of invalidism and death in industrialized countries. There are conflicting reports about the effects of Angiotensin II on ischemia-reperfusion brain injuries and most data have come from chronic hypertensive rats. In this study, hypotensive and non-hypotensive doses of candesartan were used to investigate the effects of angiotensin II AT1 receptor blockade by transient focal cerebral ischemia in normotensive rats. In this experimental study, 48 male Sprague-Dawley rats were randomly divided into four groups (n=12). Sham group, the control ischemic group, and two ischemic groups received candesartan at doses of 0.1 or 0.5 mg/kg at one hour before ischemia. Transient focal cerebral ischemia was induced by 60 minutes occlusion of the middle cerebral artery, followed by 24 h reperfusion. The neurological deficit score was evaluated at the end of the reperfusion period. The total cortical and striatal infarct volumes were determined using triphenyltetrazolium chloride staining technique. Tissue swelling was calculated for the investigation of ischemic brain edema formation. In comparison with the control ischemic group, AT1 receptor blockade with both doses of candesartan (0.1 or 0.5 mg/kg) significantly improved neurological deficit and lowered cortical and striatal infarct sizes. In addition, pretreatment with candesartan significantly reduced ischemia induced tissue swelling. Angiotensin II by stimulating AT1 receptors, participates in ischemia-reperfusion injuries and edema formation. AT1 receptor blockade with candesartan decreased ischemic brain injury and edema and improved neurological outcome.

Folic acid deficiency increases delayed neuronal death, DNA damage, platelet endothelial cell adhesion molecule-1 immunoreactivity, and gliosis in the hippocampus after transient cerebral ischemia.

PubMed

Hwang, In Koo; Yoo, Ki-Yeon; Suh, Hong-Won; Kim, Young Sup; Kwon, Dae Young; Kwon, Young-Guen; Yoo, Jun-Hyun; Won, Moo-Ho

2008-07-01

Folic acid deficiency increases stroke risk. In the present study, we examined whether folic acid deficiency enhances neuronal damage and gliosis via oxidative stress in the gerbil hippocampus after transient forebrain ischemia. Animals were exposed to a folic acid-deficient diet (FAD) for 3 months and then subjected to occlusion of both common carotid arteries for 5 min. Exposure to an FAD increased plasma homocysteine levels by five- to eightfold compared with those of animals fed with a control diet (CD). In CD-treated animals, most neurons were dead in the hippocampal CA1 region 4 days after ischemia/reperfusion, whereas, in FAD-treated animals, this occurred 3 days after ischemia/reperfusion. Immunostaining for 8-hydroxy-2'-deoxyguanosine (8-OHdG) was performed to examine DNA damage in CA1 neurons in both groups after ischemia, and it was found that 8-OHdG immunoreactivity in both FAD and CD groups peaked at 12 hr after reperfusion, although the immunoreactivity in the FAD group was much greater than that in the CD group. Platelet endothelial cell adhesion molecule-1 (PECAM-1; a final mediator of neutrophil transendothelial migration) immunoreactivity in both groups increased with time after ischemia/reperfusion: Its immunoreactivity in the FAD group was much higher than that in the CD group 3 days after ischemia/reperfusion. In addition, reactive gliosis in the ischemic CA1 region increased with time after ischemia in both groups, but astrocytosis and microgliosis in the FAD group were more severe than in the CD group at all times after ischemia. Our results suggest that folic acid deficiency enhances neuronal damage induced by ischemia. 2008 Wiley-Liss, Inc.

The Effect of Botulinum Toxin A on Ischemia-Reperfusion Injury in a Rat Model

PubMed Central

2017-01-01

Introduction While studies using various materials to overcome ischemia-reperfusion (IR) injury are becoming increasingly common, studies on the effects of botulinum toxin A (BoTA) on IR injury in musculocutaneous flaps are still limited. The purpose of this study was to examine our hypotheses that BoTA provide protection of musculocutaneous flap from ischemia-reperfusion injury. Method Five days after pretreatment injection (BoTA versus normal saline), a right superior musculocutaneous flap (6 × 1.5 cm in size) was made. Ischemia was created by a tourniquet strictly wrapping the pedicle containing skin and muscle for 8 h. After ischemia, the tourniquet was cut, and the musculocutaneous flap was reperfused. Results The overall survival percentage of flap after 8 h of pedicle clamping followed by reperfusion was 87.32 ± 3.67% in the control group versus 95.64 ± 3.25% in the BoTA group (p < 0.001). The BoTA group had higher expression of CD34, HIF-1α, VEGF, and NF-kB comparing to control group in qRT-PCR analysis. Conclusions In this study, we found that local BoTA preconditioning yielded significant protection against IR injury in a rat musculocutaneous flap model. PMID:28589130

Effect of Ischemia Duration and Protective Interventions on the Temporal Dynamics of Tissue Composition After Myocardial Infarction

PubMed Central

Fernández-Jiménez, Rodrigo; Galán-Arriola, Carlos; Sánchez-González, Javier; Agüero, Jaume; López-Martín, Gonzalo J.; Gomez-Talavera, Sandra; Garcia-Prieto, Jaime; Benn, Austin; Molina-Iracheta, Antonio; Barreiro-Pérez, Manuel; Martin-García, Ana; García-Lunar, Inés; Pizarro, Gonzalo; Sanz, Javier; Sánchez, Pedro L.; Fuster, Valentin

2017-01-01

Rationale: The impact of cardioprotective strategies and ischemia duration on postischemia/reperfusion (I/R) myocardial tissue composition (edema, myocardium at risk, infarct size, salvage, intramyocardial hemorrhage, and microvascular obstruction) is not well understood. Objective: To study the effect of ischemia duration and protective interventions on the temporal dynamics of myocardial tissue composition in a translational animal model of I/R by the use of state-of-the-art imaging technology. Methods and Results: Four 5-pig groups underwent different I/R protocols: 40-minute I/R (prolonged ischemia, controls), 20-minute I/R (short-duration ischemia), prolonged ischemia preceded by preconditioning, or prolonged ischemia followed by postconditioning. Serial cardiac magnetic resonance (CMR)-based tissue characterization was done in all pigs at baseline and at 120 minutes, day 1, day 4, and day 7 after I/R. Reference myocardium at risk was assessed by multidetector computed tomography during the index coronary occlusion. After the final CMR, hearts were excised and processed for water content quantification and histology. Five additional healthy pigs were euthanized after baseline CMR as reference. Edema formation followed a bimodal pattern in all 40-minute I/R pigs, regardless of cardioprotective strategy and the degree of intramyocardial hemorrhage or microvascular obstruction. The hyperacute edematous wave was ameliorated only in pigs showing cardioprotection (ie, those undergoing short-duration ischemia or preconditioning). In all groups, CMR-measured edema was barely detectable at 24 hours postreperfusion. The deferred healing-related edematous wave was blunted or absent in pigs undergoing preconditioning or short-duration ischemia, respectively. CMR-measured infarct size declined progressively after reperfusion in all groups. CMR-measured myocardial salvage, and the extent of intramyocardial hemorrhage and microvascular obstruction varied dramatically

Ischemic Preconditioning Produces Comparable Protection Against Hepatic Ischemia/Reperfusion Injury Under Isoflurane and Sevoflurane Anesthesia in Rats.

PubMed

Jeong, J S; Kim, D; Kim, K Y; Ryu, S; Han, S; Shin, B S; Kim, G S; Gwak, M S; Ko, J S

2017-11-01

Various volatile anesthetics and ischemic preconditioning (IP) have been demonstrated to exert protective effect against ischemia/reperfusion (I/R) injury in liver. We aimed to determine whether application of IP under isoflurane and sevoflurane anesthesia would confer protection against hepatic I/R injury in rats. Thirty-eight rats weighing 270 to 300 grams were randomly divided into 2 groups: isoflurane (1.5%) and sevoflurane (2.5%) anesthesia groups. Each group was subdivided into sham (n = 3), non-IP (n = 8; 45 minutes of hepatic ischemia), and IP (n = 8, IP consisting of 10-minute ischemia plus 15-minute reperfusion before prolonged ischemia) groups. The degree of hepatic injury and expressions of B-cell lymphoma 2 (Bcl-2) and caspase 3 were compared at 2 hours after reperfusion. Hepatic ischemia induced significant degree of I/R injuries in both isoflurane and sevoflurane non-IP groups. In both anesthetic groups, introduction of IP dramatically attenuated I/R injuries as marked by significantly lower aspartate aminotransferase and aminotransferase levels and better histologic grades compared with corresponding non-IP groups. There were 2.3- and 1.7-fold increases in Bcl-2 mRNA levels in isoflurane and sevoflurane IP groups, respectively, compared with corresponding non-IP groups (both P < .05). Caspase 3 level was significantly high in the isoflurane non-IP group compared with the sham group; however, there were no differences among the sevoflurane groups. The degree of hepatic I/R injury was significantly high in both isoflurane and sevoflurane groups in rats. However, application of IP significantly protected against I/R injury in both volatile anesthetic groups to similar degrees, and upregulation of Bcl-2 might be an important mechanism. Copyright © 2017 Elsevier Inc. All rights reserved.

Sirtinol abrogates late phase of cardiac ischemia preconditioning in rats.

PubMed

Safari, Fereshteh; Shekarforoosh, Shahnaz; Hashemi, Tahmineh; Namvar Aghdash, Simin; Fekri, Asefeh; Safari, Fatemeh

2017-07-01

The aim of this study was to investigate the effect of sirtinol, as an inhibitor of sirtuin NAD-dependent histone deacetylases, on myocardial ischemia reperfusion injury following early and late ischemia preconditioning (IPC). Rats underwent sustained ischemia and reperfusion (IR) alone or proceeded by early or late IPC. Sirtinol (S) was administered before IPC. Arrhythmias were evaluated based on the Lambeth model. Infarct size (IS) was measured using triphenyltetrazolium chloride staining. The transcription level of antioxidant-coding genes was assessed by real-time PCR. In early and late IPC groups, IS and the number of arrhythmia were significantly decreased (P < 0.05 and P < 0.01 vs IR, respectively). In S + early IPC, incidences of arrhythmia and IS were not different compared with the early IPC group. However, in S + late IPC the IS was different from the late IPC group (P < 0.05). In late IPC but not early IPC, transcription levels of catalase (P < 0.01) and Mn-SOD (P < 0.05) increased, although this upregulation was not significant in the S + late IPC group. Our results are consistent with the notion that different mechanisms are responsible for early and late IPC. In addition, sirtuin NAD-dependent histone deacetylases may be implicated in late IPC-induced cardioprotection.

[Effects of the of renal warm ischemia time on the recovery of filtration function in the experiment].

PubMed

Guseinov, R G; Popov, S V; Gorshkov, A N; Sivak, K V; Martov, A G

2017-12-01

To investigate experimentally ultrastructural and biochemical signs of acute injury to the renal parenchyma after warm renal ischemia of various duration and subsequent reperfusion. The experiments were performed on 44 healthy conventional female rabbits of the "Chinchilla" breed weighted 2.6-2.7 kg, which were divided into four groups. In the first, control, group included pseudo-operated animals. In the remaining three groups, an experimental model of warm ischemia of renal tissue was created, followed by a 60-minute reperfusion. The renal warm ischemia time was 30, 60 and 90 minutes in the 2nd, 3rd and 4th groups, respectively. Electron microscopy was used to study ultrastructural disturbances of the renal parenchyma. Biochemical signs of acute kidney damage were detected by measuring the following blood serum and/or urine analytes: NGAL, cystatin C, KIM-1, L-FABP, interleukin-18. The glomerular filtration was evaluated by creatinine clearance, which was determined on days 1, 5, 7, 14, 21 and 35 of follow-up. A 30-minute renal warm ischemia followed by a 60-minute reperfusion induced swelling and edema of the brush membrane, vacuolation of the cytoplasm of the endothelial cells of the proximal tubules, and microvilli restructuring. The observed disorders were reversible, and the epithelial cells retained their viability. After 60 minutes of ischemia and 60 minutes of reperfusion, the observed changes in the ultrastructure of the epithelial cells were much more pronounced, some of the epithelial cells were in a state of apoptosis. 90 min of ischemia and 60 min of reperfusion resulted in electron-microscopic signs of the mass cellular death of the tubular epithelium. Concentration in serum and/or biochemical urine markers of acute renal damage increased sharply after ischemic-reperfusion injury. Restoration of indicators was observed only in cases when the renal warm ischemia time did not exceed 60 minutes. The decrease in creatinine clearance occurred in the

Modulation of the oxidative stress by metformin in the cerebrum of rats exposed to global cerebral ischemia and ischemia/reperfusion.

PubMed

Abd-Elsameea, A A; Moustaf, A A; Mohamed, A M

2014-08-01

Oxidative stress plays a major role in the pathogenesis of ischemic and reperfusion injury to many organs, including the brain. Chronic metformin treatment is associated with a lower risk of stroke in clinical populations. The aim of the present study was to investigate the effect of metformin on the oxidative stress induced in experimental model of incomplete global cerebral ischemia and ischemia/reperfusion in adult male Wistar rats. Metformin was administered to rats orally by gavage 500 mg/kg once daily for one week before induction of cerebral ischemia (rats were subjected to 30 min of ischemia before decapitation) and ischemia/reperfusion (rats were subjected to 30 min of ischemia then 60 minutes of reperfusion before decapitation). The selected parameters for oxidative stress were the activities of the antioxidant enzymes: glutathione peroxidase (GSHPx), superoxide dismutase (SOD), and catalase as well as malondialdehyde (MDA) levels. Metformin reduced the elevated activites of GSHPx, SOD and catalase as well as MDA levels in cerebrum of rats exposed to ischemia and ischemia/reperfusion injures. Metformin improved the oxidative stress induced by ischemia and ischemia/reperfusion injuries. This may be a mechanism that explains the cerebroprotective effect of the drug.

The Effects of Two Anesthetics, Propofol and Sevoflurane, on Liver Ischemia/Reperfusion Injury.

PubMed

Xu, Zhijie; Yu, Jingui; Wu, Jianbo; Qi, Feng; Wang, Huanliang; Wang, Zhigang; Wang, Zhou

2016-01-01

Propofol and sevoflurane are widely used in clinical anesthesia, and both have been reported to exert a protective effect in organ ischemia/reperfusion (IR). This study aims to investigate and compare the effects of propofol and sevoflurane on liver ischemia/reperfusion and the precise molecular mechanism. Rats were randomized into four groups: the sham group, I/R group, propofol treatment group (infused with 1% propofol at 500 μg· kg-1· min-1), and sevoflurane treatment group (infused with 3% (2 L/min) sevoflurane). The liver ischemia/reperfusion model was used to evaluate the hepatoprotective effect on ischemic injury. Liver enzyme leakage, liver cytokines and histopathological examination were used to evaluate the extent of hepatic ischemia/reperfusion injury. Oxidative stress was investigated by evaluating the levels of Malondialdehyde(MDA), Superoxide Dismutase(SOD) and NO. The terminal dexynucleotidyl transferase(TdT)-mediated dUTP nick end labeling (TUNEL) assay and western blot were applied to detect apoptosis in the ischemic liver tissue and its mechanism. Both propofol and sevoflurane attenuated the extent of hepatic ischemia/reperfusion injury which is evident from the hisopathological studies and alterations in liver enzymes such as AST and LDH by inhibiting Nuclear factor kappa B (NFx03BA;B) activation and subsequent alterations in inflammatory cytokines interleukin-1(IL-1), interleukin-6(IL-6), tumor necrosis factor-alpha (TNF-α) and increased IL10 release. Propofol exhibited a similar protective effect and a lower IL-1 release, while sevoflurane decreased TNF-α leakage more significantly. Meanwhile, oxidative stress was attenuated by reduced MDA and NO and elevated SOD release. The expression of antiapoptotic protein Bcl-2 and Bcl-xl were enhanced while that of apoptotic protein Bax and Bak were reduced by both propofol and sevoflurane to regulate hepatic apoptosis. In addition, propofol downregulated the phosphorylation of AKT and Bad protein

Anatomic renal artery branch microdissection to facilitate zero-ischemia partial nephrectomy.

PubMed

Ng, Casey K; Gill, Inderbir S; Patil, Mukul B; Hung, Andrew J; Berger, Andre K; de Castro Abreu, Andre Luis; Nakamoto, Masahiko; Eisenberg, Manuel S; Ukimura, Osamu; Thangathurai, Duraiyah; Aron, Monish; Desai, Mihir M

2012-01-01

Robot-assisted and laparoscopic partial nephrectomies (PNs) for medial tumors are technically challenging even with the hilum clamped and, until now, were impossible to perform with the hilum unclamped. Evaluate whether targeted vascular microdissection (VMD) of renal artery branches allows zero-ischemia PN to be performed even for challenging medial tumors. A prospective cohort evaluation of 44 patients with renal masses who underwent robot-assisted or laparoscopic zero-ischemia PN either with anatomic VMD (group 1; n=22) or without anatomic VMD (group 2; n=22) performed by a single surgeon from April 2010 to January 2011. Zero-ischemia PN with VMD incorporates four maneuvers: (1) preoperative computed tomographic reconstruction of renal arterial branch anatomy, (2) anatomic dissection of targeted, tumor-specific tertiary or higher-order renal arterial branches, (3) neurosurgical aneurysm microsurgical bulldog clamp(s) for superselective tumor devascularization, and (4) transient, controlled reduction of blood pressure, if necessary. Baseline, perioperative, and postoperative data were collected prospectively. Group 1 tumors were larger (4.3 vs 2.6 cm; p=0.011), were more often hilar (41% vs 9%; p=0.09), were medial (59% and 23%; p=0.017), were closer to the hilum (1.46 vs 3.26 cm; p=0.0002), and had a lower C index score (2.1 vs 3.9; p=0.004) and higher RENAL nephrometry scores (7.7 vs 6.2; p=0.013). Despite greater complexity, no group 1 tumor required hilar clamping, and perioperative outcomes were similar to those of group 2: operating room time (4.7 and 4.1h), median blood loss (200 and 100ml), surgical margins for cancer (all negative), major complications (0% and 9%), and minor complications (18% and 14%). The median serum creatinine level was similar 2 mo postoperatively (1.2 and 1.3mg/dl). The study was limited by the relatively small sample size. Anatomic targeted dissection and superselective control of tumor-specific renal arterial branches facilitate

Neuroprotection of ebselen against ischemia/reperfusion injury involves GABA shunt enzymes.

PubMed

Seo, Jeong Yeol; Lee, Choong Hyun; Cho, Jun Hwi; Choi, Jung Hoon; Yoo, Ki-Yeon; Kim, Dae Won; Park, Ok Kyu; Li, Hua; Choi, Soo Young; Hwang, In Koo; Won, Moo-Ho

2009-10-15

Seleno-organic compound, ebselen (2-phenyl-1,2-benzisoselenazol-3(2H)-one), is a substrate with radical-scavenging activity. In this study, we observed the neuroprotective effects of ebselen against ischemic damage and on GABA shunt enzymes such as glutamic acid decarboxylase 67 (GAD67), GABA transaminse (GABA-T) and succinic semialdehyde dehydrogenase (SSADH) in the hippocampal CA1 region after 5 min of transient forebrain ischemia in gerbils. For this, vehicle (physiological saline) or ebselen was administered 30 min before or after ischemia/reperfusion and sacrificed 4 days after ischemia/reperfusion. The administration of ebselen significantly reduced the neuronal death in the CA1 region induced by ischemia/reperfusion. In addition, treatment with ebselen markedly elevated GAD67, GABA-T and SSADH immunoreactivity and their protein levels compared to that in the vehicle-treated group, respectively. These results suggest that ebselen protects neurons from ischemic damage via control of the expressions of GABA shunt enzymes to enter the TCA cycle.

Mucosal injury induced by ischemia and reperfusion in the piglet intestine: Influences of age and feeding

DOE Office of Scientific and Technical Information (OSTI.GOV)

Crissinger, K.D.; Granger, D.N.

1989-10-01

The pathogenesis of neonatal necrotizing enterocolitis is unknown, but enteral alimentation, infectious agents, and mesenteric ischemia have been frequently invoked as primary initiators of the disease. To define the vulnerability of the intestinal mucosa to ischemia and reperfusion in the developing piglet, we evaluated changes in mucosal permeability using plasma-to-lumen clearance of chromium 51-labeled ethylenediaminetetraacetic acid in the ileum of anesthetized 1-day-, 3-day-, 2-wk-, and 1-mo-old piglets as a function of (a) duration of intestinal ischemia (20, 40, or 60 min of total superior mesenteric artery occlusion), (b) feeding status (fasted or nursed), and (c) composition of luminal perfusate (balancedmore » salt solution vs. predigested cow milk-based formula). Baseline chromium 51-labeled ethylenediaminetetraacetic acid clearance was not significantly altered by ischemia, irrespective of duration, or feeding in all age groups. However, clearances were significantly elevated during reperfusion after 1 h of total intestinal ischemia in all age groups, whether fasted or fed. Reperfusion-induced increases in clearance did not differ among age groups when the bowel lumen was perfused with a balanced salt solution. However, luminal perfusion with formula resulted in higher clearances in 1-day-old piglets compared with all older animals. Thus, the neonatal intestine appears to be more vulnerable to mucosal injury induced by ischemia and reperfusion in the presence of formula than the intestine of older animals.« less

The Synergistic Neuroprotective Effects of Combined Rosuvastatin and Resveratrol Pretreatment against Cerebral Ischemia/Reperfusion Injury.

PubMed

Liu, Ying; Yang, HongNa; Jia, GuoYong; Li, Lan; Chen, Hui; Bi, JianZhong; Wang, CuiLan

2018-06-01

It is well accepted that both rosuvastatin and resveratrol exert neuroprotective effects on cerebral ischemia/reperfusion injury through some common pathways. Resveratrol has also been demonstrated to protect against cerebral ischemia/reperfusion injury through enhancing autophagy. Thus, we hypothesized that combined rosuvastatin and resveratrol pretreatment had synergistic effects on cerebral ischemia/reperfusion injury. Adult male Sprague Dawley rats receiving middle cerebral artery occlusion surgery as animal model of cerebral ischemia/reperfusion injury were randomly assigned to 4 groups: control, resveratrol alone pretreatment, rosuvastatin alone pretreatment, and combined rosuvastatin and resveratrol pretreatment. Rosuvastatin (10 mg/kg) or resveratrol (50 mg/kg) was administrated once a day for 7 days before cerebral ischemia onset. We found that combined rosuvastatin and resveratrol pretreatment not only significantly decreased the neurologic defective score, cerebral infarct volume, the levels of caspase-3, and Interleukin-1β (IL-1β) but also significantly increased the ratios of Bcl-2/Bax and LC3II/LC3I, as well as the level of Becline-1, compared with resveratrol alone or rosuvastatin alone pretreatment group. Rosuvastatin alone pretreatment significantly increased the ratio of LC3II/LC3I and the level of Beclin-1. However, there were no significant differences in the neurologic defective score, cerebral infarct volume, the levels of caspase-3, IL-1β, and Beclin-1, and the ratios of Bcl-2/Bax and LC3II/LC3I between resveratrol pretreatment group and rosuvastatin pretreatment group. Synergistically enhanced antiapoptosis, anti-inflammation, and autophagy activation might be responsible for the synergistic neuroprotective effects of combining rosuvastatin with resveratrol on cerebral ischemia/reperfusion injury. Copyright © 2018 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Isoflurane reduces the ischemia reperfusion injury surge: a longitudinal study with MRI.

PubMed

Taheri, Saeid; Shunmugavel, Anandakumar; Clark, Danielle; Shi, Honglian

2014-10-24

Recent studies show neuroprotective benefits of isoflurane (ISO) administered during cerebral ischemia. However, the available studies evaluated cerebral injury only at a single time point following the intervention and thus the longitudinal effect of ISO on ischemic tissues remains to be investigated. The objective of the present study was to investigate the longitudinal effect of ISO treatment in counteracting the deleterious effect of ischemia by evoking the transcription factor, hypoxia inducible factor-1 (HIF-1), and vascular endothelial growth factor (VEGF). Focal cerebral ischemia was induced in 70 rats by filament medial cerebral artery occlusion (MCAo) method. MCAo rats were randomly assigned to control (90 min ischemia) and MCAo+ISO (90 min ischemia+2% ISO) groups. Infarct volume, edema, intracerebral hemorrhage (ICH), and regional cerebral blood flow (rCBF) were measured in eight in vivo sequential MR imaging sessions for 3 weeks. Western blot analysis and immunofluorescence were used to determine the expression level of HIF-1α (the regulatable subunit of HIF-1) and VEGF proteins. ISO inhalation during ischemia significantly decreased the surge of infarct volume, edema, ICH, and reduced the mortality rate (p<0.01). ISO transiently altered the rCBF, significantly enhanced the expression of HIF-1α and VEGF, and decreased the immune cell infiltration. Locomotor dysfunction was ameliorated at a significantly faster pace, and the benefit was seen to persist up to three weeks. Treatment with ISO during ischemia limits the deadly surge in the dynamics of ischemia reperfusion injury with no observed long-term inverse effect. Copyright © 2014 Elsevier B.V. All rights reserved.

[Effect of curcumine on the nuclear pathway of JNK during hippocampal ischemia/reperfusion injury in SHR].

PubMed

Ye, Ke-Ping; Chen, Chun-Ru; Zheng, Jin-Wei; Cao, Hong; Ji, Bin; Zhou, Rui; Meng, Zhi-Yan; Li, Jun; Lian, Qing-Quan

2010-11-01

To investigate the diversify of the nuclear pathway of c-Jun NH2-terminal kinases (JNK) during transient brain ischemia/reperfusion injury in hippocampal neuron apoptosis in spontaneously hypertensive rats (SHR) and to test whether the neuroprotection of curcumine on transient brain ischemia/reperfusion injury in SHR is related to the nuclear pathway of JNK. Male Wistar-Kyoto (WKY) rats and SHR were randomly divided into five groups (n = 6): WKY sham group (W-Sham), WKY ischemia/reperfusion group (W-I/ R), SHR sham group (S-Sham), SHR ischemia/reperfusion group (S-I/R) and SHR curcumine (a chinese traditional medicine)100 mg/kg treatment group (S-Cur), which were sacrificed at 2 h, 6 h, 24 h, 3 d and 7 d after reperfusion. Global brain ischemic model was established by 4-VO method. The TdT-mediated dUTP nick end labeling (TUNEL) method was used to detect the neuron apoptosis in hippocampal CA1 region. The immunohistochemical method was applied to investigate the expressions of c-jun and c-fos in hippocampal CA1 region. The expressions of apoptosis and c-jun and c-fos in CA1 region in S-Sham group, W-I/R group and S-I/R group were more than those in W-Sham group (P < 0.05), were significantly increased in S-I/R group than those in W-I/R group (P < 0.05), and were significantly decreased in S-Cur group than those in S-I/R group (P < 0.05). Neuronal apoptosis and the expressions of c-jun and c-fos are more in SHR hippocampal. Global brain ischemia/reperfusion injury induces more expressions of apoptosis in hippocampal neuron in SHR, and the more expressions of c-jun and c-fos may participate in that process. The neuroprotection of curcumine in SHR is related to c-jun and c-fos.

Lack of chlorpromazine effect on skeletal muscle metabolism after ischemia and a short reperfusion period.

PubMed

Piccinato, Carlos E; Salles Roselino, José E; Massuda, Carlos A; Cherri, Jesualdo

2004-01-01

The great resistance of muscle to ischemia was used to study blood flow-dependent phenomena produced by anesthetic drugs in this condition. A short reperfusion period was used in order to favor metabolic changes indicative of an effect of chlorpromazine (CPZ) on blood flow. Gracilis muscles of dogs were submitted to 5 h of ischemia and 30 min of reperfusion. CPZ-treated animals were injected I.V. (2 mg/kg) 10 min before the beginning of ischemia. Biopsies provided the material for tissue measurements. Lactate content and pH were determined in blood samples collected from a muscle efferent vein. In both the CPZ-treated and nontreated groups, ischemia induced a decline in muscle glycogen content, with a corresponding increase in muscle lactate and a decrease in mitochondrial respiratory control ratio. After 30 min of reperfusion, tissue levels of lactate did not attain preischemic values but showed a clear decline in the two experimental groups, evidencing the reversible state of the muscle. All other metabolic parameters remained unchanged. Mitochondrial respiratory control remained functional during ischemia and reperfusion. Blood pH displayed similar changes in both groups. There was no metabolic indication that the drug affected blood flow during early reperfusion and/or of a greater sensitivity of muscle endothelial cells to anesthetic drugs. Copyright 2004 Wiley-Liss, Inc.

Effect of enriched environment on angiogenesis and neurological functions in rats with focal cerebral ischemia.

PubMed

Zhang, Xin; Chen, Xiu-Ping; Lin, Jun-Bin; Xiong, Yu; Liao, Wei-Jing; Wan, Qi

2017-01-15

The purpose of this study was to investigate the effect of enriched environment (EE) on cerebral angiogenesis after ischemia-reperfusion injury. Middle cerebral artery occlusion (MCAO) followed by reperfusion was performed in rats to set up an animal model of ischemia-reperfusion injury. In a set of behavioral tests, we demonstrated that the animals in the IEE (ischemia + enriched environment) group exhibited significantly improved neurological functions compared to those in the standard housing condition group. In consistent with the functional tests, smaller infarction volumes were observed in the animals of IEE group. Laser scanning confocal microscopy and 3D quantitative analysis of cerebral microvessels revealed that EE treatment increased the total vessel surface area and number of branch point in the ischemic boundary zone. IgG extraction assay showed that the blood brain barrier (BBB) leakage in the ischemic brain was attenuated after EE treatment. EE treatment also enhanced endothelial cells (ECs) proliferation and increased the expression levels of VEGF and its receptor Flk-1 after ischemia-reperfusion injury. Analyses of Spearman's correlation coefficients indicated a correlation of mNSS scores with enhanced cerebral angiogenesis. Together, the results suggest that EE treatment-induced cerebral angiogenesis may contribute to the improved neurological outcome of stroke animals after ischemia-reperfusion injury. Copyright © 2016 Elsevier B.V. All rights reserved.

Neuroprotective Effect of Resveratrol on Acute Brain Ischemia Reperfusion Injury by Measuring Annexin V, p53, Bcl-2 Levels in Rats.

PubMed

Kizmazoglu, Ceren; Aydin, Hasan Emre; Sevin, Ismail Ertan; Kalemci, Orhan; Yüceer, Nurullah; Atasoy, Metin Ant

2015-12-01

Cerebral ischemia is as a result of insufficient cerebral blood flow for cerebral metabolic functions. Resveratrol is a natural phytoalexin that can be extracted from grape's skin and had potent role in treating the cerebral ischemia. Apoptosis, a genetically programmed cellular event which occurs after ischemia and leads to biochemical and morphological changes in cells. There are some useful markers for apoptosis like Bcl-2, bax, and p53. The last reports, researchers verify the apoptosis with early markers like Annexin V. We preferred in this experimental study a model of global cerebral infarction which was induced by bilateral common carotid artery occlusion method. Rats were randomly divided into 4 groups : sham, ischemia-reperfusion (I/R), I/R plus 20 mg/kg resveratrol and I/R plus 40 mg/kg resveratrol. Statistical analysis was performed using Sigmastat 3.5 ve IBM SPSS Statistics 20. We considered a result significant when p<0.001. After administration of resveratrol, Bcl-2 and Annexin levels were significantly increased (p<0.001). Depending on the dose of resveratrol, Bcl2 levels increased, p53 levels decreased but Annexin V did not effected. P53 levels were significantly increased in ishemia group, so apoptosis is higher compared to other groups. In the acute period, Annexin V levels misleading us because the apoptotic cell counts could not reach a certain level. Therefore we should support our results with bcl-2 and p53.

Blockade of Central Angiotensin II AT1 Receptor Protects the Brain from Ischemia/Reperfusion Injury in Normotensive Rats

PubMed Central

Panahpour, Hamdolah; Nekooeian, Ali Akbar; Dehghani, Gholam Abbas

2014-01-01

Background: Stroke is the third leading cause of invalidism and death in industrialized countries. There are conflicting reports about the effects of Angiotensin II on ischemia-reperfusion brain injuries and most data have come from chronic hypertensive rats. In this study, hypotensive and non-hypotensive doses of candesartan were used to investigate the effects of angiotensin II AT1 receptor blockade by transient focal cerebral ischemia in normotensive rats. Methods: In this experimental study, 48 male Sprague-Dawley rats were randomly divided into four groups (n=12). Sham group, the control ischemic group, and two ischemic groups received candesartan at doses of 0.1 or 0.5 mg/kg at one hour before ischemia. Transient focal cerebral ischemia was induced by 60 minutes occlusion of the middle cerebral artery, followed by 24 h reperfusion. The neurological deficit score was evaluated at the end of the reperfusion period. The total cortical and striatal infarct volumes were determined using triphenyltetrazolium chloride staining technique. Tissue swelling was calculated for the investigation of ischemic brain edema formation. Results: In comparison with the control ischemic group, AT1 receptor blockade with both doses of candesartan (0.1 or 0.5 mg/kg) significantly improved neurological deficit and lowered cortical and striatal infarct sizes. In addition, pretreatment with candesartan significantly reduced ischemia induced tissue swelling. Conclusion: Angiotensin II by stimulating AT1 receptors, participates in ischemia-reperfusion injuries and edema formation. AT1 receptor blockade with candesartan decreased ischemic brain injury and edema and improved neurological outcome. PMID:25429176

Ischemia and No Obstructive Coronary Artery Disease (INOCA): Developing Evidence-based Therapies and Research Agenda for the Next Decade

PubMed Central

Merz, C. Noel Bairey; Pepine, Carl J.; Walsh, Mary Norine; Fleg, Jerome L.

2017-01-01

The Cardiovascular Disease in Women Committee of the American College of Cardiology, in conjunction with interested parties (from the National Heart, Lung, and Blood Institute, American Heart Association, European Society of Cardiology), convened a working group to develop a consensus on the syndrome of myocardial ischemia with no obstructive coronary arteries (INOCA). In general, these patients have elevated risk for a cardiovascular event (including acute coronary syndrome, heart failure hospitalization, stroke, and repeated cardiovascular procedures) vs reference subjects, and appear to be at higher risk for development of heart failure with preserved ejection fraction (HFpEF). A subgroup of these patients also has coronary microvascular dysfunction (CMD) and evidence of inflammation. This document provides a summary of findings and recommendations toward the development of an integrated approach for identifying and managing patients with INOCA, and outlining knowledge gaps in the area. Working group members critically reviewed available literature and current practices for risk assessment and state-of-the-science techniques in multiple areas, with a focus on next steps needed to develop evidence-based therapies. This report presents highlights of this working group review and a summary of suggested research directions to advance this field in the next decade. PMID:28289007

Renal sympathetic denervation suppresses atrial fibrillation induced by acute atrial ischemia/infarction through inhibition of cardiac sympathetic activity.

PubMed

Zhou, Qina; Zhou, Xianhui; TuEr-Hong, ZuKe-la; Wang, Hongli; Yin, Tingting; Li, Yaodong; Zhang, Ling; Lu, Yanmei; Xing, Qiang; Zhang, Jianghua; Yang, Yining; Tang, Baopeng

2016-01-15

This study aims to explore the effects of renal sympathetic denervation (RSD) on atrial fibrillation (AF) inducibility and sympathetic activity induced by acute atrial ischemia/infarction. Acute ischemia/infarction was induced in 12 beagle dogs by ligating coronary arteries that supply the atria. Six dogs in the sham-RSD group did not undergo RSD, and six dogs without coronary artery ligation served as controls. AF induction rate, sympathetic discharge, catecholamine concentration and densities of tyrosine hydroxylase-positive nerves were measured. Acute atrial ischemia/infarction resulted in a significant increase of AF induction rate, which was decreased by RSD compared to controls (P<0.05). The root-mean-square peak value, peak area and number of sympathetic discharges were significantly augmented by atrial ischemia relative to the baseline and control (P<0.05). The number of sympathetic discharges was significantly reduced in the RSD group, compared to the control and sham-RSD groups (P<0.05). Norepinephrine and epinephrine concentrations in the atria, ventricle and kidney were elevated by atrial ischemia/infarction, but were reduced by RSD (P<0.05). Sympathetic hyperactivity was associated with pacing-induced AF after acute atrial ischemia/infarction. RSD has the potential to reduce the incidence of new-onset AF after acute atrial ischemia/infarction. The inhibition of cardiac sympathetic activity by RSD may be one of the major underlying mechanisms for the marked reduction of AF inducibility. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Use of OCTA, FA, and Ultra-Widefield Imaging in Quantifying Retinal Ischemia: A Review.

PubMed

Or, Chris; Sabrosa, Almyr S; Sorour, Osama; Arya, Malvika; Waheed, Nadia

2018-01-01

As ischemia remains a key prognostic factor in the management of various diseases including diabetic retinopathy, an increasing amount of research has been dedicated to its quantification as a potential biomarker. Advancements in the quantification of retinal ischemia have been made with the imaging modalities of fluorescein angiography (FA), ultra-widefield imaging (UWF), and optical coherence tomography angiography (OCTA), with each imaging modality offering certain benefits over the others. FA remains the gold standard in assessing the extent of ischemia. UWF imaging has allowed for the assessment of peripheral ischemia via FA. It is, however, OCTA that offers the best visualization of retinal vasculature with its noninvasive depth-resolved imaging and therefore has the potential to become a mainstay in the assessment of retinal ischemia. The primary purpose of this article is to review the use of FA, UWF, and OCTA to quantify retinal ischemia and the various methods described in the literature by which this is achieved. Copyright 2018 Asia-Pacific Academy of Ophthalmology.

Intraperitoneal Administration of Silymarin Protects End Organs from Multivisceral Ischemia/Reperfusion Injury in a Rat Model

PubMed Central

Koçarslan, Aydemir; Koçarslan, Sezen; Aydin, Mehmet Salih; Gunay, Şamil; Karahan, Mahmut Alp; Taşkın, Abdullah; Üstunel, Murat; Aksoy, Nurten

2016-01-01

Objective To determine whether intraperitoneal silymarin administration has favorable effects on the heart, lungs, kidney, and liver and on oxidative stress in a rat model of supraceliac aorta ischemia/reperfusion injury. Methods Thirty male Wistar albino rats were divided equally into three groups: sham, control, and silymarin. The control and silymarin groups underwent supraceliac aortic occlusion for 45 min, followed by a 60 min period of reperfusion under terminal anesthesia. In the silymarin group, silymarin was administered intraperitoneally during ischemia at a dose of 200 mg/kg. Rats were euthanized using terminal anesthesia, and blood was collected from the inferior vena cava for total antioxidant capacity, total oxidative status, and oxidative stress index measurement. Lungs, heart, liver and kidney tissues were histologically examined. Results Ischemia/reperfusion injury significantly increased histopathological damage as well as the total oxidative status and oxidative stress index levels in the blood samples. The silymarin group incurred significantly lesser damage to the lungs, liver and kidneys than the control group, while no differences were observed in the myocardium. Furthermore, the silymarin group had significantly lower total oxidative status and oxidative stress index levels than the control group. Conclusion Intraperitoneal administration of silymarin reduces oxidative stress and protects the liver, kidney, and lungs from acute supraceliac abdominal aorta ischemia/reperfusion injury in the rat model. PMID:28076620

Protective effect of Shenfu injection preconditioning on lung ischemia-reperfusion injury

PubMed Central

Zhang, Hong; Wan, Zhanhai; Yan, Xiang; Wang, De-Gui; Leng, Yufang; Liu, Yongqiang; Zhang, Yan; Zhang, Haijun; Han, Xuena

2016-01-01

Lung ischemia-reperfusion injury remains a problem in thoracic surgery, as minimal progress has been made concerning its prevention and control. In the present study, the protective effects and the underlying mechanism of Shenfu injection preconditioning on a rat lung ischemia-reperfusion model was investigated. Shenfu injection is a well-known Chinese traditional medicine, which is composed of Red Radix Ginseng and Radix Aconitum carmichaelii, with ginseng saponin and aconitum alkaloids as the active ingredients. A total of 72 specific pathogen-free, healthy male Wistar rats were randomly divided into control, model and Shenfu injection (10 ml/kg injection prior to injury) groups and were assessed at the following points: Ischemia 45 min; reperfusion 60 min; and reperfusion 120 min. Blood collected from the aorta abdominalis was cryopreserved at −70°C for the analysis of malondialdehyde (MDA) and superoxide dismutase (SOD) activity. Lung tissues were divided into three equal sections in order to assess the wet-to-dry (W/D) lung ratio, tumor necrosis factor (TNF)-α expression levels, myeloperoxidase (MPO) activity, alveolar damage, total protein and hematoxylin and eosin staining. The results demonstrated that the lung W/D weight ratio, TNF-α expression levels and SOD activity in the Shenfu group were significantly lower at 120 min reperfusion (P<0.05), as compared with the model group. MPO and MDA activity significantly decreased following reperfusion at 60 and 120 min (P<0.05), as compared with the model group. In addition, the degree of alveolar damage in the Shenfu group was significantly decreased (P<0.05), as compared with the model group. In addition, compared with the model group, the degree of alveolar damage in the Shenfu group was significantly lower (P<0.05); however, no significant changes in total protein were observed. The extent of alveolar structural damage and the proportion of interstitial neutrophils and alveolar and interstitial red blood

Outcomes of lower extremity bypass performed for acute limb ischemia

PubMed Central

Baril, Donald T.; Patel, Virendra I.; Judelson, Dejah R.; Goodney, Philip P.; McPhee, James T.; Hevelone, Nathanael D.; Cronenwett, Jack L.; Schanzer, Andres

2013-01-01

Objective Acute limb ischemia remains one of the most challenging emergencies in vascular surgery. Historically, outcomes following interventions for acute limb ischemia have been associated with high rates of morbidity and mortality. The purpose of this study was to determine contemporary outcomes following lower extremity bypass performed for acute limb ischemia. Methods All patients undergoing infrainguinal lower extremity bypass between 2003 and 2011 within hospitals comprising the Vascular Study Group of New England were identified. Patients were stratified according to whether or not the indication for lower extremity bypass was acute limb ischemia. Primary end points included bypass graft occlusion, major amputation, and mortality at 1 year postoperatively as determined by Kaplan-Meier life table analysis. Multivariable Cox proportional hazards models were constructed to evaluate independent predictors of mortality and major amputation at 1 year. Results Of 5712 lower extremity bypass procedures, 323 (5.7%) were performed for acute limb ischemia. Patients undergoing lower extremity bypass for acute limb ischemia were similar in age (66 vs 67; P = .084) and sex (68% male vs 69% male; P = .617) compared with chronic ischemia patients, but were less likely to be on aspirin (63% vs 75%; P < .0001) or a statin (55% vs 68%; P < .0001). Patients with acute limb ischemia were more likely to be current smokers (49% vs 39%; P < .0001), to have had a prior ipsilateral bypass (33% vs 24%; P = .004) or a prior ipsilateral percutaneous intervention (41% vs 29%; P = .001). Bypasses performed for acute limb ischemia were longer in duration (270 vs 244 minutes; P = .007), had greater blood loss (363 vs 272 mL; P < .0001), and more commonly utilized prosthetic conduits (41% vs 33%; P = .003). Acute limb ischemia patients experienced increased in-hospital major adverse events (20% vs 12%; P < .0001) including myocardial infarction, congestive heart failure exacerbation

Outcomes of lower extremity bypass performed for acute limb ischemia.

PubMed

Baril, Donald T; Patel, Virendra I; Judelson, Dejah R; Goodney, Philip P; McPhee, James T; Hevelone, Nathanael D; Cronenwett, Jack L; Schanzer, Andres

2013-10-01

Acute limb ischemia remains one of the most challenging emergencies in vascular surgery. Historically, outcomes following interventions for acute limb ischemia have been associated with high rates of morbidity and mortality. The purpose of this study was to determine contemporary outcomes following lower extremity bypass performed for acute limb ischemia. All patients undergoing infrainguinal lower extremity bypass between 2003 and 2011 within hospitals comprising the Vascular Study Group of New England were identified. Patients were stratified according to whether or not the indication for lower extremity bypass was acute limb ischemia. Primary end points included bypass graft occlusion, major amputation, and mortality at 1 year postoperatively as determined by Kaplan-Meier life table analysis. Multivariable Cox proportional hazards models were constructed to evaluate independent predictors of mortality and major amputation at 1 year. Of 5712 lower extremity bypass procedures, 323 (5.7%) were performed for acute limb ischemia. Patients undergoing lower extremity bypass for acute limb ischemia were similar in age (66 vs 67; P = .084) and sex (68% male vs 69% male; P = .617) compared with chronic ischemia patients, but were less likely to be on aspirin (63% vs 75%; P < .0001) or a statin (55% vs 68%; P < .0001). Patients with acute limb ischemia were more likely to be current smokers (49% vs 39%; P < .0001), to have had a prior ipsilateral bypass (33% vs 24%; P = .004) or a prior ipsilateral percutaneous intervention (41% vs 29%; P = .001). Bypasses performed for acute limb ischemia were longer in duration (270 vs 244 minutes; P = .007), had greater blood loss (363 vs 272 mL; P < .0001), and more commonly utilized prosthetic conduits (41% vs 33%; P = .003). Acute limb ischemia patients experienced increased in-hospital major adverse events (20% vs 12%; P < .0001) including myocardial infarction, congestive heart failure exacerbation, deterioration in renal function

Exercise preconditioning improves behavioral functions following transient cerebral ischemia induced by 4-vessel occlusion (4-VO) in rats.

PubMed

Tahamtan, Mahshid; Allahtavakoli, Mohammad; Abbasnejad, Mehdi; Roohbakhsh, Ali; Taghipour, Zahra; Taghavi, Mohsen; Khodadadi, Hassan; Shamsizadeh, Ali

2013-12-01

There is evidence that exercise decreases ischemia/reperfusion injury in rats. Since behavioral deficits are the main outcome in patients after stroke, our study was designed to investigate whether exercise preconditioning improves the acute behavioral functions and also brain inflammatory injury following cerebral ischemia. Male rats weighing 250-300 g were randomly allocated into five experimental groups. Exercise was performed on a treadmill 30min/day for 3 weeks. Ischemia was induced by 4-vessel occlusion method. Recognition memory was assessed by novel object recognition task (NORT) and step-through passive avoidance task. Sensorimotor function and motor movements were evaluated by adhesive removal test and ledged beam-walking test, respectively. Brain inflammatory injury was evaluated by histological assessment. In NORT, the discrimination ratio was decreased after ischemia (P < 0.05) and exercise preconditioning improved it in ischemic animals. In the passive avoidance test, a significant reduction in response latency was observed in the ischemic group. Exercise preconditioning significantly decreased the response latency in the ischemic rats (P < 0.001). In the adhesive removal test, latency to touch and remove the sticky labels from forepaw was increased following induction of ischemia (all P < 0.001) and exercise preconditioning decreased these indices compared to the ischemic group (all P < 0.001). In the ledged beam-walking test, the slip ratio was increased following ischemia (P < 0.05).  In the ischemia group, marked neuronal injury in hippocampus was observed. These neuropathological changes were attenuated by exercise preconditioning (P < 0.001). Our results showed that exercise preconditioning improves behavioral functions and maintains more viable cells in the dorsal hippocampus of the ischemic brain.

Failure of Ibuprofen to prevent progressive dermal ischemia after burning in guinea pigs.

PubMed

Tan, Qian; Lin, Zihao; Ma, Wenxi; Chen, Huairen; Wang, Lei; Ning, Guansen; Zhou, Xu

2002-08-01

It is controversial whether the use of prostaglandin inhibitors could prevent progressive dermal ischemia in the postburn stasis zone. This study evaluated the effect of Ibuprofen on preventing postburn dermal ischemia using an animal model of India ink perfusion and skin transparent preparation techniques. The closely clipped backs of the guinea pigs were bathed in 75 degrees C water for 10s. Ibuprofen-treated groups were fed intragastrically with Ibuprofen (12.5mg/kg) every 6h. All animals were perfused with 70% India ink via a cervical artery cannula at 16 kPa constant pressure at 0, 8, 16, 24h postburn. Skin transparent preparations were made, and 6-keto-PGF(1 alpha) and T x B(2) levels in skin tissue were assessed. India ink filling rates in skin capillary plexuses decreased gradually with postburn time elapsing (P<0.01). 6-keto-PGF(1 alpha) and T x B(2) levels in two groups increased. The increase of T x B(2) was dominant, which was related to postburn dermal ischemia (r=0.742, P<0.01). Though levels of 6-keto-PGF(1 alpha) and T x B(2) decreased in Ibuprofen-treated groups, India ink filling rates showed no significant difference between controls and experimental groups (P>0.05). The results were also confirmed by observation of skin transparent preparations. This study suggests that Ibuprofen has no preventive effect on progressive dermal ischemia after burning.

Effect of short-term ornithine alpha-ketoglutarate pretreatment on intestinal ischemia-reperfusion in rats.

PubMed

Gonçalves, Eduardo Silvio Gouveia; Rabelo, Camila Menezes; Prado Neto, Alberico Ximenes do; Garcia, José Huygens Parente; Guimarães, Sérgio Botelho; Vasconcelos, Paulo Roberto Leitão de

2011-01-01

To investigate the effects of preventive enteral administration of ornithine alpha-ketoglutarate (OKG) in an ischemia-reperfusion rat model. Sixty rats were randomized into five groups (G1-G5, n = 12). Each group was divided into two subgroups (n = 6) and treated with calcium carbonate (CaCa) or OKG by gavage. Thirty minutes later, the animals were anesthetized with xylazine 15mg + ketamine 1mg ip and subjected to laparotomy. G1-G3 rats served as controls. Rats in groups G4 and G5 were subjected to ischemia for 30 minutes. Ischemia was achieved by clamping the small intestine and its mesentery, delimiting a segment of bowel 5 cm long and 5 cm apart from the ileocecal valve. In addition, G5 rats underwent reperfusion for 30 minutes. Blood samples were collected at the end of the laparotomy (G1), after 30 minutes (G2, G4) and 60 minutes (G3, G5) to determine concentrations of metabolites (pyruvate, lactate), creatine phosphokinase (CPK), thiobarbituric acid reactive substances (TBARS) and glutathione (GSH). There was a significant decrease in tissue pyruvate and lactate and plasma CPK levels in OKG-treated rats at the end of reperfusion period. GSH levels did not change significantly in ischemia and reperfusion groups. However, TBARS levels increased significantly (p<0.05) in tissue samples in OKG-treated rats subjected to ischemia for 30 minutes. Short-term pretreatment with OKG before induction of I/R decreases tissue damage, increases pyruvate utilization for energy production in the Krebs cycle and does not attenuate the oxidative stress in this animal model.

