Organotypic lung culture: A new model for studying ischemia and ex vivo perfusion in lung transplantation.

PubMed

Baste, Jean-Marc; Gay, Arnaud; Smail, Hassiba; Noël, Romain; Bubenheim, Michael; Begueret, Hugues; Morin, Jean-Paul; Litzler, Pierre-Yves

2015-01-01

Donors after cardiac death (DCD) in lung transplantation is considered as a solution for organ shortage. However, it is characterized by warm ischemic period, which could be involved in severe Ischemia-Reperfusion lesion (IR) with early graft dysfunction. We describe a new hybrid model combining in vivo ischemia followed by in vitro reoxygenation using organ-specific culture. A hybrid model using in vivo ischemic period followed by in vitro lung slice reoxygenation was set up in rat to mimic DCD in lung transplantation with in vitro perfusion. Different markers (bioenergetics, oxidant stress assays, and histology) were measured to evaluate the viability of lung tissue after different ischemic times (I-0, I-1, I-2, I-4, I-15 hours) and reoxygenation times (R-0, R-1, R-4, R-24 hours). No differences were found in cell viability, ATP concentrations, extracellular LDH assays or histology, demonstrating extensive viability of up to 4 hours in lung tissue warm ischemia. We found oxidative stress mainly during the ischemic period with no burst at reoxygenation. Cytosolic anti-oxidant system was involved first (I-0,I-1,I-2) followed by mitochondrial anti-oxidant system for extensive ischemia (I-4). Histological features showed differences in this model of ischemia-reoxygenation between bronchial epithelium and lung parenchymal cells, with epithelium regeneration after 2 hours of warm ischemia and 24 hours of perfusion. The results of our hybrid model experiment suggest extensive lung viability of up to 4 hours ischemia. Our model could be an interesting tool to evaluate ex vivo reconditioning techniques after different in vivo lung insults.

Daytime warming has stronger negative effects on soil nematodes than night-time warming.

PubMed

Yan, Xiumin; Wang, Kehong; Song, Lihong; Wang, Xuefeng; Wu, Donghui

2017-03-07

Warming of the climate system is unequivocal, that is, stronger warming during night-time than during daytime. Here we focus on how soil nematodes respond to the current asymmetric warming. A field infrared heating experiment was performed in the western of the Songnen Plain, Northeast China. Three warming modes, i.e. daytime warming, night-time warming and diurnal warming, were taken to perform the asymmetric warming condition. Our results showed that the daytime and diurnal warming treatment significantly decreased soil nematodes density, and night-time warming treatment marginally affected the density. The response of bacterivorous nematode and fungivorous nematode to experimental warming showed the same trend with the total density. Redundancy analysis revealed an opposite effect of soil moisture and soil temperature, and the most important of soil moisture and temperature in night-time among the measured environment factors, affecting soil nematode community. Our findings suggested that daily minimum temperature and warming induced drying are most important factors affecting soil nematode community under the current global asymmetric warming.

Daytime warming has stronger negative effects on soil nematodes than night-time warming.

PubMed

Yan, Xiumin; Wang, Kehong; Song, Lihong; Wang, Xuefeng; Wu, Donghui

2017-03-20

Warming of the climate system is unequivocal, that is, stronger warming during night-time than during daytime. Here we focus on how soil nematodes respond to the current asymmetric warming. A field infrared heating experiment was performed in the western of the Songnen Plain, Northeast China. Three warming modes, i.e. daytime warming, night-time warming and diurnal warming, were taken to perform the asymmetric warming condition. Our results showed that the daytime and diurnal warming treatment significantly decreased soil nematodes density, and night-time warming treatment marginally affected the density. The response of bacterivorous nematode and fungivorous nematode to experimental warming showed the same trend with the total density. Redundancy analysis revealed an opposite effect of soil moisture and soil temperature, and the most important of soil moisture and temperature in night-time among the measured environment factors, affecting soil nematode community. Our findings suggested that daily minimum temperature and warming induced drying are most important factors affecting soil nematode community under the current global asymmetric warming.

Daytime warming has stronger negative effects on soil nematodes than night-time warming

PubMed Central

Yan, Xiumin; Wang, Kehong; Song, Lihong; Wang, Xuefeng; Wu, Donghui

2017-01-01

Warming of the climate system is unequivocal, that is, stronger warming during night-time than during daytime. Here we focus on how soil nematodes respond to the current asymmetric warming. A field infrared heating experiment was performed in the western of the Songnen Plain, Northeast China. Three warming modes, i.e. daytime warming, night-time warming and diurnal warming, were taken to perform the asymmetric warming condition. Our results showed that the daytime and diurnal warming treatment significantly decreased soil nematodes density, and night-time warming treatment marginally affected the density. The response of bacterivorous nematode and fungivorous nematode to experimental warming showed the same trend with the total density. Redundancy analysis revealed an opposite effect of soil moisture and soil temperature, and the most important of soil moisture and temperature in night-time among the measured environment factors, affecting soil nematode community. Our findings suggested that daily minimum temperature and warming induced drying are most important factors affecting soil nematode community under the current global asymmetric warming. PMID:28317914

Daytime warming has stronger negative effects on soil nematodes than night-time warming

NASA Astrophysics Data System (ADS)

Yan, Xiumin; Wang, Kehong; Song, Lihong; Wang, Xuefeng; Wu, Donghui

2017-03-01

Warming of the climate system is unequivocal, that is, stronger warming during night-time than during daytime. Here we focus on how soil nematodes respond to the current asymmetric warming. A field infrared heating experiment was performed in the western of the Songnen Plain, Northeast China. Three warming modes, i.e. daytime warming, night-time warming and diurnal warming, were taken to perform the asymmetric warming condition. Our results showed that the daytime and diurnal warming treatment significantly decreased soil nematodes density, and night-time warming treatment marginally affected the density. The response of bacterivorous nematode and fungivorous nematode to experimental warming showed the same trend with the total density. Redundancy analysis revealed an opposite effect of soil moisture and soil temperature, and the most important of soil moisture and temperature in night-time among the measured environment factors, affecting soil nematode community. Our findings suggested that daily minimum temperature and warming induced drying are most important factors affecting soil nematode community under the current global asymmetric warming.

Protective effect of curcumin against liver warm ischemia/reperfusion injury in rat model is associated with regulation of heat shock protein and antioxidant enzymes

PubMed Central

Shen, Shi-Qiang; Zhang, Yuan; Xiang, Jin-Jian; Xiong, Cheng-Long

2007-01-01

AIM: To investigate the hypothesis that the protective effects of curcumin in hepatic warm ischemia/reperfusion (I/R) injury are associated with increasing heat shock protein 70 (Hsp70) expression and antioxidant enzyme activity. METHODS: Sixty Sprague-Dawley male rats were randomly divided into sham, I/R, C + I/R groups. The model of reduced-size liver warm ischemia and reperfusion was used. Curcumin (50 mg/kg) was administered by injection through a branch of superior mesenteric vein at 30 min before ischemia in C + I/R group. Five rats were used to investigate the survival during 1 wk after operation in each group. Blood samples and liver tissues were obtained in the remaining animals after 3, 12, and 24 h of reperfusion to assess serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), liver tissue NO2- + NO3-, malondialdehyde (MDA) content, superoxide dismutase (SOD), catalase (CAT), nitricoxide synthase (NOS) and myeloperoxidase (MPO) activity, Hsp70 expression and apoptosis ratio. RESULTS: Compared with I/R group, curcumin pretreatment group showed less ischemia/reperfusion-induced injury. CAT and SOD activity and Hsp70 expression increased significantly. A higher rate of apoptosis was observed in I/R group than in C + I/R group, and a significant increase of MDA, NO2- + NO3- and MPO level in liver tissues and serum transaminase concentration was also observed in I/R group compared to C + I/R group. Curcumin also decreased the activity of inducible NO synthase (iNOS) in liver after reperfusion, but had no effect on the level of endothelial NO synthase (eNOS) after reperfusion in liver. The 7 d survival rate was significantly higher in C + I/R group than in I/R group. CONCLUSION: Curcumin has protective effects against hepatic I/R injury. Its mechanism might be related to the overexpression of Hsp70 and antioxidant enzymes. PMID:17461496

Effect of donor fasting on survival of pancreas and heart grafts after warm ischemia.

PubMed

Nishihara, M; Sumimoto, R; Asahara, T; Fukuda, Y; Southard, J H; Dohi, K

1996-09-01

Livers from fasted animals are believed to be more vulnerable to ischemic injury than those from fed donors. However, we have recently shown the opposite: livers from fasted rats were more tolerant to ischemic injury. Indeed, the survival rate of 60 min warm ischemic damaged livers increased from 0 to 90% if donor rats were fasted for three days. In this study, we examined how donor fasting affects the outcome of pancreas and heart preservation. BN rats were used as both donors and recipients, and recipients of pancreatic grafts were rendered diabetic prior to transplantation. Pancreatic or heart grafts were subjected to 90 min or 25 min of warm ischemia and were transplanted into the right side of the necks of recipients rats. The viability rate of hearts transplanted from fed donors into fed recipients was only about 11% (1/9) after transplantation. However, the viability rate with fasted donors was 75% (6/8). The rate of successful pancreatic grafting from fed donors into fed recipients was 28.6% (2/7), and that from fasted donors to fed recipients was 41.7% (5/12). These results confirm that the nutritional status of the donor is an important factor in the outcome of not only liver, but also pancreas and heart preservation during transplantation, although the effect of fasting on pancreatic graft is marginal.

S-Adenosylmethionine attenuates bile duct early warm ischemia reperfusion injury after rat liver transplantation.

PubMed

Tang, Yong; Chu, Hongpeng; Cao, Guojun; Du, Xiaolong; Min, Xiaobo; Wan, Chidan

2018-03-01

Warm ischemia reperfusion injury (IRI) plays a key role in biliary complication, which is a substantial vulnerability of liver transplantation. The early pathophysiological changes of IRI are characterized by an excessive inflammatory response. S-Adenosylmethionine (SAM) is an important metabolic intermediate that modulates inflammatory reactions; however, its role in bile duct warm IRI is not known. In this study, male rats were treated with or without SAM (170 μmol/kg body weight) after orthotopic autologous liver transplantation. The histopathological observations showed that bile duct injury in the IRI group was more serious than in the SAM group. The alanine aminotransferase (ALT), alkaline phosphatase (ALP) and direct bilirubin (DBIL) levels in the serum of the IRI group were significantly increased compared to the SAM group (P < .05). Simultaneously, SAM effectively improved the survival of the transplant recipients. Furthermore, the H 2 O 2 and malondialdehyde (MDA) of the IRI group were much higher compared to the SAM group (P < .05). The GSH/GSSG ratio in the SAM group was significantly increased by SAM treatment compared to the IRI group (P < .05). SAM administration significantly inhibited macrophage infiltration in liver and bile duct tissues, down-regulated TNF-α levels and up-regulated IL-10 expression in bile duct tissues compared to the IRI group (P < .05). The number of apoptotic biliary epithelial cells and caspase-3-positive cells in IRI rat livers were much higher compared to those in SAM-treated rats at 24 h after liver transplantation (P < .05). These data suggested that SAM protected bile ducts against warm IRI by suppressing oxidative stress, inflammatory reactions and apoptosis of biliary epithelial cells after liver transplantation.α. Copyright © 2018 Elsevier Ltd. All rights reserved.

Role of inflammatory cells and adenosine in lung ischemia reoxygenation injury using a model of lung donation after cardiac death.

PubMed

Smail, Hassiba; Baste, Jean-Marc; Gay, Arnaud; Begueret, Hugues; Noël, Romain; Morin, Jean-Paul; Litzler, Pierre-Yves

2016-04-01

The objective of this study is to analyze the role of inflammation in the lung ischemia reperfusion (IR) injury and determine the protective role of adenosine in an in vitro lung transplantation model. We used a hybrid model of lung donor after cardiac death, with warm ischemia in corpo of varying duration (2 h, 4 h) followed by in vitro lung slices culture for reoxygenation (1 h, 4 h and 24 h), in the presence or not of lymphocytes and of adenosine. To quantify the inflammatory lesions, we performed TNFα, IL2 assays, and histological analysis. In this model of a nonblood perfused system, the addition of lymphocytes during reoxygenation lead to higher rates of TNFα and IL2 after 4 h than after 2 h of warm ischemia (P < .05). These levels increased with the duration of reoxygenation and were maximum at 24 h (P < .05). In the presence of adenosine TNFα and IL2 decreased. After 2 h of warm ischemia, we observed a significant inflammatory infiltration, alveolar thickening and a necrosis of the bronchiolar cells. After 4 h of warm ischemia, alveolar cells necrosis was associated. This model showed that lymphocytes increased the inflammatory response and the histological lesions after 4 h of warm ischemia and that adenosine could have an anti-inflammatory role with potential reconditioning action when used in the pneumoplegia solution.

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.

The ultrastructural characteristics of porcine hepatocytes donated after cardiac death and preserved with warm machine perfusion preservation.

PubMed

Bochimoto, Hiroki; Matsuno, Naoto; Ishihara, Yo; Shonaka, Tatsuya; Koga, Daisuke; Hira, Yoshiki; Nishikawa, Yuji; Furukawa, Hiroyuki; Watanabe, Tsuyoshi

2017-01-01

The effects of warm machine perfusion preservation of liver grafts donated after cardiac death on the intracellular three-dimensional ultrastructure of the organelles in hepatocytes remain unclear. Here we analyzed comparatively the ultrastructure of the endomembrane systems in porcine hepatocytes under warm ischemia and successive hypothermic and midthermic machine perfusion preservation, a type of the warm machine perfusion. Porcine liver grafts which had a warm ischemia time of 60 minutes were perfused for 4 hours with modified University of Wisconsin gluconate solution. Group A grafts were preserved with hypothermic machine perfusion preservation at 8°C constantly for 4 hours. Group B grafts were preserved with rewarming up to 22°C by warm machine perfusion preservation for 4 hours. An analysis of hepatocytes after 60 minutes of warm ischemia by scanning electron microscope revealed the appearance of abnormal vacuoles and invagination of mitochondria. In the hepatocytes preserved by subsequent hypothermic machine perfusion preservation, strongly swollen mitochondria were observed. In contrast, the warm machine perfusion preservation could preserve the functional appearance of mitochondria in hepatocytes. Furthermore, abundant vacuoles and membranous structures sequestrating cellular organelles like autophagic vacuoles were frequently observed in hepatocytes after warm machine perfusion preservation. In conclusion, the ultrastructure of the endomembrane systems in the hepatocytes of liver grafts changed in accordance with the temperature conditions of machine perfusion preservation. In addition, temperature condition of the machine perfusion preservation may also affect the condition of the hepatic graft attributed to autophagy systems, and consequently alleviate the damage of the hepatocytes.