Intraperitoneal administration of apigenin in liver ischemia/reperfusion injury protective effects.

PubMed

Tsaroucha, Alexandra K; Tsiaousidou, Anastasia; Ouzounidis, Nikolaos; Tsalkidou, Evanthia; Lambropoulou, Maria; Giakoustidis, Dimitrios; Chatzaki, Ekaterini; Simopoulos, Constantinos

2016-11-01

Hepatic injury caused by ischemia/reperfusion (I/R) is a clinical problem associated with major liver surgery. Among other flavonoids, apigenin has shown a promising effect on I/R cases. In this study, we have investigated the effects of apigenin after liver I/R injury in rats. Forty eight rats were randomized into the following eight groups: (1) Control-sham group: rats subjected to the surgical procedure, except for liver I/R; (2) DMSO group: rats subjected to surgery, except for liver I/R given the apigenin solvent dimethyl-sulfoxide intraperitoneally; (3) C60 group; (4) C120 group; (5) C240 group: rats underwent liver ischemia for 45 min followed by reperfusion for 60 min, 120 min, and 240 min; (6) AP60 group; (7) AP120 group; (8) AP240 group: rats underwent liver ischemia for 45 min, and then given apigenin (5 mg) intraperitoneally followed by reperfusion for 60 min, 120 min, and 240 min. Reverse transcription polymerase chain reaction was performed on liver tissues to measure BCL-2/BAX expression, enzyme-linked immunosorbent assay to measure M30/M65 and ICAM-1. Immunohistochemistry was used to identify M30 biomarker in liver tissues. Quantitative variables were tested by Kolmogorov-Smirnov test, repeated measures analysis of variance/Friedman test. Gene levels were assessed by Student's t-test/Mann-Whitney U-test. BCL-2 levels were significantly higher in I/R apigenin groups than in I/R control groups. BAX levels were lower in the AP240 group than in C240 group. Prolongation of reperfusion resulted in increased activation of M30. ICAM-1 levels were lower in the AP240 group than in C240 group. Apigenin seems to inhibit the process of apoptosis and ameliorate the hepatic I/R injury.

Intra-Abdominal Cooling System Limits Ischemia-Reperfusion Injury During Robot-Assisted Renal Transplantation.

PubMed

Meier, R P H; Piller, V; Hagen, M E; Joliat, C; Buchs, J-B; Nastasi, A; Ruttimann, R; Buchs, N C; Moll, S; Vallée, J-P; Lazeyras, F; Morel, P; Bühler, L

2018-01-01

Robot-assisted kidney transplantation is feasible; however, concerns have been raised about possible increases in warm ischemia times. We describe a novel intra-abdominal cooling system to continuously cool the kidney during the procedure. Porcine kidneys were procured by standard open technique. Groups were as follows: Robotic renal transplantation with (n = 11) and without (n = 6) continuous intra-abdominal cooling and conventional open technique with intermittent 4°C saline cooling (n = 6). Renal cortex temperature, magnetic resonance imaging, and histology were analyzed. Robotic renal transplantation required a longer anastomosis time, either with or without the cooling system, compared to the open approach (70.4 ± 17.7 min and 74.0 ± 21.5 min vs. 48.7 ± 11.2 min, p-values < 0.05). The temperature was lower in the robotic group with cooling system compared to the open approach group (6.5 ± 3.1°C vs. 22.5 ± 6.5°C; p = 0.001) or compared to the robotic group without the cooling system (28.7 ± 3.3°C; p < 0.001). Magnetic resonance imaging parenchymal heterogeneities and histologic ischemia-reperfusion lesions were more severe in the robotic group without cooling than in the cooled (open and robotic) groups. Robot-assisted kidney transplantation prolongs the warm ischemia time of the donor kidney. We developed a novel intra-abdominal cooling system that suppresses the noncontrolled rewarming of donor kidneys during the transplant procedure and prevents ischemia-reperfusion injuries. © 2017 The Authors. American Journal of Transplantation published by Wiley Periodicals, Inc. on behalf of American Society of Transplant Surgeons.

Controversies in cardiovascular care: silent myocardial ischemia

NASA Technical Reports Server (NTRS)

Hollenberg, N. K.

1987-01-01

The objective evidence of silent myocardial ischemia--ischemia in the absence of classical chest pain--includes ST-segment shifts (usually depression), momentary left ventricular failure, and perfusion defects on scintigraphic studies. Assessment of angina patients with 24-hour ambulatory monitoring may uncover episodes of silent ischemia, the existence of which may give important information regarding prognosis and may help structure a more effective therapeutic regimen. The emerging recognition of silent ischemia as a significant clinical entity may eventually result in an expansion of current therapy--not only to ameliorate chest pain, but to minimize or eliminate ischemia in the absence of chest pain.

Delayed hippocampal neuronal death in young gerbil following transient global cerebral ischemia is related to higher and longer-term expression of p63 in the ischemic hippocampus

PubMed Central

Bae, Eun Joo; Chen, Bai Hui; Yan, Bing Chun; Shin, Bich Na; Cho, Jeong Hwi; Kim, In Hye; Ahn, Ji Hyeon; Lee, Jae Chul; Tae, Hyun-Jin; Hong, Seongkweon; Kim, Dong Won; Cho, Jun Hwi; Lee, Yun Lyul; Won, Moo-Ho; Park, Joon Ha

2015-01-01

The tumor suppressor p63 is one of p53 family members and plays a vital role as a regulator of neuronal apoptosis in the development of the nervous system. However, the role of p63 in mature neuronal death has not been addressed yet. In this study, we first compared ischemia-induced effects on p63 expression in the hippocampal regions (CA1–3) between the young and adult gerbils subjected to 5 minutes of transient global cerebral ischemia. Neuronal death in the hippocampal CA1 region of young gerbils was significantly slow compared with that in the adult gerbils after transient global cerebral ischemia. p63 immunoreactivity in the hippocampal CA1 pyramidal neurons in the sham-operated young group was significantly low compared with that in the sham-operated adult group. p63 immunoreactivity was apparently changed in ischemic hippocampal CA1 pyramidal neurons in both ischemia-operated young and adult groups. In the ischemia-operated adult groups, p63 immunoreactivity in the hippocampal CA1 pyramidal neurons was significantly decreased at 4 days post-ischemia; however, p63 immunoreactivity in the ischemia-operated young group was significantly higher than that in the ischemia-operated adult group. At 7 days post-ischemia, p63 immunoreactivity was decreased in the hippocampal CA1 pyramidal neurons in both ischemia-operated young and adult groups. Change patterns of p63 level in the hippocampal CA1 region of adult and young gerbils after ischemic damage were similar to those observed in the immunohistochemical results. These findings indicate that higher and longer-term expression of p63 in the hippocampal CA1 region of the young gerbils after ischemia/reperfusion may be related to more delayed neuronal death compared to that in the adults. PMID:26199612

Revascularization and Muscle Adaptation to Limb Demand Ischemia in Diet Induced Obese Mice

PubMed Central

Albadawi, Hassan; Tzika, Aria; Rask-Madsen, Christian; Crowley, Lindsey M.; Koulopoulos, Michael W.; Yoo, Hyung-Jin; Watkins, Michael T.

2016-01-01

Background Obesity and type 2 diabetes are major risk factors for peripheral arterial disease (PAD) in humans which can result in lower limb demand ischemia and exercise intolerance. Exercise triggers skeletal muscle adaptation including increased vasculogenesis. The goal of this study was to determine whether demand ischemia modulates revascularization, fiber size, and signaling pathways in the ischemic hind limb muscles of mice with diet-induced obesity (DIO). Materials and Methods DIO mice (n=7) underwent unilateral femoral artery ligation (FAL) and recovered for 2-weeks followed by 4-weeks with daily treadmill exercise to induce demand ischemia. A parallel sedentary ischemia group (n=7) had FAL without exercise. The contralateral limb muscles of sedentary ischemia served as control. Muscles were examined for capillary density, myofiber cross-sectional area (CSA), cytokine levels, and phosphorylation of STAT3 and ERK1/2. Results Exercise significantly enhanced capillary density (p<0.01) and markedly lowered CSA (p<0.001) in demand ischemia compared to sedentary ischemia. These findings coincided with a significant increase in G-CSF (p<0.001) and IL-7 (p<0.01) levels. In addition, phosphorylation of STAT3 and ERK1/2 (p<0.01) were increased while UCP-1 and MCP-1 protein levels were lower (p<0.05) without altering VEGF and TNFα protein levels. Demand ischemia increased the PGC1α mRNA (p<0.001) without augmenting PGC1α protein levels. Conclusions Exercise induced limb demands ischemia in the setting of DIO causes myofiber atrophy despite an increase in muscle capillary density. The combination of persistent increase in TNFα, lower VEGF and failure to increase PGC1α protein may reflect a deficient adaption to demand ischemia in DIO. PMID:27620999

Protective effect of FK506 on myocardial ischemia/reperfusion injury by suppression of CaN and ASK1 signaling circuitry.

PubMed

Feng, Xing; Li, Jing; Liu, Jinyu; Jin, Minghua; Liu, Xiaomei; Du, Haiying; Zhang, Long; Sun, Zhiwei; Li, Xiaoguang

2011-03-01

We investigated protective effect of FK506 on rat hearts subjected to ischemia/reperfusion (I/R) injury by regulating CaN and ASK1. Wistar rats were divided into four groups: Ischemia/reperfusion group (I/R), FK506 + Ischemia/reperfusion group (FK506-I/R), sham group, and FK506 + sham group (FK506-sham). Ischemia/reperfusion was achieved by occluding left coronary artery for 30 min and subsequently reperfusing for 120 min. FK506 was administered 15 min before ischemia. Rats in sham group and FK506-sham group were operated only by placing a ligature around the coronary artery, and the blood supply was not blocked. I/R group showed a rapid increase in TUNEL-positive cells and high risks of histopathological changes in damaged cardiac tissues. FK506 reduced the infarct size and inhibited the activation of CaN enzyme in FK506-I/R group. Increase in Bcl-2/Bax ratio in FK506-IR group indicated that FK506 protected myocardium from apoptosis induced by IR. The activity of CaN and ASK1 protein level decreased significantly after I/R injury in FK506-treated I/R heart. FK506 suppresses the activation of CaN and ASK1 through CaN-mediated apoptosis pathway, and ASK1 negatively regulates CaN activity. Suppression of CaN and ASK1 signaling circuitry are involved in protective effect of FK506 on rat myocardium I/R injury.

Remifentanil ameliorates intestinal ischemia-reperfusion injury

PubMed Central

2013-01-01

Background Intestinal ischemia-reperfusion injury (IRI) can occur in clinical scenarios such as organ transplantation, trauma and cardio-pulmonary bypass, as well as in neonatal necrotizing enterocolitis or persistent ductus arteriosus. Pharmacological protection by pretreating (“preconditioning”) with opioids attenuates IRI in a number of organs. Remifentanil appears particularly attractive for this purpose because of its ultra-short duration of action and favorable safety profile. To date, little is known about opioid preconditioning of the intestine. Methods Young adult C57BL/6J mice were randomly assigned to receive tail vein injections of 1 μg/kg of remifentanil or normal saline and underwent either ischemia-reperfusion of the intestine or a sham laparotomy. Under isoflurane anesthesia, the mice were subjected to intestinal ischemia-reperfusion by occlusion (clamping) of the superior mesenteric artery for 30 min, followed by unclamping and 60 min of reperfusion. After completion of this protocol, tissue injury and lipid peroxidation in jejunum and ileum were analyzed by histology and malondialdehyde (MDA), respectively. Systemic interleukin (IL)-6 was determined in the plasma by ELISA. Results Pretreatment with remifentanil markedly reduced intestinal IRI (P < 0.001): In the ileum, we observed a more than 8-fold decrease in injured villi (4% vs 34% in saline-pretreated animals). In fact, the mucosa in the remifentanil group was as healthy as that of sham-operated animals. This protective effect was not as pronounced in the jejunum, but the percentage of damaged villi was still reduced considerably (18% vs 42%). There was up to 3-fold more tissue MDA after intestinal ischemia-reperfusion than after sham laparotomy, but this increase in lipid peroxidation was prevented by preconditioning with remifentanil (P < 0.05). The systemic inflammatory response triggered by intestinal IRI was significantly attenuated in mice pretreated with remifentanil (159 vs 805

Prolonged therapeutic hypothermia does not adversely impact neuroplasticity after global ischemia in rats

PubMed Central

Silasi, Gergely; Klahr, Ana C; Hackett, Mark J; Auriat, Angela M; Nichol, Helen; Colbourne, Frederick

2012-01-01

Hypothermia improves clinical outcome after cardiac arrest in adults. Animal data show that a day or more of cooling optimally reduces edema and tissue injury after cerebral ischemia, especially after longer intervention delays. Lengthy treatments, however, may inhibit repair processes (e.g., synaptogenesis). Thus, we evaluated whether unilateral brain hypothermia (∼33°C) affects neuroplasticity in the rat 2-vessel occlusion model. In the first experiment, we cooled starting 1 hour after ischemia for 2, 4, or 7 days. Another group was cooled for 2 days starting 48 hours after ischemia. One group remained normothermic throughout. All hypothermia treatments started 1 hour after ischemia equally reduced hippocampal CA1 injury in the cooled hemisphere compared with the normothermic side and the normothermic group. Cooling only on days 3 and 4 was not beneficial. Importantly, no treatment influenced neurogenesis (Ki67/Doublecortin (DCX) staining), synapse formation (synaptophysin), or brain-derived neurotropic factor (BDNF) immunohistochemistry. A second experiment confirmed that BDNF levels (ELISA) were equivalent in normothermic and 7-day cooled rats. Last, we measured zinc (Zn), which is important in plasticity, with X-ray fluorescence imaging in normothermic and 7-day cooled rats. Hypothermia did not alter the postischemic distribution of Zn within the hippocampus. In summary, cooling significantly mitigates injury without compromising neuroplasticity. PMID:22434072

[Effects of xenon preconditioning against ischemia/reperfusion injury and oxidative stress in immature heart].

PubMed

Li, Qian; Lian, Chun-Wei; Fang, Li-Qun; Liu, Bin; Yang, Bo

2014-09-01

To investigate whether xenon preconditioning (PC) could protect immature myocardium against ischemia-reperfusion (I/R) injury in a dose-dependent manner and clarify the role of xenon PC on oxidative stress. Forty-eight isolated perfused immature rabbit hearts were randomly divided into four groups (n = 12): The sham group had the hearts perfused continuously for 300 min. In I/R group, the hearts were subjected to 60 min perfusion followed by 60 min ischemia and 180 min reperfusion. In 1 minimum alveolar concentration (MAC) and 0.5 MAC xenon PC groups, the hearts were preconditioned with 1 MAC or 0.5 MAC xenon respectively, following 60 min ischemia and 180 min reperfusion. The cardiac function, myocardial infarct size, mitochondrial structure, superoxide dismutase (SOD) activity and malondialdehyde (MDA) level in each group were determined after reperfusion. Compared with I/R group, both 1 MAC and 0. 5 MAC xenon preconditioning significantly improved cardiac function (P < 0.01), reduced myocardial infarct size (P < 0.01) and mitochondrial damage, increased SOD activity and decreased MDA level (P < 0.01). There were no differences between 1 MAC group and 0.5 MAC xenon group (P > 0.05). Xenon preconditioning at 0. 5 and 1 MAC produce similar cardioprotective effects against I/R injury in isolated perfused immature heart.

Sevoflurane anesthesia during acute right ventricular ischemia in pigs preserves cardiac function better than propofol anesthesia.

PubMed

Haraldsen, Pernille; Metzsch, Carsten; Lindstedt, Sandra; Algotsson, Lars; Ingemansson, Richard

2016-09-01

The intention of the present study was to evaluate possible cardioprotective properties of inhalation anesthesia with sevoflurane. A porcine, open-chest model of right ventricular ischemia was used in 7 pigs receiving inhalation anesthesia with sevoflurane. The model was earlier developed and published by our group, using pigs receiving intravenous anesthesia with propofol. They served as controls. The animals were observed for three hours after the induction of right ventricular ischemia by ligation of the main branches supplying the right ventricular free wall. In the sevoflurane group, the cardiac output recovered 2 hours after the induction of ischemia and intact right ventricular stroke work was observed. In the propofol group, no such recovery occurred. The release of troponin T was significantly lower than in the sevoflurane group. Inhalation anesthesia with sevoflurane seems superior to intravenous anesthesia with propofol in acute right ventricular ischemic dysfunction. © The Author(s) 2016.

A vigilant, hypoxia-regulated heme oxygenase-1 gene vector in the heart limits cardiac injury after ischemia-reperfusion in vivo.

PubMed

Tang, Yao Liang; Qian, Keping; Zhang, Y Clare; Shen, Leping; Phillips, M Ian

2005-12-01

The effect of a cardiac specific, hypoxia-regulated, human heme oxygenase-1 (hHO-1) vector to provide cardioprotection from ischemia-reperfusion injury was assessed. When myocardial ischemia and reperfusion is asymptomatic, the damaging effects are cumulative and patients miss timely treatment. A gene therapy approach that expresses therapeutic genes only when ischemia is experienced is a desirable strategy. We have developed a cardiac-specific, hypoxia-regulated gene therapy "vigilant vector'' system that amplifies cardioprotective gene expression. Vigilant hHO-1 plasmids, LacZ plasmids, or saline (n = 40 per group) were injected into mouse heart 2 days in advance of ischemia-reperfusion injury. Animals were exposed to 60 minutes of ischemia followed by 24 hours of reperfusion. For that term (24 hours) effects, the protein levels of HO-1, inflammatory responses, apoptosis, and infarct size were determined. For long-term (3 week) effects, the left ventricular remodeling and recovery of cardiac function were assessed. Ischemia-reperfusion resulted in a timely overexpression of HO-1 protein. Infarct size at 24 hours after ischemia-reperfusion was significantly reduced in the HO-1-treated animals compared with the LacZ-treated group or saline-treated group (P < .001). The reduction of infarct size was accompanied by a decrease in lipid peroxidant activity, inflammatory cell infiltration, and proapoptotic protein level in ischemia-reperfusion-injured myocardium. The long-term study demonstrated that timely, hypoxia-induced HO-1 overexpression is beneficial in conserving cardiac function and attenuating left ventricle remodelling. The vigilant HO-1 vector provides a protective therapy in the heart for reducing cellular damage during ischemia-reperfusion injury and preserving heart function.

AMPD1 gene polymorphism and the vasodilatory response to ischemia.

PubMed

Hand, Brian D; Roth, Stephen M; Roltsch, Mark H; Park, Jung-Jun; Kostek, Matthew C; Ferrell, Robert E; Brown, Michael D

2006-09-05

Peripheral vasculature resistance can play an important role in affecting blood pressure and the development of cardiovascular disease. A better understanding of the genes that encode vasodilators, such as adenosine, will provide insight into the mechanisms underlying cardiovascular disease. We tested whether the adenosine monophosphate deaminase-1 (AMPD1) C34T gene polymorphism was associated with the vasodilatory response to ischemia in Caucasian females aged 18-35 years. Blood samples (n = 58) were analyzed for the C34T variant and resulted in the following genotype groups: CC (n = 45) and CT (n = 13). Mean blood pressure (MBP), heart rate, and forearm blood flow (FBF) measured by venous occlusion plethysmography were measured at baseline and at 1 (peak FBF), 2 and 3 min of vasodilation during reactive hyperemia following 5 min of arm ischemia. To control for interindividual variability in baseline FBF and forearm vascular resistance (FVR) the percent change in FBF and FVR were calculated for each min. The percent decrease in FVR was significantly greater in the CT compared to the CC genotype group (-40+/-4% vs. -24+/-3%, P = 0.01) during the 2nd min of reactive hyperemia. The percent increase in FBF tended to be greater in the CT compared to the CC genotype group (+69+/-9% vs. +42+/-9%, P = 0.07) during the 2nd min of reactive hyperemia after adjustment for percent body fat. Consistent with previous findings of increased production of adenosine during exercise in individuals carrying a T allele, our findings suggest that the AMPD1 C34T polymorphism is associated with vasodilatory response to ischemia in the peripheral vasculature because individuals with the T allele had a greater vasodilatory response to ischemia.

Extending the duration of hypothermia does not further improve white matter protection after ischemia in term-equivalent fetal sheep.

PubMed

Davidson, Joanne O; Yuill, Caroline A; Zhang, Frank G; Wassink, Guido; Bennet, Laura; Gunn, Alistair J

2016-04-28

A major challenge in modern neonatal care is to further improve outcomes after therapeutic hypothermia for hypoxic ischemic encephalopathy. In this study we tested whether extending the duration of cooling might reduce white matter damage. Term-equivalent fetal sheep (0.85 gestation) received either sham ischemia followed by normothermia (n = 8) or 30 minutes of bilateral carotid artery occlusion followed by three days of normothermia (n = 8), three days of hypothermia (n = 8) or five days of hypothermia (n = 8) started three hours after ischemia. Histology was assessed 7 days after ischemia. Ischemia was associated with loss of myelin basic protein (MBP) and Olig-2 positive oligodendrocytes and increased Iba-1-positive microglia compared to sham controls (p < 0.05). Three days and five days of hypothermia were associated with a similar, partial improvement in MBP and numbers of oligodendrocytes compared to ischemia-normothermia (p < 0.05). Both hypothermia groups had reduced microglial activation compared to ischemia-normothermia (p < 0.05). In the ischemia-five-day hypothermia group, but not ischemia-three-day, numbers of microglia remained higher than in sham controls (p < 0.05). In conclusion, delayed cerebral hypothermia partially protected white matter after global cerebral ischemia in fetal sheep. Extending cooling from 3 to 5 days did not further improve outcomes, and may be associated with greater numbers of residual microglia.

Effects of kefir on ischemia-reperfusion injury.

PubMed

Yener, A U; Sehitoglu, M H; Ozkan, M T A; Bekler, A; Ekin, A; Cokkalender, O; Deniz, M; Sacar, M; Karaca, T; Ozcan, S; Kurt, T

2015-01-01

We aimed to investigate the effect of kefir on Ischemia-Reperfusion (I/R) injury on rats. 24 male Sprague-Dawley rats between 250-350 g were selected. Rats were divided into three groups, and there were eight rats in each group. Rats were fed for 60 days. All of the rats were fed with the same diet for the first 30 days. In the second thirty days, kefir [10 cc/kg/day body weight (2 x 109 cfu/kg/day)] was added to the diet of the study group by gavage method. In all groups, lung and kidney tissues were removed after the procedure and rats were sacrificed. The biochemical and histopathological changes were observed in the lung and kidney within the samples. Serum urea, creatinine and tumor necrosis factor (TNF-α) were determined. Kefir + I/R groups was compared with I/R groups, a significant decrease (p < 0.05) was seen in Lipid peroxidation (MDA) levels of lung and renal tissues. Superoxide dismutase (SOD), Catalase (CAT) and Glutathione peroxidase (GSH-Px) activities of lung and kidney tissues decreased in I/R groups (p < 0.05). The enzyme activities in Kefir + I/R groups of renal tissues were significantly (p < 0.05) higher than I/R, not significantly different in lung tissues (p < 0.05). Kefir reduced the levels of serum urea, creatinine and TNF-α significantly.   This would be useful in this model against ischemia/reperfusion, and shows the protective effect of kefir in tissue and serum functions.

Difference in transient ischemia-induced neuronal damage and glucose transporter-1 immunoreactivity in the hippocampus between adult and young gerbils

PubMed Central

Park, Seung Min; Lee, Jae-Chul; Chen, Bai Hui; Shin, Bich-Na; Cho, Jeong Hwi; Kim, In Hye; Park, Joon Ha; Won, Moo-Ho; Ahn, Ji Hyeon; Tae, Hyun-Jin; Shin, Myoung Cheol; Park, Chan Woo; Cho, Jun Hwi; Lee, Hui Young

2016-01-01

Objective(s): The alteration of glucose transporters is closely related with the pathogenesis of brain edema. We compared neuronal damage/death in the hippocampus between adult and young gerbils following transient cerebral ischemia/reperfusion and changes of glucose transporter-1(GLUT-1)-immunoreactive microvessels in their ischemic hippocampal CA1 region. Materials and Methods: Transient cerebral ischemia was developed by 5-min occlusion of both common carotid arteries. Neuronal damage was examined by cresyl violet staining, NeuN immunohistochemistry and Fluoro-Jade B histofluorescence staining and changes in GLUT-1 expression was carried out by immunohistochemistry. Results: About 90% of pyramidal neurons only in the adult CA1 region were damaged after ischemia/reperfusion; in the young, about 53 % of pyramidal neurons were damaged from 7 days after ischemia/reperfusion. The density of GLUT-1-immunoreactive microvessels was significantly higher in the young sham-group than that in the adult sham-group. In the ischemia-operated-groups, the density of GLUT-1-immunoreactive microvessels was significantly decreased in the adult and young at 1 and 4 days post-ischemia, respectively, thereafter, the density of GLUT-1-immunoreactive microvessels was gradually increased in both groups after ischemia/reperfusion. Conclusion: CA1 pyramidal neurons of the young gerbil were damaged much later than that in the adult and that GLUT-1-immunoreactive microvessels were significantly decreased later in the young. These data indicate that GLUT-1 might differently contribute to neuronal damage according to age after ischemic insults. PMID:27403259

Role of sirtuins in ischemia-reperfusion injury.

PubMed

Pantazi, Eirini; Zaouali, Mohamed Amine; Bejaoui, Mohamed; Folch-Puy, Emma; Ben Abdennebi, Hassen; Roselló-Catafau, Joan

2013-01-01

Ischemia-reperfusion injury (IRI) remains an unresolved and complicated situation in clinical practice, especially in the case of organ transplantation. Several factors contribute to its complexity; the depletion of energy during ischemia and the induction of oxidative stress during reperfusion initiate a cascade of pathways that lead to cell death and finally to severe organ injury. Recently, the sirtuin family of nicotinamide adenine dinucleotide-dependent deacetylases has gained increasing attention from researchers, due to their involvement in the modulation of a wide variety of cellular functions. There are seven mammalian sirtuins and, among them, the nuclear/cytoplasmic sirtuin 1 (SIRT1) and the mitochondrial sirtuin 3 (SIRT3) are ubiquitously expressed in many tissue types. Sirtuins are known to play major roles in protecting against cellular stress and in controlling metabolic pathways, which are key processes during IRI. In this review, we mainly focus on SIRT1 and SIRT3 and examine their role in modulating pathways against energy depletion during ischemia and their involvement in oxidative stress, apoptosis, microcirculatory stress and inflammation during reperfusion. We present evidence of the beneficial effects of sirtuins against IRI and emphasize the importance of developing new strategies by enhancing their action.

Capsaicin-sensitive muscle afferents modulate the monosynaptic reflex in response to muscle ischemia and fatigue in the rat.

PubMed

Della Torre, G; Brunetti, O; Pettorossi, V E

2002-01-01

The role of muscle ischemia and fatigue in modulating the monosynaptic reflex was investigated in decerebrate and spinalized rats. Field potentials and fast motoneuron single units in the lateral gastrocnemious (LG) motor pool were evoked by dorsal root stimulation. Muscle ischemia was induced by occluding the LG vascular supply and muscle fatigue by prolonged tetanic electrical stimulation of the LG motor nerve. Under muscle ischemia the monosynaptic reflex was facilitated since the size of the early and late waves of the field potential and the excitability of the motoneuron units increased. This effect was abolished after L3-L6 dorsal rhizotomy, but it was unaffected after L3-L6 ventral rhizotomy. By contrast, the monosynaptic reflex was inhibited by muscle fatiguing stimulation, and this effect did not fully depend on the integrity of the dorsal root. However, when ischemia was combined with repetitive tetanic muscle stimulation the inhibitory effect of fatigue was significantly enhanced. Both the ischemia and fatigue effects were abolished by capsaicin injected into the LG muscle at a dose that blocked a large number of group III and IV muscle afferents. We concluded that muscle ischemia and fatigue activate different groups of muscle afferents that are both sensitive to capsaicin, but enter the spinal cord through different roots. They are responsible for opposite effects, when given separately: facilitation during ischemia and inhibition during fatigue; however, in combination, ischemia enhances the responsiveness of the afferent fibres to fatigue.

Diagnostic Performance of Artificial Neural Network for Detecting Ischemia in Myocardial Perfusion Imaging.

PubMed

Nakajima, Kenichi; Matsuo, Shinro; Wakabayashi, Hiroshi; Yokoyama, Kunihiko; Bunko, Hisashi; Okuda, Koichi; Kinuya, Seigo; Nyström, Karin; Edenbrandt, Lars

2015-01-01

The purpose of this study was to apply an artificial neural network (ANN) in patients with coronary artery disease (CAD) and to characterize its diagnostic ability compared with conventional visual and quantitative methods in myocardial perfusion imaging (MPI). A total of 106 patients with CAD were studied with MPI, including multiple vessel disease (49%), history of myocardial infarction (27%) and coronary intervention (30%). The ANN detected abnormal areas with a probability of stress defect and ischemia. The consensus diagnosis based on expert interpretation and coronary stenosis was used as the gold standard. The left ventricular ANN value was higher in the stress-defect group than in the no-defect group (0.92±0.11 vs. 0.25±0.32, P<0.0001) and higher in the ischemia group than in the no-ischemia group (0.70±0.40 vs. 0.004±0.032, P<0.0001). Receiver-operating characteristics curve analysis showed comparable diagnostic accuracy between ANN and the scoring methods (0.971 vs. 0.980 for stress defect, and 0.882 vs. 0.937 for ischemia, both P=NS). The relationship between the ANN and defect scores was non-linear, with the ANN rapidly increased in ranges of summed stress score of 2-7 and summed defect score of 2-4. Although the diagnostic ability of ANN was similar to that of conventional scoring methods, the ANN could provide a different viewpoint for judging abnormality, and thus is a promising method for evaluating abnormality in MPI.

Oxidative stress gene expression profile in inbred mouse after ischemia/reperfusion small bowel injury.

PubMed

Bertoletto, Paulo Roberto; Ikejiri, Adauto Tsutomu; Somaio Neto, Frederico; Chaves, José Carlos; Teruya, Roberto; Bertoletto, Eduardo Rodrigues; Taha, Murched Omar; Fagundes, Djalma José

2012-11-01

To determine the profile of gene expressions associated with oxidative stress and thereby contribute to establish parameters about the role of enzyme clusters related to the ischemia/reperfusion intestinal injury. Twelve male inbred mice (C57BL/6) were randomly assigned: Control Group (CG) submitted to anesthesia, laparotomy and observed by 120 min; Ischemia/reperfusion Group (IRG) submitted to anesthesia, laparotomy, 60 min of small bowel ischemia and 60 min of reperfusion. A pool of six samples was submitted to the qPCR-RT protocol (six clusters) for mouse oxidative stress and antioxidant defense pathways. On the 84 genes investigated, 64 (76.2%) had statistic significant expression and 20 (23.8%) showed no statistical difference to the control group. From these 64 significantly expressed genes, 60 (93.7%) were up-regulated and 04 (6.3%) were down-regulated. From the group with no statistical significantly expression, 12 genes were up-regulated and 8 genes were down-regulated. Surprisingly, 37 (44.04%) showed a higher than threefold up-regulation and then arbitrarily the values was considered as a very significant. Thus, 37 genes (44.04%) were expressed very significantly up-regulated. The remained 47 (55.9%) genes were up-regulated less than three folds (35 genes - 41.6%) or down-regulated less than three folds (12 genes - 14.3%). The intestinal ischemia and reperfusion promote a global hyper-expression profile of six different clusters genes related to antioxidant defense and oxidative stress.

Expression of HSP 70 and its mRNAS during ischemia-reperfusion in the rat bladder.

PubMed

Saito, Motoaki; Tominaga, Lika; Nanba, Eiji; Kinoshita, Yukako; Housi, Daisuke; Miyagawa, Ikuo; Satoh, Keisuke

2004-08-27

HSP 70 is an important protein that repairs damaged tissue after injury. In the present study, we investigated the expression of HSP 70 and its mRNAs during ischemia-reperfusion in the rat bladder. Rat abdominal aorta was clamped with a small clip to induce ischemia-reperfusion injury in the bladder dome. Male Wistar rats, 8 weeks old, were divided into six groups: controls, 30-min ischemia, 30-min ischemia and 30-, 60-minute, 1- and 7-day reperfusion, groups A, B, C, D, E, and F, respectively. In functional studies, contractile responses to carbachol were measured in these groups. The expression of HSP 70-1/2 mRNAs was quantified using a real-time PCR method, and that of HSP 70 proteins was measured using ELISA in the bladders. In the functional study, Emax values of carbachol to bladders in the A, B, C, D, E and F groups were 9.3 +/- 1.3, 7.9 +/- 1.7, 4.3 +/- 0.8, 4.2 +/- 0.7, 4.5 +/- 0.6, and 8.1 +/- 1.2 g/mm2, respectively. In the control group, the expression of HSP 70-1/2 mRNA was detected, and the expression of HSP 70-1 mRNAs was significantly higher than that of HSP 70-2 mRNAs in each group. The expression of HSP 70-1 mRNA increased in groups B and C, but decreased in groups D, E, and F. The expression of HSP 70-2 mRNA in group C was significantly higher than that of groups A, D, E, and F. The expression of HSP 70-1/2 mRNAs after 1 day or 1 week of reperfusion was similar to control levels. The expression of HSP 70 proteins was increased shortly after the expression of their mRNAs. The expression of HSP 70 after 1 day or 1 week of reperfusion was almost identical to control levels. Our data indicate that contractile responses of the bladder were decreased by ischemia reperfusion, and that expression of HSP 70 and its mRNAs appeared to increase after a short period of the insult.

Transgenic expression of Bcl-2 modulates energy metabolism, prevents cytosolic acidification during ischemia, and reduces ischemia/reperfusion injury.

PubMed

Imahashi, Kenichi; Schneider, Michael D; Steenbergen, Charles; Murphy, Elizabeth

2004-10-01

The antiapoptotic protein Bcl-2 is targeted to the mitochondria, but it is uncertain whether Bcl-2 affects only myocyte survival after ischemia, or whether it also affects metabolic functions of mitochondria during ischemia. Hearts from mice overexpressing human Bcl-2 and from their wild-type littermates (WT) were subjected to 24 minutes of global ischemia followed by reperfusion. During ischemia, the decrease in pH(i) and the initial rate of decline in ATP were significantly reduced in Bcl-2 hearts compared with WT hearts (P<0.05). The reduced acidification during ischemia was dependent on the activity of mitochondrial F1F0-ATPase. In the presence of oligomycin (Oligo), an F1F0-ATPase inhibitor, the decrease in pH(i) was attenuated in WT hearts, but in Bcl-2 hearts, Oligo had no additional effect on pH(i) during ischemia. Likewise, addition of Oligo to WT hearts slowed the rate of decline in ATP during ischemia to a level similar to that observed in Bcl-2 hearts, but addition of Oligo had no significant effect on the rate of decline in ATP in Bcl-2 hearts during ischemia. These data are consistent with Bcl-2-mediated inhibition of consumption of glycolytic ATP. Furthermore, mitochondria from Bcl-2 hearts have a reduced rate of consumption of ATP on uncoupler addition. This could be accomplished by limiting ATP entry into the mitochondria through the voltage-dependent anion channel, and/or the adenine nucleotide transporter, or by direct inhibition of the F1F0-ATPase. Immunoprecipitation showed greater interaction between Bcl-2 and voltage-dependent anion channel during ischemia. These data indicate that Bcl-2 modulation of metabolism contributes to cardioprotection.

Moderate hypothermia suppresses jugular venous superoxide anion radical, oxidative stress, early inflammation, and endothelial injury in forebrain ischemia/reperfusion rats.

PubMed

Koda, Yoichi; Tsuruta, Ryosuke; Fujita, Motoki; Miyauchi, Takashi; Kaneda, Kotaro; Todani, Masaki; Aoki, Tetsuya; Shitara, Masaki; Izumi, Tomonori; Kasaoka, Shunji; Yuasa, Makoto; Maekawa, Tsuyoshi

2010-01-22

The aim of this study was to assess the effect of moderate hypothermia (MH) on generation of jugular venous superoxide radical (O2-.), oxidative stress, early inflammation, and endothelial injury in forebrain ischemia/reperfusion (FBI/R) rats. Twenty-one Wistar rats were allocated to a control group (n=7, 37 degrees C), a pre-MH group (n=7, 32 degrees C before ischemia), and a post-MH group (n=7, 32 degrees C after reperfusion). MH was induced before induction of ischemia in the pre-MH group and just after reperfusion in the post-MH group. Forebrain ischemia was induced by occlusion of bilateral common carotid arteries with hemorrhagic hypotension for 10 min, followed by reperfusion. O(2)(-)(.) in the jugular vein was measured from the produced current using a novel O2-. sensor. The O2-. current showed a gradual increase during forebrain ischemia in the control and post-MH groups but was attenuated in the pre-MH group. Following reperfusion, the current showed a marked increase in the control group but was strongly attenuated in the pre- and post-MH groups. Concentrations of malondialdehyde, high-mobility group box 1 (HMGB1) protein, and intercellular adhesion molecule-1 (ICAM-1) in the brain and plasma 120 min after reperfusion in the pre- and post-MH groups were significantly lower than those in the control group, except for plasma HMGB1 in the post-MH group. In conclusion, MH suppressed O2-. measured in the jugular vein, oxidative stress, early inflammation, and endothelial injury in FBI/R rats. Copyright 2009 Elsevier B.V. All rights reserved.

Lipoate ameliorates ischemia-reperfusion in animal models.

PubMed

Freisleben, H J

2000-01-01

Ischemia and reperfusion were studied in isolated working rat hearts and in exarticulated rat hind limbs. Free radicals are known to be generated in ischemia/reperfusion and to propagate complications. To reduce reperfusion injury, conditions were ameliorated including the treatment with antioxidants, lipoate or dihydrolipoate. In isolated working rat hearts, cardiac and mitochondrial parameters are impaired during hypoxia and partially recover in reperfusion. Dihydrolipoate, if added into the perfusion buffer at 0.3 microM concentration, keeps the pH higher (7.15) during hypoxia, as compared to controls (6.98). This compound accelerates and stabilizes the recovery of the aortic flow. With dihydrolipoate, ATP synthesis is increased, ATPase activity (ATP hydrolysis) reduced, intracellular creatine kinase activity maintained and thus phosphocreatine contents are higher than in controls. For exarticulated rat hind limbs, the dihydrolipoate group contained 8.3 microM in the modified reperfusate. Recovery of the contractile function was 49% vs. 34% in controls and muscle flexibility was maintained whereas it decreased by 15% in the controls. Release of creatine kinase from cells was significantly lower with dihydrolipoate. Lipoate/dihydrolipoate effectively reduced reperfusion injury in isolated working rat hearts and in exarticulated rat hind limbs after extended ischemia. Finally, the compound was successfully applied in an in vivo pig hind limb model.

Neuroprotective effects of ebselen following forebrain ischemia: involvement of glutamate and nitric oxide.

PubMed

Koizumi, Hiroyasu; Fujisawa, Hirosuke; Suehiro, Eiichi; Shirao, Satoshi; Suzuki, Michiyasu

2011-01-01

Ebselen is a mimic of glutathione peroxidase that reacts with peroxynitrite and inhibits nitric oxide (NO) synthase. Ebselen has beneficial effects on the neurological outcome of patients with stroke. In this study, the mechanisms by which ebselen can elicit neuroprotective effects against ischemic brain injury were investigated in male Wistar rats. Experimental forebrain ischemia was induced by bilateral common carotid artery occlusion with hemorrhagic hypotension. Ebselen was administered to animals in the treatment group 2 hours prior to the induction of forebrain ischemia, and placebo was administered in the control group. Cerebral blood flow (CBF) was measured by the hydrogen clearance method. Cortical extracellular levels of excitatory amino acids (EAAs) and NO were evaluated using in vivo microdialysis. Neuronal damage in the CA1 subfield of the hippocampus was assessed in brains harvested after a 24-hour period of survival. CBF did not recover to normal physiological levels after ischemic insults in either the control or treatment groups. The differences in the sequential changes in extracellular EAA and NO levels between groups were not statistically significant. There was a significantly larger mean density of intact, undamaged neurons in the CA1 subfield in the treatment group than in the control group. The neuroprotective effects of ebselen were reflected in the histological findings, without significant inhibition of glutamate release or NO synthesis during the acute phase of experimentally induced cerebral ischemia.

Protective effect of Naringin on experimental hindlimb ischemia/reperfusion injury in rats.

PubMed

Gürsul, Cebrail; Ekinci Akdemir, Fazile Nur; Akkoyun, Turan; Can, İsmail; Gül, Mustafa; Gülçin, İlhami

2016-01-01

This study was designed to investigate the antioxidant effects of Naringin, in ischemia/reperfusion (I/R)-induced skeletal muscle injury in rats. The rats were randomly allocated into three groups including control, I/R and I/R + Naringin groups. Muscle tissues of I/R groups revealed significantly higher antioxidant enzyme activities, and increased levels of malondialdehyde, as specific a marker of the lipid peroxidation and tissue damage, compared to the control group (p < 0.05). Levels of these parameters in muscle revealed significant reductions in the I/R + Naringin group compared to the I/R group (p < 0.05). Histopathological examination of ischemia muscles in the I/R group showed significant degeneration and inflammation compared to the control group, whereas ischemic muscles of Naringin-administered group showed significant reduction in degeneration and inflammation compared to the I/R group (p < 0.05). We suggest that the protective effect of Naringin may reduce the I/R injury in cases of extremity injuries with acute vascular complications, extremity surgery with prolonged tourniquet application.

Neuroprotective effect of humic Acid on focal cerebral ischemia injury: an experimental study in rats.

PubMed

Ozkan, Adile; Sen, Halil Murat; Sehitoglu, Ibrahim; Alacam, Hasan; Guven, Mustafa; Aras, Adem Bozkurt; Akman, Tarik; Silan, Coşkun; Cosar, Murat; Karaman, Handan Isin Ozisik

2015-02-01

Stroke is still a major cause of death and permanent neurological disability. As humic acids are well-known antioxidant molecules, the purpose of this study was to investigate the potential neuroprotective effects of humic acid in a focal cerebral ischemia model. Twenty-four rats were divided equally into three groups. A middle cerebral artery occlusion model was performed in this study where control (group II) and humic acid (group III) were administered intraperitoneally following an ischemic experimental procedure. Group I was evaluated as sham. Malondialdehyde (MDA), superoxide dismutase (SOD), and nuclear respiratory factor-1 (NRF-1) levels were analyzed biochemically on the right side of the ischemic cerebral hemisphere, while ischemic histopathological studies were completed on the left side to investigate the antioxidant status. Biochemical results showed that SOD and NRF-1 levels were significantly increased in the humic acid group (III) compared with the control group (II) while MDA levels were significantly decreased. On histopathological examination, cerebral edema, vacuolization, degeneration, and destruction of neural elements were decreased in the humic acid group (III) compared with the control group (II). Cerebral ischemia was attenuated by humic acid administration. These observations indicate that humic acid may have potential as a therapeutic agent in cerebral ischemia by preventing oxidative stress.

Hypothermic machine perfusion permits extended cold ischemia times with improved early graft function.

PubMed

Guy, Alison; McGrogan, Damian; Inston, Nicholas; Ready, Andrew

2015-04-01

The logistics of deceased-donor renal transplants are largely affected by cold ischemia time. However, to attain successful outcomes, other issues must be considered. Extending cold ischemia time to accommodate these issues would be valuable. We investigated the role of hypothermic machine perfusion to extend cold ischaemia time. Deceased-donor kidneys were allocated to a storage method, depending on predicted time to operation. Kidneys to be transplanted from 8:00 AM to 8:00 PM in the transplant room remained in static cold storage. If predicted operating time was out of hours, the kidney was transferred to hypothermic machine perfusion and transplanted at the earliest opportunity on the dedicated transplant list. There were 74 kidneys transplanted from hypothermic machine perfusion and 101 kidneys from static cold storage. Median cold ischemia time was 23.85 hours in the hypothermic machine perfusion group, compared with 13 hours in the static cold storage group (P ≤ .0001). There were 20 kidneys (27%) from hypothermic machine perfusion that had delayed graft function, compared with 47 kidneys (47%) in the static cold storage group (P = .012). There were no other significant differences in graft or postoperative complications. This study demonstrated that improved early graft outcomes can be achieved following longer cold ischemia time by using hypothermic machine perfusion rather than static cold storage. This effect is likely multifactorial including the inherent effects of hypothermic machine perfusion, improved recipient preparation, and possibly better perioperative conditions.

Repetitive postprandial hyperglycemia increases cardiac ischemia/reperfusion injury: prevention by the alpha-glucosidase inhibitor acarbose.

PubMed

Frantz, Stefan; Calvillo, Laura; Tillmanns, Jochen; Elbing, Inka; Dienesch, Charlotte; Bischoff, Hilmar; Ertl, Georg; Bauersachs, Johann

2005-04-01

Protective effects of the alpha-glucosidase inhibitor acarbose have been reported for various diabetic complications. In the STOP-NIDDM study, even patients without overt diabetes, but with impaired glucose tolerance, had a reduction in cardiovascular events when treated with acarbose. Therefore, we investigated the effect of repetitive postprandial hyperglycemia on the cardiac ischemia/reperfusion injury in vivo. Mice were treated daily by single applications of placebo, sucrose (4 g/kg body weight), or sucrose + acarbose (10 mg/kg body weight) by gavage for 7 days. Acarbose treatment significantly reduced the sucrose-induced increase in plasma glucose concentration. Subsequently, animals underwent 30 min of ischemia by coronary artery ligation and 24 h of reperfusion in vivo. In the sucrose group, ischemia/reperfusion damage was significantly increased (infarct/area at risk, placebo vs. sucrose, 38.8+/-7.5% vs. 62.2+/-4.8%, P<0.05). This was prevented by acarbose treatment (infarct/area at risk 30.7+/-7.2%). While myocardial inflammation was similar in all groups, oxidative stress as indicated by a significant increase in lipid peroxides was enhanced in the sucrose, but not in the sucrose + acarbose group. In summary, repetitive postprandial hyperglycemia increases ischemia/reperfusion damage. This effect can be prevented by treatment with the alpha-glucosidase inhibitor acarbose.

Hemorheological changes in ischemia-reperfusion: an overview on our experimental surgical data.

PubMed

Nemeth, Norbert; Furka, Istvan; Miko, Iren

2014-01-01

Blood vessel occlusions of various origin, depending on the duration and extension, result in tissue damage, causing ischemic or ischemia-reperfusion injuries. Necessary surgical clamping of vessels in vascular-, gastrointestinal or parenchymal organ surgery, flap preparation-transplantation in reconstructive surgery, as well as traumatological vascular occlusions, all present special aspects. Ischemia and reperfusion have effects on hemorheological state by numerous ways: besides the local metabolic and micro-environmental changes, by hemodynamic alterations, free-radical and inflammatory pathways, acute phase reactions and coagulation changes. These processes may be harmful for red blood cells, impairing their deformability and influencing their aggregation behavior. However, there are still many unsolved or non-completely answered questions on relation of hemorheology and ischemia-reperfusion. How do various organ (liver, kidney, small intestine) or limb ischemic-reperfusionic processes of different duration and temperature affect the hemorheological factors? What is the expected magnitude and dynamics of these alterations? Where is the border of irreversibility? How can hemorheological investigations be applied to experimental models using laboratory animals in respect of inter-species differences? This paper gives a summary on some of our research data on organ/tissue ischemia-reperfusion, hemorheology and microcirculation, related to surgical research and experimental microsurgery.

The effects of propofol on hippocampal caspase-3 and Bcl-2 expression following forebrain ischemia-reperfusion in rats.

PubMed

Li, Jun; Han, Baoqing; Ma, Xuesong; Qi, Sihua

2010-10-14

Transient cerebral ischemia may result in neuronal apoptosis. During this process, several apoptosis-regulatory genes are induced in apoptotic cells. Among these genes, cysteinyl aspartate-specific protease-3 (caspase-3) and B-cell leukemia-2 (Bcl-2) are the most effective apoptotic regulators because they play a decisive role in the occurrence of apoptosis. Research has shown that propofol, which is an intravenous anesthetic agent, exhibits neuroprotective effects against cerebral ischemia-reperfusion injury, although the neuroprotective mechanism is still unclear. In this study, we examined the effects of propofol in rats after forebrain ischemia-reperfusion. We assessed the expression of hippocampal caspase-3, which acts as an apoptotic activator, and Bcl-2, which acts as an apoptotic suppressor. Forebrain ischemia was induced in hypotensive rats by clamping the bilateral common carotid arteries for 10 min. Propofol was administered via a lateral cerebral ventricle injection using a microsyringe after the induction of ischemia. Neuronal damage was determined by histological examination of brain sections at the level of the dorsal hippocampus. Caspase-3 and Bcl-2 expression in the hippocampus were detected using semiquantitative reverse transcription-polymerase chain reaction (RT-PCR) and Western blot analysis. We also used an immunohistochemical method after ischemia-reperfusion. In the hippocampus, caspase-3 and Bcl-2 mRNA were dramatically increased at 24h after forebrain ischemia. Following 6-24h of reperfusion, forebrain ischemia for 10 min induced a gradual increase in the expression of caspase-3 and Bcl-2 protein in the rat hippocampus, which peaked at 24h. In the propofol (1.0mg/kg) intervention group, the hippocampal expression of caspase-3 mRNA decreased significantly in rats 24h after ischemia; Bcl-2 mRNA was increased at the same time point. During the 24-h reperfusion period and after treatment with propofol, the level of caspase-3 protein expression

Biochemical markers of acute limb ischemia, rhabdomyolysis, and impact on limb salvage.

PubMed

Watson, J Devin B; Gifford, Shaun M; Clouse, W Darrin

2014-12-01

Biochemical markers of ischemia reperfusion injury have been of interest to vascular surgeons and researchers for many years. Acute limb ischemia is the quintessential clinical scenario where these markers would seem relevant. The use of biomarkers to preoperatively or perioperatively predict which patients will not tolerate limb-salvage efforts or who will have poor functional outcomes after salvage is of immense interest. Creatinine phosphokinase, myoglobin, lactate, lactate dehydrogenase, potassium, bicarbonate, and neutrophil/leukocyte ratios are a few of the studied biomarkers available. Currently, the most well-studied aspect of ischemia reperfusion injury is rhabdomyolysis leading to acute kidney injury. The last 10 years have seen significant progression and improvement in the treatment of rhabdomyolysis, from minor supportive care to use of continuous renal replacement therapy. Identification of specific biomarkers with predictive outcome characteristics in the setting of ischemia reperfusion injury will help guide therapeutic development and potentially mitigate pathophysiologic changes in acute limb ischemia, including rhabdomyolysis. These may further lead to improvements in short- and long-term surgical outcomes and limb salvage, as well as a better understanding of the timing and selection of intervention. Copyright © 2015 Elsevier Inc. All rights reserved.

Curcumin and dexmedetomidine prevents oxidative stress and renal injury in hind limb ischemia/reperfusion injury in a rat model.

PubMed

Karahan, M A; Yalcin, S; Aydogan, H; Büyükfirat, E; Kücük, A; Kocarslan, S; Yüce, H H; Taskın, A; Aksoy, N

2016-06-01

Curcumin and dexmedetomidine have been shown to have protective effects in ischemia-reperfusion injury on various organs. However, their protective effects on kidney tissue against ischemia-reperfusion injury remain unclear. We aimed to determine whether curcumin or dexmedetomidine prevents renal tissue from injury that was induced by hind limb ischemia-reperfusion in rats. Fifty rats were divided into five groups: sham, control, curcumin (CUR) group (200 mg/kg curcumin, n = 10), dexmedetomidine (DEX) group (25 μg/kg dexmedetomidine, n = 10), and curcumin-dexmedetomidine (CUR-DEX) group (200 mg/kg curcumin and 25 μg/kg dexmedetomidine). Curcumin and dexmedetomidine were administered intraperitoneally immediately after the end of 4 h ischemia, just 5 min before reperfusion. The extremity re-perfused for 2 h and then blood samples were taken and total antioxidant capacity (TAC), total oxidative status (TOS) levels, and oxidative stress index (OSI) were measured, and renal tissue samples were histopathologically examined. The TAC activity levels in blood samples were significantly lower in the control than the other groups (p < 0.01 for all comparisons). The TOS activity levels in blood samples were significantly higher in Control group and than the other groups (p <  0.01 for all comparison). The OSI were found to be significantly increased in the control group compared to others groups (p < 0.001 for all comparisons). Histopathological examination revealed less severe lesions in the sham, CUR, DEX, and CUR-DEX groups, compared with the control group (p < 0.01). Rat hind limb ischemia-reperfusion causes histopathological changes in the kidneys. Curcumin and dexmedetomidine administered intraperitoneally was effective in reducing oxidative stress and renal histopathologic injury in an acute hind limb I/R rat model.

Comparison of erythropoietin and sildenafil protective role against ischemia/reperfusion injury of the testis in adult rats.

PubMed

Zavras, Nick; Kostakis, Ioannis D; Sakellariou, Stratigoula; Damaskos, Christos; Roupakas, Evangelos; Tsagkari, Eleni; Spartalis, Eleftherios; Velaoras, Konstantinos; Dontas, Ismene A; Karatzas, Theodore

2014-04-01

Tissue damage in testicular torsion/detorsion is caused not only by the ischemia, but also by the ischemia/reperfusion injury after detorsion. Erythropoietin and sildenafil are considered to protect against ischemia/reperfusion injury. Here, we studied and compared their actions in testicular torsion/detorsion in adult rats. Twenty-two adult male Wistar Albino rats were divided into four groups. Rats in group A (n = 5) were sham operated. Rats in group B (n = 5), group C (n = 6) and group D (n = 6) underwent torsion of the right testis and detorsion after 90 min. No pharmaceutical intervention was performed in group B. Erythropoietin (1,000 IU/kg) and sildenafil (0.7 mg/kg) were injected intraperitoneally in groups C and D, respectively, after 60 min of torsion. All animals were killed 24 h after detorsion, and their right testis was extracted, placed into 10 % formalin solution and sent for histopathological examination. The histological changes in the testes were scored according to the four-point grading system proposed by Cosentino et al. All rats in group A had normal testicular architecture (grade 1). The untreated group B had a mean grade of 3.81 (range 3.65-4). The treated groups C (mean grade 3.24; range 3.05-3.45) and D (2.69, range 2.4-2.9) presented statistically significant better results (lower grades) compared with the untreated group B. Group D had significantly better results (lower grades) than group C. The intraperitoneal injection of erythropoietin and sildenafil protects against ischemia/reperfusion injury after testicular torsion and detorsion. Sildenafil may have a stronger action than erythropoietin at the doses used in this study.

The protective effect of prophylactic ozone administration against retinal ischemia-reperfusion injury.

PubMed

Kal, Ali; Kal, Oznur; Akillioglu, Ishak; Celik, Esin; Yilmaz, Mustafa; Gonul, Saban; Solmaz, Merve; Onal, Ozkan

2017-03-01

Retinal ischemia-reperfusion (IR) injury is associated with many ocular diseases. Retinal IR injury leads to the death of retinal ganglion cells (RGCs), loss of retinal function and ultimately vision loss. The aim of this study was to show the protective effects of prophylactic ozone administration against retinal IR injury. A sham group (S) (n = 7) was administered physiological saline (PS) intraperitoneally (i.p.) for 7 d. An ischemia reperfusion (IR) group (n = 7) was subjected to retinal ischemia followed by reperfusion for 2 h. An ozone group (O) (n = 7) was administered 1 mg/kg of ozone i.p. for 7 d. In the ozone + IR (O + IR) group (n = 7), 1 mg/kg of ozone was administered i.p. for 7 d before the IR procedure and at 8 d, the IR injury was created (as in IR group). The rats were anesthetized after second hour of reperfusion and their intracardiac blood was drawn completely and they were sacrificed. Blood samples were sent to a laboratory for analysis of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), malondialdehyde (MDA), total oxidant score (TOS) and total antioxidant capacity (TAC). The degree of retinal injury was evaluated according to changes in retinal cells and necrotic and apoptotic cells using the TUNEL method. Data were evaluated statistically with the Kruskal-Wallis test. The number of RGCs and the inner retinal thickness were significantly decreased after ischemia, and treatment with ozone significantly inhibited retinal ischemic injury. In the IR group, the degree of retinal injury was found to be the highest. In the O + IR group, retinal injury was found to be decreased in comparison to the IR group. In the ozone group without retinal IR injury, the retinal injury score was the lowest. The differences in the antioxidant parameters SOD, GSH-Px and TAC were increased in the ozone group and the lowest in the IR group. The oxidant parameters MDA and TOS were found to be the highest in the IR group and

Effect of trapidil in myocardial ischemia-reperfusion injury in rabbit.

PubMed

Liu, Mingjie; Sun, Qi; Wang, Qiang; Wang, Xiuying; Lin, Peng; Yang, Ming; Yan, Yuanyuan

2014-01-01

To evaluate the cardioprotective effects of trapidil on myocardial ischemia-reperfusion injury (MIRI) in rabbits. Rabbits were subjected to 40 min of myocardial ischemia followed by 120 min of reperfusion. Blood for superoxide dismutase (SOD) and malondialdehyde (MDA) were estimated. At the end of reperfusion, the rabbits were sacrificed and the hearts were isolated for histological examination. An apoptotic index (AI) was determined using the terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick-end-labeling (TUNEL) method. The expression of apoptosis-related proteins Bax and Bcl-2 was analyzed using immunohistochemistry. Statistical analyses were performed by one-way analysis of variance (ANOVA), P < 0.05 considered statistically significant. Trapidil caused a significant (P < 0.05) increase in SOD activity, as decreased MDA levels and significantly (P < 0.05) reduced the expression of Bax as compared with the ischemia-reperfusion (IR) control group. Trapidil may attenuate the myocardial damage produced by IR injury and offer potential cardioprotective action.

The Effect of Rosa Damascena Extract on Expression of Neurotrophic Factors in the CA1 Neurons of Adult Rat Hippocampus Following Ischemia.

PubMed

Moniri, Seyedeh Farzaneh; Hedayatpour, Azim; Hassanzadeh, Gholamreza; Vazirian, Mahdi; Karimian, Morteza; Belaran, Maryam; Ejtemaie Mehr, Shahram; Akbari, Mohamad

2017-12-01

Ischemic stroke is an important cause of death and disability in the world. Brain ischemia causes damage to brain cell, and among brain neurons, pyramidal neurons of the hippocampal CA1 region are more susceptive to ischemic injury. Recent findings suggest that neurotrophic factors protect against ischemic cell death. A dietary component of Rosa damascene extract possibly is associated with expression of neurotrophic factors mRNA following ischemia, so it can have therapeutic effect on cerebral ischemia. The present study attempts to evaluate the neuroprotective effect of Rosa damascene extract on adult rat hippocampal neurons following ischemic brain injury. Forty-eight adult male Wistar rats (weighing 250±20 gr and ages 10-12 weeks) used in this study, animals randomly were divided into 6 groups including Control, ischemia/ reperfusion (IR), vehicle and three treated groups (IR+0.5, 1, 2 mg/ml extract). Global ischemia was induced by bilateral common carotid arteries occlusion for 20 minutes. The treatment was done by different doses of Rosa damascena extract for 30 days. After 30 days cell death and gene expression in neurons of the CA1 region of the hippocampus were evaluated by Nissl staining and real time PCR assay. We found a significant decrease in NGF, BDNF and NT3 mRNA expression in neurons of CA1 region of the hippocampus in ischemia group compared to control group (P<0.0001). Our results also revealed that the number of dark neurons significantly increases in ischemia group compared to control group (P<0.0001). Following treatment with Rosa damascene extract reduced the number of dark neurons that was associated with NGF, NT3, and BDNF mRNA expression. All doses level had positive effects, but the most effective dose of Rosa damascena extract was 1 mg/ml. Our results suggest that neuroprotective activity of Rosa damascena can enhance hippocampal CA1 neuronal survival after global ischemia.

The effect of ozone and naringin on intestinal ischemia/reperfusion injury in an experimental model.

PubMed

Isik, Arda; Peker, Kemal; Gursul, Cebrail; Sayar, Ilyas; Firat, Deniz; Yilmaz, Ismayil; Demiryilmaz, Ismail

2015-09-01

The aim of the study was to evaulate the effect of ozone and naringin on the intestine after intestinal ischemia-reperfusion(II/R) injury. Thirty five rats divided into 5 groups of 7 animals: control, II/R, ozone, naringin and naringin + ozone. Only laparotomy and exploration of the superior mesenteric artery (SMA) were done in control group. In the experimental groups, SAM was occluded for 1 h and reperfused for 1 h. 15 min after ischemia, ozone (25 μg/ml, 0.5 mg/kg), naringin (80 mg/kg) and naringin + ozone(80 mg/kg + 25 μg/ml, 0.5 mg/kg) were infused intraperitoneally to each groups. Ileum tissues were harvested to determine intestinal mucosal injury and oxidative stress markers. For SMA occlusion, different than literature, silk suture binding was used. Oxidative stress markers were significantly low in experimental groups compared with II/R group (p < 0.05). Histopathologically, the injury score was significantly low at experimental groups compared with II/R group (p < 0.05). The lowest injury score was encountered at naringine + ozone group. Ozone alone or combined with naringin has a protective effect for mesenteric ischemia. Instead of using instruments such as clamps in the II/R rat model, silk binding may be used safely. Copyright © 2015 IJS Publishing Group Limited. Published by Elsevier Ltd. All rights reserved.

Delayed brain ischemia tolerance induced by electroacupuncture pretreatment is mediated via MCP-induced protein 1

PubMed Central

2013-01-01

Background Emerging studies have demonstrated that pretreatment with electroacupuncture (EA) induces significant tolerance to focal cerebral ischemia. The present study seeks to determine the involvement of monocyte chemotactic protein-induced protein 1 (MCPIP1), a recently identified novel modulator of inflammatory reactions, in the cerebral neuroprotection conferred by EA pretreatment in the animal model of focal cerebral ischemia and to elucidate the mechanisms of EA pretreatment-induced ischemic brain tolerance. Methods Twenty-four hours after the end of the last EA pretreatment, focal cerebral ischemia was induced by middle cerebral artery occlusion (MCAO) for 90 minutes in male C57BL/6 mice and MCPIP1 knockout mice. Transcription and expression of MCPIP1 gene was monitored by qRT-PCR, Western blot and immunohistochemistry. The neurobehavioral scores, infarction volumes, proinflammatory cytokines and leukocyte infiltration in brain and NF-κB signaling were evaluated after ischemia/reperfusion. Results MCPIP1 protein and mRNA levels significantly increased specifically in mouse brain undergoing EA pretreatment. EA pretreatment significantly attenuated the infarct volume, neurological deficits, upregulation of proinflammatory cytokines and leukocyte infiltration in the brain of wild-type mice after MCAO compared with that of the non-EA group. MCPIP1-deficient mice failed to evoke EA pretreatment-induced tolerance compared with that of the control MCPIP1 knockout group without EA treatment. Furthermore, the activation of NF-κB signaling was significantly reduced in EA-pretreated wild-type mice after MCAO compared to that of the non-EA control group and MCPIP1-deficient mice failed to confer the EA pretreatment-induced inhibition of NF-κB signaling after MCAO. Conclusions Our data demonstrated that MCPIP1 deficiency caused significant lack of EA pretreatment-induced cerebral protective effects after MCAO compared with the control group and that MCPIP1 is

Exercise-induced ischemia initiates the second window of protection in humans independent of collateral recruitment.

PubMed

Lambiase, Pier D; Edwards, Richard J; Cusack, Michael R; Bucknall, Clifford A; Redwood, Simon R; Marber, Michael S

2003-04-02

This study was designed to examine if exercise-induced ischemia initiated late preconditioning in humans that becomes manifest during subsequent exercise and serial balloon occlusion of the left anterior descending coronary artery (LAD). The existence of late preconditioning in humans is controversial. We therefore compared myocardial responses to exercise-induced and intracoronary balloon inflation-induced ischemia in two groups of patients subjected to different temporal patterns of ischemia. Thirty patients with stable angina secondary to single-vessel LAD disease underwent percutaneous coronary intervention (PCI) after two separate exercise tolerance test (ETT) protocols designed to investigate isolated early preconditioning (IEP) alone or the second window of protection (SWOP). The IEP subjects underwent three sequential ETTs at least two weeks before PCI. The SWOP subjects underwent five sequential ETTs commencing 24 h before PCI. During PCI there was no significant difference in intracoronary pressure-derived collateral flow index (CFI) between groups (IEP = 0.15 +/- 0.13, SWOP = 0.19 +/- 0.15). In SWOP patients, compared with the initial ETT, the ETT performed 24 h later had a 40% (p < 0.001) increase in time to 0.1-mV ST depression and a 60% (p < 0.05) decrease in ventricular ectopic frequency. During the first balloon inflation, peak ST elevation was reduced by 49% (p < 0.05) in the SWOP versus the IEP group, and the dependence on CFI observed in the IEP group was abolished (analysis of covariance, p < 0.05). The significant attenuation of ST elevation (47%, p < 0.005) seen at the time of the second inflation in the IEP patients was not seen in the SWOP patients. Exercise-induced ischemia triggers late preconditioning in humans, which becomes manifest during exercise and PCI. This is the first evidence that ischemia induced by coronary occlusion is attenuated in humans by a late preconditioning effect induced by exercise.

Prophylactic Ozone Administration Reduces Intestinal Mucosa Injury Induced by Intestinal Ischemia-Reperfusion in the Rat

PubMed Central

Onal, Ozkan; Yetisir, Fahri; Sarer, A. Ebru Salman; Zeybek, N. Dilara; Onal, C. Oztug; Yurekli, Banu; Celik, H. Tugrul; Sirma, Ayse; Kılıc, Mehmet

2015-01-01

Objectives. Intestinal ischemia-reperfusion injury is associated with mucosal damage and has a high rate of mortality. Various beneficial effects of ozone have been shown. The aim of the present study was to show the effects of ozone in ischemia reperfusion model in intestine. Material and Method. Twenty eight Wistar rats were randomized into four groups with seven rats in each group. Control group was administered serum physiologic (SF) intraperitoneally (ip) for five days. Ozone group was administered 1 mg/kg ozone ip for five days. Ischemia Reperfusion (IR) group underwent superior mesenteric artery occlusion for one hour and then reperfusion for two hours. Ozone + IR group was administered 1 mg/kg ozone ip for five days and at sixth day IR model was applied. Rats were anesthetized with ketamine∖xyzlazine and their intracardiac blood was drawn completely and they were sacrificed. Intestinal tissue samples were examined under light microscope. Levels of superoxide dismutase (SOD), catalase (CAT), glutathioneperoxidase (GSH-Px), malondyaldehide (MDA), and protein carbonyl (PCO) were analyzed in tissue samples. Total oxidant status (TOS), and total antioxidant capacity (TAC) were analyzed in blood samples. Data were evaluated statistically by Kruskal Wallis test. Results. In the ozone administered group, degree of intestinal injury was not different from the control group. IR caused an increase in intestinal injury score. The intestinal epithelium maintained its integrity and decrease in intestinal injury score was detected in Ozone + IR group. SOD, GSH-Px, and CAT values were high in ozone group and low in IR. TOS parameter was highest in the IR group and the TAC parameter was highest in the ozone group and lowest in the IR group. Conclusion. In the present study, IR model caused an increase in intestinal injury.In the present study, ozone administration had an effect improving IR associated tissue injury. In the present study, ozone therapy prevented

Aspergillus fumigatus Invasion Increases with Progressive Airway Ischemia

PubMed Central

Hsu, Joe L.; Khan, Mohammad A.; Sobel, Raymond A.; Jiang, Xinguo; Clemons, Karl V.; Nguyen, Tom T.; Stevens, David A.; Martinez, Marife; Nicolls, Mark R.

2013-01-01

Despite the prevalence of Aspergillus-related disease in immune suppressed lung transplant patients, little is known of the host-pathogen interaction. Because of the mould’s angiotropic nature and because of its capacity to thrive in hypoxic conditions, we hypothesized that the degree of Aspergillus invasion would increase with progressive rejection-mediated ischemia of the allograft. To study this relationship, we utilized a novel orthotopic tracheal transplant model of Aspergillus infection, in which it was possible to assess the effects of tissue hypoxia and ischemia on airway infectivity. Laser Doppler flowmetry and FITC-lectin were used to determine blood perfusion, and a fiber optic microsensor was used to measure airway tissue oxygen tension. Fungal burden and depth of invasion were graded using histopathology. We demonstrated a high efficacy (80%) for producing a localized fungal tracheal infection with the majority of infection occurring at the donor-recipient anastomosis; Aspergillus was more invasive in allogeneic compared to syngeneic groups. During the study period, the overall kinetics of both non-infected and infected allografts was similar, demonstrating a progressive loss of perfusion and oxygenation, which reached a nadir by days 10-12 post-transplantation. The extent of Aspergillus invasion directly correlated with the degree of graft hypoxia and ischemia. Compared to the midtrachea, the donor-recipient anastomotic site exhibited lower perfusion and more invasive disease; a finding consistent with clinical experience. For the first time, we identify ischemia as a putative risk factor for Aspergillus invasion. Therapeutic approaches focused on preserving vascular health may play an important role in limiting Aspergillus infections. PMID:24155924

Effects of hypothermia and cerebral ischemia on cold-inducible RNA-binding protein mRNA expression in rat brain.

PubMed

Liu, Aijun; Zhang, Zhiwen; Li, Anmin; Xue, Jinghui

2010-08-06

CIRP (cold-inducible RNA-binding protein) mRNA is highly expressed in hypothermic conditions in mammalian cells, and the relationship between CIRP and neuroprotection for cerebral ischemia under hypothermia has been focused upon. At present, however, the expression characteristics of CIRP under hypothermia and cerebral ischemia in vivo are not clearly elucidated. In this study, CIRP mRNA expression in various regions of rat brain was examined by reverse transcriptase polymerase chain reaction (RT-PCR). CIRP expression levels were found to be similar in the hippocampus and cortex. Real-time quantitative PCR analysis revealed increasing CIRP mRNA expression in the cortex during the 24-h observation period following treatment with hypothermia or cerebral ischemia, with a greater increase in the hypothermia group. When cerebral ischemia was induced following hypothermia, CIRP mRNA expression in the cortex again showed a significant increasing tendency, but ischemia delayed the appearance of this increase. To reveal the relationship between CIRP and energy metabolism in the rat brain, lactate and pyruvate concentrations in the cortex of the rats treated with hypothermia, ischemia and ischemia after hypothermia were determined by spectrophotometric assay, and levels of phosphofructokinas-1 (PFK-1), the major regulatory enzyme of the glycolytic pathway, in the rat cortex in the three groups was also analyzed by Western blot. Using linear correlation, lactate and pyruvate concentrations, and PFK-1 levels, were each analyzed in the three groups in association with CIRP mRNA expression levels. The analysis did not reveal any correlation between the three metabolic parameters and CIRP mRNA expression induced by hypothermia, suggesting that while playing a role in neuroprotection under hypothermia, CIRP does not affect cerebral energy metabolism. Copyright 2010. Published by Elsevier B.V.

Allowable warm ischemic time and morphological and biochemical changes in uterine ischemia/reperfusion injury in cynomolgus macaque: a basic study for uterus transplantation.

PubMed

Kisu, Iori; Umene, Kiyoko; Adachi, Masataka; Emoto, Katsura; Nogami, Yuya; Banno, Kouji; Itagaki, Iori; Kawamoto, Ikuo; Nakagawa, Takahiro; Narita, Hayato; Yoshida, Atsushi; Tsuchiya, Hideaki; Ogasawara, Kazumasa; Aoki, Daisuke

2017-10-01

How long is the allowable warm ischemic time of the uterus and what morphological and biochemical changes are caused by uterine ischemia/reperfusion injury in cynomolgus macaques? Warm ischemia in the uterus of cynomolgus macaques is tolerated for up to 4 h and reperfusion after uterine ischemia caused no further morphological and biochemical changes. Uterus transplantation is a potential option for women with uterine factor infertility. The allowable warm ischemic time and ischemia/reperfusion injury of the uterus in humans and non-human primates is unknown. This experimental study included 18 female cynomolgus macaques with periodic menstruation. Animals were divided into six groups of three monkeys each: a control group and groups with uterine ischemia for 0.5, 1, 2, 4 and 8 h. Biopsies of uterine tissues were performed before blood flow blockage, after each blockage time, and after reperfusion for 3 h. Blood sampling was performed after each blockage time, and after reperfusion for 5, 15 and 30 min for measurement of biochemical data. Resumption of menstruation was monitored after the surgical procedure. Morphological, physiological and biochemical changes after ischemia and reperfusion were evaluated. Mild muscle degeneration and zonal degeneration were observed in all animals subjected to warm ischemia for 4 or 8 h, but there were no marked differences in the appearance of specimens immediately after ischemia and after reperfusion for 3 h in animals subjected to 4 or 8 h of warm ischemia. There were no significant changes in any biochemical parameters at any time point in each group. Periodical menstruation resumed in all animals with warm ischemia up to 4 h, but did not recover in animals with warm ischemia for 8 h with atrophic uteri. Warm ischemia in actual transplantation was not exactly mimicked in this study because uteri were not perfused, cooled, transplanted or reanastomosed with vessels. Results in non-human primates cannot always be extrapolated to

Protective Effects of Hydrocortisone, Vitamin C and E Alone or in Combination against Renal Ischemia-Reperfusion Injury in Rat.

PubMed

Azari, Omid; Kheirandish, Reza; Azizi, Shahrzad; Farajli Abbasi, Mohammad; Ghahramani Gareh Chaman, Shahin; Bidi, Masoud

2015-01-01

Renal ischemia reperfusion injury may occur in a variety of clinical situations, following a transient drop in total or regional blood flow to the kidney. This study was performed to investigate the protective effects of different antioxidants such as vitamin C, vitamin E, hydrocortisone and combination of these agents against experimental renal ischemia-reperfusion injury. Thirty male rats were divided into six groups. Group Sham, Group I/R: (45 min of ischemia followed by 1h of reperfusion), Group I/R+Vit C: (50 mg/kg Vit C, IV, immediately after reperfusion), Group I/R+Vit E: (20 mg/kg Vit E, IM, 15 min before reperfusion), Group I/R+Hydrocortisone: (50 mg/kg, IV, immediately after reperfusion), and Group Combination: Ischemia-reperfusion plus combination of Vit C, E and hydrocortisone. After the experiments, the left kidney was removed and the tissues were processed for histopathological examination. Severe injuries such as necrosis of tubules, atrophy of glomerulus, and hemorrhage were observed in group I/R. Histological scores indicating tissue injury significantly decreased in all treatment groups compared to the group I/R. The renal tissue in group treatment was preserved in comparison with the group I/R. Comparison between the treatment groups showed that group combination was more effective and group vit E was less effective in protecting of renal tissue against I/R injuries. The results demonstrated simultaneous administration of combination of Vit C, E and hydrocortisone before reperfusion of blood flow to the ischemic tissue could show a synergy against deleterious effects of I/R injuries in kidney.

Ischemia-reperfusion injury in rat fatty liver: role of nutritional status.

PubMed

Caraceni, P; Nardo, B; Domenicali, M; Turi, P; Vici, M; Simoncini, M; De Maria, N; Trevisani, F; Van Thiel, D H; Derenzini, M; Cavallari, A; Bernardi, M

1999-04-01

Fatty livers are more sensitive to the deleterious effects of ischemia-reperfusion than normal livers. Nutritional status greatly modulates this injury in normal livers, but its role in the specific setting of fatty liver is unknown. This study aimed to determine the effect of nutritional status on warm ischemia-reperfusion injury in rat fatty livers. Fed and fasted rats with normal or fatty liver induced by a choline deficient diet underwent 1 hour of lobar ischemia and reperfusion. Rat survival was determined for 7 days. Serum transaminases, liver histology and cell ultrastructure were assessed before and after ischemia, and at 30 minutes, 2 hours, 8 hours, and 24 hours after reperfusion. Survival was also determined in fatty fasted rats supplemented with glucose before surgery. The preischemic hepatic glycogen was measured in all groups. Whereas survival was similar in fasted and fed rats with normal liver (90% vs. 100%), fasting dramatically reduced survival in rats with fatty liver (14% vs. 64%, P <.01). Accordingly, fasting and fatty degeneration had a synergistic effect in exacerbating liver injury. Mitochondrial damage was a predominant feature of ultrastructural hepatocyte injury in fasted fatty livers. Glucose supplementation partially prevented the fasting-induced depletion of glycogen and improved the 7-day rat survival to 45%. These data indicate that rat fatty livers exposed to normothermic ischemia-reperfusion injury are much more sensitive to fasting than histologically normal livers. Because glucose supplementation improves both the hepatic glycogen stores and the rat survival, a nutritional repletion procedure may be part of a treatment strategy aimed to prevent ischemia-reperfusion injury in fatty livers.

Comparison of Aerobic Preservation by Venous Systemic Oxygen Persufflation or Oxygenated Machine Perfusion of Warm-Ischemia-Damaged Porcine Kidneys.

PubMed

Kalenski, Julia; Mancina, Elina; Paschenda, Pascal; Beckers, Christian; Bleilevens, Christian; Tóthová, Ľubomíra; Boor, Peter; Gross, Dominik; Tolba, René H; Doorschodt, Benedict M

2016-01-01

The global shortage of donor organs for transplantation has necessitated the expansion of the organ pool through increased use of organs from less ideal donors. Venous systemic oxygen persufflation (VSOP) and oxygenated machine perfusion (OMP) have previously demonstrated beneficial results compared to cold storage (CS) in the preservation of warm-ischemia-damaged kidney grafts. The aim of this study was to compare the efficacy of VSOP and OMP for the preservation of warm-ischemia-damaged porcine kidneys using the recently introduced Ecosol preservation solution compared to CS using Ecosol or histidine-tryptophan-ketoglutarate solution (HTK). Kidneys from German Landrace pigs (n = 5/group) were retrieved and washed out with either Ecosol or HTK after 45 min of clamping of the renal pedicle. As controls, kidneys without warm ischemia, cold stored for 24 h in HTK, were employed. Following 24 h of preservation by VSOP, OMP, CS-Ecosol, or CS-HTK, renal function and damage were assessed during 1 h using the isolated perfused porcine kidney model. During reperfusion, urine production was significantly higher in the VSOP and OMP groups than in the CS-HTK group; however, only VSOP could demonstrate lower urine protein concentrations and fractional excretion of sodium, which did not differ from the non-warm-ischemia-damaged control group. VSOP, CS-Ecosol, and controls showed better maintenance of the acid-base balance than CS-HTK. Reduced lipid peroxidation, as reflected in postreperfusion tissue thiobarbituric acid-reactive substance levels, was observed in the VSOP group compared to the OMP group, and the VSOP and CS-Ecosol groups had concentrations similar to the controls. The ratio of reduced to oxidized glutathione was higher in the VSOP, OMP, and CS-Ecosol groups than in the CS-HTK group and controls, with a higher ratio in the VSOP than in the OMP group. VSOP was associated with mitigation of oxidative stress in comparison to OMP and CS. Preservation of warm-ischemia

Protective effects of hydrogen enriched saline on liver ischemia reperfusion injury by reducing oxidative stress and HMGB1 release

PubMed Central

2014-01-01

Background The nuclear protein high-mobility group box 1 (HMGB1) is a key trigger for the inflammatory reaction during liver ischemia reperfusion injury (IRI). Hydrogen treatment was recently associated with down-regulation of the expression of HMGB1 and pro-inflammatory cytokines during sepsis and myocardial IRI, but it is not known whether hydrogen has an effect on HMGB1 in liver IRI. Methods A rat model of 60 minutes 70% partial liver ischemia reperfusion injury was used. Hydrogen enriched saline (2.5, 5 or 10 ml/kg) was injected intraperitoneally 10 minutes before hepatic reperfusion. Liver injury was assessed by serum alanine aminotransferase (ALT) enzyme levels and histological changes. We also measured malondialdehyde (MDA), hydroxynonenal (HNE) and 8-hydroxy-guanosine (8-OH-G) levels as markers of the peroxidation injury induced by reactive oxygen species (ROS). In addition, pro-inflammatory cytokines including TNF-α and IL-6, and high mobility group box B1 protein (HMGB1) were measured as markers of post ischemia-reperfusion inflammation. Results Hydrogen enriched saline treatment significantly attenuated the severity of liver injury induced by ischemia-reperfusion. The treatment group showed reduced serum ALT activity and markers of lipid peroxidation and post ischemia reperfusion histological changes were reduced. Hydrogen enriched saline treatment inhibited HMGB1 expression and release, reflecting a reduced local and systemic inflammatory response to hepatic ischemia reperfusion. Conclusion These results suggest that, in our model, hydrogen enriched saline treatment is protective against liver ischemia-reperfusion injury. This effect may be mediated by both the anti-oxidative and anti-inflammatory effects of the solution. PMID:24410860

[The influence with block the endotoxin signal transduction for ischemia/reperfusion injury of graft liver in rats].

PubMed

Liu, Zuo-jin; Li, Sheng-wei; Li, Xu-hong; Peng, Yong; You, Hai-bo; Li, Shou-bai; Gong, Jian-ping

2006-09-01

To explore the feasibility of interleukin 1 receptor associated kinase-4 (IRAK-4) as gene therapy target for liver ischemia/reperfusion injury (I/RI) and effective approach in vivo for short hairpin RNA (shRNA) interference used to gene therapy in liver graft hqappened. Sprague-Dawley rats were randomly divided into three groups: the control group, the in vivo transfection group (IVT) and the cold ischemia transfection group (CIT). Experiments of orthotopic liver transplantation were performed by two-cuff method. CIT were perfused with IRAK-4-shRNA plasmid (pSIIRAK-4) during cold ischemia phase, IVT received the equivalent volumes (2 mL) of pSIIRAK-4 after portal vein inosculated, and the control group leaved without any treatment. At 0 min, 60 min and 180 min after reperfusion, the expression of IRAK-4 gene and protein level were determined by RT-PCR and Western blot. The serum TNF-alpha level was detected by ELISA. Liver histopathological changes and cell apoptosis were observed by electron microscope and TUNEL. After reperfusion, the expression of IRAK-4 were largely depressed in CIT than that of IVT and the control group (P < 0.01), and furthermore, the serum TNF-alpha level, proportion of hepatocyte apoptosis and severity of hepatocyte injury were also lower than the latter. These results indicate that depression IRAK-4 expression with IRAK-4-shRNA through portal vein perfusion during cold ischemia phase could effectively blunt graft hepatic I/RI.

[The role of Leptin on neuron apoptosis in mice with cerebral ischemia/reperfusion injury].

PubMed

Yan, Guang-tao; Si, Yi-ling; Zhang, Jin-ying; Deng, Zi-hui; Xue, Hui

2011-06-01

To study the effect of Leptin on neuron apoptosis in mice with cerebral ischemia injury and its mechanism. Seventy-five mice were randomly divided into three groups. Focal cerebral ischemia/reperfusion injury model in mice was reproduced by middle cerebral artery occlusion for 2 hours followed by reperfusion. In Leptin intervention group mice were given Leptin 1 μg/g during cerebral ischemia by intraperitoneal injection. Mice in the model group were given equal amount of phosphate buffer saline. After reperfusion for 24 hours, the neuron apoptosis was detected by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining. The mRNA and protein expression of apoptosis relative gene caspase-3 and bcl-2 were determined by reverse transcription-polymerase chain reaction (RT-PCR) and immuno histochemistry. Most of neuron necrosis was observed in cerebral ischemia center in model group. Compared with sham-operation group, neuron apoptosis rate, mRNA and protein expression of caspase-3 and bcl-2 in model group increased significantly [apoptosis rate: (68.65 ± 0.79)% vs. (4.40 ± 0.00)%, caspase-3 mRNA: 2.563 ± 0.250 vs. 0.153 ± 0.020, bcl-2 mRNA: 0.337 ± 0.100 vs. 0.125 ± 0.030, caspase-3 protein (absorbance value, A value): 0.57 ± 0.05 vs. 0.37 ± 0.03, bcl-2 protein (A value): 0.51 ± 0.04 vs. 0.35 ± 0.01, all P<0.01]. The apoptosis rate of penumbra neurons was reduced in Leptin intervention group significantly compared with model group [(42.30 ± 8.45)% vs. (68.65 ± 0.79)%, P<0.01]. Compared with model group, the mRNA and protein expression of caspase-3 in Leptin intervention group were reduced significantly [caspase-3 mRNA: 2.267 ± 0.040 vs. 2.563 ± 0.250, caspase-3 protein (A value): 0.45 ± 0.04 vs. 0.57 ± 0.05, P>0.05 and P<0.01], and the mRNA and protein expression of bcl-2 in Leptin intervention group upregulated significantly [bcl-2 mRNA: 0.662 ± 0.040 vs. 0.337 ± 0.100, bcl-2 protein (A value): 0.76 ± 0.09 vs. 0.51 ± 0

Zero Flow Global Ischemia-Induced Injuries in Rat Heart Are Attenuated by Natural Honey

PubMed Central

Najafi, Moslem; Zahednezhad, Fahimeh; Samadzadeh, Mehrban; Vaez, Haleh

2012-01-01

Purpose: In the present study, effects of preischemic administration of natural honey on cardiac arrhythmias and myocardial infarction size during zero flow global ischemia were investigated in isolated rat heart. Methods: The isolated hearts were subjected to 30 min zero flow global ischemia followed by 120 min reperfusion then perfused by a modified drug free Krebs-Henseleit solution throughout the experiment (control) or the solution containing 0.25, 0.5, 1 and 2% of natural honey for 15 min before induction of global ischemia (treated groups), respectively. Cardiac arrhythmias were determined based on the Lambeth conventions and the infarct size was measured by computerized planimetry. Results: Myocardial infarction size was 55.8±7.8% in the control group, while preischemic perfusion of honey (0.25, 0.5, 1 and 2%) reduced it to 39.3±11, 30.6±5.5 (P<0.01), 17.9±5.6 (P<0.001) and 8.7±1.1% (P<0.001), respectively. A direct linear correlation between honey concentrations and infarction size reduction was observed (R2=0.9948). In addition, total number of ventricular ectopic beats were significantly decreased by all used concentrations of honey (P<0.05) during reperfusion time. Honey (0.25, 0.5 and 1 %) also lowered incidence of irreversible ventricular fibrillation (P<0.05). Moreover, number and duration of ventricular tachycardia were reduced in all honey treated groups. Conclusion: Preischemic administration of natural honey before zero flow global ischemia can protect isolated rat heart against ischemia/reperfusion injuries as reduction of infarction size and arrhythmias. Maybe, antioxidant and free radical scavenging activities of honey, reduction of necrotized tissue and providing energy sources may involve in these cardioprotective effects of honey. PMID:24312788

Intestinal Ischemia

MedlinePlus

... and hormone medications, such as estrogen Cocaine or methamphetamine use Vigorous exercise, such as long-distance running ... anti-phospholipid syndrome. Illegal drug use. Cocaine and methamphetamine use have been linked to intestinal ischemia. Complications ...

Protective effects of tempol in an experimental ovarian ischemia-reperfusion injury model in female Wistar albino rats.

PubMed

Pınar, Neslihan; Soylu Karapınar, Oya; Özcan, Oğuzhan; Atik Doğan, Esin; Bayraktar, Suphi

2017-07-01

The aim of this study was to investigate the antioxidant effects of tempol on ovarian ischemia-reperfusion (I/R) injury in rats. Forty female Wistar albino rats were randomly divided into 5 groups: Group I, sham; Group II, ischemia (I); Group III, I/R; Group IV, I/R + tempol 30 mg/kg i.p; Group V, I/R + tempol 50 mg/kg i.p. Oxidative stress index (OSI) was significantly higher in the ischemia group and the I/R group than in the sham group. Catalase levels were significantly lower in the I/R group than in the I/R + tempol 30 mg/kg i.p. and the I/R + tempol 50 mg/kg i.p. groups. Glutathione peroxidase levels were lower in the I/R group than in the I/R + tempol 30 mg/kg i.p. and the I/R + tempol 50 mg/kg i.p. groups. MDA levels were significantly lower in the I/R + tempol 30 mg/kg i.p. group and the I/R + tempol 50 mg/kg i.p. group than in the I/R group. The levels of the histopathological parameters were significantly decreased in the I/R + tempol 50 mg/kg i.p. group compared with the I/R group. Tempol can be used for reducing ovarian I/R injury.

Protection of donor lung inflation in the setting of cold ischemia against ischemia-reperfusion injury with carbon monoxide, hydrogen, or both in rats.

PubMed

Meng, Chao; Ma, Liangjuan; Niu, Li; Cui, Xiaoguang; Liu, Jinfeng; Kang, Jiyu; Liu, Rongfang; Xing, Jingchun; Jiang, Changlin; Zhou, Huacheng

2016-04-15

Lung ischemia-reperfusion injury (IRI) may be attenuated through carbon monoxide (CO)'s anti-inflammatory effect or hydrogen (H2)'s anti-oxidant effect. In this study, the effects of lung inflation with CO, H2, or both during the cold ischemia phase on graft function were observed. Rat donor lungs, inflated with 40% oxygen (control group), 500ppm CO (CO group), 3% H2 (H2 group) or 500ppm CO+3% H2 (COH group), were kept at 4°C for 180min. After transplantation, the recipients' artery blood gas and pressure-volume (P-V) curves were analyzed. The inflammatory response, oxidative stress and apoptosis in the recipients were assessed at 180min after reperfusion. Oxygenation in the CO and H2 groups were improved compared with the control group. The CO and H2 groups also exhibited significantly improved P-V curves, reduced lung injury, and decreased inflammatory response, malonaldehyde content, and cell apoptosis in the grafts. Furthermore, the COH group experienced enhanced improvements in oxygenation, P-V curves, inflammatory response, lipid peroxidation, and graft apoptosis compared to the CO and H2 groups. Lung inflation with CO or H2 protected against IRI via anti-inflammatory, anti-oxidant and anti-apoptotic mechanisms in a model of lung transplantation in rats, which was enhanced by combined treatment with CO and H2. Copyright © 2016 Elsevier Inc. All rights reserved.

[Effects of tanshinone- II A sulfonate on expression of nuclear factor-kappaB, vascular cell adhesion molecule-1 and hemorrheology during spinal cord ischemia reperfusion injury].

PubMed

Zhang, Li; An, Guo-Yao; Zhang, Wen-Guang; Chen, Kai

2012-12-01

To observe effects of Tanshinone- II A sulfonate on expression of Nuclear factor-kappaB (NF-kappaB), Vascular Cell Adhesion Molecule-1 (VCAM-1) and hemorrheology during spinal cord ischemia reperfusion injury,and explore the function and mechnism. Fifty-four New Zealand rabbits (aged 3 months,weighted 2.0 +/- 0.2 kg) were randomly divided into 6 in sham group (lumbar artery were separated in operation,0.8 ml/kg saline were injected at 0.5 h before and after operation), 24 in ischemia group ( lumbar artery were clipped after seperation, and the same dose of saline), 24 in Tanshinone group (lumbar artery were clipped after seperation, and the same dose of Tanshinone- II A sulfonate) . Abdomincal aorta blood were drawed after treatment respectively at 0.5 h, 1 h, 4 h and 8 h, and tesetd whole blood viscosity [high cut (mpa.s)/150(l/s), middle cut (mpa.s)/60(l/s) and low cut (mpa.s)/10(l/s)], capillary plasma viscosity, red cell aggregation index, rigid index, deformation index and electrophoresis index. Spinal cord tissues were divided into two sections,one fixed in 4% paraformaldehyde, another stored in liquid nitrogen. Immunohistochemical method and ELISA were used to test change of content of NF-kappaB and VCAM-1. 1) The expression of NF-kappaB in Tanshinone group were lowest, and in ischemia group were highest. 2) Compared with sham group, VCAM-1 in ischemia group at different time were obviously increased,especially at 0.5, 1 and 4 h (P<0.01), and had meaning at 8 h (P<0.05). Compare between Tanshinone group and ischemia group, VCAM-1 at 0.5 h were obviously decreased (P<0.01), and had meaning at 1 h, 4 h and 8 h (P<0.05). 3) There were no postive vasvular expression in sham group, and at 0.5 h in Tanshinone group and ischemia group. The highest postive vasvular expression in ischemia group were at 1 h, 4 h and 8 h, and had significant meaning at 1 h and 4 h between ischemia group and Tanshinone group (P<0.05), and 8 h were obviously most. 4) The whole blood

Low energy shock wave therapy induces angiogenesis in acute hind-limb ischemia via VEGF receptor 2 phosphorylation.

PubMed

Holfeld, Johannes; Tepeköylü, Can; Blunder, Stefan; Lobenwein, Daniela; Kirchmair, Elke; Dietl, Marion; Kozaryn, Radoslaw; Lener, Daniela; Theurl, Markus; Paulus, Patrick; Kirchmair, Rudolf; Grimm, Michael

2014-01-01

Low energy shock waves have been shown to induce angiogenesis, improve left ventricular ejection fraction and decrease angina symptoms in patients suffering from chronic ischemic heart disease. Whether there is as well an effect in acute ischemia was not yet investigated. Hind-limb ischemia was induced in 10-12 weeks old male C57/Bl6 wild-type mice by excision of the left femoral artery. Animals were randomly divided in a treatment group (SWT, 300 shock waves at 0.1 mJ/mm2, 5 Hz) and untreated controls (CTR), n = 10 per group. The treatment group received shock wave therapy immediately after surgery. Higher gene expression and protein levels of angiogenic factors VEGF-A and PlGF, as well as their receptors Flt-1 and KDR have been found. This resulted in significantly more vessels per high-power field in SWT compared to controls. Improvement of blood perfusion in treatment animals was confirmed by laser Doppler perfusion imaging. Receptor tyrosine kinase profiler revealed significant phosphorylation of VEGF receptor 2 as an underlying mechanism of action. The effect of VEGF signaling was abolished upon incubation with a VEGFR2 inhibitor indicating that the effect is indeed VEGFR 2 dependent. Low energy shock wave treatment induces angiogenesis in acute ischemia via VEGF receptor 2 stimulation and shows the same promising effects as known from chronic myocardial ischemia. It may therefore develop as an adjunct to the treatment armentarium of acute muscle ischemia in limbs and myocardium.

Placental Growth Factor Administration Abolishes Placental Ischemia-Induced Hypertension.

PubMed

Spradley, Frank T; Tan, Adelene Y; Joo, Woo S; Daniels, Garrett; Kussie, Paul; Karumanchi, S Ananth; Granger, Joey P

2016-04-01

Preeclampsia is a pregnancy-specific disorder of new-onset hypertension. Unfortunately, the most effective treatment is early delivery of the fetus and placenta. Placental ischemia appears central to the pathogenesis of preeclampsia because placental ischemia/hypoxia induced in animals by reduced uterine perfusion pressure (RUPP) or in humans stimulates release of hypertensive placental factors into the maternal circulation. The anti-angiogenic factor soluble fms-like tyrosine kinase-1 (sFlt-1), which antagonizes and reduces bioavailable vascular endothelial growth factor and placental growth factor (PlGF), is elevated in RUPP rats and preeclampsia. Although PlGF and vascular endothelial growth factor are both natural ligands for sFlt-1, vascular endothelial growth factor also has high affinity to VEGFR2 (Flk-1) causing side effects like edema. PlGF is specific for sFlt-1. We tested the hypothesis that PlGF treatment reduces placental ischemia-induced hypertension by antagonizing sFlt-1 without adverse consequences to the mother or fetus. On gestational day 14, rats were randomized to 4 groups: normal pregnant or RUPP±infusion of recombinant human PlGF (180 μg/kg per day; AG31, a purified, recombinant human form of PlGF) for 5 days via intraperitoneal osmotic minipumps. On day 19, mean arterial blood pressure and plasma sFlt-1 were higher and glomerular filtration rate lower in RUPP than normal pregnant rats. Infusion of recombinant human PlGF abolished these changes seen with RUPP along with reducing oxidative stress. These data indicate that the increased sFlt-1 and reduced PlGF resulting from placental ischemia contribute to maternal hypertension. Our novel finding that recombinant human PlGF abolishes placental ischemia-induced hypertension, without major adverse consequences, suggests a strong therapeutic potential for this growth factor in preeclampsia. © 2016 American Heart Association, Inc.

PLACENTAL GROWTH FACTOR ADMINISTRATION ABOLISHES PLACENTAL ISCHEMIA-INDUCED HYPERTENSION

PubMed Central

Spradley, Frank T.; Tan, Adelene Y.; Joo, Woo S.; Daniels, Garrett; Kussie, Paul; Karumanchi, S. Ananth; Granger, Joey P.

2016-01-01

Preeclampsia is a pregnancy-specific disorder of new-onset hypertension. Unfortunately, the most effective treatment is early delivery of the fetus and placenta. Placental ischemia appears central to the pathogenesis of preeclampsia as placental ischemia/hypoxia induced in animals by reduced uterine perfusion pressure (RUPP) or in humans stimulates release of hypertensive placental factors into the maternal circulation. The anti-angiogenic factor soluble fms-like tyrosine kinase-1 (sFlt-1), which antagonizes and reduces bioavailable vascular endothelial growth factor (VEGF) and placental growth factor (PlGF), is elevated in RUPP rats and preeclampsia. Although PlGF and VEGF are both natural ligands for sFlt-1, VEGF also has high affinity to VEGFR2 (Flk-1) causing side effects like edema. PlGF is specific for sFlt-1. We tested the hypothesis that PlGF treatment reduces placental ischemia-induced hypertension by antagonizing sFlt-1 without adverse consequences to the mother or fetus. On gestational day 14, rats were randomized to four groups: normal pregnant (NP) or RUPP ± infusion of rhPlGF (180 μg/kg/day; AG31, a purified, recombinant human form of PlGF) for 5 days via intraperitoneal osmotic minipumps. On day 19, mean arterial blood pressure and plasma sFlt-1 were higher and glomerular filtration rate lower in RUPP than NP rats. Infusion of rhPlGF abolished these changes seen with RUPP along with reducing oxidative stress. These data indicate that the increased sFlt-1 and reduced PlGF resulting from placental ischemia contribute to maternal hypertension. Our novel finding that rhPlGF abolishes placental ischemia-induced hypertension, without major adverse consequences, suggests a strong therapeutic potential for this growth factor in preeclampsia. PMID:26831193

Bowel obstruction complicated by ischemia: analysis of CT findings.

PubMed

Cox, Veronica L; Tahvildari, Ali M; Johnson, Benjamin; Wei, Wei; Jeffrey, R Brooke

2018-06-01

To analyze CT signs of bowel ischemia in patients with surgical bowel obstruction, and thereby improve CT diagnosis in this common clinical scenario. Surgical and histopathological findings were used as the reference standard. We retrospectively analyzed CT findings in patients brought to surgery for bowel obstruction over 13 years. Etiology of obstruction (adhesion, hernia, etc.) was recorded. Specific CT features of acute mesenteric ischemia (AMI) were analyzed, including bowel wall thickening, mucosal hypoenhancement, and others. 173 cases were eligible for analysis. 21% of cases were positive for bowel ischemia. Volvulus, internal hernia, and closed-loop obstructions showed ischemia rates of 60%, 43%, and 43%; ischemia rate in obstruction from simple adhesion was 21%. Patients with bowel obstruction related to malignancy were never ischemic. Sensitivities and specificities for CT features predicting ischemia were calculated, with wall thickening, hypoenhancement, and pneumatosis showing high specificity for ischemia (86%-100%). Wall thickening, hypoenhancement, and pneumatosis are highly specific CT signs of ischemia in the setting of obstruction. None of the evaluated CT signs were found to be highly sensitive. Overall frequency of ischemia in surgical bowel obstruction is 21%, and 2-3 times that for complex obstructions (volvulus, closed loop, etc.). Obstructions related to malignancy virtually never become ischemic.

DIGE Proteome Analysis Reveals Suitability of Ischemic Cardiac In Vitro Model for Studying Cellular Response to Acute Ischemia and Regeneration

PubMed Central

Haas, Sina; Jahnke, Heinz-Georg; Moerbt, Nora; von Bergen, Martin; Aharinejad, Seyedhossein; Andrukhova, Olena; Robitzki, Andrea A.