Novel critical role of Toll-like receptor 4 in lung ischemia-reperfusion injury and edema

PubMed Central

Zanotti, Giorgio; Casiraghi, Monica; Abano, John B.; Tatreau, Jason R.; Sevala, Mayura; Berlin, Hilary; Smyth, Susan; Funkhouser, William K.; Burridge, Keith; Randell, Scott H.; Egan, Thomas M.

2009-01-01

Toll-like receptors (TLRs) of the innate immune system contribute to noninfectious inflammatory processes. We employed a murine model of hilar clamping (1 h) with reperfusion times between 15 min and 3 h in TLR4-sufficient (C3H/OuJ) and TLR4-deficient (C3H/HeJ) anesthetized mice with additional studies in chimeric and myeloid differentiation factor 88 (MyD88)- and TLR4-deficient mice to determine the role of TLR4 in lung ischemia-reperfusion injury. Human pulmonary microvascular endothelial monolayers were subjected to simulated warm ischemia and reperfusion with and without CRX-526, a competitive TLR4 inhibitor. Functional TLR4 solely on pulmonary parenchymal cells, not bone marrow-derived cells, mediates early lung edema following ischemia-reperfusion independent of MyD88. Activation of MAPKs and NF-κB was significantly blunted and/or delayed in lungs of TLR4-deficient mice as a consequence of ischemia-reperfusion injury, but edema development appeared to be independent of activation of these signaling pathways. Pretreatment with a competitive TLR4 inhibitor prevented edema in vivo and reduced actin cytoskeletal rearrangement and gap formation in pulmonary microvascular endothelial monolayers subjected to simulated warm ischemia and reperfusion. In addition to its well-accepted role to alter gene transcription, functioning TLR4 on pulmonary parenchymal cells plays a key role in very early and profound pulmonary edema in murine lung ischemia-reperfusion injury. This may be due to a novel mechanism: regulation of endothelial cell cytoskeleton affecting microvascular endothelial cell permeability. PMID:19376887

Melatonin Modulates Endoplasmic Reticulum Stress and Akt/GSK3-Beta Signaling Pathway in a Rat Model of Renal Warm Ischemia Reperfusion

PubMed Central

Hadj Ayed Tka, Kaouther; Mahfoudh Boussaid, Asma; Zaouali, Mohamed Amine; Kammoun, Rym; Bejaoui, Mohamed; Ghoul Mazgar, Sonia; Rosello Catafau, Joan; Ben Abdennebi, Hassen

2015-01-01

Melatonin (Mel) is widely used to attenuate ischemia/reperfusion (I/R) injury in several organs. Nevertheless, the underlying mechanisms remain unclear. This study was conducted to explore the effect of Mel on endoplasmic reticulum (ER) stress, Akt and MAPK cascades after renal warm I/R. Eighteen Wistar rats were randomized into three groups: Sham, I/R, and Mel + I/R. The ischemia period was 60 min followed by 120 min of reperfusion. Mel (10 mg/kg) was administrated 30 min prior to ischemia. The creatinine clearance, MDA, LDH levels, and histopathological changes were evaluated. In addition, Western blot was performed to study ER stress and its downstream apoptosis as well as phosphorylation of Akt, GSK-3β, VDAC, ERK, and P38. Mel decreased cytolysis and lipid peroxidation and improved renal function and morphology compared to I/R group. Parallely, it significantly reduced the ER stress parameters including GRP 78, p-PERK, XBP 1, ATF 6, CHOP, and JNK. Simultaneously, p-Akt level was significantly enhanced and its target molecules GSK-3β and VDAC were inhibited. Furthermore, the ERK and P38 phosphorylation were evidently augmented after Mel administration in comparison to I/R group. In conclusion, Mel improves the recovery of renal function by decreasing ER stress and stimulating Akt pathway after renal I/R injury. PMID:26229743

Melatonin modulates endoplasmic reticulum stress and Akt/GSK3-beta signaling pathway in a rat model of renal warm ischemia reperfusion.

PubMed

Hadj Ayed Tka, Kaouther; Mahfoudh Boussaid, Asma; Zaouali, Mohamed Amine; Kammoun, Rym; Bejaoui, Mohamed; Ghoul Mazgar, Sonia; Rosello Catafau, Joan; Ben Abdennebi, Hassen

2015-01-01

Melatonin (Mel) is widely used to attenuate ischemia/reperfusion (I/R) injury in several organs. Nevertheless, the underlying mechanisms remain unclear. This study was conducted to explore the effect of Mel on endoplasmic reticulum (ER) stress, Akt and MAPK cascades after renal warm I/R. Eighteen Wistar rats were randomized into three groups: Sham, I/R, and Mel + I/R. The ischemia period was 60 min followed by 120 min of reperfusion. Mel (10 mg/kg) was administrated 30 min prior to ischemia. The creatinine clearance, MDA, LDH levels, and histopathological changes were evaluated. In addition, Western blot was performed to study ER stress and its downstream apoptosis as well as phosphorylation of Akt, GSK-3β, VDAC, ERK, and P38. Mel decreased cytolysis and lipid peroxidation and improved renal function and morphology compared to I/R group. Parallely, it significantly reduced the ER stress parameters including GRP 78, p-PERK, XBP 1, ATF 6, CHOP, and JNK. Simultaneously, p-Akt level was significantly enhanced and its target molecules GSK-3β and VDAC were inhibited. Furthermore, the ERK and P38 phosphorylation were evidently augmented after Mel administration in comparison to I/R group. In conclusion, Mel improves the recovery of renal function by decreasing ER stress and stimulating Akt pathway after renal I/R injury.

Liraglutide attenuates partial warm ischemia-reperfusion injury in rat livers.

PubMed

Abdelsameea, Ahmed A; Abbas, Noha A T; Abdel Raouf, Samar M

2017-03-01

Ischemia-reperfusion (IR) injury constitutes the most important cause of primary dysfunction of liver grafts. In this study, we have addressed the possible hepatoprotective action of liraglutide against partial warm hepatic IR injury in male rats. Rats were randomly assigned into: sham, IR, and liraglutide-pretreated IR groups. Liraglutide was administered 50 μg/kg s.c. twice daily for 14 days, and then, hepatic IR was induced by clamping portal vein and hepatic artery to left and median lobes for 30 min followed by reperfusion for 24 h. Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), and gamma glutamyl transferase (GGT) activities were determined. Malondialdehyde (MDA) level, reduced glutathione (GSH) content, tumor necrosis factor-α (TNF-α), phosphoralated Akt (p-Akt), and caspase-3 levels of the liver were determined. Hematoxylin and eosin (H&E) stained sections from liver were examined as well as immunohistochemical sections for detection of Bcl-2 expression. IR injury increased ALT, AST, and GGT while decreased GSH and p-Akt with increase in MDA, TNF-α, and caspase-3 levels in the liver with necrosis and inflammatory cellular infiltration with decreased Bcl-2 expression. Pretreatment with liraglutide decreased ALT, AST, and GGT activities while increased glutathione content and Akt activation with decrements in MDA, TNF-α, and caspase-3 levels with attenuation of necrosis and inflammation while enhanced Bcl-2 expression in the liver. Liraglutide protects against IR injury of the liver through antiinflammatory and antioxidant actions as well as inhibition of apoptosis.

Real-Time Visualization of Tissue Ischemia

NASA Technical Reports Server (NTRS)

Bearman, Gregory H. (Inventor); Chrien, Thomas D. (Inventor); Eastwood, Michael L. (Inventor)

2000-01-01

A real-time display of tissue ischemia which comprises three CCD video cameras, each with a narrow bandwidth filter at the correct wavelength is discussed. The cameras simultaneously view an area of tissue suspected of having ischemic areas through beamsplitters. The output from each camera is adjusted to give the correct signal intensity for combining with, the others into an image for display. If necessary a digital signal processor (DSP) can implement algorithms for image enhancement prior to display. Current DSP engines are fast enough to give real-time display. Measurement at three, wavelengths, combined into a real-time Red-Green-Blue (RGB) video display with a digital signal processing (DSP) board to implement image algorithms, provides direct visualization of ischemic areas.

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.

HDACi Valproic Acid (VPA) and Suberoylanilide Hydroxamic Acid (SAHA) Delay but Fail to Protect against Warm Hepatic Ischemia-Reperfusion Injury.

PubMed

Ruess, Dietrich A; Probst, Moriz; Marjanovic, Goran; Wittel, Uwe A; Hopt, Ulrich T; Keck, Tobias; Bausch, Dirk

2016-01-01

Histone deacetylases (HDAC) catalyze N-terminal deacetylation of lysine-residues on histones and multiple nuclear and cytoplasmic proteins. In various animal models, such as trauma/hemorrhagic shock, ischemic stroke or myocardial infarction, HDAC inhibitor (HDACi) application is cyto- and organoprotective and promotes survival. HDACi reduce stress signaling, cell death and inflammation. Hepatic ischemia-reperfusion (I/R) injury during major liver resection or transplantation increases morbidity and mortality. Assuming protective properties, the aim of this study was to investigate the effect of the HDACi VPA and SAHA on warm hepatic I/R. Male Wistar-Kyoto rats (age: 6-8 weeks) were randomized to VPA, SAHA, vehicle control (pre-) treatment or sham-groups and underwent partial no-flow liver ischemia for 90 minutes with subsequent reperfusion for 6, 12, 24 and 60 hours. Injury and regeneration was quantified by serum AST and ALT levels, by macroscopic aspect and (immuno-) histology. HDACi treatment efficiency, impact on MAPK/SAPK-activation and Hippo-YAP signaling was determined by Western blot. Treatment with HDACi significantly enhanced hyperacetylation of Histone H3-K9 during I/R, indicative of adequate treatment efficiency. Liver injury, as measured by macroscopic aspect, serum transaminases and histology, was delayed, but not alleviated in VPA and SAHA treated animals. Importantly, tissue destruction was significantly more pronounced with VPA. SAPK-activation (p38 and JNK) was reduced by VPA and SAHA in the early (6h) reperfusion phase, but augmented later on (JNK, 24h). Regeneration appeared enhanced in SAHA and VPA treated animals and was dependent on Hippo-YAP signaling. VPA and SAHA delay warm hepatic I/R injury at least in part through modulation of SAPK-activation. However, these HDACi fail to exert organoprotective effects, in this setting. For VPA, belated damage is even aggravated.

Temporary renal ischemia during nephron sparing surgery is associated with short-term but not long-term impairment in renal function.

PubMed

Yossepowitch, Ofer; Eggener, Scott E; Serio, Angel; Huang, William C; Snyder, Mark E; Vickers, Andrew J; Russo, Paul

2006-10-01

The emergence of laparoscopic nephron sparing surgery has rekindled interest in the impact of warm renal ischemia on renal function. To provide data with which warm renal ischemia can be compared we analyzed short-term and long-term changes in the glomerular filtration rate after temporary cold renal ischemia. In patients undergoing open nephron sparing surgery the estimated glomerular filtration rate was assessed preoperatively, early in the postoperative hospital stay, and 1 and 12 months after surgery using the abbreviated Modification of Diet in Renal Disease Study equation. We separately analyzed 70 patients with a solitary kidney and 592 with 2 functioning kidneys. The end point was the percent change from the baseline glomerular filtration rate. A linear regression model was used to test the association between the glomerular filtration rate change, and ischemia time, patient age, tumor size, estimated blood loss and intraoperative fluid administration. Median cold ischemia time was 31 minutes in patients with a solitary kidney and 35 minutes in those with 2 kidneys. Compared to patients with 2 kidneys those with a solitary kidney had a significantly lower preoperative estimated glomerular filtration rate (p < 0.001), which decreased a median of 30% during the early postoperative period, and 15% and 32% 1 and 12 months after surgery, respectively. In patients with 2 kidneys the corresponding glomerular filtration rate decreases were 16%, 13% and 14%, respectively. On multivariate analyses in each group cold ischemia duration and intraoperative blood loss were significantly associated with early glomerular filtration rate changes. However, 12 months after surgery age was the only independent predictor of a glomerular filtration rate decrease in patients with 2 kidneys. Cold renal ischemia during nephron sparing surgery is a significant determinant of the short-term postoperative glomerular filtration rate. Longer clamping time is particularly detrimental in

Impact of recombinant globular adiponectin on early warm ischemia-reperfusion injury in rat bile duct after liver transplantation.

PubMed

Xia, Yang; Gong, Jian-Ping

2014-09-19

Adiponectin (APN) is an adipocyte protein with anti-diabetic properties, which has been recently revealed to have anti-inflammatory activity in organ ischemia- reperfusion injury (IRI). However, little is known about its function in bile duct IRI after liver transplantation. Therefore, we investigated whether APN affects early warm IRI in rat bile duct using a liver autologous transplantation model. In our study, rats were randomly divided into three experimental groups: a sham group, a IRI group, and a APN group. The serum enzyme levels and BDISS scores of bile duct histology associated with bile duct injury, decreased after administration of APN. Subsequently, the expression of proinflammatory cytokines, such as tumor necrosis factor(TNF-α),.interleukin-6(IL-6) and myeloperoxidase (MPO) decreased. Furthermore, pretreatment with APN suppressed the activation of nuclear factor-kappa B (NF-κB) (p65), a transcription factor involved in inflammatory reactions, compared to other two groups. Administration of APN also downregulated the expression of Fas protein and attenuated caspase-3 activity to decrease bile duct apoptosis. Our results illustrate that APN protects the rat bile duct against early warm IRI by suppressing the inflammatory response and hepatocyte apoptosis, and NF-κB (p65) plays an important role in this process.