2012-01-01

Proteomic analysis of myocardial tissue from patient population is suited to yield insights into cellular and molecular mechanisms taking place in cardiovascular diseases. However, it has been limited by small sized biopsies and complicated by high variances between patients. Therefore, there is a high demand for suitable model systems with the capability to simulate ischemic and cardiotoxic effects in vitro, under defined conditions. In this context, we established an in vitro ischemia/reperfusion cardiac disease model based on the contractile HL-1 cell line. To identify pathways involved in the cellular alterations induced by ischemia and thereby defining disease-specific biomarkers and potential target structures for new drug candidates we used fluorescence 2D-difference gel electrophoresis. By comparing spot density changes in ischemic and reperfusion samples we detected several protein spots that were differentially abundant. Using MALDI-TOF/TOF-MS and ESI-MS the proteins were identified and subsequently grouped by functionality. Most prominent were changes in apoptosis signalling, cell structure and energy-metabolism. Alterations were confirmed by analysis of human biopsies from patients with ischemic cardiomyopathy. With the establishment of our in vitro disease model for ischemia injury target identification via proteomic research becomes independent from rare human material and will create new possibilities in cardiac research. PMID:22384053

Intraperitoneal curcumin decreased lung, renal and heart injury in abdominal aorta ischemia/reperfusion model in rat.

PubMed

Aydin, Mehmet Salih; Caliskan, Ahmet; Kocarslan, Aydemir; Kocarslan, Sezen; Yildiz, Ali; Günay, Samil; Savik, Emin; Hazar, Abdussemet; Yalcin, Funda

2014-01-01

Previous studies have demonstrated that curcumin (CUR) has protective effects against ischemia reperfusion injury to various organs. We aimed to determine whether CUR has favorable effects on tissues and oxidative stress in abdominal aorta ischemia-reperfusion injury. Thirty rats were divided into three groups as sham, control and treatment (CUR) group. Control and CUR groups underwent abdominal aorta ischemia for 60 min followed by a 120 min period of reperfusion. In the CUR group, CUR was given 5 min before reperfusion at a dose of 200 mg/kg via an intraperitoneal route. Total antioxidant capacity (TAC), total oxidative status (TOS), and oxidative stress index (OSI) in blood serum were measured, and lung, renal and heart tissue histopathology were evaluated with light microscopy. TOS and OSI activity in blood samples were statistically decreased in sham and CUR groups compared to the control group (p < 0.001 for TOS and OSI). Renal, lung, heart injury scores of sham and CUR groups were statistically decreased compared to control group (p < 0.001 for all comparisons). Histopathological examination revealed less severe lesions in CUR group than in the control group. CUR administered intraperitoneally was effective in reducing oxidative stress and histopathologic injury in an acute abdominal aorta I/R rat model. Copyright © 2014 Surgical Associates Ltd. Published by Elsevier Ltd. All rights reserved.

Acute mesenteric ischemia of arterial origin: importance of early revascularization.

PubMed

Plumereau, F; Mucci, S; Le Naoures, P; Finel, J B; Hamy, A

2015-02-01

The goal of our study was to show that survival was better when early revascularization was performed rather than gastrointestinal resection in the management of acute mesenteric ischemia of arterial origin. The reports of patients managed in our center between January 2005 and May 2012 for acute mesenteric ischemia of arterial origin were analyzed retrospectively. Data on clinical, laboratory and radiologic findings, the interval before treatment, the operative findings and the surgical procedures were collected. Follow-up information included the postoperative course, and mortality at 48 h, 30 days and 1 year, the latter being compared between patients undergoing revascularization versus gastrointestinal resection. Of 43 patients treated during this period, 20 had gastrointestinal lesions deemed to be beyond all therapeutic resources, 13 were treated with gastrointestinal resection without revascularization, while 10 underwent early revascularization. There were no statistically significant differences found in the extent of involvement between the two groups (P=0.22). Mortality at 48 h, 30 days and 1 year was 8% (n=1), 30% (n=4) and 68% (n=8) in patients who underwent enterectomy vs. 0% (n=0), 0% (n=0) and 10% (n=1) in patients who underwent revascularization procedures. The difference at 1 year was statistically significant (P=0.02). At 1 year, two patients in the revascularized group had a short bowel syndrome vs. one in the non-revascularized group. Acute mesenteric ischemia of arterial origin is associated with high morbidity and mortality. Optimal management should include early revascularization. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Milrinone-induced postconditioning reduces hepatic ischemia-reperfusion injury in rats: the roles of phosphatidylinositol 3-kinase and nitric oxide.

PubMed

Toyoda, Tomomi; Tosaka, Shinya; Tosaka, Reiko; Maekawa, Takuji; Cho, Sungsam; Eguchi, Susumu; Nakashima, Masahiro; Sumikawa, Koji

2014-01-01

Ischemic postconditioning (PostC) protects the liver against ischemia-reperfusion (IR) injury. Milrinone, a phosphodiesterase 3 inhibitor, has been reported to exhibit preconditioning properties against hepatic IR injury; however, its PostC properties remain unknown. This study investigated whether milrinone has PostC properties against hepatic IR injury and the roles of phosphatidylinositol 3-kinase (PI3K) and nitric oxide synthase (NOS). Male Wistar rats were separated into six groups: (1) group S: animals that underwent sham operation without ischemia, (2) group C: ischemia followed by reperfusion with no other intervention, (3) group M: milrinone administered immediately after reperfusion, (4) group MW: wortmannin, a PI3K inhibitor, injected before milrinone administration, (5) group MN: l-NAME, a NOS inhibitor, injected before milrinone administration, and (6) group MD, milrinone administered 30 min after reperfusion. Except for group S, all groups underwent 1 h of warm ischemia of median and left lateral lobes, followed by 5 h of reperfusion. Biochemical liver function analysis and histologic examination were performed. Serum aspartate aminotransferase, alanine aminotransferase, and lactic dehydrogenase levels, histologic damage scores, and apoptotic rate in group M were significantly lower than those in group C. The inhibition of PI3K or NOS prevented this protective effect. Milrinone administered 30 min after reperfusion did not show obvious protective effects. Milrinone-induced PostC protects against hepatic IR injury when it is administered immediately after reperfusion, and PI3K and NOS may play an important role in this protective effect. Copyright © 2014 Elsevier Inc. All rights reserved.

Role of REM Sleep, Melanin Concentrating Hormone and Orexin/Hypocretin Systems in the Sleep Deprivation Pre-Ischemia

PubMed Central

Pace, Marta; Adamantidis, Antoine; Facchin, Laura; Bassetti, Claudio

2017-01-01

Study Objectives Sleep reduction after stroke is linked to poor recovery in patients. Conversely, a neuroprotective effect is observed in animals subjected to acute sleep deprivation (SD) before ischemia. This neuroprotection is associated with an increase of the sleep, melanin concentrating hormone (MCH) and orexin/hypocretin (OX) systems. This study aims to 1) assess the relationship between sleep and recovery; 2) test the association between MCH and OX systems with the pathological mechanisms of stroke. Methods Sprague-Dawley rats were assigned to four experimental groups: (i) SD_IS: SD performed before ischemia; (ii) IS: ischemia; (iii) SD_Sham: SD performed before sham surgery; (iv) Sham: sham surgery. EEG and EMG were recorded. The time-course of the MCH and OX gene expression was measured at 4, 12, 24 hours and 3, 4, 7 days following ischemic surgery by qRT-PCR. Results A reduction of infarct volume was observed in the SD_IS group, which correlated with an increase of REM sleep observed during the acute phase of stroke. Conversely, the IS group showed a reduction of REM sleep. Furthermore, ischemia induces an increase of MCH and OX systems during the acute phase of stroke, although, both systems were still increased for a long period of time only in the SD_IS group. Conclusions Our data indicates that REM sleep may be involved in the neuroprotective effect of SD pre-ischemia, and that both MCH and OX systems were increased during the acute phase of stroke. Future studies should assess the role of REM sleep as a prognostic marker, and test MCH and OXA agonists as new treatment options in the acute phase of stroke. PMID:28061506

Ischemia/Reperfusion

PubMed Central

Kalogeris, Theodore; Baines, Christopher P.; Krenz, Maike; Korthuis, Ronald J.

2017-01-01

Ischemic disorders, such as myocardial infarction, stroke, and peripheral vascular disease, are the most common causes of debilitating disease and death in westernized cultures. The extent of tissue injury relates directly to the extent of blood flow reduction and to the length of the ischemic period, which influence the levels to which cellular ATP and intracellular pH are reduced. By impairing ATPase-dependent ion transport, ischemia causes intracellular and mitochondrial calcium levels to increase (calcium overload). Cell volume regulatory mechanisms are also disrupted by the lack of ATP, which can induce lysis of organelle and plasma membranes. Reperfusion, although required to salvage oxygen-starved tissues, produces paradoxical tissue responses that fuel the production of reactive oxygen species (oxygen paradox), sequestration of proinflammatory immunocytes in ischemic tissues, endoplasmic reticulum stress, and development of postischemic capillary no-reflow, which amplify tissue injury. These pathologic events culminate in opening of mitochondrial permeability transition pores as a common end-effector of ischemia/reperfusion (I/R)-induced cell lysis and death. Emerging concepts include the influence of the intestinal microbiome, fetal programming, epigenetic changes, and microparticles in the pathogenesis of I/R. The overall goal of this review is to describe these and other mechanisms that contribute to I/R injury. Because so many different deleterious events participate in I/R, it is clear that therapeutic approaches will be effective only when multiple pathologic processes are targeted. In addition, the translational significance of I/R research will be enhanced by much wider use of animal models that incorporate the complicating effects of risk factors for cardiovascular disease. PMID:28135002

Is ursodeoxycholic acid crucial for ischemia/reperfusion-induced ovarian injury in rat ovary?

PubMed

Akdemir, Ali; Sahin, Cagdas; Erbas, Oytun; Yeniel, Ahmet O; Sendag, Fatih

2015-08-01

Ursodeoxycholic acid is frequently used in cholestatic liver diseases. Also, it protects hepatocytes against oxidative stress induced by hydrophobic bile acids. We investigated the anti-oxidative effect of ursodeoxycholic acid on ischemia/reperfusion injury after ovarian de-torsion in rats. We designed five study groups. Group 1 (n = 6): Sham-operated group; group 2 (n = 6): torsion group; group 3 (n = 6): torsion and ursodeoxycholic acid, group 4 (n = 7): torsion/de-torsion group; and group 5 (n = 7): torsion/de-torsion and ursodeoxycholic acid. After that, ovarian samples were obtained and examined histologically and tissue levels of malondialdehyde were measured. Follicular degeneration, edema and inflammatory cells were significantly decreased in groups 3 and 5 in comparison with groups 2 and 4. Also, groups 4 and 5 were compared in terms of vascular congestion and hemorrhage and these were found to be significantly decreased in group 5. In addition, levels of malondialdehyde were significantly decreased in groups 3 and 5 in comparison with groups 2 and 4. We concluded that ursodeoxycholic acid might be useful to protect the ovary against ischemia and reperfusion injury.

Erythropoietin and sildenafil protect against ischemia/reperfusion injury following testicular torsion in adult rats.

PubMed

Kostakis, Ioannis D; Zavras, Nick; Damaskos, Christos; Sakellariou, Stratigoula; Korkolopoulou, Penelope; Misiakos, Evangelos P; Tsaparas, Petros; Vaos, George; Karatzas, Theodoros

2017-06-01

Testicular torsion/detorsion causes severe tissue damage due to ischemia/reperfusion injury. The present study investigated the protective effect of erythropoietin and sildenafil against ischemia/reperfusion injury following unilateral testicular torsion/detorsion in adult rats. A total of 28 adult male rats were included, and were divided into the following groups: Group A (n=5), sham operated; groups B (n=5), C (n=5), D (n=5) and E (n=8), undergoing right testis torsion and detorsion after 90 min. Group B received no drug treatment. Rats in the groups C and D received low-dose (1,000 IU/kg) or high-dose (3,000 IU/kg) erythropoietin, while those in group E received sildenafil (0.7 mg/kg), through intraperitoneal injection after 60 min of torsion. The right testis was extracted 24 h after detorsion, and the tissue was subjected to histopathological examination and immunohistochemical assessment of cleaved caspase-3 expression. Histological alterations and the quality of spermatogenesis were scored according to the Cosentino and the Johnsen scoring systems, respectively. The results demonstrated normal testicular architecture in group A, while the other groups showed ischemic cellular damages, with the worst scores observed in group B. Groups D and E presented better scores compared with group C. Regarding the quality of spermatogenesis, the best scores were observed in group A, and the worst in group B. Groups C, D and E presented similar results, which were improved in comparison to group B, however, not compared to group A. Furthermore, cleaved caspase-3 levels were lower in groups A, D and E, with equal results observed. Group C had higher levels of cleaved caspase-3 compared with these groups, but lower than group B, which presented the highest cleaved caspase-3 levels. In conclusion, erythropoietin and sildenafil protect testis from ischemia/reperfusion injury by decreasing cellular damage and attenuating apoptosis.

Erythropoietin and sildenafil protect against ischemia/reperfusion injury following testicular torsion in adult rats

PubMed Central

Kostakis, Ioannis D.; Zavras, Nick; Damaskos, Christos; Sakellariou, Stratigoula; Korkolopoulou, Penelope; Misiakos, Evangelos P.; Tsaparas, Petros; Vaos, George; Karatzas, Theodoros

2017-01-01

Testicular torsion/detorsion causes severe tissue damage due to ischemia/reperfusion injury. The present study investigated the protective effect of erythropoietin and sildenafil against ischemia/reperfusion injury following unilateral testicular torsion/detorsion in adult rats. A total of 28 adult male rats were included, and were divided into the following groups: Group A (n=5), sham operated; groups B (n=5), C (n=5), D (n=5) and E (n=8), undergoing right testis torsion and detorsion after 90 min. Group B received no drug treatment. Rats in the groups C and D received low-dose (1,000 IU/kg) or high-dose (3,000 IU/kg) erythropoietin, while those in group E received sildenafil (0.7 mg/kg), through intraperitoneal injection after 60 min of torsion. The right testis was extracted 24 h after detorsion, and the tissue was subjected to histopathological examination and immunohistochemical assessment of cleaved caspase-3 expression. Histological alterations and the quality of spermatogenesis were scored according to the Cosentino and the Johnsen scoring systems, respectively. The results demonstrated normal testicular architecture in group A, while the other groups showed ischemic cellular damages, with the worst scores observed in group B. Groups D and E presented better scores compared with group C. Regarding the quality of spermatogenesis, the best scores were observed in group A, and the worst in group B. Groups C, D and E presented similar results, which were improved in comparison to group B, however, not compared to group A. Furthermore, cleaved caspase-3 levels were lower in groups A, D and E, with equal results observed. Group C had higher levels of cleaved caspase-3 compared with these groups, but lower than group B, which presented the highest cleaved caspase-3 levels. In conclusion, erythropoietin and sildenafil protect testis from ischemia/reperfusion injury by decreasing cellular damage and attenuating apoptosis. PMID:28587411

SALVIANOLIC ACID B ALLEVIATING MYOCARDIUM INJURY IN ISCHEMIA REPERFUSION RATS.

PubMed

Qiao, Zengyong; Xu, Yawei

2016-01-01

Salvia miltiorrhiza (SM) Bunge is one of the widely-used Chinese medicinal herbs. Salvianolic acid B (Sal B), a bioactive compound isolated from the Chinese herb Radix Salviae Miltiorrhizae, has been reported to exhibit anti-inflammatory and anti-oxidantive effects. To study the cardioprotective effects of salvianolic acid B (Sal B) on acute myocardial ischemia reperfusion (MIR) injury rats, on the basis of this investigation, the possible mechanism of salvianolic acid B was elucidated. Male Sprague- Dawley rats (200-220 g) were randomly divided into five groups: sham-operated, MIR, MIR + Sal B (10 mg/kg/day, orally), MIR + Sal B (20 mg/kg/ day, orally) and MIR + Sal B (30 mg/kg/ day, orally). Before operation, the foregoing groups were pretreated with homologous drug once a day for 7 days, respectively. After twelve hours in MIR, the cardioprotective effects of SPJ were evaluated by infarct size, biochemical values, and the antioxidative and antiapoptotic relative gene expressions. Sal B significantly improved heart function and decreased infarct size; remarkably decreased levels of serum TNF-α and IL-Ιβ levels, increased contents of myocardium antioxidant enzymes activities; western blot results showed that Sal B ameliorate the increased Bax and caspase-3 protins expressions and decreased Bcl-2 proteins expression and ratios of Bcl-2 to Bax. In ischemic myocardium, oxidative stress caused the overgeneration and accumulation of reactive oxygen species (ROS), which was central of cardiac ischemic injury. Sal B exerted beneficially cardioprotective effects on myocardial ischemia injury rats, mainly scavenging oxidative stress-triggered overgeneration and accumulation of ROS, alleviating myocardial ischemia injury and cardiac cell death. List of abbreviations: salvianolic acid B (Sal B); myocardial ischemia reperfusion (MIR); reactive oxygen species (ROS); Left ventricular end-diastolic pressure (LVEDP); left ventricular end-diastolic volume (LVEDV

[Activation of autophagy pathway in hippocampus and deterioration of learning and memory ability by intermittent hypoxia in rats after cerebral ischemia].

PubMed

Guo, Xiangfei; Zhao, Yaning; Li, Jianmin; Liu, Wenqian; Chen, Changxiang

2016-09-01

Objective To investigate the effects of different duration of intermittent hypoxia on the autophagy pathway in the hippocampus and the learning and memory ability after cerebral ischemia in rats. Methods 100 male Wistar rats were randomly divided into sham operation (SO) group, ischemia/reperfusion (I/R) group, intermittent hypoxia for 7 days combined with ischemia/reperfusion (IH7-I/R) group, intermittent hypoxia for 14 days combined with ischemia/reperfusion (IH14-I/R) group, intermittent hypoxia for 21 days combined with ischemia/reperfusion (IH21-I/R) group, n =20 in each group. The rats in IH7-I/R group, IH14-I/R group and IH21-I/R group were respectively subjected to intermittent hypoxia for 7, 14 and 21 days prior to I/R modeling by improved Pulsinelli four-vessel occlusion (4-VO). The morphological changes of nerve cells in the hippocampus of rat brain were detected by HE staining; the levels of mammalian target of rapamycin (mTOR) and beclin 1 mRNA in the hippocampus were determined by quantitative real-time PCR; the distribution of mTOR and beclin 1 in the hippocampus was observed by immunohistochemistry; the learning and memory ability of rats was assessed by the Morris water maze test. Results Compared with the SO group, the never cell morphology was damaged, the number of survival neurons in the hippocampus was reduced, the expressions of mTOR and beclin 1 in the hippocampus were strengthened, and the learning and memory ability declined in the I/R group. Compared with the I/R group, the never cell morphology was damaged seriously, the number of survival neurons in the hippocampus decreased, the expressions of mTOR and beclin 1 in the hippocampus increased, and the learning and memory ability dropped in the intermittent hypoxia groups. What's more, the above changes were dependent on the duration of intermittent hypoxia. Conclusion Intermittent hypoxia aggravates the dysfunction of learning and memory after cerebral ischemia and the damages increase

Acetyl-L-carnitine and oxaloacetate in post-treatment against LTP impairment in a rat ischemia model. An in vitro electrophysiological study.

PubMed

Kocsis, K; Knapp, L; Mészáros, J; Kis, Z; Farkas, T; Vécsei, L; Toldi, J

2015-06-01

A high proportion of research relating to cerebral ischemia focuses on neuroprotection. The application of compounds normally present in the organism is popular, because they do not greatly influence the synaptic activity by receptor modulation, and can be administered without serious side effects. Oxaloacetate (OxAc) and acetyl-L-carnitine (ALC) are such favorable endogenous molecules. ALC can exert a protective effect by improving the energy state of the neurons under ischemic conditions. A promising neuroprotective strategy is glutamate scavenging, which can be achieved by the intravenous administration of OxAc. This study involved the possible protective effects of ALC and OxAc in different post-treatment protocols against long-term potentiation (LTP) impairment. Ischemia was induced in rats by 2-vessel occlusion, which led to a decreased LTP relative to the control group. High-dose (200 mg/kg) ALC or OxAc post-treatment resulted in a higher potentiation relative to the 2VO group, but it did not reach the control level, whereas low-dose ALC (100 mg/kg) in combination with OxAc completely restored the LTP function. Many previous studies have concluded that ALC can be protective only as pretreatment. The strategy described here reveals that ALC can also be neuroprotective when utilized as post-treatment against ischemia.

Small Group Research

ERIC Educational Resources Information Center

McGrath, Joseph E.

1978-01-01

Summarizes research on small group processes by giving a comprehensive account of the types of variables primarily studied in the laboratory. These include group structure, group composition, group size, and group relations. Considers effects of power, leadership, conformity to social norms, and role relationships. (Author/AV)

[Effects of pressure induced retinal ischemia on ERG in rabbit].

PubMed

Song, G; Yang, X; Zhang, Z; Zhang, D

2001-12-01

To observe the effects of pressure induced retinal ischemia on electroretinogram(ERG) in rabbit. Retinal ischemia was induced in rabbits by increasing intraocular pressure at 30 mmHg, 60 mmHg, 90 mmHg, 120 mmHg for 45 minutes, and retinal function was monitored by eletroretinography. There was no difference on ERG before or after the experiment both in 30 mmHg group and control one. In 60 mmHg pressure induced ischemia eyes, the amplitudes of the b-wave and OPs wave reduced significantly. Four hours after reperfusion, they were totally recovered. After an ischemic insult of 90 mmHg or 120 mmHg for 45 minutes, there was no response of ERG. Four hours later, the amplitudes of the b-wave and OPs wave were 66.912 +/- 20.157 and 16.423 +/- 3.965 the former, 38.852 +/- 23.438 and 8.610 +/- 12.090 the latter, respectively. These results suggest that higher intraocular pressure causes more severe retina ischemic damage, and less recovery ability.

Effect of ischemic preconditioning on antioxidant status in the gerbil hippocampal CA1 region after transient forebrain ischemia

PubMed Central

Park, Seung Min; Park, Chan Woo; Lee, Tae-Kyeong; Cho, Jeong Hwi; Park, Joon Ha; Lee, Jae-Chul; Chen, Bai Hui; Shin, Bich-Na; Ahn, Ji Hyeon; Tae, Hyun-Jin; Shin, Myoung Cheol; Ohk, Taek Geun; Cho, Jun Hwi; Won, Moo-Ho; Choi, Soo Young; Kim, In Hye

2016-01-01

Ischemic preconditioning (IPC) is a condition of sublethal transient global ischemia and exhibits neuroprotective effects against subsequent lethal ischemic insult. We, in this study, examined the neuroprotective effects of IPC and its effects on immunoreactive changes of antioxidant enzymes including superoxide dismutase (SOD) 1 and SOD2, catalase (CAT) and glutathione peroxidase (GPX) in the gerbil hippocampal CA1 region after transient forebrain ischemia. Pyramidal neurons of the stratum pyramidale (SP) in the hippocampal CA1 region of animals died 5 days after lethal transient ischemia without IPC (8.6% (ratio of remanent neurons) of the sham-operated group); however, IPC prevented the pyramidal neurons from subsequent lethal ischemic injury (92.3% (ratio of remanent neurons) of the sham-operated group). SOD1, SOD2, CAT and GPX immunoreactivities in the sham-operated animals were easily detected in pyramidal neurons in the stratum pyramidale (SP) of the hippocampal CA1 region, while all of these immunoreactivities were rarely detected in the stratum pyramidale at 5 days after lethal transient ischemia without IPC. Meanwhile, their immunoreactivities in the sham-operated animals with IPC were similar to (SOD1, SOD2 and CAT) or higher (GPX) than those in the sham-operated animals without IPC. Furthermore, their immunoreactivities in the stratum pyramidale of the ischemia-operated animals with IPC were steadily maintained after lethal ischemia/reperfusion. Results of western blot analysis for SOD1, SOD2, CAT and GPX were similar to immunohistochemical data. In conclusion, IPC maintained or increased the expression of antioxidant enzymes in the stratum pyramidale of the hippocampal CA1 region after subsequent lethal transient forebrain ischemia and IPC exhibited neuroprotective effects in the hippocampal CA1 region against transient forebrain ischemia. PMID:27630689

[Acute mesenteric ischemia: do biomarkers contribute to diagnosis?].

PubMed

Rosero, Olivér; Harsányi, László; Szijártó, Attila

2014-10-12

Acute mesenteric ischemia is an emergency condition that requires immediate therapy. Despite advances in the fields of surgery and intensive therapy, the mortality of this condition remains high. This is due to the broad variability of clinical presentations and non-specific laboratory findings, which delay the diagnosis allowing the ischemia to progress and further worsening the patients' chances of survival. Thus, there is a significant need for reliable and enhanced serological markers of intestinal ischemia. The authors review the traditionally used and novel experimental serological markers for early diagnosis of mesenteric ischemia.

Clinical Features and Outcomes of Gastric Ischemia.

PubMed

Sharma, Ayush; Mukewar, Saurabh; Chari, Suresh T; Wong Kee Song, Louis M

2017-12-01

Gastric ischemia is a rare condition associated with poor prognosis. Our study aim was to highlight the clinical features and outcomes of patients with gastric ischemia. A retrospective review of patients diagnosed with isolated gastric ischemia at our institution from January 1, 2000, to May 5, 2016, was performed. Demographic, clinical, endoscopic, radiologic, and outcome variables were abstracted for analysis. Seventeen patients (65% men) with mean age of 69.3 ± 11.3 years and body mass index of 28.8 ± 11.1 were identified. The etiologies for gastric ischemia included local vascular causes (n = 8), systemic hypoperfusion (n = 4), and mechanical obstruction (n = 5). The most common presenting symptoms were abdominal pain (65%), gastrointestinal bleeding (47%), and altered mental status (23%). The typical endoscopic appearance was mucosal congestion and erythema with or without ulceration. Gastric pneumatosis and portal venous air were more commonly seen on CT imaging. Radiologic and/or surgical intervention was needed in 9 patients, while the remaining 8 patients were managed conservatively with acid suppression, antibiotics, and nasogastric tube decompression. The median duration of hospital stay was 15 days (range 1-36 days). There were no cases of rebleeding and the mortality rate as a direct result of gastric ischemia was 24% within 6 months of diagnosis. Although uncommon, gastric ischemia is associated with significant mortality. Endoscopy and CT imaging play an important role in its diagnosis. The management of gastric ischemia is dictated by its severity and associated comorbidities.

Comparison of protective effects of safflor injection and extract of Ginkgo biloba on lung ischemia/reperfusion injury in rabbits.

PubMed

Tian, Xiao-xi; Wang, Bo-liang; Cao, Yi-zhan; Zhong, Yue-xia; Tu, Yan-yang; Xiao, Jian-bo; He, Qian-feng; Zhai, Li-na

2015-03-01

To observe the protective effects of safflor Injection (SI) and extract of Ginkgo biloba (EGB) on lung ischemia-reperfusion injury (LIRI) and investigate its mechanism. In vivo rabbit model of LIRI was reconstructed. Forty rabbits were randomly and equally divided into four groups: sham-operation group (sham group), ischemia-reperfusion group (model group), ischemia-reperfusion plus SI group (safflor group) and ischemia-reperfusion plus EGB injection group (EGB group). Malondialdehyde (MDA) content, superoxide dismutase (SOD) and xanthine oxidase (XO) activity in serum were measured. The wet/dry weight ratio (W/D) of the lung tissue and activity of myeloperoxidase (MPO) were also tested. Ultrastructure change of the lung tissue was observed by the electron microscope. The expression of intercellular adhesion molecule-1 (ICAM-1) was measured by immunohistochemistry (IHC). In the model group, MDA and XO increased and SOD decreased in serum compared with the sham group (P<0.01). The values of W/D, MPO and ICAM-1 of the model group were higher than those of the sham group (P<0.01), but those of the safflor group and EGB group were significantly lower than those of the model group (P<0.01). The IHC demonstrated that ICAM-1 expression in lung tissue of the model group was significantly higher than those of the safflor group (P<0.01). Compared with safflor group, in the EGB group MDA, XO, MPO decreased, SOD and ICAM-1 expression increased (P<0.05), but the change of W/D was not statistically significant (P>0.05). SI and EGB may attenuate LIRI through antioxidation, inhibition of neutrophil aggregation and down-regulation of ICAM-1 expression. But EGB had more effect on the antioxidation, while SI did better on regulating ICAM-1 expression.

Pharmacology of Ischemia-Reperfusion. Translational Research Considerations.

PubMed

Prieto-Moure, Beatriz; Lloris-Carsí, José M; Barrios-Pitarque, Carlos; Toledo-Pereyra, Luis-H; Lajara-Romance, José María; Berda-Antolí, M; Lloris-Cejalvo, J M; Cejalvo-Lapeña, Dolores

2016-08-01

Ischemia-reperfusion (IRI) is a complex physiopathological mechanism involving a large number of metabolic processes that can eventually lead to cell apoptosis and ultimately tissue necrosis. Treatment approaches intended to reduce or palliate the effects of IRI are varied, and are aimed basically at: inhibiting cell apoptosis and the complement system in the inflammatory process deriving from IRI, modulating calcium levels, maintaining mitochondrial membrane integrity, reducing the oxidative effects of IRI and levels of inflammatory cytokines, or minimizing the action of macrophages, neutrophils, and other cell types. This study involved an extensive, up-to-date review of the bibliography on the currently most widely used active products in the treatment and prevention of IRI, and their mechanisms of action, in an aim to obtain an overview of current and potential future treatments for this pathological process. The importance of IRI is clearly reflected by the large number of studies published year after year, and by the variety of pathophysiological processes involved in this major vascular problem. A quick study of the evolution of IRI-related publications in PubMed shows that in a single month in 2014, 263 articles were published, compared to 806 articles in the entire 1990.

Sodium 4-phenylbutyrate protects against spinal cord ischemia by inhibition of endoplasmic reticulum stress.

PubMed

Mizukami, Taketomo; Orihashi, Kazumasa; Herlambang, Bagus; Takahashi, Shinya; Hamaishi, Makoto; Okada, Kenji; Sueda, Taijiro

2010-12-01

Delayed paraplegia after operation on the thoracoabdominal aorta is considered to be related to vulnerability of motor neurons to ischemia. Previous studies have demonstrated the relationship between neuronal vulnerability and endoplasmic reticulum (ER) stress after transient ischemia in the spinal cord. The aim of this study was to investigate whether sodium 4-phenylbutyrate (PBA), a chemical chaperone that reduces the load of mutant or unfolded proteins retained in the ER during cellular stress, can protect against ischemic spinal cord damage. Spinal cord ischemia was induced in rabbits by direct aortic cross-clamping (below the renal artery and above the bifurcation) for 15 minutes at normothermia. Group A (n = 6) was a sham operation control group. In group B (n = 6) and group C (n = 6), vehicle or 15 mg/kg/h of sodium 4-PBA was infused intravenously, respectively, from 30 minutes before the induction of ischemia until 30 minutes after reperfusion. Neurologic function was assessed at 8 hours, and 2 and 7 days after reperfusion with a Tarlov score. Histologic changes were studied with hematoxylin-eosin staining. Immunohistochemistry analysis for ER stress-related molecules, including caspase12 and GRP78 were examined. The mean Tarlov scores were 4.0 in every group at 8 hours, but were 4.0, 2.5, and 3.9 at 2 days; and 4.0, 0.7, and 4.0 at 7 days in groups A, B, and C, respectively. The numbers of intact motor neurons at 7 days after reperfusion were 47.4, 21.5, and 44.9 in groups A, B, and C, respectively. There was no significant difference in terms of viable neurons between groups A and C. Caspase12 and GRP78 immunoreactivities were induced in motor neurons in group B, whereas they were not observed in groups A and C. Reduction in ER stress-induced spinal cord injury was achieved by the administration of 4-PBA. 4-PBA may be a strong candidate for use as a therapeutic agent in the treatment of ischemic spinal cord injury. Copyright © 2010 Society for Vascular

Pre-Treatment with Metformin in Comparison with Post-Treatment Reduces Cerebral Ischemia Reperfusion Induced Injuries in Rats.

PubMed

Karimipour, Mojtaba; Shojaei Zarghani, Sara; Mohajer Milani, Majid; Soraya, Hamid

2018-04-01

To explore the effects of pre versus post ischemic treatment with metformin after global cerebral ischemia in rats. Male Wister rats underwent forebrain ischemia by bilateral common carotid artery occlusion for 17 min. Metformin (200 mg/kg) or vehicle was given orally by gavage for 7-14 days. Rats were divided into: control, metformin pre-treatment, metformin post-treatment and metformin pre and post continuous treatment groups. Cerebral infarct size, histopathology, myeloperoxidase and serum malondialdehyde were measured 7 days after ischemia. Histopathological analysis showed that metformin pre-treatment significantly decreased leukocyte infiltration, myeloperoxidase activity and also malondialdehyde level. Metformin pre-treatment and metformin post-treatment reduced infarct size compared with the control group, but it was not significant in the pre and post continuous treatment group. Our findings suggest that pre-treatment with metformin in comparison with post-treatment in experimental stroke can reduce the extent of brain damage and is more neuroprotective at least in part by inhibiting oxidative stress and inflammation.

ERK phosphorylation plays an important role in the protection afforded by hypothermia against renal ischemia-reperfusion injury.

PubMed

Choi, Dae Eun; Jeong, Jin Young; Choi, Hyunsu; Chang, Yoon Kyung; Ahn, Moon Sang; Ham, Young Rok; Na, Ki Ryang; Lee, Kang Wook

2017-02-01

Although hypothermia attenuates the renal injury induced by ischemia-reperfusion, the detailed molecular pathway(s) involved remains unknown. ERK phosphorylation is known to protect against ischemia-reperfusion injury. Also, it has been reported that hypothermia may induce ERK phosphorylation in the heart and brain. We evaluated the role played by ERK in hypothermic protection against renal ischemia-reperfusion injury. C57Bl/6 mice were divided into the following groups: sham-operated (cold, 32°C) vs normal temperature (37°C); ischemia-reperfusion mice (32°C vs 37°C); and PD98059- or vehicle-treated ischemia-reperfusion mice (32°C). Kidneys were harvested 10 and 27 minutes after induction of renal ischemia and 24 hours after ischemia-reperfusion injury. Functional and molecular markers of kidney injury were evaluated. To explore the molecular mechanism involved the expression levels of renal HIF-1 and associated proteins were evaluated. The blood urea nitrogen (BUN) and serum creatinine (s-Cr) levels and the histologic renal injury scores were significantly lower in 32°C ischemia-reperfusion than 37°C ischemia-reperfusion kidneys (all P values < .05). The expression levels of Bax and caspase-3 and the extent of TUNEL and 8-OHdG cell positivity decreased, whereas the renal Bcl-2 level increased, in 32°C ischemia-reperfusion compared to 37°C ischemia-reperfusion mice. The extent of renal ERK phosphorylation was significantly higher in ischemia-reperfusion than sham-operated kidneys. Also, ERK phosphorylation was significantly increased in the kidneys of 32°C compared to 37°C ischemia-reperfusion mice. PD98059 treatment of 32°C ischemia-reperfusion mice significantly decreased the renal HIF-1 level (P < .05) and increased the BUN, s-Cr, renal Bax, and caspase-3 expression levels; the tissue injury score; and the proportions of TUNEL- and 8-OHdG-positive cells. PD98059 also increased the renal Bcl-2 level in such mice. Hypothermia attenuates the renal

Influence of physical preconditioning on the responsiveness of rat pulmonary artery after pulmonary ischemia/reperfusion.

PubMed

Delbin, Maria Andréia; Moraes, Camila; Camargo, Enilton; Mussi, Ricardo K; Antunes, Edson; de Nucci, Gilberto; Zanesco, Angelina

2007-07-01

The aim of this work was to evaluate the effect of physical preconditioning in the responsiveness of rat pulmonary rings submitted to lung ischemia/reperfusion (IR). Wistar rats were divided into three groups: Sedentary sham-operated (SD/SHAM); sedentary submitted to ischemia/reperfusion (SD/IR) and trained submitted to ischemia/reperfusion (TR/IR) animals. Exercise training consisted in sessions of 60 min/day running sessions, 5 days/week for 8 weeks. Left pulmonary IR was performed by occluding for 90 min and reperfusing for 120 min. After that, pulmonary arteries were isolated and concentration-response curves to acetylcholine (ACh), histamine (HIST), sodium nitroprusside (SNP), phenylephrine and U46619 were obtained. Neither potency (-log EC(50)) nor maximal responses (E(max)) were modified for ACh and HIST in all groups. On the other hand, the potency for SNP was significantly increased in TR/IR group (8.23+/-0.06) compared to SD/IR group (7.85+/-0.04). Contractile responses mediated by a-adrenergic receptor were markedly decreased in IR groups (SD/IR: 6.75+/-0.06 and TR/IR: 6.62+/-0.04) compared to SD/SHAM (7.33+/-0.05). No changes were seen for the U46619 in all groups. In conclusion, the present study shows that exercise training has no protective actions in the local blood vessel where the IR process takes place.

[Myocardial mechanical injury in acute ischemia: a pathophysiologic and histopathologic review].

PubMed

Rossi, L; Matturri, L

1986-03-01

The recognition of histopathologic substrates of myocardial contractile damage in human acute ischemia is still very poor, notwithstanding the impressive advances in the inherent clinical diagnostic technology and concepts. The first and foremost inotropic abnormality ensuing ischemia, easily taken for atonic in origin, actually consists of a pathologic contracture of the injured myocardium, depending upon abrupt fall of ATP, and defective extrusion calcium pump with persistence of actomyosin rigor-complexes. In sustained ischemia, further membrane damage exposes the myocell to massive calcium intrusion, with eventual precipitation of it and cell death (reperfusion stone-heart). In case of transient, "hit and run" ischemia, the "stunned" myocardium undergoes prolonged contractile abnormalities. In keeping with fundamentals in pathophysiology of contraction, ischemic myofibrils in human hyperacute infarct, showed spare I bands, accounting for contracture and followed by loss of the regular cross-striation register; then, groups of adjacent sarcomeres were seen to join into true "contraction" bands, with Z lines impinging upon A bands and obliterating the I bands. Coagulative denaturation of contractile proteins follows, presenting as irregular, amorphous degeneration stripes astride irreversibly damaged myocells. As such, these cells can be passively overstretched by the nearby functioning muscle. In turn, the fixed waviness of viable, acutely ischemic myocardium was thought to configure, histologically, the loss of ATP-dependent "plasticity" of myofilaments, in a state of contracture. The "relaxant effect" of inotropic-chronotropic-positive catecholamines, favoring diastole, has been also pointed out. The present microscopic findings are cogent to clinicopathologic problems of coronary ischemia-reperfusion, and sudden death from cardiogenic shock.

Analysis of temporal dynamics in imagery during acute limb ischemia and reperfusion

NASA Astrophysics Data System (ADS)

Irvine, John M.; Regan, John; Spain, Tammy A.; Caruso, Joseph D.; Rodriquez, Maricela; Luthra, Rajiv; Forsberg, Jonathon; Crane, Nicole J.; Elster, Eric

2014-03-01

Ischemia and reperfusion injuries present major challenges for both military and civilian medicine. Improved methods for assessing the effects and predicting outcome could guide treatment decisions. Specific issues related to ischemia and reperfusion injury can include complications arising from tourniquet use, such as microvascular leakage in the limb, loss of muscle strength and systemic failures leading to hypotension and cardiac failure. Better methods for assessing the viability of limbs/tissues during ischemia and reducing complications arising from reperfusion are critical to improving clinical outcomes for at-risk patients. The purpose of this research is to develop and assess possible prediction models of outcome for acute limb ischemia using a pre-clinical model. Our model relies only on non-invasive imaging data acquired from an animal study. Outcome is measured by pathology and functional scores. We explore color, texture, and temporal features derived from both color and thermal motion imagery acquired during ischemia and reperfusion. The imagery features form the explanatory variables in a model for predicting outcome. Comparing model performance to outcome prediction based on direct observation of blood chemistry, blood gas, urinalysis, and physiological measurements provides a reference standard. Initial results show excellent performance for the imagery-base model, compared to predictions based direct measurements. This paper will present the models and supporting analysis, followed by recommendations for future investigations.

Effects of Postconditioning on Skeletal Muscle Injury and Apoptosis Induced by Partial Ischemia and Reperfusion in Rats.

PubMed

Lintz, José Alves; Dalio, Marcelo Bellini; Tirapelli, Luiz Fernando; Ribeiro, Maurício Serra; Joviliano, Edwaldo Edner; Piccinato, Carlos Eli

2017-04-01

Analyze the effects of ischemic postconditioning on skeletal muscle injury and apoptosis produced by partial ischemia and reperfusion in rats. An experimental study was designed using 70 Wistar rats divided in 3 groups: Sham; Control-submitted to ischemia and reperfusion; and Postconditioning-submitted to ischemia and reperfusion with ischemic postconditioning. Subgroups (n = 10) were divided by duration of ischemia (4, 5, or 6 hr). A partial ischemia model using aortic clamping was used. The postconditioning protocol consisted of 3 cycles of clamping the aorta for 1 min and releasing for another minute. Skeletal muscle injury was evaluated by measuring serum levels of releasing cytoplasmic enzymes: aspartate aminotransferase (AST), lactate dehydrogenase (LDH), and total creatine phosphokinase (CPK). Lipid peroxidation was evaluated by muscular levels of malondialdehyde (MDA). Energetic cell storage was evaluated by muscular glycogen levels. Apoptosis was evaluated analyzing the expression of caspase 3 and protein B-cell lymphoma 2 (Bcl-2) by immunohistochemistry. AST levels in Sham group were 109.80 units/L, in Control subgroups were 4h 200.60 units/L/5h 392.30 units/L/6h 118.82 units/L, whereas in Postconditioning subgroups were: 4h 316.10 units/L/5h 268.40 units/L/6h 267.00 units/L. There was a 2-3-fold increase in Control and Postconditioning groups compared with Sham group (P = 0.003) There was no difference between groups with the same ischemic injury time. LDH, CPK, and MDA levels were similar in Sham, Control, and Postconditioning groups. Subgroups with the same ischemic injury time were also similar. Glycogen levels in Sham group were 0.629 mg%, in Control subgroups were 4h 0.323 mg%/5h 0.348 mg%/6h 0.183 mg%, whereas in Postconditioning subgroups were: 4h 0.443 mg%/5h 0.270 mg%/6h 0.324 mg%. Control and Postconditioning groups were decreased by half in relation with the Sham group (P = 0.002), with no difference between groups with the same

Spinal cord ischemia following thoracotomy without epidural anesthesia.

PubMed

Raz, Aeyal; Avramovich, Aharon; Saraf-Lavi, Efrat; Saute, Milton; Eidelman, Leonid A

2006-06-01

Paraplegia is an uncommon yet devastating complication following thoracotomy, usually caused by compression or ischemia of the spinal cord. Ischemia without compression may be a result of global ischemia, vascular injury and other causes. Epidural anesthesia has been implicated as a major cause. This report highlights the fact that perioperative cord ischemia and paraplegia may be unrelated to epidural intervention. A 71-yr-old woman was admitted for a left upper lobectomy for resection of a non-small cell carcinoma of the lung. The patient refused epidural catheter placement and underwent a left T5-6 thoracotomy under general anesthesia. During surgery, she was hemodynamically stable and good oxygen saturation was maintained. Several hours following surgery the patient complained of loss of sensation in her legs. Neurological examination disclosed a complete motor and sensory block at the T5-6 level. Magnetic resonance imaging (MRI) revealed spinal cord ischemia. The patient received iv steroid treatment, but remained paraplegic. Five months following the surgery there was only partial improvement in her motor symptoms. A follow-up MRI study was consistent with a diagnosis of spinal cord ischemia. In this case of paraplegia following thoracic surgery for lung resection, epidural anesthesia/analgesia was not used. The MRI demonstrated evidence of spinal cord ischemia, and no evidence of cord compression. This case highlights that etiologies other than epidural intervention, such as injury to the spinal segmental arteries during thoracotomy, should be considered as potential causes of cord ischemia and resultant paraplegia in this surgical population.

Global Cerebral Ischemia: Synaptic and Cognitive Dysfunction

PubMed Central

Neumann, Jake T.; Cohan, Charles H.; Dave, Kunjan R.; Wright, Clinton B.; Perez-Pinzon, Miguel A.

2018-01-01

Cardiopulmonary arrest is one of the leading causes of death and disability, primarily occurring in the aged population. Numerous global cerebral ischemia animal models induce neuronal damage similar to cardiac arrest. These global cerebral ischemia models range from vessel occlusion to total cessation of cardiac function, both of which have allowed for the investigation of this multifaceted disease and detection of numerous agents that are neuroprotective. Synapses endure a variety of alterations after global cerebral ischemia from the resulting excitotoxicity and have been a major target for neuroprotection; however, neuroprotective agents have proven unsuccessful in clinical trials, as neurological outcomes have not displayed significant improvements in patients. A majority of these neuroprotective agents have specific neuronal targets, where the success of future neuroprotective agents may depend on non-specific targets and numerous cognitive improvements. This review focuses on the different models of global cerebral ischemia, neuronal synaptic alterations, synaptic neuroprotection and behavioral tests that can be used to determine deficits in cognitive function after global cerebral ischemia. PMID:23170794

Intratracheal Administration of Small Interfering RNA Targeting Fas Reduces Lung Ischemia-Reperfusion Injury.

PubMed

Del Sorbo, Lorenzo; Costamagna, Andrea; Muraca, Giuseppe; Rotondo, Giuseppe; Civiletti, Federica; Vizio, Barbara; Bosco, Ornella; Martin Conte, Erica L; Frati, Giacomo; Delsedime, Luisa; Lupia, Enrico; Fanelli, Vito; Ranieri, V Marco

2016-08-01

Lung ischemia-reperfusion injury is the main cause of primary graft dysfunction after lung transplantation and results in increased morbidity and mortality. Fas-mediated apoptosis is one of the pathologic mechanisms involved in the development of ischemia-reperfusion injury. We hypothesized that the inhibition of Fas gene expression in lungs by intratracheal administration of small interfering RNA could reduce lung ischemia-reperfusion injury in an ex vivo model reproducing the procedural sequence of lung transplantation. Prospective, randomized, controlled experimental study. University research laboratory. C57/BL6 mice weighing 28-30 g. Ischemia-reperfusion injury was induced in lungs isolated from mice, 48 hours after treatment with intratracheal small interfering RNA targeting Fas, control small interfering RNA, or vehicle. Isolated lungs were exposed to 6 hours of cold ischemia (4°C), followed by 2 hours of warm (37°C) reperfusion with a solution containing 10% of fresh whole blood and mechanical ventilation with constant low driving pressure. Fas gene expression was significantly silenced at the level of messenger RNA and protein after ischemia-reperfusion in lungs treated with small interfering RNA targeting Fas compared with lungs treated with control small interfering RNA or vehicle. Silencing of Fas gene expression resulted in reduced edema formation (bronchoalveolar lavage protein concentration and lung histology) and improvement in lung compliance. These effects were associated with a significant reduction of pulmonary cell apoptosis of lungs treated with small interfering RNA targeting Fas, which did not affect cytokine release and neutrophil infiltration. Fas expression silencing in the lung by small interfering RNA is effective against ischemia-reperfusion injury. This approach represents a potential innovative strategy of organ preservation before lung transplantation.

Animal models of cerebral ischemia

NASA Astrophysics Data System (ADS)

Khodanovich, M. Yu.; Kisel, A. A.

2015-11-01

Cerebral ischemia remains one of the most frequent causes of death and disability worldwide. Animal models are necessary to understand complex molecular mechanisms of brain damage as well as for the development of new therapies for stroke. This review considers a certain range of animal models of cerebral ischemia, including several types of focal and global ischemia. Since animal models vary in specificity for the human disease which they reproduce, the complexity of surgery, infarct size, reliability of reproduction for statistical analysis, and adequate models need to be chosen according to the aim of a study. The reproduction of a particular animal model needs to be evaluated using appropriate tools, including the behavioral assessment of injury and non-invasive and post-mortem control of brain damage. These problems also have been summarized in the review.

Protective effect of chlorogenic acid on the focal cerebral ischemia reperfusion rat models.

PubMed

Miao, Mingsan; Cao, Lihua; Li, Ruiqi; Fang, Xiaoyan; Miao, Yanyan

2017-05-01

The aim of the study was to investigate the protective characteristic of chlorogenic acid, a natural glucosyl xanthone found in Lonicera Japonica on the cerebral ischemia reperfusion injury and the underlying mechanism. Focal cerebral ischemia reperfusion model was built by blocking the left middle cerebral artery in rats by using the suture-occluded method. Before operation, the corresponding drugs were given for each group once a day for 7 days. After 1 h of final administration, the model was built, after operation, reperfusion was conducted for 22 h, Before the reperfusion 10 min tail vein injection of large, medium and small dose of chlorogenic acid and then mortality was calculated, and Neurological deficit score (NDS) was conducted, and serum was collected to measure the NSE level; a 2 mm thick brain slice located at the intersection of optic nerves was collected for TTC staining, and the percentage of cerebral infarction area was calculated; brain homogenate was collected to measure the ICAM-1, VCAM-1, EPO and HIF-1α levels in brain tissue of cerebral ischemia reperfusion rat models; NGF was detected using immunohistochemical method; the morphological changes in brain tissue was observed with HE staining. All focal cerebral ischemia reperfusion rat models were duplicated successfully. Every chlorogenic acid group with different dosage can significantly reduce the mortality, NDS and cerebral infarction area of rats, and significantly increase the EPO, HIF-1α and NGF levels in brain tissue; significantly improve the pathological lesions of hippocampus and cortex in brain tissue. The results showed that chlorogenic acid could protect the focal cerebral ischemia reperfusion injury rat models by adjusting the inflammatory factor, hypoxia factor and nerve growth factor.

Effects of tadalafil on ischemia/reperfusion injury in rat brain.