Impact of parenchymal loss on renal function after laparoscopic partial nephrectomy under warm ischemia.

PubMed

Bagheri, Fariborz; Pusztai, Csaba; Farkas, László; Kallidonis, Panagiotis; Buzogány, István; Szabó, Zsuzsanna; Lantos, János; Imre, Marianna; Farkas, Nelli; Szántó, Árpád

2016-12-01

To elucidate the impact of renal parenchymal loss and the ischemic reperfusion injury (RI) on the renal function after laparoscopic partial nephrectomy (LPN) under warm ischemia (WI). Thirty-five patients with a single polar renal mass ≤4 cm and normal contralateral kidney underwent LPN. Transperitoneal LPN with WI using en bloc hilar occlusion was performed. The total differential renal function (T-DRF) using 99m Tc-dimercaptosuccinic acid was evaluated preoperatively and postoperatively over a period of 1 year. A special region of interest (ROI) was selected on the non-tumorous pole of the involved kidney, and was compared with the same ROI in the contralateral kidney. The latter comparison was defined as partial differential renal function (P-DRF). Any postoperative decline in the P-DRF of the operated kidney was attributed to the RI. Subtraction of the P-DRF decline from the T-DRF decline was attributed to the parenchymal loss caused by the resection of the tumor and suturing of the normal parenchyma. The mean WI time was 22 min, and the mean weight of resected specimen was 18 g. The mean postoperative eGFR declined to 87 ml/min/1.73 m 2 from its baseline mean value of 97 ml/min/1.73 m 2 (p value = 0.075). Mean postoperative T-DRF and P-DRF of the operated kidney declined by 7 and 3 %, respectively. After LPN of small renal mass, decline in renal function is primarily attributed to parenchymal loss caused by tumor resection and suturing of the normal parenchyma rather than the RI.

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.

A real-time Global Warming Index.

PubMed

Haustein, K; Allen, M R; Forster, P M; Otto, F E L; Mitchell, D M; Matthews, H D; Frame, D J

2017-11-13

We propose a simple real-time index of global human-induced warming and assess its robustness to uncertainties in climate forcing and short-term climate fluctuations. This index provides improved scientific context for temperature stabilisation targets and has the potential to decrease the volatility of climate policy. We quantify uncertainties arising from temperature observations, climate radiative forcings, internal variability and the model response. Our index and the associated rate of human-induced warming is compatible with a range of other more sophisticated methods to estimate the human contribution to observed global temperature change.

Prolonged Ischemia Triggers Necrotic Depletion of Tissue Resident Macrophages to Facilitate Inflammatory Immune Activation in Liver Ischemia Reperfusion Injury

PubMed Central

Yue, Shi; Zhou, Haoming; Wang, Xuehao; Busuttil, Ronald W.; Kupiec-Weglinski, Jerzy W.; Zhai, Yuan

2017-01-01

Although mechanisms of immune activation against liver ischemia reperfusion injury (IRI) have been studied extensively, questions regarding liver resident macrophages, i.e., Kupffer cells, remain controversial. Recent progress in the biology of tissue resident macrophages implicates homeostatic functions of KCs. This study aims to dissect responses and functions of KCs in liver IRI. In a murine liver partial warm ischemia model, we analyzed liver resident vs. infiltrating macrophages by fluorescence-activated cell sorting (FACS) and immunofluorescence staining. Our data showed that liver immune activation by IR was associated with not only infiltrations/activations of peripheral macrophages (iMØ), but also necrotic depletion of KCs. Inhibition of Receptor Interacting Protein 1 (RIP1) by necrostatin-1s protected KCs from ischemia-induce depletion, resulting in the reduction of iMØ infiltration, suppression of pro-inflammatory immune activation and protection of livers from IRI. The depletion of KCs by clodronate-liposomes abrogated these effects of Nec-1s. Additionally, liver reconstitutions with KCs post-ischemia exerted anti-inflammatory/cytoprotective effects against IRI. These results reveal a unique response of KCs against liver IR, i.e., RIP-1-dependent necrosis, which constitutes a novel mechanism of liver inflammatory immune activation in the pathogenesis of liver IRI. PMID:28289160

Rationale for Implementation of Warm Cardiac Surgery in Pediatrics.

PubMed

Durandy, Yves

2016-01-01

Cardiac surgery was developed thanks to the introduction of hypothermia and cardiopulmonary bypass in the early 1950s. The deep hypothermia protective effect has been essential to circulatory arrest complex cases repair. During the early times of open-heart surgery, a major concern was to decrease mortality and to improve short-term outcomes. Both mortality and morbidity dramatically decreased over a few decades. As a consequence, the drawbacks of deep hypothermia, with or without circulatory arrest, became more and more apparent. The limitation of hypothermia was particularly evident for the brain and regional perfusion was introduced as a response to this problem. Despite a gain in popularity, the results of regional perfusion were not fully convincing. In the 1990s, warm surgery was introduced in adults and proved to be safe and reliable. This option eliminates the deleterious effect of ischemia-reperfusion injuries through a continuous, systemic coronary perfusion with warm oxygenated blood. Intermittent warm blood cardioplegia was introduced later, with impressive results. We were convinced by the easiness, safety, and efficiency of warm surgery and shifted to warm pediatric surgery in a two-step program. This article outlines the limitations of hypothermic protection and the basic reasons that led us to implement pediatric warm surgery. After tens of thousands of cases performed across several centers, this reproducible technique proved a valuable alternative to hypothermic surgery.

Microvascular stent anastomosis using N-fibroin stents: feasibility, ischemia time, and complications.

PubMed

Smeets, Ralf; Vorwig, Oliver; Wöltje, Michael; Gaudin, Robert; Luebke, Andreas M; Beck-Broichsitter, Benedicta; Rheinnecker, Michael; Heiland, Max; Grupp, Katharina; Gröbe, Alexander; Hanken, Henning

2016-05-01

To evaluate a novel microvascular anastomosis technique using N-fibroin stents. Cylinder stents of 1 mm diameter and 5 mm length were fabricated using N-fibroin from silkworms. In 22 rats, aortas were dissected, and the stent was inserted into the two ends of the aorta and fixed using methylmethacrylate. Stent anastomosis was successful in 21 (96%) rats. The mean ischemia time was 7.4 minutes, significantly shorter than the 15.9 minutes in the control group with conventional sutures (P < .0001). After 4 months, anastomosis was functionally patent in all cases. However, elastic fibers remained interrupted in all stent anastomosis cases, and marked host rejection was evident at the stent anastomosis sites. Around the stents, thrombi were frequent (52%). Our study demonstrated the basic feasibility of stent anastomosis using N-fibroin stents and reduced ischemia time. However, thrombus formation, frequent and severe abdominal infections, and heavy host rejection remain critical issues. Copyright © 2016 Elsevier Inc. All rights reserved.

Bud break responds more strongly to daytime than night-time temperature under asymmetric experimental warming.

PubMed

Rossi, Sergio; Isabel, Nathalie

2017-01-01

Global warming is diurnally asymmetric, leading to a less cold, rather than warmer, climate. We investigated the effects of asymmetric experimental warming on plant phenology by testing the hypothesis that daytime warming is more effective in advancing bud break than night-time warming. Bud break was monitored daily in Picea mariana seedlings belonging to 20 provenances from Eastern Canada and subjected to daytime and night-time warming in growth chambers at temperatures varying between 8 and 16 °C. The higher advancements of bud break and shorter times required to complete the phenological phases occurred with daytime warming. Seedlings responded to night-time warming, but still with less advancement of bud break than under daytime warming. No advancement was observed when night-time warming was associated with a daytime cooling. The effect of the treatments was uniform across provenances. Our observations realized under controlled conditions allowed to experimentally demonstrate that bud break can advance under night-time warming, but to a lesser extent than under daytime warming. Prediction models using daily timescales could neglect the diverging influence of asymmetric warming and should be recalibrated for higher temporal resolutions. © 2016 John Wiley & Sons Ltd.

Timing the warm absorber in NGC4051

NASA Astrophysics Data System (ADS)

Silva, C.; Uttley, P.; Costantini, E.

2015-07-01

In this work we have combined spectral and timing analysis in the characterization of highly ionized outflows in Seyfert galaxies, the so-called warm absorbers. Here, we present our results on the extensive ˜600ks of XMM-Newton archival observations of the bright and highly variable Seyfert 1 galaxy NGC4051, whose spectrum has revealed a complex multi-component wind. Working simultaneously with RGS and PN data, we have performed a detailed analysis using a time-dependent photoionization code in combination with spectral and Fourier timing techniques. This method allows us to study in detail the response of the gas due to variations in the ionizing flux of the central source. As a result, we will show the contribution of the recombining gas to the time delays of the most highly absorbed energy bands relative to the continuum (Silva, Uttley & Costantini in prep.), which is also vital information for interpreting the continuum lags associated with propagation and reverberation effects in the inner emitting regions. Furthermore, we will illustrate how this powerful method can be applied to other sources and warm-absorber configurations, allowing for a wide range of studies.

Evidence of a heterogeneous tissue oxygenation: renal ischemia/reperfusion injury in a large animal model

NASA Astrophysics Data System (ADS)

Crane, Nicole J.; Huffman, Scott W.; Alemozaffar, Mehrdad; Gage, Frederick A.; Levin, Ira W.; Elster, Eric A.

2013-03-01

Renal ischemia that occurs intraoperatively during procedures requiring clamping of the renal artery (such as renal procurement for transplantation and partial nephrectomy for renal cancer) is known to have a significant impact on the viability of that kidney. To better understand the dynamics of intraoperative renal ischemia and recovery of renal oxygenation during reperfusion, a visible reflectance imaging system (VRIS) was developed to measure renal oxygenation during renal artery clamping in both cooled and warm porcine kidneys. For all kidneys, normothermic and hypothermic, visible reflectance imaging demonstrated a spatially distinct decrease in the relative oxy-hemoglobin concentration (%HbO2) of the superior pole of the kidney compared to the middle or inferior pole. Mean relative oxy-hemoglobin concentrations decrease more significantly during ischemia for normothermic kidneys compared to hypothermic kidneys. VRIS may be broadly applicable to provide an indicator of organ ischemia during open and laparoscopic procedures.

Real time monitoring of rat liver energy state during ischemia.

PubMed

Barbiro, E; Zurovsky, Y; Mayevsky, A

1998-11-01

Hepatic failure is one of the major problems developed during the posttransplantation period. A possible cause of hepatic failure is the prolonged ischemia induced during the implantation procedure. Hepatic ischemia leads to a reduction in oxygen supply, ATP level decline, liver metabolism impairment, and finally organ failure. The purpose of this study was to estimate the functional state of the liver by monitoring liver blood flow and the mitochondrial NADH redox state simultaneously and continuously during in situ liver ischemia followed by reperfusion. Measurements were performed using the multiprobe developed in our laboratory consisting of fibers for the measurement of relative liver blood flow (laser Doppler flowmetry) and mitochondrial redox state (NADH fluorescence). The experimental procedure included the temporary interruption of blood flow to the liver using three types of ischemia, hepatic artery occlusion, portal vein occlusion, and simultaneous occlusion of hepatic artery and portal vein, followed by a reperfusion period. These preliminary experiments showed a significant decrease in liver blood flow, following the three types of liver ischemia, and a significant increase in NADH levels. The probe used in this study incorporates the advantage of monitoring NADH and liver blood flow simultaneously and continuously from the same area on the surface of the liver. Since each of these two parameters is not calibrated in absolute units, the simultaneous monitoring decreases possible artifacts. Also, it will allow us to determine of the coupling between tissue blood flow and oxidative phosphorylation. It is believed that the measurements of respiratory chain dysfunction might predict organ viability in clinical organ transplantation situations. Using this probe may also help to decrease the variability in liver blood flow monitoring since liver blood flow monitoring is supported simultaneously with the mitochondrial redox state, which supplies the

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.

Multiparametric evaluation of hindlimb ischemia using time-series indocyanine green fluorescence imaging.

PubMed

Guang, Huizhi; Cai, Chuangjian; Zuo, Simin; Cai, Wenjuan; Zhang, Jiulou; Luo, Jianwen

2017-03-01

Peripheral arterial disease (PAD) can further cause lower limb ischemia. Quantitative evaluation of the vascular perfusion in the ischemic limb contributes to diagnosis of PAD and preclinical development of new drug. In vivo time-series indocyanine green (ICG) fluorescence imaging can noninvasively monitor blood flow and has a deep tissue penetration. The perfusion rate estimated from the time-series ICG images is not enough for the evaluation of hindlimb ischemia. The information relevant to the vascular density is also important, because angiogenesis is an essential mechanism for post-ischemic recovery. In this paper, a multiparametric evaluation method is proposed for simultaneous estimation of multiple vascular perfusion parameters, including not only the perfusion rate but also the vascular perfusion density and the time-varying ICG concentration in veins. The target method is based on a mathematical model of ICG pharmacokinetics in the mouse hindlimb. The regression analysis performed on the time-series ICG images obtained from a dynamic reflectance fluorescence imaging system. The results demonstrate that the estimated multiple parameters are effective to quantitatively evaluate the vascular perfusion and distinguish hypo-perfused tissues from well-perfused tissues in the mouse hindlimb. The proposed multiparametric evaluation method could be useful for PAD diagnosis. The estimated perfusion rate and vascular perfusion density maps (left) and the time-varying ICG concentration in veins of the ankle region (right) of the normal and ischemic hindlimbs. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Different methods of hilar clamping during partial nephrectomy: Impact on renal function.

PubMed

Lee, Jeong Woo; Kim, Hwanik; Choo, Minsoo; Park, Yong Hyun; Ku, Ja Hyeon; Kim, Hyeon Hoe; Kwak, Cheol

2014-03-01

To evaluate the impact of different hilar clamping methods on changes in renal function after partial nephrectomy. We analyzed the clinical data of 369 patients who underwent partial nephrectomy for a single renal tumor of size ≤4.0 cm and a normal contralateral kidney. Patients were separated into three groups depending on hilar clamping method: non-clamping, cold ischemia and warm ischemia. Estimated glomerular filtration rate was examined at preoperative, nadir and 1 year postoperatively. Percent change in estimated glomerular filtration rate was used as the parameter to assess the renal functional outcome. Percent change in nadir estimated glomerular filtration rate in the non-clamping group was significantly less compared with the cold ischemia and warm ischemia groups (P < 0.001). However, no significant differences among the groups were noted in percent change of estimated glomerular filtration rate at 1 year (P = 0.348). The cold ischemia group had a similar serial change of postoperative renal function compared with the warm ischemia group. Percent change in 1-year estimated glomerular filtration rate increased with increasing ischemia time in the cold ischemia (P for trend = 0.073) and warm ischemia groups (P for trend = 0.010). On multivariate analysis, hilar clamping (both warm ischemia and cold ischemia) were significantly associated with percent change in nadir estimated glomerular filtration rate, but not in 1-year estimated glomerular filtration rate. Non-clamping partial nephrectomy results in a lower percent change in nadir estimated glomerular filtration rate, whereas it carries an estimated glomerular filtration rate change at 1 year that is similar to partial nephrectomy with cold ischemia and warm ischemia. Cold ischemia and warm ischemia provide a similar effect on renal function. Therefore, when hilar clamping is required, minimization of ischemia time is necessary. © 2013 The Japanese Urological Association.

Benefits and shortcomings of superselective transarterial embolization of renal tumors before zero ischemia laparoscopic partial nephrectomy.

PubMed

D'Urso, L; Simone, G; Rosso, R; Collura, D; Castelli, E; Giacobbe, A; Muto, G L; Comelli, S; Savio, D; Muto, G

2014-12-01

To report feasibility, safety and effectiveness of "zero-ischemia" laparoscopic partial nephrectomy (LPN) following preoperative superselective transarterial embolization (STE) for clinical T1 renal tumors. We retrospectively reviewed perioperative data of 23 consecutive patients, who underwent STE prior LPN between March 2010 and November 2012 for incidental clinical T1 renal mass. STE was performed by two experienced radiologists the day before surgery. Surgical procedures were performed in extended flank position, transperitoneally, by a single surgeon. Mean patients age was 68 years (range 56-74), mean tumor size was 3.5 cm (range 2.2-6.3 cm). STE was successfully completed in 16 patients 12-15 h before surgery. In 4 cases STE failed to provide a complete occlusion of all feeding arteries, while in 3 cases the ischemic area was larger than expected. LPN was successfully completed in all patients but one where open conversion was necessary; a "zero-ischemia" approach was performed in 19/23 patients (82.6%) while hilar clamp was necessary in 4 cases, with a mean warm-ischemia time of 14.8 min (range 5-22). Mean operative time was 123 min (range 115-130) and mean intraoperative blood loss was 250 mL (range 20-450). No patient experienced postoperative acute renal failure and no patient developed new onset IV stage chronic kidney disease at 1-yr follow-up. STE is a viable option to perform "zero-ischemia" LPN at beginning of learning curve; however, hilar clamp was necessary to achieve a relatively blood-less field in 17.4% of cases. Copyright © 2014 Elsevier Ltd. All rights reserved.

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.

Successful donation after cardiac death liver transplants with prolonged warm ischemia time using normothermic regional perfusion.

PubMed

De Carlis, Riccardo; Di Sandro, Stefano; Lauterio, Andrea; Ferla, Fabio; Dell'Acqua, Antonio; Zanierato, Marinella; De Carlis, Luciano

2017-02-01

The role of donation after cardiac death (DCD) in expanding the donor pool is mainly limited by the incidence of primary nonfunction (PNF) and ischemia-related complications. Even greater concern exists toward uncontrolled DCD, which represents the largest potential pool of DCD donors. We recently started the first Italian series of DCD liver transplantation, using normothermic regional perfusion (NRP) in 6 uncontrolled donors and in 1 controlled case to deal with the legally required no-touch period of 20 minutes. We examined our first 7 cases for the incidence of PNF, early graft dysfunction, and biliary complications. Acceptance of the graft was based on the trend of serum transaminase and lactate during NRP, the macroscopic appearance, and the liver biopsy. Hypothermic machine perfusion (HMP) was associated in selected cases to improve cold storage. Most notably, no cases of PNF were observed. Median posttransplant transaminase peak was 1014 IU/L (range, 393-3268 IU/L). Patient and graft survival were both 100% after a mean follow-up of 6.1 months (range, 3-9 months). No cases of ischemic cholangiopathy occurred during the follow-up. Only 1 anastomotic stricture completely resolved with endoscopic stenting. In conclusion, DCD liver transplantation is feasible in Italy despite the protracted no-touch period. The use of NRP and HMP seems to earn good graft function and proves safe in these organs. Liver Transplantation 23 166-173 2017 AASLD. © 2016 by the American Association for the Study of Liver Diseases.

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.

The time of day effects of warm temperature on flowering time involve PIF4 and PIF5

PubMed Central

Thines, Bryan C.; Duarte, Maritza I.; Harmon, Frank G.

2014-01-01

Warm temperature promotes flowering in Arabidopsis thaliana and this response involves multiple signalling pathways. To understand the temporal dynamics of temperature perception, tests were carried out to determine if there was a daily window of enhanced sensitivity to warm temperature (28 °C). Warm temperature applied during daytime, night-time, or continuously elicited earlier flowering, but the effects of each treatment were unequal. Plants exposed to warm night (WN) conditions flowered nearly as early as those in constant warm (CW) conditions, while treatment with warm days (WD) caused later flowering than either WN or CW. Flowering in each condition relied to varying degrees on the activity of CO , FT , PIF4 , and PIF5 , as well as the action of unknown genes. The combination of signalling pathways involved in flowering depended on the time of the temperature cue. WN treatments caused a significant advance in the rhythmic expression waveform of CO, which correlated with pronounced up-regulation of FT expression, while WD caused limited changes in CO expression and no stimulation of FT expression. WN- and WD-induced flowering was partially CO independent and, unexpectedly, dependent on PIF4 and PIF5 . pif4-2, pif5-3, and pif4-2 pif5-3 mutants had delayed flowering under all three warm conditions. The double mutant was also late flowering in control conditions. In addition, WN conditions alone imposed selective changes to PIF4 and PIF5 expression. Thus, the PIF4 and PIF5 transcription factors promote flowering by at least two means: inducing FT expression in WN and acting outside of FT by an unknown mechanism in WD. PMID:24574484

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

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

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

Improved Recovery of Hepatocytes Isolated From Warm Ischemic Rat Liver by Citrate Phosphate Dextrose (CPD)-Supplemented Euro-Collins Solution

PubMed Central

Hsu, Huai-Che; Matsuno, Naoto; Machida, Noboru; Enosawa, Shin

2013-01-01

Demand for human primary hepatocytes is increasing, particularly for clinical trials of hepatocyte transplantation. However, due to the severe shortage of organ transplant donors, the source of cells for these endeavors is restricted to untransplantable livers, such as those from non-heart-beating donors and surgically resected liver tissues. To improve cell recovery from such sources after warm ischemia, we evaluated the efficacy of applying perfusion solutions, focusing on improvement of hepatocyte recovery. Warm ischemia was induced by clamping both portal vein and hepatic artery for 10 or 15 min in rats. The liver was perfused with either Euro-Collins (EC) or extracellular-type trehalose-containing Kyoto (ETK) solutions supplemented with an anticoagulant, either heparin or citrate phosphate dextrose solution (CPD), compared to Ca2+, Mg2+-free Hanks solution. While the viability of recovered cells was 81.5 ± 4.2% and cell yield was 2.27 ± 0.53 × 108 in nonwarm ischemia controls (n = 11), these values were only 74.7 ± 2.9% and 0.38 ± 0.17 × 108, respectively, in the 10-min warm ischemia group, using the Hanks as the perfusion solution. Although the addition of heparin increased the live cell number only twofold (0.71 ± 0.40 × 108, n = 4), the best improvement was achieved by adding CPD to EC. This resulted in a recovery of 1.41 ± 0.50 × 108 in the 10-min ischemia group (n = 7) and 1.37 ± 0.28 × 108 in the 15-min group (n = 3). Macroscopic observation showed that blood had been completely flushed out by the solution, suggesting good restoration of the microcirculation in ischemic liver. Using ETK instead of EC resulted in a slight decrease in efficacy. These results demonstrate that CPD, as opposed to heparin, is effective in ensuring liver microcirculation and flushing out the blood and that EC is the best perfusion solution for obtaining hepatocytes from ischemic liver. PMID:26858872

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.

Intranasal guanosine administration presents a wide therapeutic time window to reduce brain damage induced by permanent ischemia in rats.

PubMed

Ramos, Denise Barbosa; Muller, Gabriel Cardozo; Rocha, Guilherme Botter Maio; Dellavia, Gustavo Hirata; Almeida, Roberto Farina; Pettenuzzo, Leticia Ferreira; Loureiro, Samanta Oliveira; Hansel, Gisele; Horn, Ângelo Cássio Magalhães; Souza, Diogo Onofre; Ganzella, Marcelo

2016-03-01

In addition to its intracellular roles, the nucleoside guanosine (GUO) also has extracellular effects that identify it as a putative neuromodulator signaling molecule in the central nervous system. Indeed, GUO can modulate glutamatergic neurotransmission, and it can promote neuroprotective effects in animal models involving glutamate neurotoxicity, which is the case in brain ischemia. In the present study, we aimed to investigate a new in vivo GUO administration route (intranasal, IN) to determine putative improvement of GUO neuroprotective effects against an experimental model of permanent focal cerebral ischemia. Initially, we demonstrated that IN [(3)H] GUO administration reached the brain in a dose-dependent and saturable pattern in as few as 5 min, presenting a higher cerebrospinal GUO level compared with systemic administration. IN GUO treatment started immediately or even 3 h after ischemia onset prevented behavior impairment. The behavior recovery was not correlated to decreased brain infarct volume, but it was correlated to reduced mitochondrial dysfunction in the penumbra area. Therefore, we showed that the IN route is an efficient way to promptly deliver GUO to the CNS and that IN GUO treatment prevented behavioral and brain impairment caused by ischemia in a therapeutically wide time window.

Precooling and Warm-Up Effects on Time Trial Cycling During Heat Stress.

PubMed

Al-Horani, Ramzi A; Wingo, Jonathan E; Ng, Jason; Bishop, Phillip; Richardson, Mark

2018-02-01

Heat stress limits endurance exercise performance. Combining precooling and warm-up prior to endurance exercise in the heat may exploit the benefits of both strategies while avoiding the potential negative consequences of each. This study tested the hypothesis that precooling combined with warm-up improves time trial cycling performance in the heat relative to either treatment alone. Nine healthy men completed three 16.1-km time trials in 33°C after: 1) precooling (ice slurry and ice vest) alone (PREC); 2) warm-up alone (WU); or 3) PREC plus WU (COMBO). Tre was lower after PREC compared to WU throughout exercise and lower than COMBO for the first 12 km; COMBO was lower than WU for the first 4 km. Tsk during PREC was lower than COMBO and WU for the first 8 km, and lower in COMBO than WU for the first 4 km. PREC lowered pre-exercise heart rate relative to COMBO and WU (68 ± 10, 106 ± 12, 101 ± 13 bpm, respectively), but it increased similarly during exercise. Local sweat rate (SR) was lower in PREC (0.1 ± 0.1 mg · cm-2 · min-1) than COMBO (0.5 ± 0.2 mg · cm-2 · min-1) and WU (0.6 ± 0.2 mg · cm-2 · min-1) for the first 4 km. Treatments did not differentially affect performance (PREC = 31.9 ± 1.9 min, COMBO = 32.6 ± 2.7 min, WU = 33.1 ± 2.9 min). We conclude precooling alone or with warm-up mitigated thermal strain during exercise, but did not significantly improve 16.1-km cycling time trial performance.Al-horani RA, Wingo JE, Ng J, Bishop P, Richardson M. Precooling and warm-up effects on time trial cycling during heat stress. Aerosp Med Hum Perform. 2018; 89(2):87-93.

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 ...

Protective effect of tetraethyl pyrazine against focal cerebral ischemia/reperfusion injury in rats: therapeutic time window and its mechanism.

PubMed

Jia, Jie; Zhang, Xi; Hu, Yong-Shan; Wu, Yi; Wang, Qing-Zhi; Li, Na-Na; Wu, Cai-Qin; Yu, Hui-Xian; Guo, Qing-Chuan

2009-03-01

Tetramethyl pyrazine has been considered an effective agent in treating neurons ischemia/reperfusion injury, but the mechanism of its therapeutic effect remains unclear. This study was to explore the therapeutic time window and mechanism of tetramethyl pyrazine on temporary focal cerebral ischemia/reperfusion injury. Middle cerebral artery occlusion was conducted in male Sprague-Dawley rats and 20 mg/kg of tetramethyl pyrazine was intraperitoneally injected at different time points. At 72 h after reperfusion, all animals' neurologic deficit scores were evaluated. Cerebrums were removed and cerebral infarction volume was measured. The expression of thioredoxin and thioredoxin reductase mRNA was determined at 6 and 24 h after reperfusion. Cerebral infarction volume and neurological deficit scores were significantly decreased in the group with tetramethyl pyrazine treatment. The expression of thioredoxin-1/thioredoxin-2 and thioredoxin reductase-1/thioredoxin reductase-2 was significantly decreased in rats with ischemia/reperfusion injury, while it was increased by tetramethyl pyrazine administration. Treatment with tetramethyl pyrazine, within 4 h after reperfusion, protects the brain from ischemic reperfusion injury in rats. The neuroprotective mechanism of tetramethyl pyrazine treatment is, in part, mediated through the upregulation of thioredoxin transcription.

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.