PubMed

Altaş, Murat; Aras, M; Meydan, S; Nacar, E; Ulutaş, K T; Serarslan, Y; Yılmaz, N

2014-03-01

Cerebral ischemia-reperfusion (I/R) injury is caused by lack of blood supply to the brain. The accumulation of toxic products such as reactive oxygen species (ROS) occurs on reperfusion, when the occlusion is removed. The resulting oxidative stress results in the initiation of pathways leading to necrotic and apoptotic cell death. Tadalafil (TAD) prevents the accumulation of ROS and increases antioxidant cellular protective mechanisms. The aim of this study was to investigate the effect of TAD treatment against short-term global brain I/R injury in rats. The study was carried out on 30 Wistar-albino rats, which were divided into three groups including a control group (n = 10), an I/R group (n = 10) and an I/R + TAD group (n = 10) (2 mg/kg/day for 4 days before ischemia). At the end of the experiment, tissue samples were collected for both biochemical and histopathological analyses. Malondialdehyde was significantly lower in the TAD-administered group (9.06 ± 0.15) than in the I/R group (p < 0.05). However, no significant difference was observed in nitric oxide levels in the TAD-administered group compared to the I/R group. The mean superoxide dismutase level was significantly higher in the I/R-TAD group than the I/R group. There was no statistically significant difference in glutathione peroxidase levels in I/R + TAD group compared to I/R group. Histopathologically, TAD-administered group provided significant morphological improvement compared to the I/R group. We concluded that TAD prevented I/R-induced neurotoxicity as shown by obtained biochemical and histopathological findings.

Astrocytic Acidosis in Hyperglycemic and Complete Ischemia

PubMed Central

Kraig, Richard P.; Chesler, Mitchell

2011-01-01

Summary Nearly complete brain ischemia under normoglycemic conditions results in death of only selectively vulnerable neurons. With prior elevation of brain glucose, such injury is enhanced to include pancel1ular necrosis (i.e., infarction), perhaps because an associated, severe lactic acidosis preferentially injures astrocytes. However, no direct physiologic measurements exist to support this hypothesis. Therefore, we used microelectrodes to measure intracellular pH and passive electrical properties of cortical astrocytes as a first approach to characterizing the physiologic behavior of these cel1s during hyperglycemic and complete ischemia, conditions that produce infarction in reperfused brain. Anesthesized rats (n = 26) were made extremely hyperglycemic (blood glucose, 51.4 ± 2.8 mM) so as to create potentially the most extreme acidic conditions possible; then ischemia was induced by cardiac arrest. Two loci more acidic than the interstitial space (6.17–6.20 pH) were found. The more acidic locus [4.30 ± 0.19 (n = 5); range: 3.82–4.89] was occasional1y seen at the onset of anoxic depolarization, 3–7 min after cardiac arrest. The less acidic locus [5.30 ± 0.07 (n = 53); range 4.46–5.93)] was seen 5–46 min after cardiac arrest. A smal1 negative change in DC potential [8 ± 1 mV (n = 5); range −3 to −12 mV and 7 ± 2 mV (n = 53); range +3 to −31 mV, respectively] was always seen upon impalement of acidic loci, suggesting cellular penetration. In a separate group of five animals, electrical characteristics of these cells were specifically measured (n = 17): membrane potential was −12 ± 0.2 mV (range −3 to −24 mY), input resistance was 114 ± 16 MΩ (range 25–250 MΩ), and time constant was 4.4 ± 0.4 ms (range 3.0–7.9 ms). Injection of horseradish peroxidase into cells from either animal group uniformly stained degenerating astrocytes. These findings establish previously unrecognized properties of ischemic astrocytes that may be

Revascularization and muscle adaptation to limb demand ischemia in diet-induced obese mice.

PubMed

Albadawi, Hassan; Tzika, A Aria; Rask-Madsen, Christian; Crowley, Lindsey M; Koulopoulos, Michael W; Yoo, Hyung-Jin; Watkins, Michael T

2016-09-01

Obesity and type 2 diabetes are major risk factors for peripheral arterial disease in humans, which can result in lower limb demand ischemia and exercise intolerance. Exercise triggers skeletal muscle adaptation including increased vasculogenesis. The goal of this study was to determine whether demand ischemia modulates revascularization, fiber size, and signaling pathways in the ischemic hind limb muscles of mice with diet-induced obesity (DIO). DIO mice (n = 7) underwent unilateral femoral artery ligation and recovered for 2 wks followed by 4 wks with daily treadmill exercise to induce demand ischemia. A parallel sedentary ischemia (SI) group (n = 7) had femoral artery ligation without exercise. The contralateral limb muscles of SI served as control. Muscles were examined for capillary density, myofiber cross-sectional area, cytokine levels, and phosphorylation of STAT3 and ERK1/2. Exercise significantly enhanced capillary density (P < 0.01) and markedly lowered cross-sectional area (P < 0.001) in demand ischemia compared with SI. These findings coincided with a significant increase in granulocyte colony-stimulating factor (P < 0.001) and interleukin-7 (P < 0.01) levels. In addition, phosphorylation levels of STAT3 and ERK1/2 (P < 0.01) were increased, whereas UCP1 and monocyte chemoattractant protein-1 protein levels were lower (P < 0.05) without altering vascular endothelial growth factor and tumor necrosis factor alpha protein levels. Demand ischemia increased the PGC1α messenger RNA (P < 0.001) without augmenting PGC1α protein levels. Exercise-induced limb demand ischemia in the setting of DIO causes myofiber atrophy despite an increase in muscle capillary density. The combination of persistent increase in tumor necrosis factor alpha, lower vascular endothelial growth factor, and failure to increase PGC1α protein may reflect a deficient adaption to demand ischemia in DIO. Copyright © 2016 Elsevier Inc. All rights reserved.

Rodent Hypoxia–Ischemia Models for Cerebral Palsy Research: A Systematic Review

PubMed Central

Rumajogee, Prakasham; Bregman, Tatiana; Miller, Steven P.; Yager, Jerome Y.; Fehlings, Michael G.

2016-01-01

Cerebral palsy (CP) is a complex multifactorial disorder, affecting approximately 2.5–3/1000 live term births, and up to 22/1000 prematurely born babies. CP results from injury to the developing brain incurred before, during, or after birth. The most common form of this condition, spastic CP, is primarily associated with injury to the cerebral cortex and subcortical white matter as well as the deep gray matter. The major etiological factors of spastic CP are hypoxia/ischemia (HI), occurring during the last third of pregnancy and around birth age. In addition, inflammation has been found to be an important factor contributing to brain injury, especially in term infants. Other factors, including genetics, are gaining importance. The classic Rice–Vannucci HI model (in which 7-day-old rat pups undergo unilateral ligation of the common carotid artery followed by exposure to 8% oxygen hypoxic air) is a model of neonatal stroke that has greatly contributed to CP research. In this model, brain damage resembles that observed in severe CP cases. This model, and its numerous adaptations, allows one to finely tune the injury parameters to mimic, and therefore study, many of the pathophysiological processes and conditions observed in human patients. Investigators can recreate the HI and inflammation, which cause brain damage and subsequent motor and cognitive deficits. This model further enables the examination of potential approaches to achieve neural repair and regeneration. In the present review, we compare and discuss the advantages, limitations, and the translational value for CP research of HI models of perinatal brain injury. PMID:27199883

Ischemic preconditioning inhibits over-expression of arginyl-tRNA synthetase gene Rars in ischemia-injured neurons.

PubMed

Shen, Yin; Zhao, Hong-Yang; Wang, Hai-Jun; Wang, Wen-Liang; Zhang, Li-Zhi; Fu, Rong

2016-08-01

The expression changes of Rars gene in ischemia-injured neurons were investigated by detecting its translational product arginyl-tRNA synthetase (ArgRS), and the inhibitory effects of ischemic preconditioning (IPC) on Rars gene were explored. Both IPC model and prolonged ischemia (PI) model were established by using the classic oxygen glucose deprivation (OGD) method. The primary cultured neurons were assigned into the following groups: the experimental group (IPC+PI group), undergoing PI after a short period of IPC; the conditional control group (PI control group), subjected to PI without IPC; blank control group, the normally cultured neurons. The Rars transcriptional activities and ArgRS expression levels were measured at different time points after re-oxygenation (3 h/6 h/12 h/24 h). Data were collected and statistically analyzed. Compared to the blank control group, the Rars activities and ArgRS levels were significantly increased in PI control group, peaking at the time point of 6 h after re-oxygenation. Rars activities and ArgRS levels were significantly lower in the experimental group than in the PI control group at different time points after re-oxygenation. PI insult can induce an escalating activity of Rars and lead to ArgRS over-expression in primary cultured neurons. IPC can inhibit the increased Rars activity and down-regulate ArgRS expression of ischemia-insulted neurons. This mechanism may confer ischemic tolerance on neurons.

Rearfoot Transcutaneous Oximetry is a Useful Tool to Highlight Ischemia of the Heel

DOE Office of Scientific and Technical Information (OSTI.GOV)

Izzo, Valentina, E-mail: valentina-izzo@virgilio.it; Meloni, Marco, E-mail: meloni.marco@libero.it; Fabiano, Sebastiano, E-mail: sebas575@yahoo.it

PurposeTo demonstrate the usefulness of rearfoot transcutaneous oximetry to assess the peripheral arterial disease in diabetic patients with heel ulcer.MethodsFrom our database of 550 critical limb ischemia diabetic patients followed after a percutaneous transluminal angioplasty, we have selected patients with below the knee arterial disease. Patients were grouped according to the dorsal transcutaneous oximetry value (Group A < 30 mmHg; Group B ≥ 30 mmHg). Patients of Group B had a second oximetry performed at the rearfoot, close to the lesion localized in all cases at the heel. Finally, the analysis of the arterial pattern disease has been done.ResultsWe selected 191 patients: Group A (151 patients),more » dorsal transcutaneous oximetry of 11.8 ± 0.7 mmHg; Group B (40 patients), dorsal transcutaneous oximetry of 44.2 ± 10.1 mmHg. In Group B, rearfoot oximetry was 20.5 ± 5 mmHg, significantly lower than dorsal oximetry (p = 0.0179). The anterior tibial artery was involved in all patients of Group A. In Group B, the anterior tibial artery was involved in 15 subjects and never alone; the posterior tibial artery was involved in 20 subjects and in 11 cases alone. The peroneal artery was affected in 20 subjects and in 14 patients alone.ConclusionWhen a heel lesion is present and the transcutaneous oximetry recorded on the dorsum of the foot does not confirm the presence of critical limb ischemia (not ≤30 mmHg), a second oximetry recorded on the rearfoot is useful to point out ischemia of the peroneal artery and/or of the posterior tibial artery.« less

Transport mechanism of L-[14C]glutamate in cortical slices and synaptosomes of rabbits exposed to brain ischemia and reperfusion.

PubMed

Solyakov, L; Dobrota, D; Drany, O; Vachova, M; Machac, S; Mezesova, V; Bachurin, S; Lombardi, V

1995-01-01

Changes in the functioning of the glutamatergic system in rabbit brain were studied after partial brain ischemia and reperfusion. In vitro studies were conducted relating to the release of L-[14C]glutamate from cortical brain slices, L-[14C]glutamate uptake in synaptosomes, and 45Ca uptake in synaptosomes. It was found that basal release of L-[14C]glutamate from rabbit brain cortical slices after 30 min of partial ischemia and 1 d of reperfusion was essentially without change compared to the control values. After 3 d of reperfusion, there was an increase in basal release of L-[14C]glutamate from rabbit brain cortical slices. K+ stimulated release of L-[14C]glutamate in normal Krebs-Ringer medium was essentially the same in the control group and in the experimental group after 30 min of ischemia. The K+ stimulated release of L-[14C]glutamate independent of calcium was increased to 145% after 30 min of ischemia and 1 d of reperfusion. The decreased Km value at the glutamate transporter may have contributed to this difference. Kinetic parameters of the L-[14C]glutamate uptake (Km and Vmax) in synaptosomes from rabbit brain were significantly lower after 30 min of ischemia. The authors discovered that during the reperfusion period, Vmax was almost the same as in the control group. The activity of the Na+/Ca2+ exchanger in synaptosomes of rat brain was about 70% of the control values after 30 min of ischemia and 72 h of reperfusion. According to our results, increased L-[14C]glutamate release after 30 min of ischemia appears to be the result of higher intracellular calcium concentration and possibly also of a higher uptake of glutamate.

The effects of Mucuna pruriens extract on histopathological and biochemical features in the rat model of ischemia.

PubMed

Nayak, Vanishri S; Kumar, Nitesh; D'Souza, Antony S; Nayak, Sunil S; Cheruku, Sri P; Pai, K Sreedhara Ranganath

2017-12-13

Stroke is considered to be one of the most important causes of death worldwide. Global ischemia causes widespread brain injury and infarctions in various regions of the brain. Oxidative stress can be considered an important factor in the development of tissue damage, which is caused because of arterial occlusion with subsequent reperfusion. Kapikacchu or Mucuna pruriens, commonly known as velvet bean, is well known for its aphrodisiac activities. It is also used in the treatment of snakebites, depressive neurosis, and Parkinson's disease. Although this plant has different pharmacological actions, its neuroprotective activity has received minimal attention. Thus, this study was carried out with the aim of evaluating the neuroprotective action of M. pruriens in bilateral carotid artery occlusion-induced global cerebral ischemia in Wistar rats. The carotid arteries of both sides were occluded for 30 min and reperfused to induce global cerebral ischemia. The methanolic plant extract was administered to the study animals for 10 days. The brains of the Wistar rats were isolated by decapitation and observed for histopathological and biochemical changes. Cerebral ischemia resulted in significant neurological damage in the brains of the rats that were not treated by M. pruriens. The group subjected to treatment by the M. pruriens extract showed significant protection against brain damage compared with the negative control group, which indicates the therapeutic potential of this plant in ischemia.

Kappa Opioid Receptor Agonist and Brain Ischemia

PubMed Central

Chunhua, Chen; Chunhua, Xi; Megumi, Sugita; Renyu, Liu

2014-01-01

Opioid receptors, especially Kappa opioid receptor (KOR) play an important role in the pathophysiological process of cerebral ischemia reperfusion injury. Previously accepted KOR agonists activity has included anti-nociception, cardiovascular, anti-pruritic, diuretic, and antitussive effects, while compelling evidence from various ischemic animal models indicate that KOR agonist have neuroprotective effects through various mechanisms. In this review, we aimed to demonstrate the property of KOR agonist and its role in global and focal cerebral ischemia. Based on current preclinical research, the KOR agonists may be useful as a neuroprotective agent. The recent discovery of salvinorin A, highly selective non-opioid KOR agonist, offers a new tool to study the role of KOR in brain HI injury and the protective effects of KOR agonist. The unique pharmacological profile of salvinorin A along with the long history of human usage provides its high candidacy as a potential alternative medication for brain HI injury. PMID:25574482

Intestinal Translocation of Clinical Isolates of Vancomycin-Resistant Enterococcus faecalis and ESBL-Producing Escherichia coli in a Rat Model of Bacterial Colonization and Liver Ischemia/Reperfusion Injury

PubMed Central

van der Heijden, Karin M.; van der Heijden, Inneke M.; Galvao, Flavio H.; Lopes, Camila G.; Costa, Silvia F.; Abdala, Edson; D’Albuquerque, Luiz A.; Levin, Anna S.

2014-01-01

The objectives of this study were to develop a rat model of gastrointestinal colonization with vancomycin-resistant Enterococcus faecalis (VRE) and extended-spectrum beta-lactamase (ESBL)-producing E. coli and to evaluate intestinal translocation to blood and tissues after total and partial hepatic ischemia. Methods - We developed a model of rat colonization with VRE and ESBL-E coli. Then we studied four groups of colonized rats: Group I (with hepatic pedicle occlusion causing complete liver ischemia and intestinal stasis); Group II (with partial liver ischemia without intestinal stasis); Group III (surgical manipulation without hepatic ischemia or intestinal stasis); Group IV (anesthetized without surgical manipulation). After sacrifice, portal and systemic blood, large intestine, small intestine, spleen, liver, lungs, and cervical and mesenteric lymph nodes were cultured. Endotoxin concentrations in portal and systemic blood were determined. Results – The best inocula were: VRE: 2.4×1010 cfu and ESBL-E. coli: 1.12×1010 cfu. The best results occurred 24 hours after inoculation and antibiotic doses of 750 µg/mL of water for vancomycin and 2.1 mg/mL for ceftriaxone. There was a significantly higher proportion of positive cultures for ESBL-E. coli in the lungs in Groups I, II and III when compared with Group IV (67%; 60%; 75% and 13%, respectively; p:0.04). VRE growth was more frequent in mesenteric lymph nodes for Groups I (67%) and III (38%) than for Groups II (13%) and IV (none) (p:0.002). LPS was significantly higher in systemic blood of Group I (9.761±13.804 EU/mL−p:0.01). No differences for endotoxin occurred in portal blood. Conclusion –We developed a model of rats colonized with resistant bacteria useful to study intestinal translocation. Translocation occurred in surgical procedures with and without hepatic ischemia-reperfusion and probably occurred via the bloodstream. Translocation was probably lymphatic in the ischemia-reperfusion groups

An Automatic Occlusion Device for Remote Control of Tumor Tissue Ischemia

PubMed Central

El-Dahdah, Hamid; Wang, Bei; He, Guanglong; Xu, Ronald X.

2015-01-01

We developed an automatic occlusion device for remote control of tumor tissue ischemia. The device consists of a flexible cannula encasing a shape memory alloy wire with its distal end connected to surgical suture. Regional tissue occlusion was tested on both the benchtop and the animal models. In the benchtop test, the occlusion device introduced quantitative and reproducible changes of blood flow in a tissue simulating phantom embedding a vessel simulator. In the animal test, the device generated a cyclic pattern of reversible ischemia in the right hinder leg tissue of a black male C57BL/6 mouse. We also developed a multimodal detector that integrates near infrared spectroscopy and electron paramagnetic resonance spectroscopy for continuous monitoring of tumor tissue oxygenation, blood content, and oxygen tension changes. The multimodal detector was tested on a cancer xenograft nude mouse undergoing reversible tumor ischemia. The automatic occlusion device and the multi-modal detector can be potentially integrated for closed-loop feedback control of tumor tissue ischemia. Such an integrated occlusion device may be used in multiple clinical applications such as regional hypoperfusion control in tumor resection surgeries and thermal ablation processes. In addition, the proposed occlusion device can also be used as a research tool to understand tumor oxygen transport and hemodynamic characteristics. PMID:20082532

Delayed Post-ischemic Conditioning Significantly Improves the Outcome after Retinal Ischemia

PubMed Central

Dreixler, John C.; Poston, Jacqueline N.; Shaikh, Afzhal R.; Alexander, Michael; Tupper, Kelsey Y.; Marcet, Marcus M.; Bernaudin, Myriam; Roth, Steven

2011-01-01

In previous studies, it was shown that post-conditioning, a transient period of brief ischemia following prolonged severe ischemia in the retina, could provide significant improvement in post-ischemic recovery, attenuation of cell loss, and decreased apoptosis. These studies showed that post-conditioning effectively prevented damage after retinal ischemia when it was instituted early (within one hour) in the post-ischemic period. While post-ischemic conditioning holds high promise of clinical translation, patients often present late after the onset of retinal ischemia and therefore immediate application of this anti-ischemic maneuver is generally not feasible. In this study, we examined the hypothesis that application of a post-conditioning stimulus at 24 h or greater following the end of prolonged ischemia would decrease the extent of ischemic injury. Ischemia was induced in rat retina in vivo. Recovery after ischemia followed by 5 minutes of post-conditioning brief ischemia 24 or 48 h after prolonged ischemia was assessed functionally (electroretinography) and histologically at 7 days after ischemia and post-conditioning or sham post-conditioning. We found that the brief ischemic stimulus applied 24, but not 48 h after prolonged ischemia significantly improved functional recovery and decreased histological damage induced by prolonged ischemia. We conclude that within a defined time window, delayed post-ischemic conditioning ameliorated post-ischemic injury in rats. Compared to earlier studies, the present work demonstrates for the first time the novel ability of a significantly delayed ischemic stimulus to provide robust neuroprotection in the retina following ischemia. PMID:21501608

Cardioprotective effects of amlodipine on ischemia and reperfusion in two experimental models.

PubMed

Hoff, P T; Tamura, Y; Lucchesi, B R

1990-11-20

The cardioprotective effect of amlodipine, a long-acting dihydropyridine derivative, was studied in 2 experimental models of ischemia and reperfusion. Isolated and blood-perfused feline hearts were made globally ischemic for 60 minutes and then reperfused for 60 minutes. Alterations of left ventricular developed pressure and compliance were monitored in both amlodipine-treated hearts and saline-treated control animals. Changes in perfusion pressure indicated that amlodipine significantly reduced myocardial oxygen consumption and coronary vascular resistance. Furthermore, a progressive increase in resting left ventricular diastolic pressure indicated that amlodipine, administered before the onset of global ischemia, attenuated the development of ischemic contracture. Return of contractile function 60 minutes after reperfusion and maintenance of tissue concentrations of electrolytes were significantly better in the amlodipine-treated group than in the control animals. In intact canine hearts, regional myocardial ischemia was induced for 90 minutes, followed by 6 hours of reperfusion. Although the hemodynamic variables and the size of the region of risk did not differ significantly between treated animals and control animals, the infarct size was significantly smaller in the amlodipine-treated group than in the control animals, and a gradual reduction in coronary blood flow was observed in the control group that was prevented in the amlodipine group. A comparison of these findings with those observed with oxygen radical scavengers also is discussed. A detailed report of these studies was published in The American Journal of Cardiology (1989;64:101I-116I). This review is included here to maintain continuity of the symposium for the convenience of the reader.

[Effect of danlou tablet on arrhythmia model rats induced by transient myocardial ischemia/ reperfusion].

PubMed

Guo, Li-Li; Wang, Jie; Lin, Fei; He, Yong-Xia

2014-09-01

To explore the effect of Danlou Tablet (DT) on arrhythmia model rats induced by transient myocardial ischemia/reperfusion (I/R). Totally 45 healthy Wistar rats were randomly divided into 3 groups, the sham-operation group, the model group, and the DT group, 15 in each group. Rats in the sham-operation group and the model group were administered with distilled water by gastrogavage at the daily dose of 0.1 mL/kg. Rats in the DT group was administered with 0.53 g/mL DT suspension by gastrogavage at the daily dose of 0.1 mL/kg. All medication was lasted for 10 successive days. The myocardial I/R experiment was performed at 1 h after the last gastrogavage. ECG was performed before ligation and at I/R. The jugular arterial blood pressure of all rats was measured during the whole course. ST segment changes were observed at each time point of I/R. The ventricular fibrillation, the premature ventricular, the number and the duration of ventricular tachycardia within 30 min reperfusion were also observed. Activities of Na(+)-K+ ATPase and Ca2+ ATPase in the myocardium homogenate were detected as well. The jugular arterial blood pressure and the heart rate were slightly lower in the DT group than in the model group, but with no statistical difference (P > 0.05). Compared with the sham-operation group, the degree of ST segment was obviously elevated in the model group at 0, 5, and 7 min (P < 0.05). It was significantly lower in the DT group than in the model group (P < 0.01). ST seg ment was more elevated at 5 min than at 0 min in the model group, but the degree of ST segment elevation was still obviously lower in the DT group than in the model group (P < 0.05). There was no statistical difference in the degree of ST segment elevation at 7 min between the two groups (P > 0.05). At 0 min when the decrement of ST segment exceeded one half the ischemia, there was no statistical difference in the degree of myocardial ischemia between the model group and the DT group (P > 0

Inflation with carbon monoxide in rat donor lung during cold ischemia phase ameliorates graft injury

PubMed Central

Meng, Chao; Ma, Liangjuan; Liu, Jinfeng; Cui, Xiaoguang; Liu, Rongfang; Xing, Jingchun

2015-01-01

Carbon monoxide (CO) attenuates lung ischemia reperfusion injury (IRI) via inhalation, and as an additive dissolved in flush/preservation solution. This study observed the effects of lung inflation with CO on lung graft function in the setting of cold ischemia. Donor lungs were inflated with 40% oxygen + 60% nitrogen (control group) or with 500 ppm CO + 40% oxygen + nitrogen (CO group) during the cold ischemia phase and were kept at 4℃ for 180 min. Recipients were sacrificed by exsanguinations at 180 min after reperfusion. Rats in the sham group had no transplantation and were performed as the recipients. Compared with the sham group, the oxygenation determined by blood gas analysis and the pressure–volume curves of the lung grafts decreased significantly, while the wet weight/dry weight (W/D) ratio, inflammatory reaction, oxidative stress, and cell apoptosis increased markedly (P < 0.05). However, compared to the control group, CO treatment improved the oxygenation (381 ± 58 vs. 308 ± 78 mm Hg) and the pressure–volume curves (15.8 ± 2.4 vs. 11.6 ± 1.7 mL/kg) (P < 0.05). The W/D ratio (4.6 ± 0.6) and the serum levels of interleukin-8 (279 ± 46 pg/mL) and tumor necrosis factor-α (377 ± 59 pg/mL) in the CO group decreased significantly compared to the control group (5.8 ± 0.8, 456 ± 63 pg/mL, and 520 ± 91 pg/mL) (P < 0.05). In addition, CO inflation also significantly decreased malondialdehyde activity and apoptotic cells in grafts, and increased the superoxide dismutase content. Briefly, CO inflation in donor lungs in the setting of cold ischemia attenuated lung IRI and improved the graft function compared with oxygen. PMID:26290141

Inflation with carbon monoxide in rat donor lung during cold ischemia phase ameliorates graft injury.

PubMed

Meng, Chao; Ma, Liangjuan; Liu, Jinfeng; Cui, Xiaoguang; Liu, Rongfang; Xing, Jingchun; Zhou, Huacheng

2016-02-01

Carbon monoxide (CO) attenuates lung ischemia reperfusion injury (IRI) via inhalation, and as an additive dissolved in flush/preservation solution. This study observed the effects of lung inflation with CO on lung graft function in the setting of cold ischemia. Donor lungs were inflated with 40% oxygen + 60% nitrogen (control group) or with 500 ppm CO + 40% oxygen + nitrogen (CO group) during the cold ischemia phase and were kept at 4℃ for 180 min. Recipients were sacrificed by exsanguinations at 180 min after reperfusion. Rats in the sham group had no transplantation and were performed as the recipients. Compared with the sham group, the oxygenation determined by blood gas analysis and the pressure-volume curves of the lung grafts decreased significantly, while the wet weight/dry weight (W/D) ratio, inflammatory reaction, oxidative stress, and cell apoptosis increased markedly (P < 0.05). However, compared to the control group, CO treatment improved the oxygenation (381 ± 58 vs. 308 ± 78 mm Hg) and the pressure-volume curves (15.8 ± 2.4 vs. 11.6 ± 1.7 mL/kg) (P < 0.05). The W/D ratio (4.6 ± 0.6) and the serum levels of interleukin-8 (279 ± 46 pg/mL) and tumor necrosis factor-α (377 ± 59 pg/mL) in the CO group decreased significantly compared to the control group (5.8 ± 0.8, 456 ± 63 pg/mL, and 520 ± 91 pg/mL) (P < 0.05). In addition, CO inflation also significantly decreased malondialdehyde activity and apoptotic cells in grafts, and increased the superoxide dismutase content. Briefly, CO inflation in donor lungs in the setting of cold ischemia attenuated lung IRI and improved the graft function compared with oxygen. © 2015 by the Society for Experimental Biology and Medicine.

The effect of melatonin on bacterial translocation following ischemia/reperfusion injury in a rat model of superior mesenteric artery occlusion.

PubMed

Ozban, Murat; Aydin, Cagatay; Cevahir, Nural; Yenisey, Cigdem; Birsen, Onur; Gumrukcu, Gulistan; Aydin, Berrin; Berber, Ibrahim

2015-03-08

Acute mesenteric ischemia is a life-threatening vascular emergency resulting in tissue destruction due to ischemia-reperfusion injury. Melatonin, the primary hormone of the pineal gland, is a powerful scavenger of reactive oxygen species (ROS), including the hydroxyl and peroxyl radicals, as well as singlet oxygen, and nitric oxide. In this study, we aimed to investigate whether melatonin prevents harmful effects of superior mesenteric ischemia-reperfusion on intestinal tissues in rats. Rats were randomly divided into three groups, each having 10 animals. In group I, the superior mesenteric artery (SMA) was isolated but not occluded. In group II and group III, the SMA was occluded immediately distal to the aorta for 60 minutes. After that, the clamp was removed and the reperfusion period began. In group III, 30 minutes before the start of reperfusion, 10 mg/kg melatonin was administered intraperitonally. All animals were sacrified 24 hours after reperfusion. Tissue samples were collected to evaluate the I/R-induced intestinal injury and bacterial translocation (BT). There was a statistically significant increase in myeloperoxidase activity, malondialdehyde levels and in the incidence of bacterial translocation in group II, along with a decrease in glutathione levels. These investigated parameters were found to be normalized in melatonin treated animals (group III). We conclude that melatonin prevents bacterial translocation while precluding the harmful effects of ischemia/reperfusion injury on intestinal tissues in a rat model of superior mesenteric artery occlusion.

[Evaluation of myocardial ischemia using Holter monitoring].

PubMed

Kodama, Y

1995-07-01

To establish the diagnostic criteria for myocardial ischemia, Holter monitoring and coronary angiography were performed on 46 cases (24 males (51.8 +/- 9.3 years), 22 females (47.5 +/- 10.5 years)). These patients were retrospectively selected from about 12000 patients who had the Holter monitorings from 1980 to 1993. The criteria for the entry were 1) reliable trend recordings of heart rate and 2) reliable recording of ST trend with accurate 1 mV calibration. The coronary stenosis greater than 75% in diameter was considered to be significant. Results were as follows: 1) ST trend pattern was classified into typical type, atypical type and box type. There were no significant differences in the incidence of typical and atypical types between ischemic and nonischemic groups, 2) Diagnostic accuracy of the criteria for myocardial ischemia, that is, the horizontal or downsloping ST segment depression with 0.1 mV at the point of 80 msec from the J point lasting for 1 minute, was higher in male than in female: the sensitivity was 93.3% and the specificity was 55.6% for men respectively, whereas the sensitivity was 66.7% and the specificity was 37.5% for women respectively, 3) Diagnostic accuracy of the ST/Heart rate ratio was 80.0% for the sensitivity and 64.7% for the specificity, indicating an improvement of specificity, 4) Maximal ST segment depression was accompanied by pain by 88.8% in true positive group (significant ST segment depression with significant coronary stenosis), whereas that was 28.6% in false positive group (significant ST segment depression without significant coronary stenosis), 5) Comparison of the degree of maximal ST segment depression, duration and frequency between computer and manual measurement showed a good correlation for the degree of maximal ST segment depression, whereas the duration and the frequency showed no significant correlations. The above results suggest that combined evaluation of the ST segment depression criteria (downsloping or

The effects of L-carnitine on spinal cord ischemia/reperfusion injury in rabbits.

PubMed

Tetik, O; Yagdi, T; Islamoglu, F; Calkavur, T; Posacioglu, H; Atay, Y; Ayik, F; Canpolat, L; Yuksel, M

2002-02-01

Paraplegia after distal aortic aneurysm repair remains a persistent clinical problem. We hypothesized that the tolerance of the spinal cord to an ischemic period could be improved with hypothermic Ringer's Lactate containing L-Carnitine. Twenty-eight New Zealand white rabbits were used as spinal cord ischemia models. We separated rabbits into four equal groups and clamped each animal's abdominal aorta distal to the left renal artery. We occluded the aortas above the iliac bifurcation for 30 minutes. In group I, the infrarenal aorta was clamped without infusing any solution. In group II, Ringer's Lactate solution was infused at + 25degrees C for 3 minutes at a rate of 5 ml/min into the isolated aortic segments immediately after cross-clamping and the last 3 minutes of ischemia. In group III, Ringer's Lactate solution at +3 degrees C was given in the same method as that of group II. In group IV, Ringer's Lactate solution at +3 degrees C plus 100 mg/kg of L-carnitine was infused using the same technique. We assessed the neurological status of the hind limbs 24 and 48 hours after operation according to Tarlov's criteria. All animals were sacrificed and spinal cords were harvested for histological analyses. The neurological status in groups III and IV was significantly superior to that of groups I and II. All the animals in group I had complete hind-limb paraplegia. Complete hind-limb paraplegia occurred in 5 rabbits in group II. Two of the 7 animals in group III had spastic paraplegia, and none at all in group IV. Histological analysis of the cross-clamped segments of the rabbits with paraplegia in group I, II and III revealed changes consistent with ischemic injury, while findings were normal for the normal animals in group III and IV. In this model, the infusion of hypothermic Ringer's Lactate contained L-carnitine provided sufficient spinal cord protection against ischemia. Clinically, this may be a useful adjunct for prevention of paraplegia during surgery of the

Neuroprotective effects of tanshinone I from Danshen extract in a mouse model of hypoxia-ischemia

PubMed Central

Lee, Jae-Chul; Park, Joon Ha; Park, Ok Kyu; Kim, In Hye; Yan, Bing Chun; Ahn, Ji Hyeon; Kwon, Seung-Hae; Choi, Jung Hoon

2013-01-01

Hypoxia-ischemia leads to serious neuronal damage in some brain regions and is a strong risk factor for stroke. The aim of this study was to investigate the neuroprotective effect of tanshinone I (TsI) derived from Danshen (Radix Salvia miltiorrhiza root extract) against neuronal damage using a mouse model of cerebral hypoxia-ischemia. Brain infarction and neuronal damage were examined using 2,3,5-triphenyltetrazolium chloride (TTC) staining, hematoxylin and eosin histochemistry, and Fluoro-Jade B histofluorescence. Pre-treatment with TsI (10 mg/kg) was associated with a significant reduction in infarct volume 1 day after hypoxia-ischemia was induced. In addition, TsI protected against hypoxia-ischemia-induced neuronal death in the ipsilateral region. Our present findings suggest that TsI has strong potential for neuroprotection against hypoxic-ischemic damage. These results may be used in research into new anti-stroke medications. PMID:24179693

Neuroprotective effect of oral choline administration after global brain ischemia in rats.

PubMed

Borges, Andrea Aurélio; El-Batah, Philipe Nicolas; Yamashita, Lilia Fumie; Santana, Aline dos Santos; Lopes, Antonio Carlos; Freymuller-Haapalainen, Edna; Coimbra, Cicero Galli; Sinigaglia-Coimbra, Rita

2015-08-01

Choline - now recognized as an essential nutrient - is the most common polar group found in the outer leaflet of the plasma membrane bilayer. Brain ischemia-reperfusion causes lipid peroxidation triggering multiple cell death pathways involving necrosis and apoptosis. Membrane breakdown is, therefore, a major pathophysiologic event in brain ischemia. The ability to achieve membrane repair is a critical step for survival of ischemic neurons following reperfusion injury. The availability of choline is a rate-limiting factor in phospholipid synthesis and, therefore, may be important for timely membrane repair and cell survival. This work aimed at verifying the effects of 7-day oral administration with different doses of choline on survival of CA1 hippocampal neurons following transient global forebrain ischemia in rats. The administration of 400 mg/kg/day divided into two daily doses for 7 consecutive days significantly improved CA1 pyramidal cell survival, indicating that the local availability of this essential nutrient may limit postischemic neuronal survival.

Protective effect of agmatine on a reperfusion model after transient cerebral ischemia: Temporal evolution on perfusion MR imaging and histopathologic findings.

PubMed

Kim, D J; Kim, D I; Lee, S K; Suh, S H; Lee, Y J; Kim, J; Chung, T S; Lee, J E

2006-04-01

The goal of thrombolytic therapy in patients with acute ischemic stroke is early recanalization, but this may result in delayed reperfusion injury. The purpose of this study was to evaluate the neuroprotective effect of agmatine in a transient ischemic cat model by using MR perfusion imaging and histopathologic analyses. One-hour temporary occlusion of the left middle cerebral artery of cats was performed in the control ischemia group (n = 10), and 100 mg/kg of agmatine was intravenously injected immediately after recanalization in the agmatine-treated group (n = 15). MR imaging was performed at 1, 24, and 48 hours after recanalization, and the perfusion patterns were investigated. Terminal-deoxynucleotidyl transferase mediated nick and end-labeling (TUNEL) and hematoxylin-eosin (H&E) stainings were performed at the corresponding sections. In the control ischemia group, the number of TUNEL-positive cells was significantly increased in the areas with reperfusion hyperemia (P < .05). In the agmatine-treated group, no significant increase in the number of TUNEL-positive cells was noted in the areas of reperfusion hyperemia. The difference in the number of TUNEL-positive cells between the control ischemia and agmatine-treated group in the areas of reperfusion hyperemia was significant (P < .05). The total number of TUNEL-positive cells and the area of severe ischemic neuronal damage on H&E stain were also significantly attenuated in the agmatine-treated cats compared with the control ischemia cats (P < .05). Our results suggest that agmatine has neuroprotective effects against reperfusion injury and ischemia.

Occurance of apoptosis during ischemia in porcine pancreas islet cells.

PubMed

Stadlbauer, V; Schaffellner, S; Iberer, F; Lackner, C; Liegl, B; Zink, B; Kniepeiss, D; Tscheliessnigg, K H

2003-03-01

Pancreas islet transplantation is a potential treatment of diabetes mellitus and porcine organs provide an easily available source of cells. Unfortunately quality and quantity of isolated islets are still not satisfactory. Apoptosis occurs in freshly isolated islets and plays a significant role in early graft loss. We evaluated the influence of four storage solutions on porcine pancreas islets. After warm ischemia of 15-20 minutes 12 organs were stored in 4 cold preservation solutions: Histidine-Tryptophan-Ketoglutarate solution (HTK), Hank's buffered saline solution (HBSS), University of Wisconsin (UW) solution and Ringer-Lactate (R). After cold ischemia for 100 minutes, organs were fixed in 3% formalin. Apoptotic cells were counted on hematocylin-eosin stainings. Most apoptotic cells were found in organs stored in R. Low numbers were found in the other groups. The difference between organs stored in R and organs stored in UW, HTK, or HBSS was highly significant. No significant difference could be found between UW, HTK and HBSS. Cold and warm ischemia of the pancreas seems to induce apoptosis in islet cells. Preservation solutions cause less apoptosis than electrolyte solution. No significant differences could be found among the preservation solutions.

Protective effect of melatonin on experimental spinal cord ischemia.

PubMed

Erten, S F; Kocak, A; Ozdemir, I; Aydemir, S; Colak, A; Reeder, B S

2003-10-01

Experimental animal model to assess ischemic spinal cord injury following occlusion of the thoraco-abdominal aorta. To measure whether melatonin administered to rabbits before and after occlusion exerts an effect on the repair of ischemia-reperfusion (IR) injury. Medical Biology Laboratory, Inonu University, Malatya, Turkey. Rabbits were divided into three IR treatment groups and one sham-operated (ShOp) control group. The three treatment groups had their infrarenal aorta temporarily occluded for 25 min, while the ShOp group had laparotomy without aortic occlusion. Melatonin was administered either 10 min before aortic occlusion or 10 min after the clamp was removed. Physiologic saline was administered to the control animals. After treatment, the animals were euthanized and lumbosacral spinal cord tissue was removed for the determination of relevant enzyme activities. Malondialdehyde levels, indicating the extent of lipid peroxidation, were found to be significantly increased in the nonmelatonin treated (IR) group when compared to the ShOp group. Melatonin, whether given to pre- or post occlusion groups, suppressed malondialdehyde levels below that of the ShOp group. Catalase (CAT) and glutathione peroxidase (GSH-Px) enzyme activities were increased in the IR group compared to the ShOp group. Melatonin given preocclusion resulted in a significant decrease in both CAT and GSH-Px enzyme levels. The superoxide dismutase (SOD) enzyme activity was decreased in the ischemia-reperfusion treatment group. However, the melatonin treatment increased SOD enzyme activity to levels approximating that of the ShOp group. To our knowledge, this is the first study that shows the effects of melatonin administered both pre- and postischemia on induced oxidative damage to injured spinal cords. Our data also expands on reports that melatonin administration may significantly reduce the incidence of spinal cord injury following temporary aortic occlusion.

Protective role of silymarin in a mouse model of renal Ischemia-Reperfusion injury.

PubMed

Tan, Jian; Hu, Jianpeng; He, Yonghui; Cui, Feilun

2015-10-31

We investigated the mechanism of action of silymarin in a mouse model of renal ischemia-reperfusion injury (I/R) to ascertain its role in the treatment of I/R injury. Twenty-four C57BL/6 male mice were divided randomly into three groups: control (sham); ischemia-reperfusion (I/R); silymarin + ischemia-reperfusion (silymarin + I/R). In sham mice, an abdominal incision was made, followed by dissection of the bilateral renal pedicle, with no further cross-clamping of arteries. Silymarin + I/R mice were administered 100 mg/kg silymarin daily for 7 consecutive days before surgery, whereas I/R mice were administered (i.g.) 0.9 % saline + 0.1 % (v/v) ethanol daily for 7 consecutive days before surgery. Silymarin + I/R and I/R mice were subjected to renal ischemia to induce acute kidney injury after 45-min clamping of bilateral renal arteries. Serum levels of creatinine and blood urea nitrogen levels were measured. Periodic acid-Schiff (PAS) staining was undertaken to detect damaged renal tissue. Myeloperoxidase (MPO) activity and immunofluorescent detection of CD68 expression was undertaken for each group. Levels of inflammatory cytokines secreted by renal tissue were monitored by ELISA. Apoptosis was detected by TUNEL staining. Expression of cleaved-caspase-3, Bcl-2 and Bax was detected by western blotting. Serum creatinine and blood urea nitrogen levels were elevated in silymarin + I/R and I/R groups compared with sham mice (p < 0.05), whereas those in the I/R group were significantly higher than in the silymarin + I/R group (p < 0.05). Number of damaged renal tubule cells and apoptotic cells in sham and silymarin + I/R groups was significantly lower than in I/R mice. MPO activity and secretion of inflammatory cytokines in silymarin + I/R and I/R groups was reduced (p < 0.05), and CD68 expression in silymarin + I/R mice was lower than in I/R mice (p < 0.05). Expression of cleaved-caspase-3 and Bax in the I/R group

Beneficial effects of dexpanthenol on mesenteric ischemia and reperfusion injury in experimental rat model.

PubMed

Cagin, Yasir Furkan; Atayan, Yahya; Sahin, Nurhan; Parlakpinar, Hakan; Polat, Alaadin; Vardi, Nigar; Tagluk, Mehmet Emin; Tanbek, Kevser; Yildiz, Azibe

2016-01-01

It has been reported that intestinal ischemia-reperfusion (I/R) injury results from oxidative stress caused by increased reactive oxygen species. Dexpanthenol (Dxp) is an alcohol analogue with epitelization, anti-inflammatory, antioxidant, and increasing peristalsis activities. In the present study, the aim was to investigate protective and therapeutic effects of Dxp against intestinal I/R injury. Overall, 40 rats were assigned into five groups including one control, one alone Dxp, and three I/R groups (40-min ischemia; followed by 2-h reperfusion). In two I/R groups, Dxp (500 mg/kg, i.m.) was given before or during ischemia. The histopathological findings including apoptotic changes, and also tissue and serum biochemical parameters levels, were determined. Oxidative stress and ileum damage were assessed by biochemical and histological examination. In the control (n = 8) and alone Dxp (n = 8; 500 mg/kg, i.m. of Dxp was given at least 30 min before recording), groups were incised via laparotomy, and electrical activity was recorded from their intestines. In this experiment, the effect of Dxp on the motility of the intestine was examined by analyzing electrical activity. In ileum, oxidant levels were found to be higher, while antioxidant levels were found to be lower in I/R groups when compared with controls. Dxp approximated high levels of oxidants than those in the control group, while it increased antioxidant values compared with I/R groups. Histopathological changes caused by intestinal I/R injury and histological improvements were observed in both groups given Dxp. In the Dxp group, electrical signal activity markedly increased compared with the control group. Here, it was seen that Dxp had protective and therapeutic effects on intestinal I/R injury and gastrointestinal system peristaltism.

Hydrogen-rich saline protects against small-scale liver ischemia-reperfusion injury by inhibiting endoplasmic reticulum stress.

PubMed

Li, Hui; Bai, Ge; Ge, Yansong; Zhang, Qianzhen; Kong, Xiangdong; Meng, Weijing; Wang, Hongbin

2018-02-01

Our research investigated the role of Hydrogen-rich saline (HRS) on the Endoplasmic reticulum stress (ERS) pathway and the effect of HRS on tissue injury in small Bama pig model of hepatic ischemia-reperfusion combined with partial hepatectomy. Eighteen healthy Bama miniature pigs were randomly divided equally into three groups: Sham, IRI, and HRS. Laparoscopic technique was employed to establish the model of hepatic ischemia-reperfusion combined with partial hepatectomy. HRS (10mL/kg) was injected into the portal vein 10min before perfusion. Histological examinations of the liver tissues were performed after HE staining. Additionally, transmission electron microscopy was performed to detect liver cell microstructure. Real-time PCR, Western blotting, and immunohistochemical staining were performed to analyze various ERS molecules including GRP78, p-eIF2α, XBP-1s, Full-length ATF6α, p-JNK, ATF4, and CHOP. We observed that HRS visibly improved ischemia-reperfusion injury (IRI) by reducing various parameters of ERS stress as evidenced by down-regulation of the mRNA as well as protein levels of GRP78, p-eIF2α, XBP-1s, p-JNK, and CHOP, and reducing the cleavage of Full-length ATF6α. Our study demonstrates that HRS protects the liver from IRI by inhibiting ERS. Copyright © 2017 Elsevier Inc. All rights reserved.

Non-occlusive Mesenteric Ischemia in Patients with Methamphetamine Use.

PubMed

Anderson, Jamie E; Brown, Ian E; Olson, Kristin A; Iverson, Katherine; Cocanour, Christine S; Galante, Joseph M

2018-02-17

Data suggest that methamphetamine may increase the risk of non-occlusive mesenteric ischemia (NOMI). We describe patterns of presentation and outcomes of patients with methamphetamine use who present with NOMI to a single institution. This is an observational study of patients from January 2015 to September 2017 with methamphetamine use who presented with NOMI at an academic medical center in Northern California. We summarize patient co-morbidities, clinical presentation, operative findings, pathologic findings, hospital course, and survival. Ten patients with methamphetamine use and severe NOMI were identified. One patient was readmitted with a perforated duodenal ulcer, for a total of 11 encounters. Most presented with acute (n=3) or acute-on-chronic (n=4) abdominal pain. Distribution of ischemia ranged from perforated duodenal ulcer (n=3), ischemia of the distal ileum (n=1), ischemia of entire small bowel (n=2), and patchy necrosis of entire small bowel and colon (n=5). Six patients died, three within one week of admission and three between 3-8 months. Methamphetamine use may be associated with significant microvascular compromise, increasing the risk of mesenteric ischemia. Providers in areas with high prevalence of methamphetamine use should have a high index of suspicion for intestinal ischemia in this patient population. Patients with methamphetamine use admitted for trauma or other pathology may be at particular risk of ischemia and septic shock, especially in the setting of dehydration. Use of vasoconstrictors in this patient population may also exacerbate intestinal ischemia. Level 5; Case series.

L-Arginine Modulates Intestinal Inflammation in Rats Submitted to Mesenteric Ischemia-Reperfusion Injury.

PubMed

Taha, M O; de Oliveira, J V; Dias Borges, M; de Lucca Melo, F; Gualtieri, F G; E Silva Aidar, A L; Pacheco, R L; de Melo Alexandre E Silva, T; Klajner, R K; Iuamoto, L R; Munhoz Torres, L; Morais Mendes de Paula, B J; de Campos, K; Oliveira-Junior, I S; Fagundes, D J

2016-03-01

The goal of this study was to investigate whether exogenous offer of L-arginine (LARG) modulates the gene expression of intestinal dysfunction caused by ischemia and reperfusion. Eighteen Wistar-EPM1 male rats (250-300 g) were anesthetized and subjected to laparotomy. The superior mesenteric vessels were exposed, and the rats were randomized into 3 groups (n = 6): the control group (CG), with no superior mesenteric artery interruption; the ischemia/reperfusion group (IRG), with 60 minutes of ischemia and 120 minutes of reperfusion and saline injections; and the L-arginine group (IRG + LARG), with L-arginine injected in the femoral vein 5 minutes before ischemia, 5 minutes after reperfusion, and after 55 minutes of reperfusion. The total RNA was extracted and purified from samples of the small intestine. The concentration of each total RNA sample was determined by using spectrophotometry. The first-strand complementary DNA (cDNA) was synthesized in equal amounts of cDNA and the Master Mix SYBR Green qPCR Mastermix (SABiosciences, a Qiagen Company, Frederick, Md). Amounts of cDNA and Master Mix SYBR Green qPCR Mastermix were distributed to each well of the polymerase chain reaction microarray plate containing the predispensed gene-specific primer sets for Bax and Bcl2. Each sample was evaluated in triplicate, and the Student t test was applied to validate the homogeneity of each gene expression reaction (P < .05). The gene expression of Bax in IRG (+1.48) was significantly higher than in IRG-LARG (+9.69); the expression of Bcl2L1 in IRG (+1.01) was significantly higher than IRG-LARG (+22.89). The apoptotic cell pathway of 2 protagonists showed that LARG improves the gene expression of anti-apoptotic Bcl2l1 (Bcl2-like 1) more than the pro-apoptotic Bax (Bcl2-associated X protein). Copyright © 2016. Published by Elsevier Inc.

Real-time monitoring of ischemia inside stomach.

PubMed

Tahirbegi, Islam Bogachan; Mir, Mònica; Samitier, Josep

2013-02-15

The low pH in the gastric juice of the stomach makes it difficult to fabricate stable and functional all-solid-state pH ISE sensors to sense ischemia, mainly because of anion interference and adhesion problem between the ISE membrane and the electrode surface. In this work, the adhesion of ISE membrane on solid surface at low pH was improved by modifying the surface with a conductive substrate containing hydrophilic and hydrophobic groups. This creates a stable and robust candidate for low pH applications. Moreover, anion interference problem at low pH was solved by integration of all-solid-state ISE and internal reference electrodes on an array. So, the same tendencies of anion interferences for all-solid-state ISE and all-solid-state reference electrodes cancel each other in differential potentiometric detection. The developed sensor presents a novel all-solid-state potentiometric, miniaturized and mass producible pH ISE sensor for detecting ischemia on the stomach tissue on an array designed for endoscopic applications. Copyright © 2012 Elsevier B.V. All rights reserved.

Inhalation of water electrolysis-derived hydrogen ameliorates cerebral ischemia-reperfusion injury in rats - A possible new hydrogen resource for clinical use.