Intestinal ischemia/reperfusion injury triggers activation of innate toll-like receptor 4 and adaptive chemokine programs.

PubMed

Watson, M J; Ke, B; Shen, X-D; Gao, F; Busuttil, R W; Kupiec-Weglinski, J W; Farmer, D G

2008-12-01

Ischemia/reperfusion injury (IRI) is a major problem in intestinal transplantation. Toll-like receptor 4 (TLR4) has been implicated as a possible link between the innate and adaptive immune systems, however little data exists regarding TLR4 in intestinal IRI. The goal of this study is to evaluate the involvement of TLR4 in intestinal IRI and to assess the effect on T cell related chemokine programs. C57BL6 mice underwent 100 minutes of warm intestinal ischemia by SMA clamping. Control WT mice underwent laparotomy without vascular occlusion. Separate survival and analysis groups were performed, and intestinal tissue was harvested at 1 hour, 2 hours, 4 hours, and 24 hours post-reperfusion. Analysis included histology, CD3 immunostaining, myeloperoxidase activity, Western blot, and PCR. Survival was significantly worse in the IRI group vs control (50% vs. 100%). IRI caused severe histopathological injury including mucosal erosions and villous congestion and hemorrhage. Myeloperoxidase activity increased in a time-dependent manner after IRI (2.71 0.25 at 1 hour, 2.92 0.25 at 2 hours, 4 0.16 at 4 hours, 5.1 0.25 at 24 hours vs 0.47 0.11 controls, P < .05). Protein expression of TLR4 followed by NF-kappaB was increased after IRI. Additionally, mRNA production of IP-10, MIP-2, MCP-1, and RANTES was increased at all time-points, as was mRNA for ICAM-1 and E-selectin. This study is the first to demonstrate increased expression of TLR4 and NF-kappaB after warm intestinal IRI. This detrimental cascade may be initiated by TLR4 via NF-kappaB signaling pathways, implicating TLR4 as a potential therapeutic target for the prevention of intestinal IRI.

Topical Nitroglycerine for Neonatal Arterial Associated Peripheral Ischemia following Cannulation: A Case Report and Comprehensive Literature Review

PubMed Central

Mosalli, Rafat; Elbaz, Mohamed; Paes, Bosco

2013-01-01

Arterial cannulation in neonates is usually performed for frequent blood pressure monitoring and blood sampling. The procedure, while easily executed by skilled neonatal staff, can be associated with serious complications such as vasospasm, thrombosis, embolism, hematoma, infection, peripheral nerve damage, ischemia, and tissue necrosis. Several treatment options are available to reverse vascular induced ischemia and tissue damage. Applied interventions depend on the extent of tissue involvement and whether the condition is progressive and deemed life threatening. Standard, noninvasive measures include immediate catheter removal, limb elevation, and warming the contralateral extremity. Topical vasodilators, anticoagulation, thrombolysis, and surgery are considered secondary therapeutic strategies. A comprehensive literature search indicates that topical nitroglycerin has been utilized for the treatment of tissue ischemia in three preterms with umbilical arterial catheters and four with peripheral arterial lines. We report the first successful use of nitroglycerine ointment in a critically ill preterm infant with ischemic hand changes after brachial artery cannulation. PMID:24251058

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.

Histologic evaluation of post-implantation immediate C4d deposition in 13 intestinal grafts: correlation with cell-based crossmatching, cold ischemia time, and preservation injury.

PubMed

López-García, P; Calvo Pulido, J; Colina, F; Ballestin Carcavilla, C; Jiménez-Romero, C; Martinez González, M A; Ibarrola de Andrés, C; López-Alonso, G; Cambra Molero, F; Justo Alonso, I; Moreno-González, E

2014-01-01

C4d deposits are predictive of humoral rejection in kidney and heart transplantation. The aim of this study was to identify C4d deposit patterns in intestinal mucosa of the grafts on biopsy specimens obtained immediately after implantation and to detect if it could be a valuable tool to predict humoral or acute rejection. A second objective was to search for a statistically significant relationship between positive C4d deposition and other collected variables. Thirteen immediately post-transplantation mucosal graft biopsy specimens, formalin fixed, underwent immunohistochemical stain for C4d deposits. Diffuse intense staining of capillary endothelium was considered positive and absent, focal or weak stains as negative. Preservation injury grade and cold ischemia times were registered for each case. Donor-specific preformed antibodies were detected by complement dependent cytotoxicity serologic technique (crossmatching). Another 19 endoscopic follow-up biopsy specimens from days 2 to 6 were also evaluated. Statistical studies were made using the index of correlation ρ (Spearman's test). Diffuse intense C4d deposits were observed in 2 grafts, focal and weak in 5, and completely negative in 6. The mean cold ischemia time was 327 ± 101 minutes. Two cases showed diffuse positive deposits, 1 had a positive crossmatch and the cold ischemia time was 360 minutes whereas the other had not preformed antibodies and its cold ischemia time was 475 minutes. Humoral or acute rejection was not observed in follow-up mucosal biopsy specimens. There was no statistically significant relationship between the C4d deposition, cold ischemia time, crossmatching results, and preservation injury degree. In conclusion, C4d deposition was not a helpful tool for diagnosis of humoral rejection and prediction of acute rejection during the early post-transplantation period. Copyright © 2014 Elsevier Inc. All rights reserved.

Critical role of acidic sphingomyelinase in murine hepatic ischemia-reperfusion injury.

PubMed

Llacuna, Laura; Marí, Montserrat; Garcia-Ruiz, Carmen; Fernandez-Checa, José C; Morales, Albert

2006-09-01

The molecular mechanisms of hepatic ischemia/reperfusion (I/R) damage are incompletely understood. We investigated the role of ceramide in a murine model of warm hepatic I/R injury. This sphingolipid induces cell death and participates in tumor necrosis factor (TNF) signaling. Hepatic ceramide levels transiently increased after the reperfusion phase of the ischemic liver in mice, because of an early activation of acidic sphingomyelinase (ASMase) followed by acid ceramidase stimulation. In vivo administration of an ASMase inhibitor, imipramine, or ASMase knockdown by siRNA decreased ceramide generation during I/R, and attenuated serum ALT levels, hepatocellular necrosis, cytochrome c release, and caspase-3 activation. ASMase-induced ceramide generation activated JNK resulting in BimL phosphorylation and translocation to mitochondria, as the inhibition of ASMase by imipramine prevented these events. In contrast, blockade of ceramide catabolism by N-oleyolethanolamine (NOE), a ceramidase inhibitor, enhanced ceramide levels and potentiated I/R injury compared with vehicle-treated mice. Pentoxifylline treatment prevented TNF upregulation and ASMase activation. Furthermore, 9 of 11 mice treated with imipramine survived 7 days after total liver ischemia, compared with 4 of 12 vehicle-treated mice, whereas 8 of 8 NOE-treated mice died within 2 days of total liver ischemia. In conclusion, ceramide generated from ASMase plays a key role in I/R-induced liver damage, and its modulation may be of therapeutic relevance.

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.

Isoproterenol reduces ischemia-reperfusion lung injury despite beta-blockade.

PubMed

Takashima, Seiki; Schlidt, Scott A; Koukoulis, Giovanna; Sevala, Mayura; Egan, Thomas M

2005-06-01

If lungs could be retrieved from non-heart-beating donors (NHBDs), the shortage of lungs for transplantation could be alleviated. The use of lungs from NHBDs is associated with a mandatory warm ischemic interval, which results in ischemia-reperfusion injury upon reperfusion. In an earlier study, rat lungs retrieved 2-h postmortem from NHBDs had reduced capillary leak measured by filtration coefficient (Kfc) when reperfused with isoproterenol (iso), associated with an increase in lung tissue levels of cyclic AMP (cAMP). The objective was to determine if this decrease in Kfc was because of beta-stimulation, or would persist despite beta-blockade. Donor rats were treated intraperitoneally with beta-blockade (propranolol or pindolol) or carrier, sacrificed, and lungs were retrieved immediately or 2 h postmortem. The lungs were reperfused with or without iso and the beta-blockers in the reperfusate. Outcome measures were Kfc, wet:dry weight ratio (W/D), lung levels of adenine nucleotides and cAMP. Lungs retrieved immediately after death had normal Kfc and W/D. After 2 h of ischemia, Kfc and W/D were markedly elevated in controls (no drug) and lungs reperfused with beta-blockers alone. Isoproterenol-reperfusion decreased Kfc and W/D significantly (P < 0.01) even in the presence of beta-blockade. Lung cAMP levels were increased only with iso in the absence of beta-blockade. The attenuation of ischemia-reperfusion injury because of iso occurs even in the presence of beta-blockade, and may not be a result of beta-stimulated increased cAMP.

Climate warming and Bergmann's rule through time: is there any evidence?

PubMed Central

Teplitsky, Celine; Millien, Virginie

2014-01-01

Climate change is expected to induce many ecological and evolutionary changes. Among these is the hypothesis that climate warming will cause a reduction in body size. This hypothesis stems from Bergmann's rule, a trend whereby species exhibit a smaller body size in warmer climates, and larger body size under colder conditions in endotherms. The mechanisms behind this rule are still debated, and it is not clear whether Bergmann's rule can be extended to predict the effects of climate change through time. We reviewed the primary literature for evidence (i) of a decrease in body size in response to climate warming, (ii) that changing body size is an adaptive response and (iii) that these responses are evolutionary or plastic. We found weak evidence for changes in body size through time as predicted by Bergmann's rule. Only three studies investigated the adaptive nature of these size decreases. Of these, none reported evidence of selection for smaller size or of a genetic basis for the size change, suggesting that size decreases could be due to nonadaptive plasticity in response to changing environmental conditions. More studies are needed before firm conclusions can be drawn about the underlying causes of these changes in body size in response to a warming climate. PMID:24454554

Reproducable Paraplegia by Thoracic Aortic Occlusion in a Murine Model of Spinal Cord Ischemia-reperfusion

PubMed Central

Bell, Marshall T.; Reece, T. Brett; Smith, Phillip D.; Mares, Joshua; Weyant, Michael J.; Cleveland, Joseph C.; Freeman, Kirsten A.; Fullerton, David A.; Puskas, Ferenc

2014-01-01

Background Lower extremity paralysis continues to complicate aortic interventions. The lack of understanding of the underlying pathology has hindered advancements to decrease the occurrence this injury. The current model demonstrates reproducible lower extremity paralysis following thoracic aortic occlusion. Methods Adult male C57BL6 mice were anesthetized with isoflurane. Through a cervicosternal incision the aorta was exposed. The descending thoracic aorta and left subclavian arteries were identified without entrance into pleural space. Skeletonization of these arteries was followed by immediate closure (Sham) or occlusion for 4 min (moderate ischemia) or 8 min (prolonged ischemia). The sternotomy and skin were closed and the mouse was transferred to warming bed for recovery.  Following recovery, functional analysis was obtained at 12 hr intervals until 48 hr. Results Mice that underwent sham surgery showed no observable hind limb deficit. Mice subjected to moderate ischemia for 4 min had minimal functional deficit at 12 hr followed by progression to complete paralysis at 48 hr. Mice subjected to prolonged ischemia had an immediate paralysis with no observable hind-limb movement at any point in the postoperative period. There was no observed intraoperative or post operative mortality. Conclusion Reproducible lower extremity paralysis whether immediate or delayed can be achieved in a murine model. Additionally, by using a median sternotomy and careful dissection, high survival rates, and reproducibility can be achieved. PMID:24637534

Reproducable paraplegia by thoracic aortic occlusion in a murine model of spinal cord ischemia-reperfusion.

PubMed

Bell, Marshall T; Reece, T Brett; Smith, Phillip D; Mares, Joshua; Weyant, Michael J; Cleveland, Joseph C; Freeman, Kirsten A; Fullerton, David A; Puskas, Ferenc

2014-03-03

Lower extremity paralysis continues to complicate aortic interventions. The lack of understanding of the underlying pathology has hindered advancements to decrease the occurrence this injury. The current model demonstrates reproducible lower extremity paralysis following thoracic aortic occlusion. Adult male C57BL6 mice were anesthetized with isoflurane. Through a cervicosternal incision the aorta was exposed. The descending thoracic aorta and left subclavian arteries were identified without entrance into pleural space. Skeletonization of these arteries was followed by immediate closure (Sham) or occlusion for 4 min (moderate ischemia) or 8 min (prolonged ischemia). The sternotomy and skin were closed and the mouse was transferred to warming bed for recovery. Following recovery, functional analysis was obtained at 12 hr intervals until 48 hr. Mice that underwent sham surgery showed no observable hind limb deficit. Mice subjected to moderate ischemia for 4 min had minimal functional deficit at 12 hr followed by progression to complete paralysis at 48 hr. Mice subjected to prolonged ischemia had an immediate paralysis with no observable hind-limb movement at any point in the postoperative period. There was no observed intraoperative or post operative mortality. Reproducible lower extremity paralysis whether immediate or delayed can be achieved in a murine model. Additionally, by using a median sternotomy and careful dissection, high survival rates, and reproducibility can be achieved.

Real-time imaging for cerebral ischemia in rats using the multi-wavelength handheld photoacoustic system

NASA Astrophysics Data System (ADS)

Liu, Yu-Hang; Xu, Yu; Chan, Kim Chuan; Mehta, Kalpesh; Thakor, Nitish; Liao, Lun-De

2017-02-01

Stroke is the second leading cause of death worldwide. Rapid and precise diagnosis is essential to expedite clinical decision and improve functional outcomes in stroke patients; therefore, real-time imaging plays an important role to provide crucial information for post-stroke recovery analysis. In this study, based on the multi-wavelength laser and 18.5 MHz array-based ultrasound platform, a real-time handheld photoacoustic (PA) system was developed to evaluate cerebrovascular functions pre- and post-stroke in rats. Using this system, hemodynamic information such as cerebral blood volume (CBV) can be acquired for assessment. One rat stroke model (i.e., photothrombotic ischemia (PTI)) was employed for evaluating the effect of local ischemia. For achieving better intrinsic PA contrast, Vantage and COMSOL simulations were applied to optimize the light delivery (e.g., interval between two arms) from customized fiber bundle, while phantom experiment was conducted to evaluate the imaging performance of this system. Results of phantom experiment showed that hairs ( 150 μm diameter) and pencil lead (500 μm diameter) can be imaged clearly. On the other hand, results of in vivo experiments also demonstrated that stroke symptoms can be observed in PTI model poststroke. In the near future, with the help of PA specific contrast agent, the system would be able to achieve blood-brain barrier leakage imaging post-stroke. Overall, the real-time handheld PA system holds great potential in disease models involving impairments in cerebrovascular functions.

Efficient Warm-ups: Creating a Warm-up That Works.

ERIC Educational Resources Information Center

Lauffenburger, Sandra Kay

1992-01-01

Proper warm-up is important for any activity, but designing an effective warm-up can be time consuming. An alternative approach is to take a cue from Laban Movement Analysis (LMA) and consider movement design from the perspective of space and planes of motion. Efficient warm-up exercises using LMA are described. (SM)

Regulation of body temperature and neuroprotection by endogenous interleukin-6 in cerebral ischemia.

PubMed

Herrmann, Oliver; Tarabin, Victoria; Suzuki, Shigeaki; Attigah, Nicolas; Coserea, Irinel; Schneider, Armin; Vogel, Johannes; Prinz, Simone; Schwab, Stefan; Monyer, Hannah; Brombacher, Frank; Schwaninger, Markus

2003-04-01

Although the function of fever is still unclear, it is now beyond doubt that body temperature influences the outcome of brain damage. An elevated body temperature is often found in stroke patients and denotes a bad prognosis. However, the pathophysiologic basis and treatment options of elevated body temperature after stroke are still unknown. Cerebral ischemia rapidly induced neuronal interleukin-6 (IL-6) expression in mice. In IL-6-deficient mice, body temperature was markedly decreased after middle cerebral artery occlusion (MCAO), but infarct size was comparable to that in control mice. If body temperature was controlled by external warming after MCAO, IL-6-deficient mice had a reduced survival, worse neurologic status, and larger infarcts than control animals. In cell culture, IL-6 exerted an antiapoptotic and neuroprotective effect. These data suggest that IL-6 is a key regulator of body temperature and an endogenous neuroprotectant in cerebral ischemia. Neuroprotective properties apparently compensate for its pyretic action after MCAO and enhance the safety of this endogenous pyrogen.

Effect of complete hilar versus only renal artery clamping on renal histomorphology following ischemia/reperfusion injury in an experimental model.

PubMed

Umul, M; Cal, A C; Turna, B; Oktem, G; Aydın, H H

2016-01-01

To evaluate the effect of temporary complete hilar versus only renal artery clamping with different duration of warm ischemia on renal functions, and possibly identify a "safe" clamping type and duration of renal ischemia. Fifty male rabbits have been incorporated to study. Rabbits were subjected to ischemia/reperfusion injury by temporary vascular clamping. Reagents were randomized to 3 experimental groups (only renal artery clamping, complete hilar clamping, sham surgery) and sub-groups were determined according to different clamping times (30 and 60 minutes). Median laparotomy and left renal hilus dissection were performed to sham group. Only artery or complete hilar clamping was performed for 30 or 60 minutes by microvascular bulldog clamps to other reagents. Rabbits were sacrificed 10 days after primary surgery and left nephrectomy performed. Nephrectomy materials were evaluated for the level of nitric-oxide synthase (NOS) immunoreactivity, malondialdehyde (MDA) level and superoxide dismutase (SOD) activity and an electron microscopic examination was performed. NOS immunoreactivity was correlated with the temporary clamping time. We also observed that complete hilar vascular clamping entails an increase on NOS immunoreactivity. MDA levels were similar for all experimental surgery groups (p = 0.42). The SOD activity was decreased among all subgroups compared with sham surgery. But the significant decrease occurred in 30 minutes only artery and 30 minutes complete hilar clamping groups in proportion to sham surgery (p = 0.026 and p = 0.019, respectively). This current study suggested that only renal artery clamping under 30 minutes is more appropriate during renal surgical procedures requiring temporary vascular clamping.

Effect of limited ischemia time on the amount and function of mitochondria within human skeletal muscle cells.

PubMed

Jawhar, A; Ponelies, N; Schild, L

2016-12-01

The clinical success of total knee arthroplasty (TKA) depends substantially on the quadriceps muscle function. A frequently applied thigh tourniquet during TKA may induce ischemia related injuries to quadriceps muscle cells. Animal limb muscles subjected to 2-5 h ischemia revealed dysfunctional mitochondria, which in turn compromised the cellular bioenergetics and increased the level of reactive oxygen species. The hypothesis of the present study was that tourniquet application during TKA for 60 min (min) affects the amount and function of mitochondria within musculus vastus medialis cells. In a randomized clinical trial, 10 patients enrolled to undergo primary TKA. The patients were randomly assigned to the tourniquet (n = 5) or non-tourniquet group (n = 5) after obtaining a written informed consent. For each of the groups, the first muscle biopsy was harvested immediately after performing the surgical approach and the second biopsy exactly 60 min later. All biopsies (5 × 5 × 5 mm) 125 mm 3 were harvested from musculus vastus medialis and snap-frozen in liquid nitrogen. The biochemical analysis of the prepared muscle tissues included the measurement of activities of mitochondrial respiratory chain enzyme complexes I-III and citrate synthase. Tourniquet-induced 60 min ischemia time did not significantly change the activities of the mitochondrial respiratory chain enzymes complexes I-III of the skeletal muscle cells. The citrate synthase activities found to be not significantly different between both groups. The use of tourniquet during TKA within a limited time period of 60 min remained without substantial effects on the amount and function of mitochondria within human skeletal muscle cells.

Global assessment of experimental climate warming on tundra vegetation: heterogeneity over space and time.

PubMed

Elmendorf, Sarah C; Henry, Gregory H R; Hollister, Robert D; Björk, Robert G; Bjorkman, Anne D; Callaghan, Terry V; Collier, Laura Siegwart; Cooper, Elisabeth J; Cornelissen, Johannes H C; Day, Thomas A; Fosaa, Anna Maria; Gould, William A; Grétarsdóttir, Járngerður; Harte, John; Hermanutz, Luise; Hik, David S; Hofgaard, Annika; Jarrad, Frith; Jónsdóttir, Ingibjörg Svala; Keuper, Frida; Klanderud, Kari; Klein, Julia A; Koh, Saewan; Kudo, Gaku; Lang, Simone I; Loewen, Val; May, Jeremy L; Mercado, Joel; Michelsen, Anders; Molau, Ulf; Myers-Smith, Isla H; Oberbauer, Steven F; Pieper, Sara; Post, Eric; Rixen, Christian; Robinson, Clare H; Schmidt, Niels Martin; Shaver, Gaius R; Stenström, Anna; Tolvanen, Anne; Totland, Orjan; Troxler, Tiffany; Wahren, Carl-Henrik; Webber, Patrick J; Welker, Jeffery M; Wookey, Philip A

2012-02-01

Understanding the sensitivity of tundra vegetation to climate warming is critical to forecasting future biodiversity and vegetation feedbacks to climate. In situ warming experiments accelerate climate change on a small scale to forecast responses of local plant communities. Limitations of this approach include the apparent site-specificity of results and uncertainty about the power of short-term studies to anticipate longer term change. We address these issues with a synthesis of 61 experimental warming studies, of up to 20 years duration, in tundra sites worldwide. The response of plant groups to warming often differed with ambient summer temperature, soil moisture and experimental duration. Shrubs increased with warming only where ambient temperature was high, whereas graminoids increased primarily in the coldest study sites. Linear increases in effect size over time were frequently observed. There was little indication of saturating or accelerating effects, as would be predicted if negative or positive vegetation feedbacks were common. These results indicate that tundra vegetation exhibits strong regional variation in response to warming, and that in vulnerable regions, cumulative effects of long-term warming on tundra vegetation - and associated ecosystem consequences - have the potential to be much greater than we have observed to date. © 2011 Blackwell Publishing Ltd/CNRS.

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

Spring Temperatures Alone Cannot Explain Timing of Budburst of Boreal-Temperate Tree Species under Experimental Warming

NASA Astrophysics Data System (ADS)

Montgomery, R. A.; Reich, P. B.; Rich, R. L.; Stefanski, A.

2011-12-01

Phenology, the timing of seasonal biological events such as budburst, blossom dates, bird migration and insect development, is critical to understanding species interactions (e.g. pollination, herbivory); determines growing season length in many (i.e. seasonal) terrestrial ecosystems; and can play a role in determining species range limits. There is ample evidence that plant and animal phenology has changed in recent decades. For trees in seasonally cold climates, change is most commonly manifested as earlier budburst, likely caused by earlier onset of warming temperatures in spring. Indeed, it is often assumed that one of the major phenological responses of temperate and boreal forest ecosystems to climate change will be earlier leafing and concomitantly, a longer growing season. However, spring warming interacts with other factors such as winter chilling and photoperiod to determine timing of spring leafing. For example, warmer winters could reduce the duration and amount of chilling experienced by dormant buds and lead to delayed budburst. Despite knowledge that such interactions exist, we know little about the interactive mechanisms by which various cues influence budburst in forest tree species or whether species differ in sensitivity to those cues. This gap hinders our ability to predict phenological responses and their ecological impacts under future climate scenarios. Over the past three years, we have conducted studies of leafing phenology, germination, photosynthesis, respiration, and growth of seedlings of ten boreal-temperate tree species subjected to experimental warming using infrared heat lamps and soil heating cables. Seedlings were planted into plots receiving ambient, +1.8°C or +3.6°C temperature treatments in open, aspen forest at the Cloquet Forestry Center, Cloquet, MN, USA (46°31' N, 92°30' W, 386 m a.s.l.; 4.5°C MAT, 807 mm MAP). While all species responded to warming by advancing the absolute date of budburst, several lines of evidence

In vivo determination of acute myocardial ischemia based on photoacoustic imaging with a focused transducer

NASA Astrophysics Data System (ADS)

Li, Zhifang; Li, Hui; Chen, Haiyu; Xie, Wengming

2011-07-01

The location and ischemia extent are two important parameters for evaluating the acute myocardial ischemia (AMI). A focused-transducer-based photoacoustic imaging method was employed to assess time-dependent AMI. Our preliminary results show that the photoacoustic signal could identify the myocardium. The intensity and area of photoacoustic images of myocardium could be used for characterizing the ischemia extent and scope of myocardial ischemia. The results also imply that the intensity and area of photoacoustic images are the rapid fall of an exponential model with an increase of delaying time after the left anterior descending coronary artery (LAD) occlusion. These experimental results were consistent with the clinical characteristics. The findings suggest that the photoacoustic imaging be a potential tool for the real-time assessment of acute myocardial ischemia during surgical operation.

Considering time in LCA: dynamic LCA and its application to global warming impact assessments.

PubMed

Levasseur, Annie; Lesage, Pascal; Margni, Manuele; Deschênes, Louise; Samson, Réjean

2010-04-15

The lack of temporal information is an important limitation of life cycle assessment (LCA). A dynamic LCA approach is proposed to improve the accuracy of LCA by addressing the inconsistency of temporal assessment. This approach consists of first computing a dynamic life cycle inventory (LCI), considering the temporal profile of emissions. Then, time-dependent characterization factors are calculated to assess the dynamic LCI in real-time impact scores for any given time horizon. Although generally applicable to any impact category, this approach is developed here for global warming, based on the radiative forcing concept. This case study demonstrates that the use of global warming potentials for a given time horizon to characterize greenhouse gas emissions leads to an inconsistency between the time frame chosen for the analysis and the time period covered by the LCA results. Dynamic LCA is applied to the US EPA LCA on renewable fuels, which compares the life cycle greenhouse gas emissions of different biofuels with fossil fuels including land-use change emissions. The comparison of the results obtained with both traditional and dynamic LCA approaches shows that the difference can be important enough to change the conclusions on whether or not a biofuel meets some given global warming reduction targets.

Absolute Cerebral Blood Flow Infarction Threshold for 3-Hour Ischemia Time Determined with CT Perfusion and 18F-FFMZ-PET Imaging in a Porcine Model of Cerebral Ischemia

PubMed Central

Cockburn, Neil; Kovacs, Michael

2016-01-01

CT Perfusion (CTP) derived cerebral blood flow (CBF) thresholds have been proposed as the optimal parameter for distinguishing the infarct core prior to reperfusion. Previous threshold-derivation studies have been limited by uncertainties introduced by infarct expansion between the acute phase of stroke and follow-up imaging, or DWI lesion reversibility. In this study a model is proposed for determining infarction CBF thresholds at 3hr ischemia time by comparing contemporaneously acquired CTP derived CBF maps to 18F-FFMZ-PET imaging, with the objective of deriving a CBF threshold for infarction after 3 hours of ischemia. Endothelin-1 (ET-1) was injected into the brain of Duroc-Cross pigs (n = 11) through a burr hole in the skull. CTP images were acquired 10 and 30 minutes post ET-1 injection and then every 30 minutes for 150 minutes. 370 MBq of 18F-FFMZ was injected ~120 minutes post ET-1 injection and PET images were acquired for 25 minutes starting ~155–180 minutes post ET-1 injection. CBF maps from each CTP acquisition were co-registered and converted into a median CBF map. The median CBF map was co-registered to blood volume maps for vessel exclusion, an average CT image for grey/white matter segmentation, and 18F-FFMZ-PET images for infarct delineation. Logistic regression and ROC analysis were performed on infarcted and non-infarcted pixel CBF values for each animal that developed infarct. Six of the eleven animals developed infarction. The mean CBF value corresponding to the optimal operating point of the ROC curves for the 6 animals was 12.6 ± 2.8 mL·min-1·100g-1 for infarction after 3 hours of ischemia. The porcine ET-1 model of cerebral ischemia is easier to implement then other large animal models of stroke, and performs similarly as long as CBF is monitored using CTP to prevent reperfusion. PMID:27347877

The rise of global warming skepticism: exploring affective image associations in the United States over time.