PubMed

Cui, Jin; Chen, Xiao; Zhai, Xiao; Shi, Dongchen; Zhang, Rongjia; Zhi, Xin; Li, Xiaoqun; Gu, Zhengrong; Cao, Liehu; Weng, Weizong; Zhang, Jun; Wang, Liping; Sun, Xuejun; Ji, Fang; Hou, Jiong; Su, Jiacan

2016-10-29

Hydrogen is a kind of noble gas with the character to selectively neutralize reactive oxygen species. Former researches proved that low-concentration of hydrogen can be used to ameliorating cerebral ischemia/reperfusion injury. Hydrogen electrolyzed from water has a hydrogen concentration of 66.7%, which is much higher than that used in previous studies. And water electrolysis is a potential new hydrogen resource for regular clinical use. This study was designed and carried out for the determination of safety and neuroprotective effects of water electrolysis-derived hydrogen. Sprague-Dawley rats were used as experimental animals, and middle cerebral artery occlusion was used to make cerebral ischemia/reperfusion model. Pathologically, tissues from rats in hydrogen inhalation group showed no significant difference compared with the control group in HE staining pictures. The blood biochemical findings matched the HE staining result. TTC, Nissl, and TUNEL staining showed the significant improvement of infarction volume, neuron morphology, and neuron apoptosis in rat with hydrogen treatment. Biochemically, hydrogen inhalation decreased brain caspase-3, 3-nitrotyrosine and 8-hydroxy-2-deoxyguanosine-positive cells and inflammation factors concentration. Water electrolysis-derived hydrogen inhalation had neuroprotective effects on cerebral ischemia/reperfusion injury in rats with the effect of suppressing oxidative stress and inflammation, and it is a possible new hydrogen resource to electrolyze water at the bedside clinically. Copyright © 2016. Published by Elsevier Ltd.

The Protective Effect of Curcumin on a Spinal Cord Ischemia-Reperfusion Injury Model.

PubMed

Akar, İlker; İnce, İlker; Arici, Akgül; Benli, İsmail; Aslan, Cemal; Şenol, Sefa; Demir, Osman; Altunkas, Fatih; Altındeger, Nuray; Akbas, Ali

2017-07-01

The purpose of this study is to investigate the neurological, biochemical, and histopathologic effects of both the acute and maintenance treatment of curcumin on an experimental spinal cord ischemia-reperfusion injury model in rats. The animals were randomly divided into 4 groups: (1) Sham, (2) ischemia-reperfusion (IR), (3) curcumin, and (4) solvent. Spinal cord ischemia was induced by clamping the aorta with minivascular clamps at a position just below the left renal artery and just proximal to the aortic bifurcation for 45 min. After 72 hr of reperfusion, neurological function was evaluated with a modified Tarlov score. In spinal cords, malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GPx), and nitric oxide (NO) levels were detected biochemically. Immunohistochemical staining was performed by antibodies against interleukin-6 (IL-6) and myeloperoxidase. Histopathologic changes were examined with hematoxylin and eosin staining. Although MDA tissue levels were elevated significantly in the IR group compared with the sham group, SOD and GPx levels decreased. After the administration of curcumin, MDA levels in the spinal cord decreased, and SOD and GPx levels increased. Those changes were statistically significant. There was no significance at NO levels. Among all groups, there was no difference in IL-6 and myeloperoxidase immunostaining. Histopathological analysis showed that histopathological changes in the IR group were improved by curcumin treatment. In the curcumin group, neurological outcome scores were significantly better statistically when compared with the IR group. We believe that curcumin possesses antioxidant, antiproliferative, and anticarcinogenic properties and may be an effective drug for the prevention of spinal cord IR injury in light of the neurologic, biochemical, and histopathological data of this study and published scientific literature. Copyright © 2017 Elsevier Inc. All rights reserved.

Acute testicular ischemia caused by incarcerated inguinal hernia.

PubMed

Orth, Robert C; Towbin, Alexander J

2012-02-01

Acute testicular ischemia caused by an incarcerated inguinal hernia usually affects infants. There are few reports of diagnosis using US, and the effect of long-standing reducible hernias on testicular growth in infants and children is unknown. The objectives of this study were to determine the incidence of testicular ischemia secondary to an incarcerated inguinal hernia at scrotal sonography and to determine the effect on testicular size at diagnosis. A hospital database was used to locate scrotal sonography examinations documenting an inguinal hernia, and images were reviewed for signs of testicular ischemia. Testicular volumes were compared using the Wilcoxon signed rank test. A total of 147 patients were identified with an inguinal hernia (age 1 day to 23 years, average 6 years). Ten patients (6.8%) had associated testicular ischemia (age 3 weeks to 6 months, average 9 weeks) and showed a statistically significant increase in ipsilateral testicular size compared to the contralateral testicle (P = 0.012). Patients without testicular ischemia did not show a significant difference in testicular size, regardless of patient age. An incarcerated inguinal hernia should be considered as a cause of acute testicular ischemia in infants younger than 6 months of age.

A Program for Solving the Brain Ischemia Problem

PubMed Central

DeGracia, Donald J.

2013-01-01

Our recently described nonlinear dynamical model of cell injury is here applied to the problems of brain ischemia and neuroprotection. We discuss measurement of global brain ischemia injury dynamics by time course analysis. Solutions to proposed experiments are simulated using hypothetical values for the model parameters. The solutions solve the global brain ischemia problem in terms of “master bifurcation diagrams” that show all possible outcomes for arbitrary durations of all lethal cerebral blood flow (CBF) decrements. The global ischemia master bifurcation diagrams: (1) can map to a single focal ischemia insult, and (2) reveal all CBF decrements susceptible to neuroprotection. We simulate measuring a neuroprotectant by time course analysis, which revealed emergent nonlinear effects that set dynamical limits on neuroprotection. Using over-simplified stroke geometry, we calculate a theoretical maximum protection of approximately 50% recovery. We also calculate what is likely to be obtained in practice and obtain 38% recovery; a number close to that often reported in the literature. The hypothetical examples studied here illustrate the use of the nonlinear cell injury model as a fresh avenue of approach that has the potential, not only to solve the brain ischemia problem, but also to advance the technology of neuroprotection. PMID:24961411

Outcomes of Critical Limb Ischemia in Hemodialysis Patients After Distal Bypass Surgery　- Poor Limb Prognosis With Stage 4 Wound, Ischemia, and Foot Infection (WIfI).

PubMed

Hoshina, Katsuyuki; Yamamoto, Kota; Miyata, Tetsuro; Watanabe, Toshiaki

2016-10-25

Distal bypass is the first-line treatment for patients with critical limb ischemia (CLI). In Japanese high-volume centers, approximately half of these patients are on hemodialysis (HD). We have treated such patients first with bypass using a multidisciplinary perioperative strategy. We reveal the recent characteristics of patients who underwent distal bypass and the surgical outcomes in Japan, especially focusing on the foot conditions by using the wound, ischemia, and foot infection (WIfI) classification.Methods and Results:The 152 patients underwent distal bypass in a tertiary center hospital, and we compared patients on HD (HD group) to those not on HD (non-HD group). There were significant differences between the 2 groups in the overall survival, major adverse cardiac event-free survival and amputation-free survival (AFS) rates (P<0.0001). The procedural outcomes were analyzed via primary and secondary patency, and there was no difference. In the subanalysis of limb status using WIfI stage, the AFS rate of the HD group was significantly worse than that of the non-HD group for WIfI stage 4 patients. The life and limb prognoses of patients with CLI and HD were worse than those of non-HD patients. There was no difference in surgical outcomes suggested by the graft patency rates between the 2 groups. AFS in WIfI stage 4 was significantly worse in the HD group, which indicated the importance of preoperative limb status. (Circ J 2016; 80: 2382-2387).

Loss of c-Kit function impairs arteriogenesis in a mouse model of hindlimb ischemia.

PubMed

Hernandez, Diana R; Artiles, Adriana; Duque, Juan C; Martinez, Laisel; Pinto, Mariana T; Webster, Keith A; Velazquez, Omaida C; Vazquez-Padron, Roberto I; Lassance-Soares, Roberta M

2018-04-01

Arteriogenesis is a process whereby collateral vessels remodel usually in response to increased blood flow and/or wall stress. Remodeling of collaterals can function as a natural bypass to alleviate ischemia during arterial occlusion. Here we used a genetic approach to investigate possible roles of tyrosine receptor c-Kit in arteriogenesis. Mutant mice with loss of c-Kit function (Kit W/W-v ), and controls were subjected to hindlimb ischemia. Blood flow recovery was evaluated pre-, post-, and weekly after ischemia. Foot ischemic damage and function were assessed between days 1 to 14 post-ischemia while collaterals remodeling were measured 28 days post-ischemia. Both groups of mice also were subjected to wild type bone marrow cells transplantation 3 weeks before hindlimb ischemia to evaluate possible contributions of defective bone marrow c-Kit expression on vascular recovery. Kit W/W-v mice displayed impaired blood flow recovery, greater ischemic damage and foot dysfunction after ischemia compared to controls. Kit W/W-v mice also demonstrated impaired collateral remodeling consistent with flow recovery findings. Because arteriogenesis is a biological process that involves bone marrow-derived cells, we investigated which source of c-Kit signaling (bone marrow or vascular) plays a major role in arteriogenesis. Kit W/W-v mice transplanted with bone marrow wild type cells exhibited similar phenotype of impaired blood flow recovery, greater tissue ischemic damage and foot dysfunction as nontransplanted Kit W/W-v mice. This study provides evidence that c-Kit signaling is required during arteriogenesis. Also, it strongly suggests a vascular role for c-Kit signaling because rescue of systemic c-Kit activity by bone marrow transplantation did not augment the functional recovery of Kit W/W-v mouse hindlimbs. Copyright © 2017 Elsevier Inc. All rights reserved.

Dexmedetomidine improves neurologic outcome from incomplete ischemia in the rat. Reversal by the alpha 2-adrenergic antagonist atipamezole.

PubMed

Hoffman, W E; Kochs, E; Werner, C; Thomas, C; Albrecht, R F

1991-08-01

Dexmedetomidine is an alpha 2-adrenergic agonist that decreases central sympathetic activity and reduces the anesthetic requirement for halothane. We evaluated the effect of dexmedetomidine on neurologic and histopathologic outcome from incomplete cerebral ischemia in the rat. Anesthesia was maintained with a 25-micrograms.kg-1.h-1 fentanyl infusion combined with 70% nitrous oxide. Incomplete ischemia was produced by unilateral carotid artery ligation combined with hemorrhagic hypotension to 35 mmHg for 30 min. Arterial blood gas tensions, pH, and head temperature were maintained at normal levels during the experiment. Four ischemic groups were tested: group 1 (n = 15) received an intraperitoneal (ip) saline injection (control); group 2 (n = 10) received an ip injection of 10 micrograms/kg dexmedetomidine 30 min before ischemia; group 3 (n = 10) received 100 micrograms/kg dexmedetomidine; and group 4 (n = 10) received 100 micrograms/kg dexmedetomidine plus 1 mg/kg atipamezole (an alpha 2-adrenergic antagonist). Neurologic outcome was evaluated for 3 days using a graded deficit score. Histopathology was evaluated in coronal section in caudate and hippocampal tissue segments. Dexmedetomidine (10 and 100 micrograms/kg) significantly decreased plasma catecholamines and improved neurologic and histopathologic outcome in a dose-dependent manner compared to control rats (P less than 0.05). Atipamezole abolished the decrease in catecholamines and the improvement in outcome seen with dexmedetomidine, confirming that these effects were mediated by alpha 2-adrenergic receptors. It is concluded that alpha 2-adrenoreceptor stimulation decreases sympathetic activity and decreases ischemic injury in a model of incomplete cerebral ischemia.

HIF-1α signaling activation by post-ischemia treatment with astragaloside IV attenuates myocardial ischemia-reperfusion injury.

PubMed

Si, Jingwen; Wang, Ning; Wang, Huan; Xie, Juan; Yang, Jian; Yi, Hui; Shi, Zixuan; Ma, Jing; Wang, Wen; Yang, Lifang; Yu, Shiqiang; Li, Junchang

2014-01-01

In this study, we evaluated the effect of astragaloside IV (Ast IV) post-ischemia treatment on myocardial ischemia-reperfusion (IR) injury (IRI). We also examined whether hypoxia inducible factor-1α (HIF-1α) and its downstream gene-inducible nitric oxide (NO) synthase (iNOS) play roles in the cardioprotective effect of Ast IV. Cultured cardiomyocytes and perfused isolated rat hearts were exposed to Ast IV during reperfusion in the presence or absence of the HIF-1α inhibitor 2-methoxyestradiol (2-MeOE2). The post-ischemia treatment with Ast IV protected cardiomyocytes from the apoptosis and death induced by simulated IRI (SIRI). Additionally, in cardiomyocytes, 2-MeOE2 and HIF-1α siRNA treatment each not only abolished the anti-apoptotic effect of post-ischemia treatment with Ast IV but also reversed the upregulation of HIF-1α and iNOS expression. Furthermore, after treatment with Ast IV, post-ischemic cardiac functional recovery and lactate dehydrogenase (LDH) release in the coronary flow (CF) were improved, and the myocardial infarct size was decreased. Moreover, the number of apoptotic cells was reduced, and the upregulation of the anti-apoptotic protein Bcl2 and downregulation of the pro-apoptotic protein Caspase3 were reversed. 2-MeOE2 reversed these effects of Ast IV on IR-injured hearts. These results suggest that post-ischemia treatment with Ast IV can attenuate IRI by upregulating HIF-1α expression, which transmits a survival signal to the myocardium.

Ursolic Acid Ameliorates Inflammation in Cerebral Ischemia and Reperfusion Injury Possibly via High Mobility Group Box 1/Toll-Like Receptor 4/NFκB Pathway.

PubMed

Wang, Yanzhe; Li, Lei; Deng, Shumin; Liu, Fang; He, Zhiyi

2018-01-01

Toll-like receptors (TLRs) play key roles in cerebral ischemia and reperfusion injury by inducing the production of inflammatory mediators, such as interleukins (ILs) and tumor necrosis factor-alpha (TNF-α). According to recent studies, ursolic acid (UA) regulates TLR signaling and exhibits notable anti-inflammatory properties. In the present study, we explored the mechanism by which UA regulates inflammation in the rat middle cerebral artery occlusion and reperfusion (MCAO/R) model. The MCAO/R model was induced in male Sprague-Dawley rats (MCAO for 2 h, followed by reperfusion for 48 h). UA was administered intragastrically at 0.5, 24, and 47 h after reperfusion. The direct high mobility group box 1 (HMGB1) inhibitor glycyrrhizin (GL) was injected intravenously after 0.5 h of ischemia as a positive control. The degree of brain damage was estimated using the neurological deficit score, infarct volume, histopathological changes, and neuronal apoptosis. We assessed IL-1β, TNF-α, and IL-6 levels to evaluate post-ischemic inflammation. HMGB1 and TLR4 expression and phosphorylation of nuclear factor kappa-light-chain-enhancer of activated B cell (NFκB) were also examined to explore the underlying mechanism. UA (10 and 20 mg/kg) treatment significantly decreased the neurological deficit scores, infarct volume, apoptotic cells, and IL-1β, TNF-α, and IL-6 concentrations. The infarct area ratio was reduced by (33.07 ± 1.74), (27.05 ± 1.13), (27.49 ± 1.87), and (39.74 ± 2.14)% in the 10 and 20 mg/kg UA, GL, and control groups, respectively. Furthermore, UA (10 and 20 mg/kg) treatment significantly decreased HMGB1 release and the TLR4 level and inactivated NFκB signaling. Thus, the effects of intragastric administration of 20 mg/kg of UA and 10 mg/kg of GL were similar. We provide novel evidence that UA reduces inflammatory cytokine production to protect the brain from cerebral ischemia and reperfusion injury possibly through the

Pomegranate extract protects against cerebral ischemia/reperfusion injury and preserves brain DNA integrity in rats.

PubMed

Ahmed, Maha A E; El Morsy, Engy M; Ahmed, Amany A E

2014-08-21

Interruption to blood flow causes ischemia and infarction of brain tissues with consequent neuronal damage and brain dysfunction. Pomegranate extract is well tolerated, and safely consumed all over the world. Interestingly, pomegranate extract has shown remarkable antioxidant and anti-inflammatory effects in experimental models. Many investigators consider natural extracts as novel therapies for neurodegenerative disorders. Therefore, this study was carried out to investigate the protective effects of standardized pomegranate extract against cerebral ischemia/reperfusion-induced brain injury in rats. Adult male albino rats were randomly divided into sham-operated control group, ischemia/reperfusion (I/R) group, and two other groups that received standardized pomegranate extract at two dose levels (250, 500 mg/kg) for 15 days prior to ischemia/reperfusion (PMG250+I/R, and PMG500+I/R groups). After I/R or sham operation, all rats were sacrificed and brains were harvested for subsequent biochemical analysis. Results showed reduction in brain contents of MDA (malondialdehyde), and NO (nitric oxide), in addition to enhancement of SOD (superoxide dismutase), GPX (glutathione peroxidase), and GRD (glutathione reductase) activities in rats treated with pomegranate extract prior to cerebral I/R. Moreover, pomegranate extract decreased brain levels of NF-κB p65 (nuclear factor kappa B p65), TNF-α (tumor necrosis factor-alpha), caspase-3 and increased brain levels of IL-10 (interleukin-10), and cerebral ATP (adenosine triphosphate) production. Comet assay showed less brain DNA (deoxyribonucleic acid) damage in rats protected with pomegranate extract. The present study showed, for the first time, that pre-administration of pomegranate extract to rats, can offer a significant dose-dependent neuroprotective activity against cerebral I/R brain injury and DNA damage via antioxidant, anti-inflammatory, anti-apoptotic and ATP-replenishing effects. Copyright © 2014 Elsevier Inc

Insulin/NFκB protects against ischemia-induced necrotic cardiomyocyte death.

PubMed

Díaz, Ariel; Humeres, Claudio; González, Verónica; Gómez, María Teresa; Montt, Natalia; Sanchez, Gina; Chiong, Mario; García, Lorena

2015-11-13

In the heart, insulin controls key functions such as metabolism, muscle contraction and cell death. However, all studies have been focused on insulin action during reperfusion. Here we explore the cardioprotective action of this hormone during ischemia. Rat hearts were perfused ex vivo with an ischemia/reperfusion Langendorff model in absence or presence of insulin. Additionally, cultured rat cardiomyocytes were exposed to simulated ischemia in the absence or presence of insulin. Cytoprotective effects were measured by myocardial infarct size, trypan blue exclusion, released LDH and DNA fragmentation by flow cytometry. We found that insulin protected against cardiac ischemia ex vivo and in vitro. Moreover, insulin protected cardiomyocytes from simulated ischemia by reducing necrotic cell death. Protective effects of insulin were dependent of Akt and NFκB. These novel results show that insulin reduces ischemia-induced cardiomyocyte necrosis through an Akt/NF-κB dependent mechanism. These novel findings clarify the role of insulin during ischemia and further support its use in early GIK perfusion to treat myocardial infarction. Copyright © 2015 Elsevier Inc. All rights reserved.

[Adipose-derived stem cell transplantation promotes the expression of netrin-1 in the rat cortex after focal cerebral ischemia].

PubMed

Wang, Jiehua; Hong, Zhuquan; Pan, Ying; Li, Guoqian

2017-01-01

Objective To observe the effect of adipose-derived stem cells (ADSCs) transplantation on the expression of netrin-1 in rats after focal cerebral ischemia. Methods Male SD rats were randomly divided into control group, model group and ADSC group. ADSCs were harvested and purified. Focal cerebral ischemia models were established in rats by the suture method. ADSCs were injected into the lateral ventricle of ADSC group rats and the same does of PBS was given to model group rats. At day 4, 7 and 14 after reperfusion, six rats were sacrificed to remove the brain tissues at each time point. The expression of netrin-1 was detected by reverse-transcription PCR, Western blotting and immunohistochemistry. Results Compared with the control group, the expression of netrin-1 in the brain tissues of the model group increased after focal cerebral ischemia, reached the peak at 4 days, and the expression of netrin-1 was significantly higher than that of the control group at each time point. Compared with the model group, the expression of netrin-1 in the ADSC group increased further, reached the peak at 7 days, and the expression of netrin-1 in the ADSC group was significantly higher than that of the model group at each time point. Conclusion ADSC transplantation could up-regulate the expression of netrin-1, and promote axon regeneration and the recovery of neurological functions.

Assessment of Renal Ischemia By Optical Spectroscopy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fitzgerald, J T; Demos, S; Michalopoulou, A

2004-01-07

Introduction: No reliable method currently exists for quantifying the degree of warm ischemia in kidney grafts prior to transplantation. We describe a method for evaluating pretransplant warm ischemia time using optical spectroscopic methods. Methods: Lewis rat kidney vascular pedicles were clamped unilaterally in vivo for 0, 5, 10, 20, 30, 60, 90 or 120 minutes; 8 animals were studied at each time point. Injured and contra-lateral control kidneys were then flushed with Euro-Collins solution, resected and placed on ice. 335 nm excitation autofluorescence as well as cross polarized light scattering images were taken of each injured and control kidney usingmore » filters of various wavelengths. The intensity ratio of the injured to normal kidneys was compared to ischemia time. Results: Autofluorescence intensity ratios through a 450 nm filter and light scattering intensity ratios through an 800 nm filter both decreased significantly with increasing ischemia time (p < 0.0001 for each method, one-way ANOVA). All adjacent and non-adjacent time points between 0 and 90 minutes were distinguishable using one of these two modalities by Fisher's PLSD. Conclusions: Optical spectroscopic methods can accurately quantify warm ischemia time in kidneys that have been subsequently hypothermically preserved. Further studies are needed to correlate results with physiological damage and posttransplant performance.« less

Protective effect of edaravone for tourniquet-induced ischemia-reperfusion injury on skeletal muscle in murine hindlimb

PubMed Central

2013-01-01

Background Studies have shown that ischemia-reperfusion (I/R) produces free radicals leading to lipid peroxidation and damage to skeletal muscle. The purposes of this study were 1) to assess the histological findings of gastrocnemius muscle (GC) and tibialis anterior muscle (TA) in I/R injury model mice, 2) to histologically analyze whether a single pretreatment of edaravone inhibits I/R injury to skeletal muscle in murine models and 3) to evaluate the effect of oxidative stress on these muscles. Methods C57BL6 mice were divided in two groups, with one group receiving 3 mg/kg intraperitoneal injections of edaravone (I/R + Ed group) and the other group receiving an identical amount of saline (I/R group) 30 minutes before ischemia. Edaravone (3-methy-1-pheny1-2-pyrazolin-5-one) is a potent and novel synthetic scavenger of free radicals. This drug inhibits both nonenzymatic lipid peroxidation and the lipoxygenase pathway, in addition to having potent antioxidant effects against ischemia reperfusion. The duration of the ischemia was 1.5 hours, with reperfusion at either 24 or 72 hours (3 days). Specimens of gastrocnemius (GC) and anterior tibialis (TA) were removed for histological evaluation and biochemical analysis. Results This model of I/R injury was highly reproducible in histologic muscle damage. In the histologic damage score, the mean muscle fibers and inflammatory cell infiltration in the I/R + Ed group were significantly less than the corresponding values of observed in the I/R group. Thus, pretreatment with edaravone was observed to have a protective effect on muscle damage after a period of I/R in mice. In addition, the mean muscle injury score in the I/R + Ed group was also significantly less than the I/R group. In the I/R + Ed group, the mean malondialdehyde (MDA) level was lower than in the I/R group and western-blotting revealed that edaravone pretreatment decreased the level of inducible nitric oxide synthase (iNOS) expression. Conclusions Edaravone

Assessment of Myocardial Ischemia with Cardiovascular Magnetic Resonance

PubMed Central

Heydari, Bobak; Jerosch-Herold, Michael; Kwong, Raymond Y.

2014-01-01

Assessment of myocardial ischemia in symptomatic patients remains a common and challenging clinical situation faced by physicians. Risk stratification by presence of ischemia provides important utility for both prognostic assessment and management. Unfortunately, current noninvasive modalities possess numerous limitations and have limited prognostic capacity. More recently, ischemia assessment by cardiovascular magnetic resonance (CMR) has been shown to be a safe, available, and potentially cost-effective alternative with both high diagnostic and prognostic accuracy. Cardiovascular magnetic resonance has numerous advantages over other noninvasive methods, including high temporal and spatial resolution, relatively few contraindications, and absence of ionizing radiation. Furthermore, studies assessing the clinical utility and cost effectiveness of CMR in the short-term setting for patients without evidence of an acute myocardial infarction have also demonstrated favorable results. This review will cover techniques of ischemia assessment with CMR by both stress-induced wall motion abnormalities as well as myocardial perfusion imaging. The diagnostic and prognostic performance studies will also be reviewed, and the use of CMR for ischemia assessment will be compared with other commonly used noninvasive modalities. PMID:22014487

Platelets, diabetes and myocardial ischemia/reperfusion injury.

PubMed

Russo, Isabella; Penna, Claudia; Musso, Tiziana; Popara, Jasmin; Alloatti, Giuseppe; Cavalot, Franco; Pagliaro, Pasquale

2017-05-31

Mechanisms underlying the pathogenesis of ischemia/reperfusion injury are particularly complex, multifactorial and highly interconnected. A complex and entangled interaction is also emerging between platelet function, antiplatelet drugs, coronary diseases and ischemia/reperfusion injury, especially in diabetic conditions. Here we briefly summarize features of antiplatelet therapy in type 2 diabetes (T2DM). We also treat the influence of T2DM on ischemia/reperfusion injury and how anti-platelet therapies affect post-ischemic myocardial damage through pleiotropic properties not related to their anti-aggregating effects. miRNA-based signature associated with T2DM and its cardiovascular disease complications are also briefly considered. Influence of anti-platelet therapies and different effects of healthy and diabetic platelets on ischemia/reperfusion injury need to be further clarified in order to enhance patient benefits from antiplatelet therapy and revascularization. Here we provide insight on the difficulty to reduce the cardiovascular risk in diabetic patients and report novel information on the cardioprotective role of widely used anti-aggregant drugs.

Acute mesenteric ischemia after heart surgery.

PubMed

Goleanu, V; Alecu, L; Lazar, O

2014-01-01

Acute mesenteric ischemia (AMI) is a rare but very severe complication of heart surgery, due especially to the delay in setting the correct diagnosis and choosing the appropriate treatment. There are 4 types, but the most frequent is nonocclusive mesenteric ischemia (NOMI). The main mechanism is represented by great decrease or maldistribution of the splenic blood flow, with negative impact on the integrity of the intestinal mucosa, bacterial translocation and multiorganic failure. We present a retrospective study conducted on patients who underwent open heart surgery with cardiopulmonary bypass with non-pulsatile flow. 4 cases of angiographically confirmed NOMI (non-occlusive mesenteric ischemia) were identified. When, based on clinical examination and laboratory findings, acute mesenteric ischemia was suspicioned, superior mesenteric artery angiography was performed via the femoral artery. The main risk factors were represented by: age over 70 years old, left ventricle ejection fraction (LVEF) 35%,aortic clamping time 100 min., chronic kidney failure,counter-pulsation balloon implant, inotropic medication use,like levosimendan, use of blood components 1 unit of erythrocyte mass. Clinical signs were nonspecific. All patients presented hypoventilation, arterial hypotension, oliguria and,from a biological standpoint, metabolic acidosis and leucocytosis. Superior mesenteric artery angiography was the investigation method of choice. Treatment approach was initially medical, followed by resection of the intestine.Mortality was 100%. Acute mesenteric ischemia is a rare but very severe complication in cardiac surgery. It is primordial that the main risk factors be known, and in case of diagnosis suspicion, that it be set as early as possible, along with immediate initiation of an appropriate course of treatment. Celsius.

Acute mesenteric ischemia: a vascular emergency.

PubMed

Klar, Ernst; Rahmanian, Parwis B; Bücker, Arno; Hauenstein, Karlheinz; Jauch, Karl-Walter; Luther, Bernd

2012-04-01

Acute mesenteric ischemia is still fatal in 50% to 70% of cases. This consensus paper was written with the participation of physicians from all of the involved specialties for the purpose of improving outcomes. Mesenteric ischemia must be recognized as a vascular emergency requiring rapid and efficient clinical evaluation and treatment. We reviewed pertinent literature that was retrieved by a PubMed search on the terms "mesenteric ischemia" AND "arterial" OR "venous" OR "clinical presentation" OR "diagnosis" OR "therapy" OR "surgery" OR " interventional radiology." Our review also took account of the existing guidelines of the American College of Cardiology/American Heart Association. Intensive discussions among the participating physicians, representing all of the specialties involved in the management of mesenteric ischemia, led to the creation of this interdisciplinary paper. Biphasic contrast-enhanced computerized tomography is the diagnostic tool of choice for the detection of arterial or venous occlusion. If non-occlusive mesenteric ischemia is suspected, angiography should be performed, with the option of intraarterial pharmacotherapy to induce local vasodilation. Endovascular techniques have become increasingly important in the treatment of arterial occlusion. Embolic central mesenteric artery occlusion requires surgical treatment; surgery is also needed in case of peritonitis. Portal-vein thrombosis can be treated by local thrombolysis through a transhepatically placed catheter. This should be done within 3 to 4 weeks of the event to prevent later complications of portal hypertension. Rapid diagnosis (within 4 to 6 hours of symptom onset) and interdisciplinary cooperation in the provision of treatment are required if the poor outcome of this condition is to be improved.

Poloxamer-188 reduces muscular edema after tourniquet-induced ischemia-reperfusion injury in rats.

PubMed

Walters, Thomas J; Mase, Vincent J; Roe, Janet L; Dubick, Michael A; Christy, Robert J

2011-05-01

Skeletal muscle injury can result in significant edema, which can in turn lead to the development of acute extremity compartment syndrome (CS). Poloxamer-188 (P-188), a multiblock copolymer surfactant, has been shown to decrease edema by sealing damaged membranes in a number of tissues after a variety of injury modalities. The objective is to determine whether the administration of P-188 significantly reduces skeletal muscle edema associated with ischemia/reperfusion injury (I-R). Male Sprague-Dawley rats underwent 180 minutes of tourniquet-induced ischemia. Five minutes before tourniquet release, rats received either a bolus of (1) P-188 (150 mg/kg; P-188 group) or (2) vehicle (Vehicle group) via a jugular catheter (n=10 per group). After 240 minutes reperfusion, both groups received a second bolus of either P-188 (P-188) or vehicle (Vehicle) via a tail vein catheter. Sixteen hours later, rats were killed; muscle weights were determined, infarct size (2,3,5-triphenyltetrazolium chloride method), and blinded histologic analysis (hematoxylin and eosin) were performed on the gastrocnemius and tibialis anterior muscles, as well as indices of antioxidant status. P-188 resulted in significantly less edema (wet weight) and reduced an index of lipid peroxidation compared with Vehicle (p<0.05). Wet:dry weight ratios were less in the P-188 group (indicating less edema). Muscle viability as indicated by 2,3,5-triphenyltetrazolium chloride staining or routine histology did not reveal statistically significant differences between groups. P-188 significantly reduced ischemia-reperfusion-related muscle edema and lipid peroxidation but did not impact muscle viability. Excess edema can lead to acute extremity CS, which is associated with significant morbidity and mortality. P-188 may provide a potential adjunctive treatment for the reduction of CS.

Induction of heme oxygenase-1 protects mouse liver from apoptotic ischemia/reperfusion injury

PubMed Central

Issan, Y.; Katz, Y.; Sultan, M.; Safran, M.; Michal, Laniado-Schwartzman; Nader, G. Abraham; Kornowski, R.; Grief, F.; Pappo, O.; Hochhauser, E.

2017-01-01

Ischemia/reperfusion (I/R) injury is the main cause of primary graft dysfunction of liver allografts. Cobalt-protoporphyrin (CoPP)–dependent induction of heme oxygenase (HO)-1 has been shown to protect the liver from I/R injury. This study analyzes the apoptotic mechanisms of HO-1-mediated cytoprotection in mouse liver exposed to I/R injury. HO-1 induction was achieved by the administration of CoPP (1.5 mg/kg body weight i.p.). Mice were studied in in vivo model of hepatic segmental (70 %) ischemia for 60 min and reperfusion injury. Mice were randomly allocated to four main experimental groups (n = 10 each): (1) A control group undergoing sham operation. (2) Similar to group 1 but with the administration of CoPP 72 h before the operation. (3) Mice undergoing in vivo hepatic I/R. (4) Similar to group 3 but with the administration of CoPP 72 h before ischemia induction. When compared with the I/R mice group, in the I/R+CoPP mice group, the increased hepatic expression of HO-1 was associated with a significant reduction in liver enzyme levels, fewer apoptotic hepatocytes cells were identified by morphological criteria and by immunohistochemistry for caspase-3, there was a decreased mean number of proliferating cells (positively stained for Ki67), and a reduced hepatic expression of: C/EBP homologous protein (an index of endoplasmic reticulum stress), the NF-κB’s regulated genes (CIAP2, MCP-1 and IL-6), and increased hepatic expression of IκBa (the inhibitory protein of NF-κB). HO-1 over-expression plays a pivotal role in reducing the hepatic apoptotic IR injury. HO-1 may serve as a potential target for therapeutic intervention in hepatic I/R injury during liver transplantation. PMID:23435964

Induction of heme oxygenase-1 protects mouse liver from apoptotic ischemia/reperfusion injury.

PubMed

Ben-Ari, Z; Issan, Y; Katz, Y; Sultan, M; Safran, M; Michal, Laniado-Schwartzman; Nader, G Abraham; Kornowski, R; Grief, F; Pappo, O; Hochhauser, E

2013-05-01

Ischemia/reperfusion (I/R) injury is the main cause of primary graft dysfunction of liver allografts. Cobalt-protoporphyrin (CoPP)-dependent induction of heme oxygenase (HO)-1 has been shown to protect the liver from I/R injury. This study analyzes the apoptotic mechanisms of HO-1-mediated cytoprotection in mouse liver exposed to I/R injury. HO-1 induction was achieved by the administration of CoPP (1.5 mg/kg body weight i.p.). Mice were studied in in vivo model of hepatic segmental (70 %) ischemia for 60 min and reperfusion injury. Mice were randomly allocated to four main experimental groups (n = 10 each): (1) A control group undergoing sham operation. (2) Similar to group 1 but with the administration of CoPP 72 h before the operation. (3) Mice undergoing in vivo hepatic I/R. (4) Similar to group 3 but with the administration of CoPP 72 h before ischemia induction. When compared with the I/R mice group, in the I/R+CoPP mice group, the increased hepatic expression of HO-1 was associated with a significant reduction in liver enzyme levels, fewer apoptotic hepatocytes cells were identified by morphological criteria and by immunohistochemistry for caspase-3, there was a decreased mean number of proliferating cells (positively stained for Ki67), and a reduced hepatic expression of: C/EBP homologous protein (an index of endoplasmic reticulum stress), the NF-κB's regulated genes (CIAP2, MCP-1 and IL-6), and increased hepatic expression of IκBa (the inhibitory protein of NF-κB). HO-1 over-expression plays a pivotal role in reducing the hepatic apoptotic IR injury. HO-1 may serve as a potential target for therapeutic intervention in hepatic I/R injury during liver transplantation.

Importance of compensatory heart rate increase during myocardial ischemia to preserve appropriate oxygen kinetics.

PubMed

Yoshida, Sadamitsu; Adachi, Hitoshi; Murata, Makoto; Tomono, Junichi; Oshima, Shigeru; Kurabayashi, Masahiko

2017-09-01

Myocardial ischemia induces cardiac dysfunction, resulting in insufficient oxygen supply to peripheral tissues and mismatched energy production during exercise. To relieve the insufficient oxygen supply, heart rate (HR) response is augmented; however, beta-adrenergic receptor blockers (BB) restrict HR response. Although BB are essential drugs for angina pectoris, the effect of BB on exercise tolerance in patients with angina has not been studied. The aim of this study was to clarify the importance of HR augmentation to preserve exercise tolerance in patients with angina pectoris. Forty-two subjects who underwent cardiopulmonary exercise testing (CPX) to detect myocardial ischemia were enrolled. CPX was performed until exhaustion or onset of significant myocardial ischemia using a ramp protocol. Subjects were assigned to three groups (Group A: with ST depression during CPX with significant coronary stenosis and taking BB; Group B: with ST depression and not taking BB; Group C: without ST depression and not taking BB). HR response to exercise was evaluated during the following two periods: below and above ischemic threshold (IT). In Group C, it was evaluated during the first 2min and the last 2min of a ramp exercise. No significant differences were observed among the three groups with regard to patients' basic characteristics. Below IT, there were no differences in oxygen pulse/watt (O 2 pulse increasing rate), HR/watt (ΔHR/ΔWR), and ΔV˙O 2 /ΔWR. Above IT, O 2 pulse increasing rate was greater in Group A than in Group B. ΔHR/ΔWR was smaller in Group A than in Group B. ΔV˙O 2 /ΔWR became smaller in Group A than in Group B. There was no difference in anaerobic threshold, and peak V˙O 2 was smaller in Group A than in Group B. Restriction of HR response by a BB is shown to be one of the important factors in diminished exercise tolerance. Copyright © 2016 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.

Mental stress-induced ischemia in patients with coronary artery disease: echocardiographic characteristics and relation to exercise-induced ischemia.

PubMed

Stepanovic, Jelena; Ostojic, Miodrag; Beleslin, Branko; Vukovic, Olivera; Djordjevic-Dikic, Ana; Dikic, Ana Djordjevic; Giga, Vojislav; Nedeljkovic, Ivana; Nedeljkovic, Milan; Stojkovic, Sinisa; Vukcevic, Vladan; Dobric, Milan; Petrasinovic, Zorica; Marinkovic, Jelena; Lecic-Tosevski, Dusica

2012-09-01

The aims of this study were to investigate the incidence and parameters associated with myocardial ischemia during mental stress (MS) as measured by echocardiography and to evaluate the relation between MS-induced and exercise-induced myocardial ischemia. Study participants were 79 patients (63 men; mean [M] [standard deviation {SD}] age = 52 [8] years) with angiographically confirmed coronary artery disease and previous positive exercise test result. The MS protocol consisted of mental arithmetic and anger recall task. The patients performed a treadmill exercise test 15 to 20 minutes after the MS task. Data of post-MS exercise were compared with previous exercise stress test results. The frequency of echocardiographic abnormalities was 35% in response to the mental arithmetic task, compared with 61% with anger recall and 96% with exercise (p < .001, exercise versus MS). Electrocardiogram abnormalities and chest pain were substantially less common during MS than were echocardiographic abnormalities. Independent predictors of MS-induced myocardial ischemia were: wall motion score index at rest (p = .02), peak systolic blood pressure (p = .005), and increase in rate-pressure product (p = .004) during MS. The duration of exercise stress test was significantly shorter (p < .001) when MS preceded the exercise and in the case of earlier exercise (M [SD] = 4.4 [1.9] versus 6.7 [2.2] minutes for patients positive on MS and 5.7 [1.9] versus 8.0 [2.3] minutes for patients negative on MS). Echocardiography can be successfully used to document myocardial ischemia induced by MS. MS-induced ischemia was associated with an increase in hemodynamic parameters during MS and worse function of the left ventricle. MS may shorten the duration of subsequent exercise stress testing and can potentiate exercise-induced ischemia in susceptible patients with coronary artery disease.

Cofilin Inhibition Restores Neuronal Cell Death in Oxygen-Glucose Deprivation Model of Ischemia.

PubMed

Madineni, Anusha; Alhadidi, Qasim; Shah, Zahoor A

2016-03-01

Ischemia is a condition associated with decreased blood supply to the brain, eventually leading to death of neurons. It is associated with a diverse cascade of responses involving both degenerative and regenerative mechanisms. At the cellular level, the changes are initiated prominently in the neuronal cytoskeleton. Cofilin, a cytoskeletal actin severing protein, is known to be involved in the early stages of apoptotic cell death. Evidence supports its intervention in the progression of disease states like Alzheimer's and ischemic kidney disease. In the present study, we have hypothesized the possible involvement of cofilin in ischemia. Using PC12 cells and mouse primary cultures of cortical neurons, we investigated the potential role of cofilin in ischemia in two different in vitro ischemic models: chemical induced oxidative stress and oxygen-glucose deprivation/reperfusion (OGD/R). The expression profile studies demonstrated a decrease in phosphocofilin levels in all models of ischemia, implying stress-induced cofilin activation. Furthermore, calcineurin and slingshot 1L (SSH) phosphatases were found to be the signaling mediators of the cofilin activation. In primary cultures of cortical neurons, cofilin was found to be significantly activated after 1 h of OGD. To delineate the role of activated cofilin in ischemia, we knocked down cofilin by small interfering RNA (siRNA) technique and tested the impact of cofilin silencing on neuronal viability. Cofilin siRNA-treated neurons showed a significant reduction of cofilin levels in all treatment groups (control, OGD, and OGD/R). Additionally, cofilin siRNA-reduced cofilin mitochondrial translocation and caspase 3 cleavage, with a concomitant increase in neuronal viability. These results strongly support the active role of cofilin in ischemia-induced neuronal degeneration and apoptosis. We believe that targeting this protein mediator has a potential for therapeutic intervention in ischemic brain injury and stroke.

A comparison of the effects of epidural and spinal anesthesia with ischemia-reperfusion injury on the rat transverse rectus abdominis musculocutaneous flap.

PubMed

Acar, Yusuf; Bozkurt, Mehmet; Firat, Ugur; Selcuk, Caferi Tayyar; Kapi, Emin; Isik, Fatma Birgul; Kuvat, Samet Vasfi; Celik, Feyzi; Bozarslan, Beri Hocaoglu

2013-11-01

The purpose of this study is to compare the effects of spinal and epidural anesthesia on a rat transverse rectus abdominus myocutaneous flap ischemia-reperfusion injury model.Forty Sprague-Dawley rats were divided into 4 experimental groups: group I (n = 10), sham group; group II (n = 10), control group; group III (n = 10), epidural group; and group IV (n = 10), spinal group. After the elevation of the transverse rectus abdominus myocutaneous flaps, all groups except for the sham group were subjected to normothermic no-flow ischemia for 4 hours, followed by a reperfusion period of 2 hours. At the end of the reperfusion period, biochemical and histopathological evaluations were performed on tissue samples.Although there was no significant difference concerning the malonyldialdehyde, nitric oxide, and paraoxonase levels in the spinal and epidural groups, the total antioxidant state levels were significantly increased, and the total oxidative stress levels were significantly decreased in the epidural group in comparison to the spinal group. The pathological evaluation showed that findings related to inflammation, nuclear change rates and hyalinization were significantly higher in the spinal group compared with the epidural group.Epidural anesthesia can be considered as a more suitable method that enables a decrease in ischemia-reperfusion injuries in the muscle flaps.

Panic attack triggering myocardial ischemia documented by myocardial perfusion imaging study. A case report

PubMed Central

2012-01-01

Background Chest pain, a key element in the investigation of coronary artery disease is often regarded as a benign prognosis when present in panic attacks. However, panic disorder has been suggested as an independent risk factor for long-term prognosis of cardiovascular diseases and a trigger of acute myocardial infarction. Objective Faced with the extreme importance in differentiate from ischemic to non-ischemic chest pain, we report a case of panic attack induced by inhalation of 35% carbon dioxide triggering myocardial ischemia, documented by myocardial perfusion imaging study. Discussion Panic attack is undoubtedly a strong component of mental stress. Patients with coronary artery disease may present myocardial ischemia in mental stress response by two ways: an increase in coronary vasomotor tone or a sympathetic hyperactivity leading to a rise in myocardial oxygen consumption. Coronary artery spasm was presumed to be present in cases of cardiac ischemia linked to panic disorder. Possibly the carbon dioxide challenge test could trigger myocardial ischemia by the same mechanisms. Conclusion The use of mental stress has been suggested as an alternative method for myocardial ischemia investigation. Based on translational medicine objectives the use of CO2 challenge followed by Sestamibi SPECT could be a useful method to allow improved application of research-based knowledge to the medical field, specifically at the interface of PD and cardiovascular disease. PMID:22999016

Panic attack triggering myocardial ischemia documented by myocardial perfusion imaging study. A case report.

PubMed

Soares-Filho, Gastão Luiz Fonseca; Mesquita, Claudio Tinoco; Mesquita, Evandro Tinoco; Arias-Carrión, Oscar; Machado, Sergio; González, Manuel Menéndez; Valença, Alexandre Martins; Nardi, Antonio Egidio

2012-09-21

Chest pain, a key element in the investigation of coronary artery disease is often regarded as a benign prognosis when present in panic attacks. However, panic disorder has been suggested as an independent risk factor for long-term prognosis of cardiovascular diseases and a trigger of acute myocardial infarction. Faced with the extreme importance in differentiate from ischemic to non-ischemic chest pain, we report a case of panic attack induced by inhalation of 35% carbon dioxide triggering myocardial ischemia, documented by myocardial perfusion imaging study. Panic attack is undoubtedly a strong component of mental stress. Patients with coronary artery disease may present myocardial ischemia in mental stress response by two ways: an increase in coronary vasomotor tone or a sympathetic hyperactivity leading to a rise in myocardial oxygen consumption. Coronary artery spasm was presumed to be present in cases of cardiac ischemia linked to panic disorder. Possibly the carbon dioxide challenge test could trigger myocardial ischemia by the same mechanisms. The use of mental stress has been suggested as an alternative method for myocardial ischemia investigation. Based on translational medicine objectives the use of CO2 challenge followed by Sestamibi SPECT could be a useful method to allow improved application of research-based knowledge to the medical field, specifically at the interface of PD and cardiovascular disease.

Protective effects of melatonin on ischemia-reperfusion induced myocardial damage and hemodynamic recovery in rats.

PubMed

Liu, L-F; Qin, Q; Qian, Z-H; Shi, M; Deng, Q-C; Zhu, W-P; Zhang, H; Tao, X-M; Liu, Y

2014-01-01

To investigate the mechanism of melatonin (MT) protection of adult rate myocardial ischemia-reperfusion injury and its influence on rat's hemodynamic recovery. 48 rats were randomly divided into MT group (n=36) and the control group (n=12), MT group was divided into three sub-groups according to different dosages: Group I (n=12) was administered with 2.5 mg/kg MT; Group II (n=12) was administered with 5 mg/kg MT; Group III (n=12) was administered with 10 mg/kg MT. The electrocardiogram of four groups was observed with the left coronary artery blocked for 10min at first and then reperfused for 15min. Hemodynamic evolving was observed and changes in energy metabolism of rat myocardium were monitored. TUNEL and immunohistochemistry were applied to detect the cell apoptosis index, protein expression of Bcl-2 and Bax. LVDP (left ventricular developed pressure) and ± dp/dt in MT group presented better recovery at various time points than the control group. Among them, Group III had the optimal recovery degree (p < 0.05). After MT administration, ATP content in myocardial cells in MT group was significantly higher than the control group. Compared with the control group, the concentration of mitochondrial MDA and Ca2+ in myocardial cells in MT group showed a downward trend. But its GSH concentration was significantly higher than the control group (p < 0.05). The improvement degree of ATP, MDA, GSH and Ca2+ concentration in Group II over-performed Group I (p < 0.05). MT-intervened myocardial apoptosis index (AI) and Bax positive expression index declined while Bcl-2 positive expression index increased (p < 0.01). MT effectively inhibited myocardial apoptosis during the myocardial ischemia-reperfusion of rats, protected the structural integrity of mitochondria in myocardial cells, promoted ATP synthesis, and avoided heart damage in many ways. This protection mechanism was related with anti-oxidative damage. Meanwhile, MT could promote the hemodynamic recovery after

Curcumin inhibits endoplasmic reticulum stress induced by cerebral ischemia-reperfusion injury in rats

PubMed Central

Zhu, Haiying; Fan, Yanxia; Sun, Hongyu; Chen, Liyan; Man, Xiao

2017-01-01

The aim of the present study was to observe the dynamic changes of the growth arrest and DNA damage-inducible 153 (GADD153) gene and caspase-12 in the brain tissue of rats with cerebral ischemia-reperfusion injury (CIRI) and the impact of curcumin pretreatment. A total of 60 rats were randomly divided into the normal group (N), the sham operation group (S), the dimethyl sulfoxide control group (D) and the curcumin treatment group (C). For group D and C, 12 (T1), 24 (T2) and 72 h (T3) of reperfusion were performed after 2 h ischemia. The expression levels of GADD153 and caspase-12 in the brain tissue were detected and compared among the groups by immunohistochemistry, immunofluorescence double staining and western blotting. The expression levels of GADD153 and caspase-12 were increased at T1compared with groups N and S, and the expression of caspase-12 peaked at T2 in group D, while GADD153 was increased until T3 in group D. Compared with group D, the expression levels of GADD153 and caspase-12 in group C at T2 and T3 were significantly decreased (P<0.05). Endoplasmic reticulum stress is involved in the pathological process of CIRI. Curcumin may decrease the expression levels of the above two factors, thus exhibiting protective effects against CIRI in rats. PMID:29067098

[Mechanism of vacuum sealing drainage therapy attenuating ischemia-reperfusion injury of skeletal muscle in rabbit].

PubMed

Wang, Xiang; Yang, Fan; Guan, Zhen; Wang, Dongfang; Bai, Xiangjun; Gao, Wei

2016-04-01

To investigate the mechanism of how vacuum sealing drainage (VSD) ameliorating ischemia reperfusion (I/R) injury in skeletal muscle I/R model. Thirty New Zealand white rabbits were divided into three groups: control (sham operation) group, I/R group, VSD+ I/R group.The ischemia of the left hind limb of the animal was induced by clamping the common femoral artery and vein. After 4 hours of ischemia, the clamp was removed and the hind limp underwent 6 hours reperfusion. VSD treated animals received the treatment at the beginning of reperfusion. The concentrations of myeloperoxidase (MPO), malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT) and glutathione (GSH) in muscular tissues were assayed. HE stained pathological section was used to evaluate the degree of edema of muscular tissues, and the immunohistochemistry was used to detect the percentage of positive cells expressing high mobility group protein B1 (HMGB1). Q-RT-PCR and Western Blot were used to detect the mRNA levels and protein expression of HMGB1 in myocyte respectively. The experimental data was tested using variance analysis. The levels of inflammatory factors and antioxidant factors in muscular tissues were significantly different in the I/R group compared to the VSD group and control group (the levels of MPO in I/R group, I/R+ VSD group and control group were 0.91±0.22, 0.53±0.08, 0.31±0.10, respectively, F=26.48, P=0.000; MDA were 2.04±0.92, 1.65±1.02, 1.01±0.12, F=4.250, P=0.040; SOD were 35.97±9.23, 55.99±18.97, 61.83±14.91, F=5.240, P=0.020; CAT were 31.42±16.27, 48.50±17.86, 75.95±13.09, F=9.720, P=0.002; GSH were 1.48±0.90, 3.54±1.88, 3.84±2.08, F=5.240, P=0.020). HE staining showed an increased intercellular space ratio in the I/R group (F=16.47, P<0.05). Immunohistochemistry staining showed that percentage of HMGB1 positive myocytes in control, I/R and I/R+ VSD group are 1.94%, 18.63% and 61.36%, respectively. There was significant difference among groups (F=853

Effect of desipramine on spontaneous activity of hippocampal CA1 neuron after transient cerebral ischemia in rats.