PubMed

Smith, Nicholas; Leiserowitz, Anthony

2012-06-01

This article explores how affective image associations to global warming have changed over time. Four nationally representative surveys of the American public were conducted between 2002 and 2010 to assess public global warming risk perceptions, policy preferences, and behavior. Affective images (positive or negative feelings and cognitive representations) were collected and content analyzed. The results demonstrate a large increase in "naysayer" associations, indicating extreme skepticism about the issue of climate change. Multiple regression analyses found that holistic affect and "naysayer" associations were more significant predictors of global warming risk perceptions than cultural worldviews or sociodemographic variables, including political party and ideology. The results demonstrate the important role affective imagery plays in judgment and decision-making processes, how these variables change over time, and how global warming is currently perceived by the American public. © 2012 Society for Risk Analysis.

Isoflurane administration before ischemia and during reperfusion attenuates ischemia/reperfusion-induced injury of isolated rabbit lungs.

PubMed

Liu, R; Ishibe, Y; Ueda, M; Hang, Y

1999-09-01

To investigate the effects of isoflurane on ischemia/ reperfusion (IR)-induced lung injury, we administered isoflurane before ischemia or during reperfusion. Isolated rabbit lungs were divided into the following groups: control (n = 6), perfused and ventilated for 120 min without ischemia; ISO-control (n = 6), 1 minimum alveolar anesthetic concentration (MAC) isoflurane was administered for 30 min before 120 min continuous perfusion; IR (n = 6), ischemia for 60 min, followed by 60 min reperfusion; IR-ISO1 and IR-ISO2, ischemia followed by reperfusion and 1 MAC (n = 6) or 2 MAC (n = 6) isoflurane for 60 min; ISO-IR (n = 6), 1 MAC isoflurane was administered for 30 min before ischemia, followed by IR. During these maneuvers, we measured total pulmonary vascular resistance (Rt), coefficient of filtration (Kfc), and lung wet to dry ratio (W/D). The results indicated that administration of isoflurane during reperfusion inhibited an IR-induced increase in Kfc and W/D ratio. Furthermore, isoflurane at 2 MAC, but not 1 MAC, significantly inhibited an IR-induced increase in Rt. The administration of isoflurane before ischemia significantly attenuated the increase in IR-induced Kfc, W/D, and Rt. Our results suggest that the administration of isoflurane before ischemia and during reperfusion protects against ischemia-reperfusion-induced injury in isolated rabbit lungs.

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.

Progress towards an ab initio real-time treatment of warm dense matter

NASA Astrophysics Data System (ADS)

Baczewski, Andrew; Cangi, Attila; Hansen, Stephanie; Jensen, Daniel

2017-10-01

Time-dependent density functional theory (TDDFT) provides an accurate description of equilibrium properties of warm dense matter, such as the dynamic structure factor (Baczewski et al., Phys. Rev. Lett., 116(11), 2016). While non-equilibrium properties, such as stopping power, have also been demonstrated to be within the grasp of TDDFT, the ultrafast isochoric heating of condensed matter into the warm dense state, enabled by recent advances in XFELs, remains beyond its capabilities. In this talk, we will describe the successes of and continuing challenges for TDDFT for warm dense matter, and present progress towards a more complete ab initio treatment of isochoric x-ray heating. Sandia National Laboratories is a multi-mission laboratory managed and operated by National Technology and Engineering Solutions of Sandia, LLC, a wholly owned subsidiary of Honeywell International, Inc., for the DOE's National Nuclear Security Administration under contract DE-NA0003525.

Altered responsiveness of the guinea-pig isolated ileum to smooth muscle stimulants and to electrical stimulation after in situ ischemia.

PubMed

Rodriguez, Rodolfo; Ventura-Martinez, Rosa; Santiago-Mejia, Jacinto; Avila-Costa, Maria R; Fortoul, Teresa I

2006-02-01

1. We evaluated changes in contractility of the guinea-pig isolated ileum, using intact segments and myenteric plexus-longitudinal muscle (MPLM) preparations, after several times (5-160 min) of ischemia in situ. 2. Intestinal ischemia was produced by clamping the superior mesenteric artery. Ischemic and nonischemic segments, obtained from the same guinea-pig, were mounted in organ baths containing Krebs-bicarbonate (K-B) solution, maintained at 37 degrees C and gassed with 95% O2/5% CO2. The preparations were allowed to equilibrate for 60 min under continuous superfusion of warm K-B solution and then electrically stimulated at 40 V (0.3 Hz, 3.0 ms). Thereafter, complete noncumulative concentration-response curves were constructed for acetylcholine (ACh), histamine (HIS), potassium chloride (KCl), and barium chloride (BaCl2). Mean Emax (maximal response) values were calculated for each drug. 3. Our study shows that alterations of chemically and electrically evoked contractions are dependent on ischemic periods. It also demonstrates that contractile responses of ischemic tissues to neurogenic stimulation decreases earlier and to a significantly greater extent than the non-nerve mediated responses of the intestinal smooth muscle. Contractile responses to smooth muscle stimulants were all similarly affected by ischemia. Electron microscopy images indicated necrotic neuronal death. The decrease in reactivity of ischemic tissues to electrical stimulation was ameliorated by dexrazoxane, an antioxidant agent. 4. We consider the guinea-pig isolated ileum as a useful model system to study the processes involved in neuronal ischemia, and we propose that the reduction in maximal responses to electrical stimulation is a useful parameter to study neuroprotection.

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.

Novel Biomarkers of Arterial and Venous Ischemia in Microvascular Flaps

PubMed Central

Nguyen, Gerard K.; Monahan, John F. W.; Davis, Gabrielle B.; Lee, Yong Suk; Ragina, Neli P.; Wang, Charles; Zhou, Zhao Y.; Hong, Young Kwon; Spivak, Ryan M.; Wong, Alex K.

2013-01-01

The field of reconstructive microsurgery is experiencing tremendous growth, as evidenced by recent advances in face and hand transplantation, lower limb salvage after trauma, and breast reconstruction. Common to all of these procedures is the creation of a nutrient vascular supply by microsurgical anastomosis between a single artery and vein. Complications related to occluded arterial inflow and obstructed venous outflow are not uncommon, and can result in irreversible tissue injury, necrosis, and flap loss. At times, these complications are challenging to clinically determine. Since early intervention with return to the operating room to re-establish arterial inflow or venous outflow is key to flap salvage, the accurate diagnosis of early stage complications is essential. To date, there are no biochemical markers or serum assays that can predict these complications. In this study, we utilized a rat model of flap ischemia in order to identify the transcriptional signatures of venous congestion and arterial ischemia. We found that the critical ischemia time for the superficial inferior epigastric fasciocutaneus flap was four hours and therefore performed detailed analyses at this time point. Histolgical analysis confirmed significant differences between arterial and venous ischemia. The transcriptome of ischemic, congested, and control flap tissues was deciphered by performing Affymetrix microarray analysis and verified by qRT-PCR. Principal component analysis revealed that arterial ischemia and venous congestion were characterized by distinct transcriptomes. Arterial ischemia and venous congestion was characterized by 408 and 1536>2-fold differentially expressed genes, respectively. qRT-PCR was used to identify five candidate genes Prol1, Muc1, Fcnb, Il1b, and Vcsa1 to serve as biomarkers for flap failure in both arterial ischemia and venous congestion. Our data suggests that Prol1 and Vcsa1 may be specific indicators of venous congestion and allow clinicians to

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.

Assessing the magnitude and timing of anthropogenic warming of a shallow aquifer: example from Virginia Beach, USA

USGS Publications Warehouse

Eggleston, John R.; McCoy, Kurt J.

2015-01-01

Groundwater temperature measurements in a shallow coastal aquifer in Virginia Beach, Virginia, USA, suggest groundwater warming of +4.1 °C relative to deeper geothermal gradients. Observed warming is related to timing and depth of influence of two potential thermal drivers—atmospheric temperature increases and urbanization. Results indicate that up to 30 % of groundwater warming at the water table can be attributed to atmospheric warming while up to 70 % of warming can be attributed to urbanization. Groundwater temperature readings to 30-m depth correlate positively with percentage of impervious cover and negatively with percentage of tree canopy cover; thus, these two land-use metrics explain up to 70 % of warming at the water table. Analytical and numerical modeling results indicate that an average vertical groundwater temperature profile for the study area, constructed from repeat measurement at 11 locations over 15 months, is consistent with the timing of land-use change over the past century in Virginia Beach. The magnitude of human-induced warming at the water table (+4.1 °C) is twice the current seasonal temperature variation, indicating the potential for ecological impacts on wetlands and estuaries receiving groundwater discharge from shallow aquifers.

The influence of climate change and the timing of stratospheric warmings on Arctic ozone depletion

NASA Astrophysics Data System (ADS)

Austin, John; Butchart, Neal

1994-01-01

Satellite data are presented showing the timing of sudden warmings in the lower stratosphere during the winters 1979-1992. A three-dimensional dynamical-radiative-photochemical model is used to establish how Arctic ozone depletion will respond to a doubling of CO2 according to the timing of the warmings. In a series of idealized experiments the timing of the warmings is varied by specifying different geopotential wave amplitudes at the 316-mbar model lower boundary. Results from a "transient climate change experiment" show that the chosen wave amplitudes are appropriate for both the current and the doubled CO2 atmosphere. For doubled CO2 the experiments show that any significant risk of an Arctic ozone hole will be confined to those years with only a late stratospheric warming. In all other years the results suggest that springtime total ozone over the Arctic is more likely to increase by a small amount due to a combination of slower homogeneous chemistry and changes in transport. The predictions obtained from the idealized studies are then tested by prescribing at the model lower boundary the observed geopotential wave amplitudes from two specific years with late winter warmings. Doubling CO2 amounts produced no significant increase in ozone depletion with the 1989 wave amplitudes, but with 1990 wave amplitudes, an Arctic ozone hole occurred with minimum column of 187 Dobson Units. This contrasting response is attributed to the large midwinter pulse in the 1989 wave amplitudes compared to the less dramatic and shorter timescale fluctuations in the 1990 wave amplitudes. It is concluded that under doubled CO2 conditions an Arctic ozone hole is likely to occur in years with late stratospheric warmings following winters in which there were no significant pulses in the upper tropospheric planetary wave amplitudes.

The protective effects of shikonin on hepatic ischemia/reperfusion injury are mediated by the activation of the PI3K/Akt pathway

PubMed Central

Liu, Tong; Zhang, QingHui; Mo, Wenhui; Yu, Qiang; Xu, Shizan; Li, Jingjing; Li, Sainan; Feng, Jiao; Wu, Liwei; Lu, Xiya; Zhang, Rong; Li, Linqiang; Cheng, Keran; Zhou, Yuqing; Zhou, Shunfeng; Kong, Rui; Wang, Fan; Dai, Weiqi; Chen, Kan; Xia, Yujing; Lu, Jie; Zhou, Yingqun; Zhao, Yan; Guo, Chuanyong

2017-01-01

Hepatic ischemia/reperfusion (I/R) injury, which can result in severe liver injury and dysfunction, occurs in a variety of conditions such as liver transplantation, shock, and trauma. Cell death in hepatic I/R injury has been linked to apoptosis and autophagy. Shikonin plays a significant protective role in ischemia/reperfusion injury. The purpose of the present study was to investigate the protective effect of shikonin on hepatic I/R injury and explore the underlying mechanism. Mice were subjected to segmental (70%) hepatic warm ischemia to induce hepatic I/R injury. Two doses of shikonin (7.5 and 12.5 mg/kg) were administered 2 h before surgery. Balb/c mice were randomly divided into four groups: normal control, I/R, and shikonin preconditioning at two doses (7.5 and 12.5 mg/kg). The serum and liver tissues were collected at three time points (3, 6, and 24 h). Shikonin significantly reduced serum AST and ALT levels and improved pathological features. Shikonin affected the expression of Bcl-2, Bax, caspase 3, caspase 9, Beclin-1, and LC3, and upregulated PI3K and p-Akt compared with the levels in the I/R group. Shikonin attenuated hepatic I/R injury by inhibiting apoptosis and autophagy through a mechanism involving the activation of PI3K/Akt signaling. PMID:28322249

Effect of the timing of ice slurry ingestion for precooling on endurance exercise capacity in a warm environment.

PubMed

Takeshima, Keisuke; Onitsuka, Sumire; Xinyan, Zheng; Hasegawa, Hiroshi

2017-04-01

It has been demonstrated that precooling with ice slurry ingestion enhances endurance exercise capacity in the heat. However, no studies have yet evaluated the optimal timing of ice slurry ingestion for precooling. This study aimed to investigate the effects of varying the timing of ice slurry ingestion for precooling on endurance exercise capacity in a warm environment. Ten active male participants completed 3 experimental cycling trials to exhaustion at 55% peak power output (PPO) after 15min of warm-up at 30% PPO at 30°C and 80% relative humidity. Three experimental conditions were set: no ice slurry ingestion (CON), pre-warm-up ice slurry ingestion (-1°C; 7.5gkg -1 ) (PRE), and post-warm-up ice slurry ingestion (POST). Rectal and mean skin temperatures at the beginning of exercise in the POST condition (37.1±0.2°C, 33.8±0.9°C, respectively) were lower than those in the CON (37.5±0.3°C; P<0.001, 34.8±0.8°C; P<0.01, respectively) and PRE (37.4±0.2°C; P<0.01, 34.6±0.7°C; P<0.01, respectively) conditions. These reductions increased heat storage capacity and resulted in improved exercise capacity in the POST condition (60.2±8.7min) compared to that in the CON (52.0±11.9min; effect size [ES]=0.78) and PRE (56.9±10.4min; ES=0.34) conditions. Ice slurry ingestion after warm-up effectively reduced both rectal and skin temperatures and increased cycling time to exhaustion in a warm environment. Timing ice slurry ingestion to occur after warm-up may be effective for precooling in a warm environment. Copyright © 2017 Elsevier Ltd. All rights reserved.