PubMed

Zhu, Z T; Zhang, X X; Liu, J; Jin, G Z

1996-01-01

To study the spontaneous firing of CA1 neurons in rat hippocampus after transient cerebral ischemia and the effect of desipramine (Des) on the post-ischemic electric activity of CA1 neurons. Single-unit extracellular recordings were performed in rats on d 3 after 10 min of cerebral ischemia by occlusion of 4 arteries. Des and saline were injected into a tail vein. The histological changes of CA1 neurons was assessed by the neuronal density of the CA1 sector. The spontaneous firing rate of CA1 neurons on d 3 after ischemia was enhanced in comparison with the control value. Des (0.2 and 0.4 mg.kg-1, i.v., n = 5 & 6, respectively) reduced dose-dependently the increase of firing rate with maximal inhibition by 6 min (58% & 85%) to 9 min (69% & 94%) (vs vehicle group, P < 0.01). About 50% cells in CA1 region showed necrotic changes. Des antagonized the hyperexcitability of CA1 neurons after cerebral ischemia.

Curcumin-loaded embryonic stem cell exosomes restored neurovascular unit following ischemia-reperfusion injury.

PubMed

Kalani, Anuradha; Chaturvedi, Pankaj; Kamat, Pradip K; Maldonado, Claudio; Bauer, Philip; Joshua, Irving G; Tyagi, Suresh C; Tyagi, Neetu

2016-10-01

We tested whether the combined nano-formulation, prepared with curcumin (anti-inflammatory and neuroprotective molecule) and embryonic stem cell exosomes (MESC-exo cur ), restored neurovascular loss following an ischemia reperfusion (IR) injury in mice. IR-injury was created in 8-10 weeks old mice and divided into two groups. Out of two IR-injured groups, one group received intranasal administration of MESC-exo cur for 7days. Similarly, two sham groups were made and one group received MESC-exo cur treatment. The study determined that MESC-exo cur treatment reduced neurological score, infarct volume and edema following IR-injury. As compared to untreated IR group, MESC-exo cur treated-IR group showed reduced inflammation and N-methyl-d-aspartate receptor expression. Treatment of MESC-exo cur also reduced astrocytic GFAP expression and alleviated the expression of NeuN positive neurons in IR-injured mice. In addition, MESC-exo cur treatment restored vascular endothelial tight (claudin-5 and occludin) and adherent (VE-cadherin) junction proteins in IR-injured mice as compared to untreated IR-injured mice. These results suggest that combining the potentials of embryonic stem cell exosomes and curcumin can help neurovascular restoration following ischemia-reperfusion injury in mice. Copyright © 2016 Elsevier Ltd. All rights reserved.

[Digital ischemia in two patients treated with gemcitabine].

PubMed

Viguier, J-B; Solanilla, A; Boulon, C; Constans, J; Conri, C

2010-06-01

A 73-year-old man with an urothelial carcinoma treated with gemcitabine and carboplatinium and an 84-year-old man with a mesothelioma treated with gemcitabine alone developed digital ischemia. In the first patient, the ischemia involved all fingers except the thumbs during the second cycle of treatment. The ischemia developed during the first cycle in the second patient and involved the right major and ring fingers. In the literature, gemcitabine vascular toxicity is probably potentialized by platinium salts. Several nosological entities occur simultaneously. The most widely described involve isolated digital ischemia for doses to the order of 3000mg, and a hemolytic and uremic thrombotic microangiopathy for gemcitabine doses above 10,000mg. The vascular toxicity of platinium salts is not dose-dependent. In these two patients, the clinical course was favorable with interruption of the chemotherapy, treatment by iloprost and aspirin.

Human mesenchymal stromal cells decrease mortality after intestinal ischemia and reperfusion injury.

PubMed

Markel, Troy A; Crafts, Trevor D; Jensen, Amanda R; Hunsberger, Erin Bailey; Yoder, Mervin C

2015-11-01

Cellular therapy is a novel treatment option for intestinal ischemia. Bone marrow-derived mesenchymal stromal cells (BMSCs) have previously been shown to abate the damage caused by intestinal ischemia/reperfusion (I/R) injury. We therefore hypothesized that (1) human BMSCs (hBMSCs) would produce more beneficial growth factors and lower levels of proinflammatory mediators compared to differentiated cells, (2) direct application of hBMSCs to ischemic intestine would decrease mortality after injury, and (3) decreased mortality would be associated with an altered intestinal and hepatic inflammatory response. Adult hBMSCs and keratinocytes were cultured on polystyrene flasks. For in vitro experiments, cells were exposed to tumor necrosis factor, lipopolysaccharides, or 2% oxygen for 24 h. Supernatants were then analyzed for growth factors and chemokines by multiplex assay. For in vivo experiments, 8- to 12-wk-old male C57Bl6J mice were anesthetized and underwent a midline laparotomy. Experimental groups were exposed to temporary superior mesenteric artery occlusion for 60 min. Immediately after ischemia, 2 × 10(6) hBMSCs or keratinocytes in phosphate-buffered saline were placed into the peritoneal cavity. Animals were then closed and allowed to recover for 6 h (molecular/histologic analysis) or 7 d (survival analysis). After 6-h reperfusion, animals were euthanized. Intestines and livers were harvested and analyzed for inflammatory chemokines, growth factors, and histologic changes. hBMSCs expressed higher levels of human interleukin (IL) 6, IL-8, vascular endothelial growth factor (VEGF), and epidermal growth factor and lower levels of IL-1, IL-3, IL-7, and granulocyte-monocyte colony-stimulating factor after stimulation. In vivo, I/R resulted in significant mortality (70% mortality), whereas application of hBMSCs after ischemia decreased mortality to 10% in a dose-dependent fashion (P = 0.004). Keratinocyte therapy offered no improvements in mortality

Protectant activity of defibrotide in cardioplegia followed by ischemia/reperfusion injury in the isolated rat heart.

PubMed

Rossoni, G; Pompilio, G; Biglioli, P; Alamanni, F; Tartara, P; Rona, P; Porqueddu, M; Berti, F

1999-01-01

Previous studies have shown that defibrotide, a polydeoxyribonucleotide obtained by depolymerization of DNA from porcine tissues, has important protective effects on myocardial ischemia, which may be associated with a prostacyclin-related mechanism. The purpose of this study was to investigate the direct effects of defibrotide (given in cardioplegia or after ischemia) on a model of rat heart recovery after cardioplegia followed by ischemia/reperfusion injury. Isolated rat hearts, undergoing 5 minutes of warm cardioplegic arrest followed by 20 minutes of global ischemia and 30 minutes of reperfusion, were studied using the modified Langendorff model. The cardioplegia consisted of St. Thomas' Hospital solution augmented with defibrotide (50, 100, and 200 microg/mL) or without defibrotide (controls). Left ventricular mechanical function and the levels of creatine kinase, lactate dehydrogenase, and 6-keto-prostaglandin F1alpha (6-keto-PGF1alpha; the stable metabolite of prostacyclin) were measured during preischemic and reperfusion periods. After global ischemia, hearts receiving defibrotide in the cardioplegic solution (n = 8) manifested in a concentration-dependent fashion lower left ventricular end-diastolic pressure (p < 0.001), higher left ventricular developed pressure (p < 0.01), and lower coronary perfusion pressure (p < 0.001) compared to the control group. After reperfusion, hearts receiving defibrotide in the cardioplegic solution also had, in a dose-dependent way, lower levels of creatine-kinase (p < 0.01), lactate dehydrogenase (p < 0.001), and higher levels of 6-keto-PGF1alpha (p < 0.001) compared to the control group. Furthermore, when defibrotide was given alone to the hearts at the beginning of reperfusion (n = 7), the recovery of postischemic left ventricular function was inferior (p < 0.05) to that obtained when defibrotide was given in cardioplegia. Defibrotide confers to conventional crystalloid cardioplegia a potent concentration

Effects of ischemic preconditioning on PDGF-BB expression in the gerbil hippocampal CA1 region following transient cerebral ischemia

PubMed Central

Lee, Jae-Chul; Kim, Yang Hee; Lee, Tae-Kyeong; Kim, In Hye; Cho, Jeong Hwi; Cho, Geum-Sil; Shin, Bich-Na; Park, Joon Ha; Ahn, Ji Hyeon; Shin, Myoung Cheol; Cho, Jun Hwi; Kang, Il Jun; Won, Moo-Ho; Seo, Jeong Yeol

2017-01-01

Ischemic preconditioning (IPC) is induced by exposure to brief durations of transient ischemia, which results in ischemic tolerance to a subsequent longer or lethal period of ischemia. In the present study, the effects of IPC (2 min of transient cerebral ischemia) were examined on immunoreactivity of platelet-derived growth factor (PDGF)-BB and on neuroprotection in the gerbil hippocampal CA1 region following lethal transient cerebral ischemia (LTCI; 5 min of transient cerebral ischemia). IPC was subjected to a 2-min sublethal ischemia and a LTCI was given 5-min transient ischemia. The animals in all of the groups were given recovery times of 1, 2 and 5 days and change in PDGF-BB immunoreactivity was examined as was the neuronal damage/death in the hippocampus induced by LTCI. LTCI induced a significant loss of pyramidal neurons in the hippocampal CA1 region 5 days after LTCI, and significantly decreased PDGF-BB immunoreactivity in the CA1 pyramidal neurons from day 1 after LTCI. Conversely, IPC effectively protected the CA1 pyramidal neurons from LTCI and increased PDGF-BB immunoreactivity in the CA1 pyramidal neurons post-LTCI. In conclusion, the results demonstrated that LTCI significantly altered PDGF-BB immunoreactivity in pyramidal neurons in the hippocampal CA1 region, whereas IPC increased the immunoreactivity. These findings indicated that PDGF-BB may be associated with IPC-mediated neuroprotection. PMID:28627606

Predictive Modeling of Cardiac Ischemia

NASA Technical Reports Server (NTRS)

Anderson, Gary T.

1996-01-01

The goal of the Contextual Alarms Management System (CALMS) project is to develop sophisticated models to predict the onset of clinical cardiac ischemia before it occurs. The system will continuously monitor cardiac patients and set off an alarm when they appear about to suffer an ischemic episode. The models take as inputs information from patient history and combine it with continuously updated information extracted from blood pressure, oxygen saturation and ECG lines. Expert system, statistical, neural network and rough set methodologies are then used to forecast the onset of clinical ischemia before it transpires, thus allowing early intervention aimed at preventing morbid complications from occurring. The models will differ from previous attempts by including combinations of continuous and discrete inputs. A commercial medical instrumentation and software company has invested funds in the project with a goal of commercialization of the technology. The end product will be a system that analyzes physiologic parameters and produces an alarm when myocardial ischemia is present. If proven feasible, a CALMS-based system will be added to existing heart monitoring hardware.

Ischemic preconditioning enhances autophagy but suppresses autophagic cell death in rat spinal neurons following ischemia-reperfusion.

PubMed

Fan, Jin; Zhang, Zitao; Chao, Xie; Gu, Jun; Cai, Weihua; Zhou, Wei; Yin, Guoyong; Li, Qingqing

2014-05-08

Autophagy serves to eliminate damaged proteins and organelles under normal physiological conditions and can be accelerated by pathological stress, possibly as a cytoprotective mechanism. Brief periods of ischemia (ischemic preconditioning or IPC) can reduce neuronal death in response to subsequent severe ischemic insults. Ischemic preconditioning also induces autophagy, but the contribution of autophagy to IPC-associated neuroprotection remains unclear. We investigated the contribution of autophagy to IPC-mediated neuroprotection in rats subjected to ischemic spinal cord injury. Fifty adult rats were randomly assigned to either (1) a sham group receiving anesthesia and surgical preparation (n=5), (2) an ischemia/reperfusion (I/R) group (n=20) subjected to 0.5 h ischemia followed by 3, 6, 12, or 24 h reperfusion, (3) an IPC group receiving three cycles of 5 min ischemia followed by 5 min of reperfusion (n=5), or (4) an IPC+I/R group (n=20). Hematoxylin-eosin (HE) and immunohistochemical staining were performed to evaluate spinal neuron survival in the four treatment groups. Autophagic activity was investigated by electron microscopy and by immunohistochemical and Western blot analyses of the autophagosome marker LC3-II and the autophagy-associated BH3 protein Beclin-1. Changes in Bcl-2/Beclin-1 complex association and Bcl-2 phosphorylation (p-Bcl-2) were examined by co-immunoprecipitation and Western blot analyses. In the I/R group, LC3-II was significantly elevated after 3h of reperfusion, but declined significantly by 24 h. At 24 h, I/R rats exhibited extensive spinal damage and decreased neuronal survival. In the IPC+IR group, neuronal death was reduced and expression of LC3-II sustained throughout the 24 h reperfusion period. In the I/R group, expression of (inactive) p-Bcl-2(Ser70) was increased significantly during reperfusion and was accompanied by dissociation of the Bcl-2/Beclin-1 complex and increased Beclin-1 expression. Preconditioning inhibited these

[Silent myocardial ischemia in patients with transient ischemic attacks].

PubMed

Sánchez Valiente, S; Mostacero, E; del Río, A; Morales, F

1994-10-01

Given evidence that ischemic heart disease is the most frequent cause of death in patients with cerebrovascular disease, we used ergometrics to screen 80 patients with TIA for silent myocardial ischemia (SMI) at the neurological unit of Hospital Clínico Universitario in Zaragoza, Spain. The patients were compared with a control group of 80 with no signs of heart disease. Neither the patients nor the controls had ever shown clinical signs of coronary ischemia and their baseline electrocardiograms were normal. Stress test results were positive in 25 (31%) of the TIA patients, and in 4 (5%) (p < 0.001) of the controls, showing that the prevalence of SMI is significantly higher in TIA patients than in the general population. Hiperlipidemia (75% testing positive versus 43% negative, p < 0.01) and diabetes (31% testing positive versus 13% negative, p < 0.01) were the risk factors statistically related with a positive stress test.

The effect of hypericum perforatum on kidney ischemia/reperfusion damage.

PubMed

Cakir, Murat; Duzova, Halil; Baysal, Işil; Gül, Cemile Ceren; Kuşcu, Gülbahar; Kutluk, Fatma; Çakin, Hilal; Şeker, Şifanur; İlbeği, Esranur; Uslu, Seda; Avci, Umut; Demir, Samet; Akinci, Cihan; Atli, Sercan

2017-11-01

It has been revealed in recent studies that Hypericum Perforatum (HP) is influential on cancer, inflammatory diseases, bacterial and viral diseases, and has neuroprotective and antioxidant properties. In this study, we investigated the effect of HP, which is known to have antioxidant and anti-inflammatory effects, on kidney I/R damage. Male Sprague-Dawley rats were divided into three groups, and each of the groups had eight rats: The Control Group; the Ischemia/Reperfusion (I/R) Group; and the IR + HP Group which was treated with 50 mg/kg of HP. The right kidneys of the rats were removed, and the left kidney developed ischemia during the 45th min, and reperfusion occurred in the following 3rd h. The histopathological findings and also the level of Malondialdehyde (MDA), Glutathione (GSH) and superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-PX) enzyme activations in the renal tissues were measured. Blood Urea Nitrogen (BUN), Creatinin (Cre) from serum samples were determined. The levels of BUN, Cre, and kidney tissue MDA increased at a significant level, and the SOD, CAT, and GSH-PX enzyme activity decreased at a significant level in the I/R group, compared with the Control Group (p < 0.05). In the I/R + HP group, the levels of MDA decreased at a significant level compared to the I/R group, while the SOD, CAT, and GSH-PX activity increased (p < 0.05). In histopathological examinations, it was observed that the tubular dilatation and epithelial desquamation regressed in the IR + HP Group when compared with the I/R Group. It has been shown with the histological and biochemical results in this study that HP is protective against acute renal I/R.

Zinc translocation accelerates infarction after mild transient focal ischemia.

PubMed

Lee, J-M; Zipfel, G J; Park, K H; He, Y Y; Hsu, C Y; Choi, D W

2002-01-01

Excess release of chelatable zinc (Zn(2+)) from central synaptic vesicles may contribute to the pathogenesis of selective neuronal cell death following transient forebrain ischemia, but a role in neurodegeneration after focal ischemia has not been defined. Adult male Long-Evans rats subjected to middle cerebral artery occlusion (MCAO) for 30 min followed by reperfusion developed delayed cerebral infarction reaching completion 3 days after the insult. One day after the insult, many degenerating cerebral neurons exhibited increased intracellular Zn(2+), and some labeled with the antibody against activated caspase-3. I.c.v. administration of the Zn(2+) chelator, EDTA saturated with equimolar Ca(2+) (CaEDTA), 15 min prior to ischemia attenuated subsequent Zn(2+) translocation into cortical neurons, and reduced infarct volume measured 3 days after ischemia. Although the protective effect of CaEDTA at this endpoint was substantial (about 70% infarct reduction), it was lost when insult severity was increased (from 30 to 60 min MCAO), or when infarct volume was measured at a much later time point (14 days instead of 3 days after ischemia). These data suggest that toxic Zn(2+) translocation, from presynaptic terminals to post-synaptic cell bodies, may accelerate the development of cerebral infarction following mild transient focal ischemia.

Myocardial ischemia induced by nebulized fenoterol for severe childhood asthma.

PubMed

Zanoni, L Z; Palhares, D B; Consolo, L C T

2005-10-01

We examined for myocardial ischemia induced by continuous inhalation of fenoterol in children with severe acute asthma. Thirty children with severe acute asthma were evaluated for signs of myocardial ischemia when treated with 0.5 mg kg dose (maximum 15 mg) of inhaled fenoterol for one hour. The heart rate was measured before and after inhalation. Cardiac enzymes (creatine kinase, creatine kinase MB fraction and troponin levels) were measured at admission and 12 hours later. An EKG was recorded before inhalation was started and immediately after its completion to detect the presence of any evidence of myocardial ischemia. All patients developed significant increase in heart rate. Six patients showed EKG changes compatible with myocardial ischemia, despite normal enzyme levels. Patients with severe acute asthma show tachycardia and may show EKG changes of myocardial ischemia.

Divergent systemic and local inflammatory response to hind limb demand ischemia in wild-type and ApoE-/- mice.

PubMed

Crawford, Robert S; Albadawi, Hassan; Robaldo, Alessandro; Peck, Michael A; Abularrage, Christopher J; Yoo, Hyung-Jin; Lamuraglia, Glenn M; Watkins, Michael T

2013-08-01

We designed studies to determine whether the ApoE-/- phenotype modulates the local skeletal muscle and systemic inflammatory (plasma) responses to lower extremity demand ischemia. The ApoE-/- phenotype is an experimental model for atherosclerosis in humans. Aged female ApoE-/- and C57BL6 mice underwent femoral artery ligation, then were divided into sedentary and demand ischemia (exercise) groups on day 14. We assessed baseline and postexercise limb perfusion and hind limb function. On day 14, animals in the demand ischemia group underwent daily treadmill exercise through day 28. Sedentary mice were not exercised. On day 28, we harvested plasma and skeletal muscle from ischemic limbs from sedentary and exercised mice. We assayed muscle for angiogenic and proinflammatory proteins, markers of skeletal muscle regeneration, and evidence of skeletal muscle fiber maturation. Hind limb ischemia was similar in ApoE-/- and C57 mice before the onset of exercise. Under sedentary conditions, plasma vascular endothelial cell growth factor and interleukin-6, but not keratinocyte chemoattractant factor (KC) or macrophage inflammatory protein-2 (MIP-2), were higher in ApoE (P < 0.0001). After exercise, plasma levels of vascular endothelial cell growth factor, KC, and MIP-2, but not IL-6, were lower in ApoE (P < 0.004). The cytokines KC and MIP-2 in muscle were greater in exercised ApoE-/- mice compared with C57BL6 mice (P = 0.01). Increased poly-ADP-ribose activity and mature muscle regeneration were associated with demand ischemia in the C57BL6 mice, compared with the ApoE-/- mice (P = 0.01). Demand limb ischemia in the ApoE-/- phenotype exacerbated the expression of select systemic cytokines in plasma and blunted indices of muscle regeneration. Copyright © 2013 Elsevier Inc. All rights reserved.

Effect of N(G)-nitro-L-arginine methyl ester on intestinal permeability following intestinal ischemia-reperfusion injury in a rat model.

PubMed

Luo, C C; Chen, H M; Chiu, C H; Lin, J N; Chen, J C

2001-07-01

Subclinical intestinal ischemia-reperfusion injury (IRI) causes an increase in mucosal permeability and may represent an early event in the pathogenesis of necrotizing enterocolitis in premature infants. Previous studies suggested that continuous, endogenous formation of nitric oxide (NO) maintains the mucosal integrity of the intestine, thus protecting the gut from injuries from blood-borne toxins and tissue-destructive mediators. This study was undertaken to assess whether the inhibition of NO production causes an increase in intestinal permeability in rats following IRI. Sprague-Dawley rats weighing 200-300 g were divided into 4 groups: (1) untreated group (normal control); (2) ischemia-reperfusion group; (3) early N(G)-nitro-L-arginine methyl ester (L-NAME), a specific inhibitor of NO production, treatment group, and (4) late L-NAME treatment group. Transient IRI was induced by 30-min occlusion, followed by reperfusion of the isolated ileal loop. The L-NAME was administered 15 min before and after mesenteric ischemia as a 25-mg/kg bolus. Fluorescein isothiocyanate-dextran (FITC-D) was used to quantitatively assess the alteration in mucosal permeability of the intestine. There was no significant increase in the portal vein FITC-D level among normal controls, ischemia-reperfusion group and late L-NAME-treated group, but there was an approximately 6-fold increase in the early L-NAME treatment group. The pathological features of the intestine following IRI include denudation of the villus epithelium and reduction of villus height, associated with marked inflammatory cell infiltration over the lamina propria. These results suggest that endogenous NO may play a role in the protecting intestinal integrity after IRI. Copyright 2001 S. Karger AG, Basel

Korean red ginseng protects against neuronal damage induced by transient focal ischemia in rats

PubMed Central

BAN, JU YEON; KANG, SUNG WOOK; LEE, JONG SEOK; CHUNG, JOO-HO; KO, YOUNG GWAN; CHOI, HAN SUNG

2012-01-01

In the present study, we investigated the neuroprotective effect of Korean red ginseng (KRG) following focal brain ischemia/reperfusion injury, in relation to its antioxidant activities. The middle cerebral artery occlusion/reperfusion (MCAO/R) model in rats was employed. The KRG extract (100 mg/kg, perorally) was administered once daily for 7 days following MCAO/R. The elevated levels of lipid peroxidation in the MCAO/R group were attenuated significantly in the KRG-administered group. The significantly depleted activity of the antioxidant enzymes glutathione peroxidase, superoxide dismutase and catalase was prevented in the KRG-administered group. In the neurobehavioral evaluation expressed as the modified neurological severity score and corner-turn test, the daily intake of KRG showed consistent and significant improvement in the neurological deficits for 7 days following MCAO/R injury. These results indicate that KRG has a neuroprotective effect against ischemia/reperfusion brain injury by reducing the level of lipid peroxidation and increasing the endogenous antioxidant enzymatic activity. PMID:22969953

LC-MS/MS profiling and neuroprotective effects of Mentat® against transient global ischemia and reperfusion-induced brain injury in rats.

PubMed

Viswanatha, Gollapalle Lakshminarayanashastry; Kumar, Lakkavalli Mohan Sharath; Rafiq, Mohamed; Kavya, Kethaganahalli Jayaramaiah; Thippeswamy, Agadi Hiremath; Yuvaraj, Huvvinamadu Chandrashekarappa; Azeemuddin, Mohammed; Anturlikar, Suryakanth Dattatreya; Patki, Pralhad Sadashiv; Babu, Uddagiri Venkanna; Ramakrishnan, Shyam

2015-01-01

The aim of this study was to evaluate the possible beneficial effects of Mentat against transient global ischemia and reperfusion-induced brain injury in rats. The neuroprotective effects of Mentat were evaluated against transient global ischemia and reperfusion (I/R)-induced brain injury in rats. Various neurobehavioral and biochemical parameters were assessed, followed by morphologic and histopathologic evaluation of brain tissue to conclude the protective effect of Mentat. Additionally, in vitro antioxidant assays were performed to explore the antioxidant capacity of Mentat and detailed liquid chromatography-mass spectrometry (LC-MS/MS) profiling was carried out to identify the active phytoconstituents responsible for the protective effects of Mentat. Sixty minutes of transient global ischemia followed by 24 h reperfusion (I/R) caused significant alterations in the cognitive and neurologic functions in the ischemia control group (P < 0.01) compared with the sham control. Furthermore, 2,3,5-triphenyltetrazolium chloride staining of the ischemia control group showed 20.85% ± 0.39% of cerebral infarct area (P < 0.01), increased brain volume (% edema 17.81% ± 1.576%; P < 0.01), and increased lipid peroxidation (P < 0.01) in the brain homogenate. Additionally, the histopathology of the ischemia control group showed severe brain injury compared with the sham control group. Interestingly, pretreatment with Mentat (250 and 500 mg/kg, p.o.) and quercetin (20 mg/kg, p.o.) for 7 d has alleviated all pathological changes observed due to I/R injury. Mentat also showed very good antioxidant activity in in vitro assays (2,2-diphenyl-l-picrylhydrazyl, ferric-reducing antioxidant power, and oxygen radical absorbance capacity assays). Furthermore, the detailed LC-MS/MS analysis of Mentat was performed and enclosed for identifying the actives responsible for its protective effects. These findings suggest that Mentat is a neuroprotective agent that may be a useful adjunct in the

Hyperbaric oxygen modalities are differentially effective in distinct brain ischemia models

PubMed Central

Ostrowski, Robert P.; Stępień, Katarzyna; Pucko, Emanuela; Matyja, Ewa

2016-01-01

The effectiveness and efficacy of hyperbaric oxygen (HBO) preconditioning and post-treatment modalities have been demonstrated in experimental models of ischemic cerebrovascular diseases, including global brain ischemia, transient focal and permanent focal cerebral ischemia, and experimental neonatal hypoxia-ischemia encephalopathy. In general, early and repetitive post-treatment of HBO appears to create enhanced protection against brain ischemia whereas delayed HBO treatment after transient focal ischemia may even aggravate brain injury. This review advocates the level of injury reduction upon HBO as an important component for translational evaluation of HBO based treatment modalities. The combined preconditioning and HBO post-treatment that would provide synergistic effects is also worth considering. PMID:27826422

Steatotic livers are susceptible to normothermic ischemia-reperfusion injury from mitochondrial Complex-I dysfunction

PubMed Central

Chu, Michael JJ; Premkumar, Rakesh; Hickey, Anthony JR; Jiang, Yannan; Delahunt, Brett; Phillips, Anthony RJ; Bartlett, Adam SJR

2016-01-01

AIM: To assess the effects of ischemic preconditioning (IPC, 10-min ischemia/10-min reperfusion) on steatotic liver mitochondrial function after normothermic ischemia-reperfusion injury (IRI). METHODS: Sixty male Sprague-Dawley rats were fed 8-wk with either control chow or high-fat/high-sucrose diet inducing > 60% mixed steatosis. Three groups (n = 10/group) for each dietary state were tested: (1) the IRI group underwent 60 min partial hepatic ischemia and 4 h reperfusion; (2) the IPC group underwent IPC prior to same standard IRI; and (3) sham underwent the same surgery without IRI or IPC. Hepatic mitochondrial function was analyzed by oxygraphs. Mitochondrial Complex-I, Complex-II enzyme activity, serum alanine aminotransferase (ALT), and histological injury were measured. RESULTS: Steatotic-IRI livers had a greater increase in ALT (2476 ± 166 vs 1457 ± 103 IU/L, P < 0.01) and histological injury following IRI compared to the lean liver group. Steatotic-IRI demonstrated lower Complex-I activity at baseline [78.4 ± 2.5 vs 116.4 ± 6.0 nmol/(min.mg protein), P < 0.001] and following IRI [28.0 ± 6.2 vs 104.3 ± 12.6 nmol/(min.mg protein), P < 0.001]. Steatotic-IRI also demonstrated impaired Complex-I function post-IRI compared to the lean liver IRI group. Complex-II activity was unaffected by hepatic steatosis or IRI. Lean liver mitochondrial function was unchanged following IRI. IPC normalized ALT and histological injury in steatotic livers but had no effect on overall steatotic liver mitochondrial function or individual mitochondrial complex enzyme activities. CONCLUSION: Warm IRI impairs steatotic liver Complex-I activity and function. The protective effects of IPC in steatotic livers may not be mediated through mitochondria. PMID:27217699

Influence of sildenafil and donepezil administration on the serum redox balance in experimentally induced lower limb critical ischemia.

PubMed

Constantinescu, Mihaela Ioana; Constantinescu, Dan Petru; Andercou, Aurel; Mironiuc, Ion Aurel

2013-01-01

Chronic lower limb ischemia (CLLI) leads to endothelial cell dysfunctions and endothelial lesions. The use of substances that release nitric oxide and activate endothelial nitric oxide synthase has proved to be useful in increasing angiogenesis and arteriogenesis under critical ischemia conditions. To investigate the therapeutic effect of Sildenafil and Donepezil with a vasodilating action in experimentally induced CLLI and on serum redox homeostasis. The research was performed in 3 groups of rats (n=10 animals/group) with experimentally induced CLLI: group I - control group; group II - animals treated postoperatively with a therapeutic dose of sildenafil, and group III - animals treated postoperatively with a therapeutic dose of donepezil. Oxidative stress (OS) indicators (malondialdehyde - MDA, protein carbonyls - PC), antioxidant (AO) defense indicators (reduced glutathione - GSH and oxidized glutathione - GSSH), and ceruloplasmin (CP) were determined on days 7, 14, 21 and 30. Statistical processing was performed using the Excel application (Microsoft Office 2007), with the StatsDirect v.2.7.2 software. Changes in OS were evidenced in all groups on account of a decrease in MDA and PC. The greatest OS decrease in all groups was on day 30. AO defence changes were represented by decreased levels of GSH and GSSG in all groups, at the studied moments. Intracellular AO defense in the cytosol, nucleus and mitochondria was similar in all groups, (decreased GSH, GSSG and GSH/GSSG ratio). We found increased extracellular levels of GSH, GSSG, and CP and increased extracellular GSH/GSSG ratio at level compared to values on day 7. 1) The administration of sildenafil (group II) and donepezil (group III) has favorable effects on reducing OS in experimentally induced CLLI. 2) Sildenafil and Donepezil administration stimulates extracellular AO defense on account of CP. 3) Sildenafil and Donepezil administration influences intracellular redox homeostasis on account of the GSH

Association between aortic valve calcification and myocardial ischemia, especially in asymptomatic patients.

PubMed

Yamazato, Ryo; Yamamoto, Hideya; Tadehara, Futoshi; Teragawa, Hiroki; Kurisu, Satoshi; Dohi, Yoshihiro; Ishibashi, Ken; Kunita, Eiji; Utsunomiya, Hiroto; Oka, Toshiharu; Kihara, Yasuki

2012-08-01

Aortic valve calcification (AVC) is recognized as a manifestation of systemic arteriosclerosis. However, it is unclear whether AVC is associated with myocardial ischemia. Stress myocardial perfusion SPECT (MPS) is widely used for the diagnosis of myocardial ischemia. However, routine MPS is not recommended, particularly in asymptomatic patients. Accordingly, we investigated the hypothesis that the presence of AVC is strongly associated with inducible myocardial ischemia, even among asymptomatic patients. We investigated 669 consecutive patients who underwent both adenosine stress (201)Tl MPS and echocardiography. We evaluated the extent and severity of myocardial ischemia by the summed difference score (SDS). We defined the presence of myocardial ischemia as SDS ≥ 3 and moderate to severe ischemia as SDS ≥ 8. We classified the severity of AVC according to the number of affected aortic leaflets. We also compared the mean SDS and the prevalence of SDS ≥ 3 and SDS ≥ 8 among patients stratified by the severity of AVC. The presence of AVC was significantly associated with myocardial ischemia (odds ratio [OR], 1.56; 95% confidence interval [CI], 1.10-2.23; P = 0.013) and moderate to severe ischemia (OR, 2.16; 95% CI, 1.26-3.80; P = 0.0061). In 311 asymptomatic patients, AVC was strongly associated with moderate to severe ischemia (OR, 4.31; 95% CI, 1.67-12.8; P = 0.0043). However, the SDS value and the prevalence of SDS ≥ 3 and SDS ≥ 8 did not increase with increasing number of affected aortic leaflets. The presence of AVC may be associated with the presence of myocardial ischemia, particularly in asymptomatic patients. However, we found no association between the extent of AVC and inducible myocardial ischemia. The presence of AVC may be a useful anatomic marker to help identify patients at high risk of myocardial ischemia, particularly asymptomatic patients.

Post-ischemic conditioning in the rat retina is dependent upon ischemia duration and is not additive with ischemic pre-conditioning.

PubMed

Dreixler, John C; Shaikh, Afzhal R; Alexander, Michael; Savoie, Brian; Roth, Steven

2010-12-01

determining the percentage of TUNEL-positive cells at 24 h after ischemia. Post-C attenuated apoptosis, but when combined with IPC, TUNEL was similar in the combined group to that of ischemia alone. We also examined the role of the recruitment of an inflammatory response in ischemia and Post-C. We found that inflammatory markers increased by ischemia were not altered by Post-C. We conclude that Post-C effectiveness depends upon the duration of ischemia; Post-C is not additive with IPC, and Post-C functions, in part, by preventing apoptotic damage to the inner retina. Post-C has considerable promise for clinical translation to eye diseases that cause blindness by ischemia. Copyright © 2010 Elsevier Ltd. All rights reserved.

Mesenchymal stem cells increase antioxidant capacity in intestinal ischemia/reperfusion damage.

PubMed

Inan, M; Bakar, E; Cerkezkayabekir, A; Sanal, F; Ulucam, E; Subaşı, C; Karaöz, E

2017-07-01

Mesenchymal stem cells (MSCs) may have beneficial effects in reversing intestinal damage resulting from circulatory disorders. The hypothesis of this study is that MSCs increase antioxidant capacity of small bowel tissue following intestinal ischemia reperfusion (I/R) damage. A total of 100 rats were used for the control group and three experimental groups, as follows: the sham control, local MSC, and systemic MSC groups. Each group consisted of 10 animals on days 1, 4, and 7 of the experiment. Ischemia was established by clamping the superior mesenteric artery (SMA) for 45min; following this, reperfusion was carried out for 1, 4, and 7days in all groups. In the local and systemic groups, MSCs were administered intravenously and locally just after the ischemia, and they were investigated after 1, 4, and 7days. The superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (Gpx) activities, as well as malondialdehyde (MDA) and total protein levels, were measured. Histopathological analysis was performed using light and electron microscopy. The indicators of proliferation from the effects of anti- and pro-inflammatory cytokines were evaluated using immunohistochemistry. MDA was increased (P<0.05) in the sham control group and decreased (P<0.05) in the MSC groups. SOD, CAT, and Gpx were decreased in the local MSC group (P<0.05). The highest level of amelioration was observed on day 7 in the local MSC group via light and electron microscopy. It was found that the MSCs arrived at the damaged intestinal wall in the MSC groups immediately after injection. Pro-inflammatory cytokines interleukin-1β (IL1β), transforming growth factor-β1 (TGFβ1), tumor necrosis factor-α (TNFα), IL6, MIP2, and MPO decreased (P<0.05), while anti-inflammatory cytokines EP3 and IL1ra increased (p<0.05) in the local and systemic MSC groups. In addition, proliferation indicators, such as PCNA and KI67, increased (P<0.05) in the local and systemic MSC groups. Parallel to our

Minocycline Effectively Protects the Rabbit's Spinal Cord From Aortic Occlusion-Related Ischemia.

PubMed

Drenger, Benjamin; Fellig, Yakov; Ben-David, Dror; Mintz, Bella; Idrees, Suhel; Or, Omer; Kaplan, Leon; Ginosar, Yehuda; Barzilay, Yair

2016-04-01

To identify the minocycline anti-inflammatory and antiapoptotic mechanisms through which it is believed to exert spinal cord protection during aortic occlusion in the rabbit model. An animal model of aortic occlusion-related spinal cord ischemia. Randomized study with a control group and pre-ischemia and post-ischemia escalating doses of minocycline to high-dose minocycline in the presence of either hyperglycemia, a pro-apoptotic maneuver, or wortmannin, a specific phosphatidylinositol 3-kinase antagonist. Tertiary medical center and school of medicine laboratory. Laboratory animals-rabbits. Balloon obstruction of infrarenal aorta introduced via femoral artery incision. Severe hindlimb paralysis (mean Tarlov score 0.36±0.81 out of 3) was observed in all the control group animals (9 of 11 with paraplegia and 2 of 11 with paraparesis) compared with 11 of 12 neurologically intact animals (mean Tarlov score 2.58±0.90 [p = 0.001 compared with control]) in the high-dose minocycline group. This protective effect was observed partially during a state of hyperglycemia and was completely abrogated by wortmannin. Minocycline administration resulted in higher neurologic scores (p = 0.003) and a shift to viable neurons and more apoptotic-stained nuclei resulting from reduced necrosis (p = 0.001). In a rabbit model of infrarenal aortic occlusion, minocycline effectively reduced paraplegia by increasing the number of viable neurons in a dose-dependent manner. Its action was completely abrogated by inhibiting the phosphatidylinositol 3-kinase pathway and was inhibited partially by the pro-apoptotic hyperglycemia maneuver, indicating that the activation of cell salvage pathways and mitochondrial sites are possible targets of minocycline action in an ischemic spinal cord. Copyright © 2016. Published by Elsevier Inc.

Does the intrathecal propofol have a neuroprotective effect on spinal cord ischemia?

PubMed

Sahin, Murat; Gullu, Huriye; Peker, Kemal; Sayar, Ilyas; Binici, Orhan; Yildiz, Huseyin

2015-11-01

The neuroprotective effects of propofol have been confirmed. However, it remains unclear whether intrathecal administration of propofol exhibits neuroprotective effects on spinal cord ischemia. At 1 hour prior to spinal cord ischemia, propofol (100 and 300 µg) was intrathecally administered in rats with spinal cord ischemia. Propofol pre-treatment greatly improved rat pathological changes and neurological function deficits at 24 hours after spinal cord ischemia. These results suggest that intrathecal administration of propofol exhibits neuroprotective effects on spinal cord structural and functional damage caused by ischemia.

Vitexin exerts cardioprotective effect on chronic myocardial ischemia/reperfusion injury in rats via inhibiting myocardial apoptosis and lipid peroxidation.

PubMed

Che, Xia; Wang, Xin; Zhang, Junyan; Peng, Chengfeng; Zhen, Yilan; Shao, Xu; Zhang, Gongliang; Dong, Liuyi

2016-01-01

The aim of this study was to explore the cardioprotective effect of vitexin on chronic myocardial ischemia/reperfusion injury in rats and potential mechanisms. A chronic myocardial ischemia/reperfusion injury model was established by ligating left anterior descending coronary for 60 minutes, and followed by reperfusion for 14 days. After 2 weeks ischemia/reperfusion, cardiac function was measured to assess myocardial injury. The level of ST segment was recorded in different periods by electrocardiograph. The change of left ventricular function and myocardial reaction degree of fibrosis of heart was investigated by hematoxylin and eosin (HE) staining and Sirius red staining. Endothelium-dependent relaxations due to acetylcholine were observed in isolated rat thoracic aortic ring preparation. The blood samples were collected to measure the levels of MDA, the activities of SOD and NADPH in serum. Epac1, Rap1, Bax and Bcl-2 were examined by using Western Blotting. Vitexin exerted significant protective effect on chronic myocardial ischemia/reperfusion injury, improved obviously left ventricular diastolic function and reduced myocardial reactive fibrosis degree in rats of myocardial ischemia. Medium and high-dose vitexin groups presented a significant decrease in Bax, Epac1 and Rap1 production and increase in Bcl-2 compared to the I/R group. It may be related to preventing myocardial cells from apoptosis, improving myocardial diastolic function and inhibiting lipid peroxidation. Vitexin is a cardioprotective herb, which may be a promising useful complementary and alternative medicine for patients with coronary heart disease.

Zero ischemia anatomical partial nephrectomy: a novel approach.

PubMed

Gill, Inderbir S; Patil, Mukul B; Abreu, Andre Luis de Castro; Ng, Casey; Cai, Jie; Berger, Andre; Eisenberg, Manuel S; Nakamoto, Masahiko; Ukimura, Osamu; Goh, Alvin C; Thangathurai, Duraiyah; Aron, Monish; Desai, Mihir M

2012-03-01

We present a novel concept of zero ischemia anatomical robotic and laparoscopic partial nephrectomy. Our technique primarily involves anatomical vascular microdissection and preemptive control of tumor specific, tertiary or higher order renal arterial branch(es) using neurosurgical aneurysm micro-bulldog clamps. In 58 consecutive patients the majority (70%) had anatomically complex tumors including central (67%), hilar (26%), completely intrarenal (23%), pT1b (18%) and solitary kidney (7%). Data were prospectively collected and analyzed from an institutional review board approved database. Of 58 cases undergoing zero ischemia robotic (15) or laparoscopic (43) partial nephrectomy, 57 (98%) were completed without hilar clamping. Mean tumor size was 3.2 cm, mean ± SD R.E.N.A.L. score 7.0 ± 1.9, C-index 2.9 ± 2.4, operative time 4.4 hours, blood loss 206 cc and hospital stay 3.9 days. There were no intraoperative complications. Postoperative complications (22.8%) were low grade (Clavien grade 1 to 2) in 19.3% and high grade (Clavien grade 3 to 5) in 3.5%. All patients had negative cancer surgical margins (100%). Mean absolute and percent change in preoperative vs 4-month postoperative serum creatinine (0.2 mg/dl, 18%), estimated glomerular filtration rate (-11.4 ml/minute/1.73 m(2), 13%), and ipsilateral kidney function on radionuclide scanning at 6 months (-10%) correlated with mean percent kidney excised intraoperatively (18%). Although 21% of patients received a perioperative blood transfusion, no patient had acute or delayed renal hemorrhage, or lost a kidney. The concept of zero ischemia robotic and laparoscopic partial nephrectomy is presented. This anatomical vascular microdissection of the artery first and then tumor allows even complex tumors to be excised without hilar clamping. Global surgical renal ischemia is unnecessary for the majority of patients undergoing robotic and laparoscopic partial nephrectomy at our institution. Copyright © 2012 American

Inhibition of apoptosis by the intrinsic but not the extrinsic apoptotic pathway in myocardial ischemia-reperfusion.

PubMed

Kristen, Arnt V; Ackermann, Katrin; Buss, Sebastian; Lehmann, Lorenz; Schnabel, Philipp A; Haunstetter, Armin; Katus, Hugo A; Hardt, Stefan E

2013-01-01

The detailed molecular mechanisms following activation of apoptosis in ischemia-reperfusion injury are unknown. This study using different transgenic mouse models provided first evidence that apoptosis in myocardial ischemia-reperfusion injury is rather linked to the mitochondrial pathway than to death receptor pathway. There is a wealth of evidence for activation of apoptosis in ischemia-reperfusion injury. However, the understanding of detailed molecular mechanism is lacking. The extent of myocardial infarction after ligation of the left anterior descending artery in mice carrying different transgenes for inhibition of either the intrinsic or the extrinsic or a combination of both apoptotic cascades was evaluated. The extent of myocardial damage was assessed by echocardiographic determination of left ventricular (LV) ejection fraction, LV hemodynamics, troponin T, and histology. The rate of apoptosis was analyzed by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) and caspase-3 staining. Highest perioperative rate of death was observed in the dominant-negative form of a truncated Fas-associated death domain (FADD-DN) group. Infarction size by 2,3,5-triphenyltetrazolium chloride (TTC) staining was smaller in the Bcl-2, but not in the other groups as compared to wild-type mice. This was accompanied by lower troponin T values in Bcl-2 transgenic mice as compared to the all other groups. Troponin T correlated well with macroscopic extent of myocardial infarction by TTC staining. A lower decline of LV ejection fraction was seen in the Bcl-2 as compared to wild-type or FADD-DN mice. A smaller number of TUNEL- and caspase-3-positive myocyte nuclei were observed in the Bcl-2 and FADD-DN group as compared to wild-type mice. We provide first evidence for protective effects on the myocardium in a transgenic mouse model of myocardial ischemia-reperfusion due to inhibition of the Bcl-2, but not the FADD pathway despite that reduced apoptotic cells were

Effect on intensity of treadmill running on learning, memory and expressions of cell cycle-related proteins in rats with cerebral ischemia.

PubMed

Zhao, Ya-Ning; Li, Jian-Min; Chen, Chang-Xiang; Li, Shu-Xing; Xue, Cheng-Jing

2017-06-20

We discussed the intensity of treadmill running on learning, memory and expression of cell cycle-related proteins in rats with cerebral ischemia. Eighty healthy male SD rats were randomly divided into normal group, model group, intensity I group and intensity II group, with 20 rats in each group. The four-vessel occlusion method of Pulsinelli (4-VO) was used to induce global cerebral ischemia. Brain neuronal morphology was observed by hematoxylin-eosin (HE) staining at 3h, 6h, 24h and 48h after modeling, respectively. Hippocampal expressions of cyclin A and cyclin E were detected by immunohistochemistry. At 48h after modeling, the learning and memory performance of rats was tested by water maze experiment. Compared with the normal group, the other three groups had a significant reduction in surviving neurons, prolonging of escape latency and decreased number of passes over the former position of the platform (P<0.05). The number of surviving neurons and the number of passes over the former position of the platform were obviously lower in the model group than in intensity I group (P<0.05), but significantly higher compared with intensity II group (P<0.05). Escape latency of the model group was obviously prolonged as compared with intensity I group (P<0.05), but much shorter than that of intensity II group (P<0.05). Compared with the normal group, the expressions of cyclin A and cyclin E were significantly upregulated at different time points after modeling (P<0.05). The expression of the model group was higher than that of intensity I group, but lower than that of intensity II group (P<0.05). Moderate intensity of treadmill running can help protect brain neurons and improve learning and memory performance of rats with global cerebral ischemia. But high intensity of treadmill running has a negative impact, possibly through the regulation of cell cycle-related proteins in ischemia/reperfusion injury.

Blood-brain barrier transport of an essential amino acid after cerebral ischemia reperfusion injury.

PubMed

Suzuki, Toyofumi; Miyazaki, Yumiko; Ohmuro, Aya; Watanabe, Masaki; Furuishi, Takayuki; Fukami, Toshiro; Tomono, Kazuo

2013-01-01

Under pathophysiological conditions such as -cerebral ischemia-reperfusion (IR), damage to cerebrovascular endothelial cells causes alterations in the blood-brain barrier (BBB) function that can exacerbate neuronal cell injury and death. Clarifying changes in BBB transport in the early period of IR is important for understanding BBB function during therapy after cerebral ischemia. The present study was aimed at clarifying changes during IR in the BBB transport of L-phenylalanine (Phe) as a substrate of L-type amino acid transporter 1. An IR model was produced in mice by blood recirculation following occlusion of the middle cerebral artery. Permeability of the BBB to [(3)H]Phe was measured after IR injury using the brain perfusion method. Confocal microscopy of the IR injury showed no brain penetration of fluorescent tracer, thus confirming BBB integrity during 45 min of ischemia. Tight junction opening was not observed at 30 min after reperfusion following ischemia for 45 min. At the time of IR, [(3)H]Phe uptake into the brain appeared saturated. The Michaelis constant and maximum transport velocity in the IR group was reduced by 22 % compared with those in controls. These results suggest that the intrinsic transport clearance of Phe is slightly decreased in the early phase of IR.

[Application of locomotor activity test to evaluate functional injury after global cerebral ischemia in C57BL/6 mice].

PubMed

Zhang, Li-quan; Xu, Jia-ni; Wang, Zhen-zhen; Zeng, Li-jun; Ye, Yi-lu; Zhang, Wei-ping; Wei, Er-qing; Zhang, Qi

2014-05-01

To evaluate the application of locomotor activity test in functional injury after global cerebral ischemia (GCI) in C57BL/6 mice. GCI was induced by bilateral carotid arteries occlusion for 30 min in C57BL/6 mice. Mice were divided into sham group, GCI group and minocycline group. Saline or minocycline (45 mg/kg) was i.p. injected once daily for 6 d after ischemia. At Day 6 after ischemia, locomotor activity was recorded for 1 h in open field test. Total distance, central distance, central distance ratio, periphery distance, periphery distance ratio, central time and periphery time were used to evaluate the behavior characteristics of locomotor activity in C57BL/6 mice after ischemia. The survival neuron density was detected by Nissl staining in hippocampus, cortex and striatum. Compared with sham group, total distance, central distance and central time increased and periphery time decreased in C57BL/6 mice after GCI (Ps<0.05). However, minocycline significantly reduced the central distance and central time and increased the periphery time (Ps<0.05). Neurons were damaged in hippocampus, cortex and striatum after GCI, which manifested by decreased neurons and the most serious damage in hippocampal CA1 region. Minocycline significantly improved the neuron appearance and increased the neuron number in hippocampus and striatum (P<0.001 or P<0.05). Locomotor activity in open field test can objectively evaluate the behavior injury after GCI in mice. Central distance and central time can be used as indexes of quantitative assessment.

Temporal relationship of serum markers and tissue damage during acute intestinal ischemia/reperfusion

PubMed Central

la Garza, Francisco Javier Guzmán-de; Ibarra-Hernández, Juan Manuel; Cordero-Pérez, Paula; Villegas-Quintero, Pablo; Villarreal-Ovalle, Claudia Ivette; Torres-González, Liliana; Oliva-Sosa, Norma Edith; Alarcón-Galván, Gabriela; Fernández-Garza, Nancy Esthela; Muñoz-Espinosa, Linda Elsa; Cámara-Lemarroy, Carlos Rodrigo; Carrillo-Arriaga, José Gerardo

2013-01-01

OBJECTIVE: It is essential to identify a serological marker of injury in order to study the pathophysiology of intestinal ischemia reperfusion. In this work, we studied the evolution of several serological markers after intestinal ischemia reperfusion injury in rats. The markers of non-specific cell damage were aspartate aminotransferase, alanine aminotransaminase, and lactic dehydrogenase, the markers of inflammation were tumor necrosis factor alpha, interleukin-6, and interleukin-1 beta, and the markers of intestinal mucosal damage were intestinal fatty acid binding protein and D-lactate. We used Chiús classification to grade the histopathological damage. METHODS: We studied 35 Wistar rats divided into groups according to reperfusion time. The superior mesenteric artery was clamped for 30 minutes, and blood and biopsies were collected at 1, 3, 6, 12, 24, and 48 hours after reperfusion. We plotted the mean ± standard deviation and compared the baseline and maximum values for each marker using Student's t-test. RESULTS: The maximum values of interleukin-1 beta and lactic dehydrogenase were present before the maximal histopathological damage. The maximum tumor necrosis factor alpha and D-lactate expressions coincided with histopathological damage. Alanine aminotransaminase and aspartate aminotransferase had a maximum expression level that increased following the histopathological damage. The maximum expressions of interluken-6 and intestinal fatty acid binding protein were not significantly different from the Sham treated group. CONCLUSION: For the evaluation of injury secondary to acute intestinal ischemia reperfusion with a 30 minute ischemia period, we recommend performing histopathological grading, quantification of D-lactate, which is synthesized by intestinal bacteria and is considered an indicator of mucosal injury, and quantification of tumor necrosis factor alpha as indicators of acute inflammation three hours after reperfusion. PMID:23917671

[Effects of BNP preconditioning on myocardial cell apoptosis and expressions of bcl-2 and Bax during myocardial ischemia-reperfusion injury in rats].

PubMed

Deng, Yu-Jun; Tan, Ning; Zeng, Hong-Ke; Fu, Yong-Heng; Dong, Xiao-Li

2010-12-28

To study the effects of B-type natriuretic peptide (BNP) preconditioning on the apoptosis and expressions of Bcl-2 and Bax in rat cardiomyocytes during myocardial ischemia-reperfusion. Twenty-one male Sprague-Dawley rats weighing (250 ± 50) g were randomly divided into 3 groups of sham operation (SHAM), ischemia-reperfusion (I/R) and B-type natriuretic peptide (BNP). A rat model of in vivo myocardial ischemia-reperfusion injury was established by ligating the left anterior descending coronary artery for 35 minutes and then reperfusing for 240 minutes. The apoptosis of myocardial cell was determined by terminal deoxynucleotidyl transferase mediated dUTP-biotin nick end-labeling (TUNEL) method. Real-time polymerase chain reaction and Western blot were used to detect the expression changes of Bcl-2 and Bax in rat ischemia myocardium. The apoptotic indices of SHAM, BNP and I/R groups were 5.4% ± 4.2%, 22.5% ± 9.5% and 45.2% ± 13.0% respectively (P < 0.05). The Bcl-2 protein expression of SHAM, BNP and I/R groups were 0.87 ± 0.09, 0.70 ± 0.07 and 0.38 ± 0.09 respectively (P < 0.05). The Bax protein expression of SHAM, BNP and I/R groups were 0.08 ± 0.04, 0.39 ± 0.09 and 0.71 ± 0.18 respectively (P < 0.01). The Bcl-2/Bax mRNA ratio of SHAN, BNP and I/R groups were 0.763 ± 0.154, 0.099 ± 0.025 and 0.022 ± 0.024 respectively (P < 0.05). The BNP preconditioning can decrease the myocardial apoptosis induced by ischemia-reperfusion injury. The mechanisms may be associated with an elevated expression of Bcl-2, an increased ratio of Bcl-2/Bax and a lowered expression of Bax.

Effects of cyclooxygenase inhibition on cardiovascular function in a hypercholesterolemic swine model of chronic ischemia

PubMed Central

Chu, Louis M.; Robich, Michael P.; Bianchi, Cesario; Feng, Jun; Liu, Yuhong; Xu, Shu-Hua; Burgess, Thomas

2012-01-01

The cardiovascular effects of cyclooxygenase (COX) inhibition remain controversial, especially in the setting of cardiovascular comorbidities. We examined the effects of nonselective and selective COX inhibition on cardiovascular function in a hypercholesterolemic swine model of chronic ischemia. Twenty-four intact male Yorkshire swine underwent left circumflex ameroid constrictor placement and were subsequently given either no drug (HCC; n = 8), a nonselective COX inhibitor (440 mg/day naproxen; HCNS; n = 8), or a selective COX-2 inhibitor (200 mg/day celecoxib; HCCX; n = 8). After 7 wk, myocardial functional was measured and myocardium from the nonischemic ventricle and ischemic area-at-risk (AAR) were analyzed. Regional function as measured by segmental shortening was improved in the AAR of HCCX compared with HCC. There was no significant difference in perfusion to the nonischemic ventricle between groups, but myocardial perfusion in the AAR was significantly improved in the HCCX group compared with controls at rest and during pacing. Endothelium-dependent microvessel relaxation was diminished by ischemia in HCC animals, but both naproxen and celecoxib improved vessel relaxation in the AAR compared with controls, and also decreased the vasoconstrictive response to serotonin. Thromboxane levels in the AAR were decreased in both HCNS and HCCX compared with HCC, whereas prostacyclin levels were decreased only in HCNS, corresponding to a decrease in prostacyclin synthase expression. Chronic ischemia increased apoptosis in Troponin T negative cells and intramyocardial fibrosis, both of which were reduced by celecoxib administration in the AAR. Capillary density was decreased in both the HCNS and HCCX groups. Protein oxidative stress was decreased in both HCNS and HCCX, whereas lipid oxidative stress was decreased only in the HCCX group. Thus nonselective and especially selective COX inhibition may have beneficial myocardial effects in the setting of

Effects of cyclooxygenase inhibition on cardiovascular function in a hypercholesterolemic swine model of chronic ischemia.

PubMed

Chu, Louis M; Robich, Michael P; Bianchi, Cesario; Feng, Jun; Liu, Yuhong; Xu, Shu-Hua; Burgess, Thomas; Sellke, Frank W

2012-01-01

The cardiovascular effects of cyclooxygenase (COX) inhibition remain controversial, especially in the setting of cardiovascular comorbidities. We examined the effects of nonselective and selective COX inhibition on cardiovascular function in a hypercholesterolemic swine model of chronic ischemia. Twenty-four intact male Yorkshire swine underwent left circumflex ameroid constrictor placement and were subsequently given either no drug (HCC; n = 8), a nonselective COX inhibitor (440 mg/day naproxen; HCNS; n = 8), or a selective COX-2 inhibitor (200 mg/day celecoxib; HCCX; n = 8). After 7 wk, myocardial functional was measured and myocardium from the nonischemic ventricle and ischemic area-at-risk (AAR) were analyzed. Regional function as measured by segmental shortening was improved in the AAR of HCCX compared with HCC. There was no significant difference in perfusion to the nonischemic ventricle between groups, but myocardial perfusion in the AAR was significantly improved in the HCCX group compared with controls at rest and during pacing. Endothelium-dependent microvessel relaxation was diminished by ischemia in HCC animals, but both naproxen and celecoxib improved vessel relaxation in the AAR compared with controls, and also decreased the vasoconstrictive response to serotonin. Thromboxane levels in the AAR were decreased in both HCNS and HCCX compared with HCC, whereas prostacyclin levels were decreased only in HCNS, corresponding to a decrease in prostacyclin synthase expression. Chronic ischemia increased apoptosis in Troponin T negative cells and intramyocardial fibrosis, both of which were reduced by celecoxib administration in the AAR. Capillary density was decreased in both the HCNS and HCCX groups. Protein oxidative stress was decreased in both HCNS and HCCX, whereas lipid oxidative stress was decreased only in the HCCX group. Thus nonselective and especially selective COX inhibition may have beneficial myocardial effects in the setting of

Mechanism underlying impaired cardiac pacemaking rhythm during ischemia: A simulation study

NASA Astrophysics Data System (ADS)

Bai, Xiangyun; Wang, Kuanquan; Yuan, Yongfeng; Li, Qince; Dobrzynski, Halina; Boyett, Mark R.; Hancox, Jules C.; Zhang, Henggui

2017-09-01

Ischemia in the heart impairs function of the cardiac pacemaker, the sinoatrial node (SAN). However, the ionic mechanisms underlying the ischemia-induced dysfunction of the SAN remain elusive. In order to investigate the ionic mechanisms by which ischemia causes SAN dysfunction, action potential models of rabbit SAN and atrial cells were modified to incorporate extant experimental data of ischemia-induced changes to membrane ion channels and intracellular ion homeostasis. The cell models were incorporated into an anatomically detailed 2D model of the intact SAN-atrium. Using the multi-scale models, the functional impact of ischemia-induced electrical alterations on cardiac pacemaking action potentials (APs) and their conduction was investigated. The effects of vagal tone activity on the regulation of cardiac pacemaker activity in control and ischemic conditions were also investigated. The simulation results showed that at the cellular level ischemia slowed the SAN pacemaking rate, which was mainly attributable to the altered Na+-Ca2+ exchange current and the ATP-sensitive potassium current. In the 2D SAN-atrium tissue model, ischemia slowed down both the pacemaking rate and the conduction velocity of APs into the surrounding atrial tissue. Simulated vagal nerve activity, including the actions of acetylcholine in the model, amplified the effects of ischemia, leading to possible SAN arrest and/or conduction exit block, which are major features of the sick sinus syndrome. In conclusion, this study provides novel insights into understanding the mechanisms by which ischemia alters SAN function, identifying specific conductances as contributors to bradycardia and conduction block.

Effect of Mailuoning injection on 8-iso-prostaglandin F2 alpha and superoxide dismutase in rabbits with extremity ischemia-reperfusion injury.

PubMed

Wang, Dai-Jun; Tian, Hua

2014-12-01

To date, there are no effective treatments for extremity ischemia-reperfusion (IR) injury. The objective of the present study was to explore the protective effect of Mailuoning on IR injury by investigating the plasma levels of 8-iso-prostaglandin F2 alpha (8-iso-PGF2α) and the activity of superoxide dismutase (SOD) in rabbits. The experimental models of posterior limb IR injury were established in thirty rabbits that were divided into three groups: the sham, IR, and IR + Mailuoning groups. At the end of ischemia, Mailuoning was injected intravenously into the rabbits in the IR + Mailuoning group, and normal saline solution was administered to the rabbits in the sham and IR groups. Venous blood samples were collected to measure the levels of 8-iso-PGF2α and the activity of SOD in the plasma at the following time points: at the onset of ischemia, the end of ischemia, and 2, 4, 8, 12, and 24 h after reperfusion. The skeletal muscles were harvested to examine the ultrastructure. The levels of 8-iso-PGF2α increased significantly and SOD activity decreased in the IR group at every time point after reperfusion (P <0.01 or P <0.05). In contrast, the levels of 8-iso-PGF2α and SOD activity were not significantly different after reperfusion in the IR + Mailuoning group (P >0.05) but were significantly different compared with the IR group (P <0.01). Using electron microscopy, the skeletal muscle injury was shown to be milder in the IR+ Mailuoning group after reperfusion compared with the IR group. The Mailuoning is capable of decreasing the excessive production of 8-iso-PGF2α and protecting SOD activity, thereby exhibiting a protective effect on extremity IR injury. Copyright © 2014 Elsevier Inc. All rights reserved.

Does the intrathecal propofol have a neuroprotective effect on spinal cord ischemia?

PubMed Central

Sahin, Murat; Gullu, Huriye; Peker, Kemal; Sayar, Ilyas; Binici, Orhan; Yildiz, Huseyin

2015-01-01

The neuroprotective effects of propofol have been confirmed. However, it remains unclear whether intrathecal administration of propofol exhibits neuroprotective effects on spinal cord ischemia. At 1 hour prior to spinal cord ischemia, propofol (100 and 300 µg) was intrathecally administered in rats with spinal cord ischemia. Propofol pre-treatment greatly improved rat pathological changes and neurological function deficits at 24 hours after spinal cord ischemia. These results suggest that intrathecal administration of propofol exhibits neuroprotective effects on spinal cord structural and functional damage caused by ischemia. PMID:26807119

Livers from fasted rats acquire resistance to warm and cold ischemia injury.

PubMed

Sumimoto, R; Southard, J H; Belzer, F O

1993-04-01

Successful liver transplantation is dependent upon many factors, one of which is the quality of the donor organ. Previous studies have suggested that the donor nutritional status may affect the outcome of liver transplantation and starvation, due to prolonged stay in the intensive care unit, may adversely affect the liver. In this study we have used the orthotopic rat liver transplant model to measure how fasting the donor affects the outcome of liver transplantation. Rat livers were preserved with UW solution either at 37 degrees C (warm ischemia for 45-60 min) or at 4 degrees C (cold ischemia for 30 or 44 hr). After preservation the livers were orthotopically transplanted and survival (for 7 days) was measured, as well as liver functions 6 hr after transplantation. After 45 min of warm ischemia 50% (3 of 6) animals survived when the liver was obtained from a fed donor about 80% (4 of 5) survived when the liver was obtained from a three-day-fasted donor. After 60 min warm ischemia no animal survived (0 of 8, fed group). However, if the donor was fasted for 3 days 89% (8 of 9) of the animals survived for 7 days. Livers cold-stored for 30 hr were 50% viable (3 of 6) and fasting for 1-3 days did not affect this outcome. However, if the donor was fasted for 4 days 100% (9 of 9) survival was obtained. After 44-hr preservation only 29% (2/7) of the recipients survived for 7 days. If the donor was fasted for 4 days, survival increased to 83% (5/6). Liver functions, bile production, and serum enzymes were better in livers from the fasted rats than from the fed rats. Fasting caused a 95% decrease in liver glycogen content. Even with this low concentration of glycogen, liver viability (animal survival) after warm or cold ischemia was not affected, and livers with a low glycogen content were fully viable. Thus liver glycogen does not appear to be important in liver preservation. This study shows that fasting the donor does not cause injury to the liver after warm or cold

Anticerebral Ischemia-Reperfusion Injury Activity of Synthesized Puerarin Derivatives

PubMed Central

Ji, Yubin; Yan, Xinjia

2016-01-01

When cerebral ischemia-reperfusion injury happened in patients, multiple pathological processes occur, such as leukocyte infiltration, platelet, and complement activation, which would result in cognitive dysfunction and inflammation. Puerarin has shown protective effect on injury of neural cell. In order to enhance this protective effect of puerarin, puerarin derivatives with different log⁡P values were designed and synthesized. The original phenolic hydroxyl in the puerarin molecules was substituted in order to change the blood-brain barrier permeability and thus enhance the efficacy for preventing cerebral ischemia/reperfusion injury. And the structure of the newly synthesized molecules was confirmed by 1H NMR spectroscopy and mass spectrometry. The mouse model of cerebral artery ischemia/reperfusion injury was established to test the anticerebral ischemia-reperfusion injury activity of the puerarin derivatives. The assays of the water maze, Y maze, brain cortex Ca2+-Mg2+-ATP enzyme, and iNOS enzyme activity were performed in this mouse model. The results showed that puerarin derivative P1-EA and P2-EA were resulting in an increased lipophilicity that enabled the derivatives to pass more efficiently through the blood-brain barrier, thus, improving the protective effects against cerebral ischemia/reperfusion injury. Therefore, derivatives of puerarin may serve as promising approach to improve neuron function in ischemia-reperfusion brain injury-related disorders. PMID:27807543

Vinpocetine modulates metabolic activity and function during retinal ischemia.

PubMed

Nivison-Smith, Lisa; O'Brien, Brendan J; Truong, Mai; Guo, Cindy X; Kalloniatis, Michael; Acosta, Monica L

2015-05-01

Vinpocetine protects against a range of degenerative conditions and insults of the central nervous system via multiple modes of action. Little is known, however, of its effects on metabolism. This may be highly relevant, as vinpocetine is highly protective against ischemia, a process that inhibits normal metabolic function. This study uses the ischemic retina as a model to characterize vinpocetine's effects on metabolism. Vinpocetine reduced the metabolic demand of the retina following ex vivo hypoxia and ischemia to normal levels based on lactate dehydrogenase activity. Vinpocetine delivered similar effects in an in vivo model of retinal ischemia-reperfusion, possibly through increasing glucose availability. Vinpocetine's effects on glucose also appeared to improve glutamate homeostasis in ischemic Müller cells. Other actions of vinpocetine following ischemia-reperfusion, such as reduced cell death and improved retinal function, were possibly a combination of the drug's actions on metabolism and other retinal pathways. Vinpocetine's metabolic effects appeared independent of its other known actions in ischemia, as it recovered retinal function in a separate metabolic model where the glutamate-to-glutamine metabolic pathway was inhibited in Müller cells. The results of this study indicate that vinpocetine mediates ischemic damage partly through altered metabolism and has potential beneficial effects as a treatment for ischemia of neuronal tissues. Copyright © 2015 the American Physiological Society.

Postsynaptic density protein (PSD)-95 expression is markedly decreased in the hippocampal CA1 region after experimental ischemia-reperfusion injury.

PubMed

Yan, Bing Chun; Park, Joon Ha; Ahn, Ji Hyeon; Lee, Jae-Chul; Won, Moo-Ho; Kang, Il-Jun

2013-07-15

Synaptic plasticity is important for functional recovery after cerebral ischemic injury. In the present study, we investigated chronological change in the immunoreactivity of PSD-95, a kind of postsynaptic density protein, in the hippocampus proper (CA1-3 regions) after 5 min of transient cerebral ischemia in gerbils. PSD-95 immunoreactivity was observed in MAP-2-immunoreactive dendrites in the CA1-3 regions of the sham group. The PSD-95 immunoreactivity was shown as beaded structure in the MAP-2-immunoreactive dendrites. However, PSD-95 immunoreactivity began to be dramatically decreased in MAP-2-immunoreactive dendrites in the CA1 region, not CA2-3 region, at early time after ischemia-reperfusion. At 5 days after ischemia-reperfusion, MAP-2 immunoreactivity almost disappeared in the ischemic CA1 region, and PSD-95 immunoreactivity was much lower than that in the sham group. In brief, PSD-95 immunoreactivity in the CA1 dendrites was markedly decreased at early time after ischemia-reperfusion. We suggest that decreased PSD-95 immunoreactivity in the ischemic CA1 region may lead to a deficit of postsynaptic plasticity in the brain. Copyright © 2013 Elsevier B.V. All rights reserved.

Zinc mitigates renal ischemia-reperfusion injury in rats by modulating oxidative stress, endoplasmic reticulum stress, and autophagy.

PubMed

Hadj Abdallah, Najet; Baulies, Anna; Bouhlel, Ahlem; Bejaoui, Mohamed; Zaouali, Mohamed A; Ben Mimouna, Safa; Messaoudi, Imed; Fernandez-Checa, José C; García Ruiz, Carmen; Ben Abdennebi, Hassen

2018-05-15

Oxidative stress is a major factor involved in the pathogenesis of renal ischemia/reperfusion (I/R). Exogenous zinc (Zn) was suggested as a potent antioxidant; however, the mechanism by which it strengthens the organ resistance against the effects of reactive oxygen species (ROS) is not yet investigated. The present study aims to determine whether acute zinc chloride (ZnCl 2 ) administration could attenuate endoplasmic reticulum (ER) stress, autophagy, and inflammation after renal I/R. Rats were subjected to either sham operation (Sham group, n = 6), or 1 hr of bilateral ischemia followed by 2 hr of reperfusion (I/R groups, n = 6), or they received ZnCl 2 orally 24 hr and 30 min before ischemia (ZnCl 2 group, n = 6). Rats were subjected to 1 hr of bilateral renal ischemia followed by 2 hr of reperfusion (I/R group, n = 6). Our results showed that ZnCl 2 enhances renal function and reduces cytolysis (p < 0,05). In addition, it increased significantly the activities of antioxidant enzymes (SOD, CAT, and GPX) and the level of GSH in comparison to I/R (p < 0,05). Interestingly, ZnCl 2 treatment resulted in significant decreased ER stress, as reflected by GRP78, ATF-6,p-eIF-2α, XPB-1, and CHOP downregulaion. Rats undergoing ZnCl 2 treatment demonstrated a low expression of autophagy parameters (Beclin-1 and LAMP-2), which was correlated with low induction of apoptosis (caspase-9, caspase-3, and p-JNK), and reduction of inflammation (IL-1ß, IL-6, and MCP-1) (p < 0,05). In conclusion, we demonstrated the potential effect of Zn supplementation to modulate ER pathway and autophagic process after I/R. © 2018 Wiley Periodicals, Inc.

Study on the effect of black cumin (Nigella sativa Linn.) on experimental renal ischemia-reperfusion injury in rats.

PubMed

Mousavi, Ghafour

2015-08-01

To evaluate the effect of Black cumin (Nigella sativa Linn.) pre-treatment on renal ischemia/reperfusion (I/R) induced injury in the rats. A total of 40 male Wistar rats were randomly allocated into five equal groups including Sham, I/R model and three I/R+ Black cumin (0.5, 1 and 2%)-treated groups. I/R groups' kidneys were subjected to 60 min of global ischemia at 37°C followed by 24 h of reperfusion. At the end of reperfusion period, the rats were euthanized. Superoxide dismutase, catalase and glutathione peroxidase activities as well as reduced glutathione and renal malondialdehyde contents were determined in renal tissues. Kidney function tests and histopathological examination were also performed. High serum creatinine, blood urea nitrogen and uric acid as well as malondialhehyde (MDA) levels, and low antioxidant enzyme activities were observed in I/R rats compared to the sham rats. Pre-treatment with Black cumin for three weeks prior to IR operation improved renal function and reduced I/R induced renal inflammation and oxidative injury. These biochemical observations were supported by histopathological test of kidney sections. Black cumin significantly prevented renal ischemia/reperfusion induced functional and histological injuries.

Beneficial effects of remote organ ischemic preconditioning on micro-rheological parameters during liver ischemia-reperfusion in the rat.

PubMed

Magyar, Zsuzsanna; Mester, Anita; Nadubinszky, Gabor; Varga, Gabor; Ghanem, Souleiman; Somogyi, Viktoria; Tanczos, Bence; Deak, Adam; Bidiga, Laszlo; Oltean, Mihai; Peto, Katalin; Nemeth, Norbert

2018-04-14

Remote ischemic preconditioning (RIPC) can be protective against the damage. However, there is no consensus on the optimal amount of tissue, the number and duration of the ischemic cycles, and the timing of the preconditioning. The hemorheological background of the process is also unknown. To investigate the effects of remote organ ischemic preconditioning on micro-rheological parameters during liver ischemia-reperfusion in rats. In anesthetized rats 60-minute partial liver ischemia was induced with 120-minute reperfusion (Control, n = 7). In the preconditioned groups a tourniquet was applied on the left thigh for 3×10 minutes 1 hour (RIPC-1, n = 7) or 24 hours (RIPC-24, n = 7) prior to the liver ischemia. Blood samples were taken before the operation and during the reperfusion. Acid-base, hematological parameters, erythrocyte aggregation and deformability were tested. Lactate concentration significantly increased by the end of the reperfusion. Erythrocyte deformability was improved in the RIPC-1 group, erythrocyte aggregation increased during the reperfusion, particularly in the RIPC-24 group. RIPC alleviated several hemorheological changes caused by the liver I/R. However, the optimal timing of the RIPC cannot be defined based on these results.

Ischemia-Reperfusion Injury and Volatile Anesthetics

PubMed Central

Erturk, Engin

2014-01-01

Ischemia-reperfusion injury (IRI) is induced as a result of reentry of the blood and oxygen to ischemic tissue. Antioxidant and some other drugs have protective effect on IRI. In many surgeries and clinical conditions IRI is counteract inevitable. Some anesthetic agents may have a protective role in this procedure. It is known that inhalational anesthetics possess protective effects against IRI. In this review the mechanism of preventive effects of volatile anesthetics and different ischemia-reperfusion models are discussed. PMID:24524079

Effect of taurine on ischemia-reperfusion injury.

PubMed

Schaffer, Stephen W; Jong, Chian Ju; Ito, Takashi; Azuma, Junichi

2014-01-01

Taurine is an abundant β-amino acid that regulates several events that dramatically influence the development of ischemia-reperfusion injury. One of these events is the extrusion of taurine and Na+ from the cell via the taurine/Na+ symport. The loss of Na+ during the ischemia-reperfusion insult limits the amount of available Na+ for Na+/Ca2+ exchange, an important process in the development of Ca2+ overload and the activation of the mitochondrial permeability transition, a key process in ischemia-reperfusion mediated cell death. Taurine also prevents excessive generation of reactive oxygen species by the respiratory chain, an event that also limits the activation of the MPT. Because taurine is an osmoregulator, changes in taurine concentration trigger "osmotic preconditioning," a process that activates an Akt-dependent cytoprotective signaling pathway that inhibits MPT pore formation. These effects of taurine have clinical implications, as experimental evidence reveals potential promise of taurine therapy in preventing cardiac damage during bypass surgery, heart transplantation and myocardial infarction. Moreover, severe loss of taurine from the heart during an ischemia-reperfusion insult may increase the risk of ventricular remodeling and development of heart failure.

Understanding STAT3 signaling in cardiac ischemia.

PubMed

O'Sullivan, K E; Breen, E P; Gallagher, H C; Buggy, D J; Hurley, J P

2016-05-01

Cardiovascular disease is the leading cause of death worldwide. It remains one of the greatest challenges to global health and will continue to dominate mortality trends in the future. Acute myocardial infarction results in 7.4 million deaths globally per annum. Current management strategies are centered on restoration of coronary blood flow via percutaneous coronary intervention, coronary artery bypass grafting and administration of anti-platelet agents. Such myocardial reperfusion accounts for 40-50 % of the final infarct size in most cases. Signaling transducer and activator of transcription 3 (STAT3) has been shown to have cardioprotective effects via canonical and non-canonical activation and modulation of mitochondrial and transcriptional responses. A significant body of in vitro and in vivo evidence suggests that activation of the STAT3 signal transduction pathway results in a cardio protective response to ischemia and attempts have been made to modulate this with therapeutic effect. Not only is STAT3 important for cardiomyocyte function, but it also modulates the cardiac microenvironment and communicates with cardiac fibroblasts. To this end, we here review the current evidence supporting the manipulation of STAT3 for therapeutic benefit in cardiac ischemia and identify areas for future research.

K(ATP) channel blocker HMR 1883 reduces monophasic action potential shortening during coronary ischemia in anesthetised pigs.

PubMed

Wirth, K J; Uhde, J; Rosenstein, B; Englert, H C; Gögelein, H; Schölkens, B A; Busch, A E

2000-02-01

ATP-sensitive potassium channels (KATP) open during myocardial ischemia. The ensuing repolarising potassium efflux shortens the action potential. Accumulation of extracellular potassium is able to partially depolarise the membrane, reducing the upstroke velocity of the action potential and thereby impairing impulse conduction. Both mechanisms are believed to be involved in the development of reentrant arrhythmias during cardiac ischemia. The sulfonylthiourea HMR 1883 (1-[[5-[2-(5-chloro-O-anisamido)ethyl]-methoxyphenyl]sulfonyl]-3-m ethylthiourea) was designed as a cardioselective KATP channel blocker for the prevention of arrhythmic sudden death in patients with ischemic heart disease. The aim of this study was to show that this compound, which has already shown antifibrillatory efficacy in dogs and rats, is able to inhibit ischemic changes of the action potential induced by coronary artery occlusion in anesthetised pigs. Action potentials were taken in situ with the technique of monophasic action potential (MAP) recording. In a control group (n=7), three consecutive occlusions of a small branch of the left circumflex coronary artery resulted in reproducible reductions in MAP duration and a decrease in upstroke velocity. In a separate group (n=7), HMR 1883 (3 mg/kg i.v.) significantly (P<0.05) reduced the ischemia-induced shortening of the MAP: during the first and second control occlusion of the coronary artery in the HMR 1883-group, MAP50 duration shortened from 218.5 +/- 3.0 ms to 166.7 +/- 3.3 ms and from 219.7 +/- 4.5 ms to 164.9 +/- 1.8 ms, respectively. After HMR 1883, during the third occlusion, MAP duration decreased from 226.9 +/- 3.6 ms to 205.3 +/- 4.3 ms only corresponding to 59% inhibition. HMR 1883 also improved the upstroke velocity of the MAP, which was depressed by ischemia: in the two preceding control occlusions ischemia prolonged the time to peak of the MAP, an index for upstroke velocity, from 10.83 +/- 0.43 ms to 39.42 +/- 1.60 ms and from

[Effects of sodium aescinate on the apoptosis-related genes in lung injury induced by intestinal ischemia reperfusion in rats].

PubMed

Wang, Yan-Lei; Jing, You-Ling; Cai, Qing-Yan; Cui, Guo-Jin; Zhang, Yi-Bing; Zhang, Feng-Yu

2012-03-01

To investigate the relationship between apoptosis-related genes and lung injury induced by intestinal ischemia reperfusion and to explore the effects and its possible mechanism of sodium aescinate. Rat model of intestinal I/R injury was established with clamping of the superior mesenteric artery for 60 min and then clamping was relieved for 60 min. Twenty-four SD rats were randomly divided into three groups with eight rats in each: sham group, intestinal ischemia/reperfusion group (I/R group) and sodium aescinate group (SA + I/R group). Lung wet/dry weight ratio, lung coefficient and Superoxide dismutase (SOD), malondialdehyde (MDA) in plasma and lung tissue were measured, as well as the expression levels of Bcl-2 and Bax proteins in lung tissue were examined using immunohistochemical method. Compared with sham group, lung wet/dry weight ratio, lung coefficient and MDA in plasma and lung tissue were significantly increased, and while the activity of SOD in plasma and lung tissue were decreased significantly in I/R group. At the same time, the protein expression level of Bcl-2 and Bax were significantly increased. But Bax protein expression was much greater than that of Bcl-2, the ratio of Bcl-2 to Bax was decreased significantly in I/R group than that in sham group. Compared with I/R group, lung wet/dry weight ratio, lung coefficient and MDA in plasma and lung tissue were significantly decreased, and while the activity of SOD in serum and lung tissue were significantly increased in SA + I/R group. At the same time, Bax protein expression was significantly decreased, both Bcl-2 protein expression and the ratio of Bcl-2 to Bax were significantly increased in SA + I/R group than that in I/R group. Lung injury induced by intestinal ischemia reperfusion is correlated with abnormal expression levels of Bcl-2 and Bax protein which is caused by oxidative injury. Sodium aescinate can protect the lung injury induced by intestinal ischemia/reperfusion (I/R), which may be

Changes in muscle tissue oxygenation during stagnant ischemia in septic patients.

PubMed

Pareznik, Roman; Knezevic, Rajko; Voga, Gorazd; Podbregar, Matej

2006-01-01

To determine changes in the rate of thenar muscles tissue deoxygenation during stagnant ischemia in patients with severe sepsis and septic shock. Prospective observational study in the medical ICU of a general hospital. Consecutive patients admitted to ICU with septic shock (n=6), severe sepsis (n=6), localized infection (n=3), and healthy volunteers (n=15). Upper limb ischemia was induced by rapid automatic pneumatic cuff inflation around upper arm. Thenar muscle tissue oxygen saturation (StO2) was measured continuously by near-infrared spectroscopy before and during upper limb ischemia. StO(2) before intervention was comparable in patients with septic shock, severe sepsis, or localized infection and healthy volunteers (89 [65, 92]% vs. 82 [72, 91]% vs. 87 [85, 92]% vs. 83 [79, 93]%, respectively; p>0.1). The rate of StO(2) decrease during stagnant ischemia after initial hemodynamic stabilization was slower in septic shock patients than in those with severe sepsis or localized infection and in controls (-7.0 [-3.6, -11.0] %/min vs. -10.4 [-7.8, -13.3] %/min vs. -19.5 [-12.3, -23.3] vs. -37.4 [-27.3, -56.2] %/min, respectively; p=0.041). At ICU discharge the rate of StO2 decrease did not differ between the septic shock, severe sepsis, and localized infection groups (-17.0 [-9.3, -28.9] %/min vs. -19.9 [-13.3, -23.6] %/min vs. -23.1 [-20.7, -26.2] %/min, respectively), but remained slower than in controls (p<0.01). The rate of StO2 decrease was correlated with Sequential Organ Failure Assessment (SOFA) score (r=0.739, p<0.001). After hemodynamic stabilization thenar muscle tissue oxygen saturation during stagnant ischemia decreases slower in septic shock patients than in patients with severe sepsis or localized infection and in healthy volunteers. During ICU stay and improvement of sepsis the muscle tissue deoxygenation rate increases in survivors of both septic shock and severe sepsis and was correlated with SOFA score.

Effect of infliximab on acute hepatic ischemia/reperfusion injury in rats.

PubMed

Yucel, Ahmet Fikret; Pergel, Ahmet; Aydin, Ibrahim; Alacam, Hasan; Karabicak, Ilhan; Kesicioglu, Tugrul; Tumkaya, Levent; Kalkan, Yildiray; Ozer, Ender; Arslan, Zakir; Sehitoglu, Ibrahim; Sahin, Dursun Ali

2015-01-01

This study aimed to investigate the hepatoprotective and antioxidant effects of infliximab (IFX) against liver ischemia/reperfusion (I/R) injury in rats. A total of 30 male Wistar albino rats were divided into three groups: sham, I/R, and I/R+IFX. IFX was given at a dose of 3 mg/kg for three days before I/R. Rat livers were subjected to 60 min of ischemia followed by 90 h of reperfusion. Aspartate aminotransferase (AST), alanine aminotransferase (ALT), TNF-α, malondialdehyde (MDA), and glutathione peroxidase (GSH-Px) levels were measured in the serum. The liver was removed to evaluate the histopathologic changes. The I/R group had a significant increase in AST, ALT, MDA, and TNF-α levels, and a decrease in GSH-Px activity compared with the sham group. The use of IFX significantly reduced the ALT, AST, MDA and TNF-α levels and significantly increased GSH-Px activity. IFX attenuated the histopathologic changes. IFX has a protective effect on liver I/R injury. This liver protective effect may be related to antioxidant and anti-TNF-α effects. We propose that, for the relief of liver injury subsequent to transplantation, liver resection, trauma, and shock, tentative treatments can be incorporated with IFX, which is already approved for clinical use.

Effect of infliximab on acute hepatic ischemia/reperfusion injury in rats

PubMed Central

Yucel, Ahmet Fikret; Pergel, Ahmet; Aydin, Ibrahim; Alacam, Hasan; Karabicak, Ilhan; Kesicioglu, Tugrul; Tumkaya, Levent; Kalkan, Yildiray; Ozer, Ender; Arslan, Zakir; Sehitoglu, Ibrahim; Sahin, Dursun Ali

2015-01-01

This study aimed to investigate the hepatoprotective and antioxidant effects of infliximab (IFX) against liver ischemia/reperfusion (I/R) injury in rats. A total of 30 male Wistar albino rats were divided into three groups: sham, I/R, and I/R+IFX. IFX was given at a dose of 3 mg/kg for three days before I/R. Rat livers were subjected to 60 min of ischemia followed by 90 h of reperfusion. Aspartate aminotransferase (AST), alanine aminotransferase (ALT), TNF-α, malondialdehyde (MDA), and glutathione peroxidase (GSH-Px) levels were measured in the serum. The liver was removed to evaluate the histopathologic changes. The I/R group had a significant increase in AST, ALT, MDA, and TNF-α levels, and a decrease in GSH-Px activity compared with the sham group. The use of IFX significantly reduced the ALT, AST, MDA and TNF-α levels and significantly increased GSH-Px activity. IFX attenuated the histopathologic changes. IFX has a protective effect on liver I/R injury. This liver protective effect may be related to antioxidant and anti-TNF-α effects. We propose that, for the relief of liver injury subsequent to transplantation, liver resection, trauma, and shock, tentative treatments can be incorporated with IFX, which is already approved for clinical use. PMID:26885068

Hypoxic-Preconditioned Bone Marrow Stem Cell Medium Significantly Improves Outcome After Retinal Ischemia in Rats

PubMed Central

Roth, Steven; Dreixler, John C.; Mathew, Biji; Balyasnikova, Irina; Mann, Jacob R.; Boddapati, Venkat; Xue, Lai; Lesniak, Maciej S.

2016-01-01

Purpose We have previously demonstrated the protective effect of bone marrow stem cell (BMSC)-conditioned medium in retinal ischemic injury. We hypothesized here that hypoxic preconditioning of stem cells significantly enhances the neuroprotective effect of the conditioned medium and thereby augments the protective effect in ischemic retina. Methods Rats were subjected to retinal ischemia by increasing intraocular pressure to 130 to 135 mm Hg for 55 minutes. Hypoxic-preconditioned, hypoxic unconditioned, or normoxic medium was injected into the vitreous 24 hours after ischemia ended. Recovery was assessed 7 days after injections by comparing electroretinography measurements, histologic examination, and apoptosis (TUNEL, terminal deoxynucleotidyl transferase–mediated dUTP nick end labeling assay). To compare proteins secreted into the medium in the groups and the effect of hypoxic exposure, we used rat cytokine arrays. Results Eyes injected with hypoxic BMSC–conditioned medium 24 hours after ischemia demonstrated significantly enhanced return of retinal function, decreased retinal ganglion cell layer loss, and attenuated apoptosis compared to those administered normoxic or hypoxic unconditioned medium. Hypoxic-preconditioned medium had 21 significantly increased protein levels compared to normoxic medium. Conclusions The medium from hypoxic-preconditioned BMSCs robustly restored retinal function and prevented cell loss after ischemia when injected 24 hours after ischemia. The protective effect was even more pronounced than in our previous studies of normoxic conditioned medium. Prosurvival signals triggered by the secretome may play a role in this neuroprotective effect. PMID:27367588

Divergent Systemic and Local Inflammatory Response to Hind Limb Demand Ischemia in Wild Type And ApoE−/− Mice

PubMed Central

Crawford, Robert S.; Albadawi, Hassan; Robaldo, Alessandro; Peck, Michael A.; Abularrage, Christopher J.; Yoo, Hyung-Jin; LaMuraglia, Glenn M.; Watkins, Michael T.

2013-01-01

Introduction Studies were designed to determine whether the ApoE−/− phenotype modulates the local skeletal muscle and systemic inflammatory (plasma) responses to lower extremity demand ischemia. The ApoE−/− phenotype is an experimental model for atherosclerosis in humans. Methods Aged female ApoE −/− and C57BL6 mice underwent femoral artery ligation, then divided into sedentary and demand ischemia (exercise) groups on day 14. Baseline and post exercise limb perfusion and hind limb function were assessed. On day 14, animals in the demand ischemia group underwent daily treadmill exercise through day 28. Sedentary mice were not exercised. On day 28, plasma and skeletal muscle from ischemic limbs were harvested from sedentary and exercised mice. Muscle was assayed for angiogenic and pro-inflammatory proteins, markers of skeletal muscle regeneration, and evidence of skeletal muscle fiber maturation. Results Hind limb ischemia was similar in ApoE −/− and C57 mice prior to the onset of exercise. Under sedentary conditions, plasma VEGF, IL-6, but not KC or MIP-2 were higher in ApoE (P<0.0001). Following exercise, plasma levels of VEGF, KC and MIP-2, but not IL-6 were lower in ApoE (P<0.004). The cytokines KC and MIP-2 in muscle was greater in exercised ApoE−/− mice as compared to C57BL6 mice (p=0.01). Increased PAR activity, and mature muscle regeneration was associated with demand ischemia in the C57BL6 mice as compared to the ApoE −/− mice (p=0.01). Conclusion Demand limb ischemia in the ApoE−/− phenotype exacerbated the expression of select systemic cytokines in plasma and blunted indices of muscle regeneration. PMID:23528286

Acute tryptophan pretreatment protects against behavioral changes caused by cerebral ischemia.

PubMed

Carney, J M

1986-05-15

Male gerbils (Meronies ungulata) were treated with various doses of tryptophan and the changes in spontaneous motor activity determined. Tryptophan decreased behavior at a dose of 200 mg/kg. Cerebral ischemia was produced by bilateral carotid occlusion for 5 min. This duration of ischemia produced a large increase in activity at both 6 h and 24 h postischemia. Tryptophan (200 mg/kg) prevented the ischemia-induced increases in locomotor activity. These data suggest that dietary amino acids may play a role in determining the effects of ischemia.

Neural correlates of brain state in chronic ischemia and stroke: combined resting state electroencephalogram and transcranial Doppler ultrasonographic study.

PubMed

Martynova, Olga V; Portnova, Galina V; Gladun, Ksenya V

2017-02-08

Clinical neurology is constantly searching for reliable indices of ischemic brain damage to prevent a possible development of stroke. We suggest that resting state electroencephalogram (rsEEG) with respect to other clinical data may provide important information about the severity of ischemia. We carried out correlation analysis of rsEEG, data of transcranial Doppler ultrasonography of head vessels, and clinical assessment scores collected from healthy volunteers and four groups of patients with mild chronic microvascular ischemia (CMI-1), moderate CMI (CMI-2), severe atrophy of the cerebral hemisphere, ischemic stroke in the left middle cerebral artery stroke, and ischemic stroke in the right middle cerebral artery stroke. Using independent component analysis and k-mean clustering of EEG data, we observed prominent changes in rsEEG reflected in specific distributions of spectral peaks in all groups of patients. We found a significant correlation of EEG spectral distribution and the blood flow velocity in coronal arteries, which was also affected by the severity of ischemia and the localization of stroke. Moreover, EEG spectral distribution was more indicative of early stages of ischemia than the blood flow velocity. Our data support the hypothesis that rsEEG may reflect altered neural activity caused by ischemic brain damage.

IMM-H004, A New Coumarin Derivative, Improved Focal Cerebral Ischemia via Blood-Brain Barrier Protection in Rats.

PubMed

Niu, Fei; Song, Xiu-Yun; Hu, Jin-Feng; Zuo, Wei; Kong, Ling-Lei; Wang, Xiao-Feng; Han, Ning; Chen, Nai-Hong

2017-10-01

IMM-H004 (7-hydroxy-5-methoxy-4-methyl-3-[4-methylpiperazin-1-yl]-2H-chromen-2-one) is a novel coumarin derivative that showed better effect in improving global cerebral ischemia in rats. However, the effects and mechanisms in focal cerebral ischemia were not clear. Blood-brain barrier (BBB) protection is a vital strategy for the treatment of cerebral ischemia. This study is to investigate whether IMM-H004 improves brain ischemia injury via BBB protection. Focal brain ischemia model was induced by middle cerebral artery occlusion for 1 hour and reperfusion (MCAO/R) for 24 hours in rats. IMM-H004 (1.5, 3, 6 mg/kg) and edaravone (positive drug, 6 mg/kg) were administered after 5 minutes of occlusion. Neurological score and TTC staining were used to evaluate the effect of IMM-H004. Evans Blue (EB) staining and electron microscopy were used to assess BBB permeability. Western blot, reverse transcription-polymerase chain reaction, and immunohistochemistry were used to detect the expression of BBB structure-related proteins. Compared with the model group, IMM-H004 in the focal brain ischemia model improved neurological function and reduced cerebral infarction size and edema content. IMM-H004 sharply reduced the EB content and alleviated BBB structure. In addition, IMM-H004 increased the level of zonula occludens (ZO-1) and occluding, decreased the level of aquaporin 4 and matrix metalloproteinase 9, either in cortex or in hippocampus. And all of these changed were related to BBB protection. IMM-H004 improved cerebral ischemia injury via BBB protection. For a potential therapy drug of cerebral ischemia, IMM-H004 merits further study. Copyright © 2017. Published by Elsevier Inc.

[Coenzyme Q10 enhances the expression of Bcl-2 and inhibits the expressions of Bax and GSK-3β in the hippocampus of rats exposed to ischemia/reperfusion injury].

PubMed

Tian, Shuang; Wang, Di; Li, Xiaodong; Tang, Jianjie; Han, Guang; Dai, Yongyi

2013-07-01

To investigate the effects of coenzyme Q10 pretreatment on the expressions of Bcl-2, Bax and glycogen synthase kinase-3β (GSK-3β) in rats suffering from ischemia/reperfusion injury. Thirty-six adult male SD rats were randomly assigned into 3 groups: sham-operated group (sham), ischemia/reperfusion group (I/R) and coenzyme Q10 preconditioning group (Q10). Focal cerebral ischemia/reperfusion models were established in experimental rats by blocking middle cerebral artery with suture. Histological changes of hippocampal neurons were observed by HE staining. The expressions of Bcl-2, Bax and GSK-3β were detected by immunohistochemistry and Western blotting. Immunohistochemistry showed that the percentage of Bcl-2 positive cells increased in the hippocampus, while the percentages of Bax and GSK-3β positive cells decreased in Q10 group compared with I/R group. Western blotting revealed that the expression level of Bcl-2 was higher and the expression levels of Bax and GSK-3β were lower in Q10 group than in I/R group. There were significant differences between the two groups (P<0.05). Coenzyme Q10 promoted the expression of Bcl-2 and suppressed the expressions of Bax and GSK-3β in the hippocampus of rats exposed to cerebral ischemia/reperfusion.

[Cardiovascular effects of sodium chloride bath and underwater shower in coronary ischemia].

PubMed

Ghighineishvili, G R; Sirtori, P G; Balsamo, V; Miani, A; Di Francesco, A; Lanfranchi, M; Dagnoni, L; Mauro, F

Two hundred and eighteen patients (209 males and 9 females, mean age 57.1 +/- 0.6 years) with I class coronary ischemia were subdivided into two groups of 109 subjects each. Group I received NaCl baths, group II underwater massage-showers. On days 2-3 and 23-24 of treatment all underwent incremental stress testing until exhaustion. In group I, only subjects with moderate maximal muscular power improved their stress endurance. In group II, stress endurance significantly improved in all subjects: all hemodynamic indices (cardiac, output, stroke volume, systemic vascular resistances) showed variations indicative of improved cardiorespiratory function and peripheral blood supply.

Protective effect of Crataegus oxyacantha against reperfusion arrhythmias after global no-flow ischemia in the rat heart.

PubMed

al Makdessi, S; Sweidan, H; Dietz, K; Jacob, R

1999-04-01

The protective effect against reperfusion arrhythmias of a 3-month oral pretreatment with a dried extract of Crataegus oxyacantha (LI 132)(standardized to 2.2% flavonoids) was studied with the Langendorff heart of the rat after global no-flow ischemia. The heart was perfused with a modified Krebs-Henseleit solution in which the K+ content was reduced to 3.4 mmol/l in order to lower the fibrillation threshold. According to pilot experiments which considered various durations of global no-flow ischemia ranging from 10 to 20 minutes, two durations were chosen for the present study: 20 minutes (group 20) in which ventricular fibrillation (VF) was the predominant form of arrhythmias, and 18 minutes (group 18) in which the prevalence of VF was markedly lower despite the small difference in the duration of ischemia. Crataegus pretreatment significantly (p = 0.02) reduced the average prevalence of malignant arrhythmias (VF + Flutter) as observed during the 20-min-period of reperfusion as follows: group 20: from 89% (control, n = 9) to 51% (LI 132, n = 7), group 18: from 48% (control, n = 8) to 8% (LI 132, n = 8). In group 20, ventricular tachycardia (VT) could be observed only in the treated group, because of the predominance of VF in the control group. LI 132 pretreatment reduced the average prevalence of VT in group 18 in spite of the identical percentage of occurrence (6 out of 8 rats, with and without treatment) due to a shorter duration of the VT episodes. Thus, under the conditions of our experiments, effective prevention against reperfusion arrhythmias by Crataegus pretreatment was evident.

[Keap1-tat peptide attenuates oxidative stress damage in hippocampal CA1 region and learning and memory deficits following global cerebral ischemia].

PubMed

Tu, Jing-yi; Zhu, Ying; Shang, Shu-ling; Zhang, Xi; Tang, Hui; Wang, Rui-min

2016-02-18

To design Keap1-tat peptide and explore its neuroprotective role on hipocampal CA1 neuron, as well as the effect on spacial learning and memory function following global cerebral ischemia. Adult male Sprague Dawley (SD) rats were subjected to global cerebral ischemia (GCI) by four-vessel occlusion for 15 min and randomly divided into five groups: sham, sham+Keap1-tat, ischemia/reperfusion (I/R), Keap1-tat peptide- and vehicle-administrated groups. For Keap1-tat or vehicle groups, the rats were treated with Keap1-tat (30, 50, 100 μg in 5 μL 0.9% saline) or the same volume vehicle by intracerebroventricular injection (icv) 30 min prior to ischemia. Cresyl violet staining was used to observe the surviving neurons and 4-hydroxy-2-noneal (4-HNE) and 8-hydroxy-2'-deoxyguanosine (8-OHdG) immunostaining were used to detect the change of markers response to oxidative stress in hippocampal CA1 region. The spatial learning and memory function of the rats was evaluated using Morris water maze. Compared with sham group, the number of surviving neurons in ischemia-reperfusion and vehicle groups significantly decreased in the hippocampal CA1 region (P<0.05), while administration of Keap1-tat significantly decreased the damage following GCI (P<0.05), and the dose of 50 μg existed the most effective neuroprotective role. Furthermore, immunostaining intensity of 4-HNE and 8-OHdG, markers of oxidative stress damage attenuated by Keap1-tat peptide as compared with vehicle group in CA1 region. Of significant interest, the time of finding underwater platform in Keap1-tat group animals was significantly short, and after removing the platform, the probe time of Keap1-tat group animals in the original quadrant where the platform was significantly increased compared with that of vehicle and I/R group animals (P<0.05). Keap1-tat peptide can effectively attenuate neuronal damage in hippocampal CA1 region and improve learning and memory function, which might bedue to the attenuation of

[Spectrum-Effect Relationship of GualouXiebai Dropping Pills on Myocardial Ischemia].