Real-Time 12-Lead High-Frequency QRS Electrocardiography for Enhanced Detection of Myocardial Ischemia and Coronary Artery Disease

NASA Technical Reports Server (NTRS)

Schlegel, Todd T.; Kulecz, Walter B.; DePalma, Jude L.; Feiveson, Alan H.; Wilson, John S.; Rahman, M. Atiar; Bungo, Michael W.

2004-01-01

Several studies have shown that diminution of the high-frequency (HF; 150-250 Hz) components present within the central portion of the QRS complex of an electrocardiogram (ECG) is a more sensitive indicator for the presence of myocardial ischemia than are changes in the ST segments of the conventional low-frequency ECG. However, until now, no device has been capable of displaying, in real time on a beat-to-beat basis, changes in these HF QRS ECG components in a continuously monitored patient. Although several software programs have been designed to acquire the HF components over the entire QRS interval, such programs have involved laborious off-line calculations and postprocessing, limiting their clinical utility. We describe a personal computer-based ECG software program developed recently at the National Aeronautics and Space Administration (NASA) that acquires, analyzes, and displays HF QRS components in each of the 12 conventional ECG leads in real time. The system also updates these signals and their related derived parameters in real time on a beat-to-beat basis for any chosen monitoring period and simultaneously displays the diagnostic information from the conventional (low-frequency) 12-lead ECG. The real-time NASA HF QRS ECG software is being evaluated currently in multiple clinical settings in North America. We describe its potential usefulness in the diagnosis of myocardial ischemia and coronary artery disease.

Left ventricular function abnormalities as a manifestation of silent myocardial ischemia.

PubMed

Lambert, C R; Conti, C R; Pepine, C J

1986-11-01

A large body of evidence exists indicating that left ventricular dysfunction is a common occurrence in patients with severe coronary artery disease and represents silent or asymptomatic myocardial ischemia. Such dysfunction probably occurs early in the time course of every ischemic episode in patients with coronary artery disease whether symptoms are eventually manifested or not. The pathophysiology of silent versus symptomatic left ventricular dysfunction due to ischemia appears to be identical. Silent ischemia-related left ventricular dysfunction can be documented during spontaneous or stress-induced perturbations in the myocardial oxygen supply/demand ratio. It also may be detected by nitroglycerin-induced improvement in ventricular function or by salutary changes in wall motion following revascularization. Silent left ventricular dysfunction is a very early occurrence during ischemia and precedes electrocardiographic abnormalities. In this light, its existence should always be kept in mind when dealing with patients with ischemic heart disease. It can be hypothesized that because silent ischemia appears to be identical to ischemia with symptoms in a pathophysiologic sense, prognosis and treatment in both cases should be the same.

Repetitive ischemia increases myocardial dimethylarginine dimethylaminohydrolase 1 expression.

PubMed

Zhang, Ping; Fassett, John T; Zhu, Guangshuo; Li, Jingxin; Hu, Xinli; Xu, Xin; Chen, Yingjie; Bache, Robert J

2017-06-01

Pharmacologic inhibition of nitric oxide production inhibits growth of coronary collateral vessels. Dimethylarginine dimethylaminohydrolase 1 (DDAH1) is the major enzyme that degrades asymmetric dimethylarginine (ADMA), a potent inhibitor of nitric oxide synthase. Here we examined regulation of the ADMA-DDAH1 pathway in a canine model of recurrent myocardial ischemia during the time when coronary collateral growth is known to occur. Under basal conditions, DDAH1 expression was non-uniform across the left ventricular (LV) wall, with expression strongest in the subepicardium. In response to ischemia, DDAH1 expression was up-regulated in the midmyocardium of the ischemic zone, and this was associated with a significant reduction in myocardial interstitial fluid (MIF) ADMA. The decrease in MIF ADMA during ischemia was likely due to increased DDAH1 because myocardial protein arginine N-methyl transferase 1 (PRMT1) and the methylated arginine protein content (the source of ADMA) were unchanged or increased, respectively, at this time. The inflammatory mediators interleukin (IL-1β) and tumor necrosis factor (TNF-α) were also elevated in the midmyocardium where DDAH1 expression was increased. Both of these factors significantly up-regulated DDAH1 expression in cultured human coronary artery endothelial cells. Taken together, these results suggest that inflammatory factors expressed in response to myocardial ischemia contributed to up-regulation of DDAH1, which was responsible for the decrease in MIF ADMA.

Limb remote-preconditioning protects against focal ischemia in rats and contradicts the dogma of therapeutic time windows for preconditioning

PubMed Central

Ren, Chuancheng; Gao, Xuwen; Steinberg, Gary K.; Zhao, Heng

2009-01-01

Remote ischemic preconditioning is an emerging concept for stroke treatment, but its protection against focal stroke has not been established. We tested whether remote preconditioning, performed in the ipsilateral hind limb, protects against focal stroke and explored its protective parameters. Stroke was generated by a permanent occlusion of the left distal middle cerebral artery (MCA) combined with a 30 minute occlusion of the bilateral common carotid arteries (CCA) in male rats. Limb preconditioning was generated by 5 or 15 minute occlusion followed with the same period of reperfusion of the left hind femoral artery, and repeated for 2 or 3 cycles. Infarct was measured 2 days later. The results showed that rapid preconditioning with 3 cycles of 15 minutes performed immediately before stroke reduced infarct size from 47.7±7.6% of control ischemia to 9.8±8.6%; at 2 cycles of 15 minutes, infarct was reduced to 24.7±7.3%; at 2 cycles of 5 minutes, infarct was not reduced. Delayed preconditioning with 3 cycles of 15 minutes conducted 2 days before stroke also reduced infarct to 23.0 ±10.9%, but with 2 cycles of 15 minutes it offered no protection. The protective effects at these two therapeutic time windows of remote preconditioning are consistent with those of conventional preconditioning, in which the preconditioning ischemia is induced in the brain itself. Unexpectedly, intermediate preconditioning with 3 cycles of 15 minutes performed 12 hours before stroke also reduced infarct to 24.7±4.7%, which contradicts the current dogma for therapeutic time windows for the conventional preconditioning that has no protection at this time point. In conclusion, remote preconditioning performed in one limb protected against ischemic damage after focal cerebral ischemia. PMID:18201834

Global warming and flowering times in Thoreau's Concord: a community perspective.

PubMed

Miller-Rushing, Abraham J; Primack, Richard B

2008-02-01

As a result of climate change, many plants are now flowering measurably earlier than they did in the past. However, some species' flowering times have changed much more than others. Data at the community level can clarify the variation in flowering responses to climate change. In order to determine how North American species' flowering times respond to climate, we analyzed a series of previously unstudied records of the dates of first flowering for over 500 plant taxa in Concord, Massachusetts, USA. These records began with six years of observations by the famous naturalist Henry David Thoreau from 1852 to 1858, continued with 16 years of observations by the botanist Alfred Hosmer in 1878 and 1888-1902, and concluded with our own observations in 2004, 2005, and 2006. From 1852 through 2006, Concord warmed by 2.4 degrees C due to global climate change and urbanization. Using a subset of 43 common species, we determined that plants are now flowering seven days earlier on average than they did in Thoreau's times. Plant flowering times were most correlated with mean temperatures in the one or two months just before flowering and were also correlated with January temperatures. Summer-flowering species showed more interannual variation in flowering time than did spring-flowering species, but the flowering times of spring-flowering species correlated more strongly to mean monthly temperatures. In many cases, such as within the genera Betula and Solidago, closely related, co-occurring species responded to climate very differently from one another. The differences in flowering responses to warming could affect relationships in plant communities as warming continues. Common St. John's wort (Hypericum perforatum) and highbush blueberry (Vaccinium corymbosum) are particularly responsive to changes in climate, are common across much of the United States, and could serve as indicators of biological responses to climate change. We discuss the need for researchers to be aware

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.

Hypoxia-regulated therapeutic gene as a preemptive treatment strategy against ischemia/reperfusion tissue injury.

PubMed

Pachori, Alok S; Melo, Luis G; Hart, Melanie L; Noiseux, Nicholas; Zhang, Lunan; Morello, Fulvio; Solomon, Scott D; Stahl, Gregory L; Pratt, Richard E; Dzau, Victor J

2004-08-17

Ischemia and reperfusion represent major mechanisms of tissue injury and organ failure. The timing of administration and the duration of action limit current treatment approaches using pharmacological agents. In this study, we have successfully developed a preemptive strategy for tissue protection using an adenoassociated vector system containing erythropoietin hypoxia response elements for ischemia-regulated expression of the therapeutic gene human heme-oxygenase-1 (hHO-1). We demonstrate that a single administration of this vector several weeks in advance of ischemia/reperfusion injury to multiple tissues such as heart, liver, and skeletal muscle yields rapid and timely induction of hHO-1 during ischemia that resulted in dramatic reduction in tissue damage. In addition, overexpression of therapeutic transgene prevented long-term pathological tissue remodeling and normalized tissue function. Application of this regulatable system using an endogenous physiological stimulus for expression of a therapeutic gene may be a feasible strategy for protecting tissues at risk of ischemia/reperfusion injury.

Hypoxia-regulated therapeutic gene as a preemptive treatment strategy against ischemia/reperfusion tissue injury

PubMed Central

Pachori, Alok S.; Melo, Luis G.; Hart, Melanie L.; Noiseux, Nicholas; Zhang, Lunan; Morello, Fulvio; Solomon, Scott D.; Stahl, Gregory L.; Pratt, Richard E.; Dzau, Victor J.

2004-01-01

Ischemia and reperfusion represent major mechanisms of tissue injury and organ failure. The timing of administration and the duration of action limit current treatment approaches using pharmacological agents. In this study, we have successfully developed a preemptive strategy for tissue protection using an adenoassociated vector system containing erythropoietin hypoxia response elements for ischemia-regulated expression of the therapeutic gene human heme-oxygenase-1 (hHO-1). We demonstrate that a single administration of this vector several weeks in advance of ischemia/reperfusion injury to multiple tissues such as heart, liver, and skeletal muscle yields rapid and timely induction of hHO-1 during ischemia that resulted in dramatic reduction in tissue damage. In addition, overexpression of therapeutic transgene prevented long-term pathological tissue remodeling and normalized tissue function. Application of this regulatable system using an endogenous physiological stimulus for expression of a therapeutic gene may be a feasible strategy for protecting tissues at risk of ischemia/reperfusion injury. PMID:15302924

Hypoxia-regulated therapeutic gene as a preemptive treatment strategy against ischemia/reperfusion tissue injury

NASA Astrophysics Data System (ADS)

Pachori, Alok S.; Melo, Luis G.; Hart, Melanie L.; Noiseux, Nicholas; Zhang, Lunan; Morello, Fulvio; Solomon, Scott D.; Stahl, Gregory L.; Pratt, Richard E.; Dzau, Victor J.

2004-08-01

Ischemia and reperfusion represent major mechanisms of tissue injury and organ failure. The timing of administration and the duration of action limit current treatment approaches using pharmacological agents. In this study, we have successfully developed a preemptive strategy for tissue protection using an adenoassociated vector system containing erythropoietin hypoxia response elements for ischemia-regulated expression of the therapeutic gene human heme-oxygenase-1 (hHO-1). We demonstrate that a single administration of this vector several weeks in advance of ischemia/reperfusion injury to multiple tissues such as heart, liver, and skeletal muscle yields rapid and timely induction of hHO-1 during ischemia that resulted in dramatic reduction in tissue damage. In addition, overexpression of therapeutic transgene prevented long-term pathological tissue remodeling and normalized tissue function. Application of this regulatable system using an endogenous physiological stimulus for expression of a therapeutic gene may be a feasible strategy for protecting tissues at risk of ischemia/reperfusion injury.

Anterior Segment Ischemia after Strabismus Surgery

PubMed Central

Göçmen, Emine Seyhan; Atalay, Yonca; Evren Kemer, Özlem; Sarıkatipoğlu, Hikmet Yavuz

2017-01-01

A 46-year-old male patient was referred to our clinic with complaints of diplopia and esotropia in his right eye that developed after a car accident. The patient had right esotropia in primary position and abduction of the right eye was totally limited. Primary deviation was over 40 prism diopters at near and distance. The patient was diagnosed with sixth nerve palsy and 18 months after trauma, he underwent right medial rectus muscle recession. Ten months after the first operation, full-thickness tendon transposition of the superior and inferior rectus muscles (with Foster suture) was performed. On the first postoperative day, slit-lamp examination revealed corneal edema, 3+ cells in the anterior chamber and an irregular pupil. According to these findings, the diagnosis was anterior segment ischemia. Treatment with 0.1/5 mL topical dexamethasone drops (16 times/day), cyclopentolate hydrochloride drops (3 times/day) and 20 mg oral fluocortolone (3 times/day) was initiated. After 1 week of treatment, corneal edema regressed and the anterior chamber was clean. Topical and systemic steroid treatment was gradually discontinued. At postoperative 1 month, the patient was orthophoric and there were no pathologic symptoms besides the irregular pupil. Anterior segment ischemia is one of the most serious complications of strabismus surgery. Despite the fact that in most cases the only remaining sequel is an irregular pupil, serious circulation deficits could lead to phthisis bulbi. Clinical properties of anterior segment ischemia should be well recognized and in especially risky cases, preventative measures should be taken. PMID:28182149

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

Liver ischemia and ischemia-reperfusion induces and trafficks the multi-specific metal transporter Atp7b to bile duct canaliculi: possible preferential transport of iron into bile.

PubMed

Goss, John A; Barshes, Neal R; Karpen, Saul J; Gao, Feng-Qin; Wyllie, Samuel

2008-04-01

Both Atp7b (Wilson disease gene) and Atp7a (Menkes disease gene) have been reported to be trafficked by copper. Atp7b is trafficked to the bile duct canaliculi and Atp7a to the plasma membrane. Whether or not liver ischemia or ischemia-reperfusion modulates Atp7b expression and trafficking has not been reported. In this study, we report for the first time that the multi-specific metal transporter Atp7b is significantly induced and trafficked by both liver ischemia alone and liver ischemia-reperfusion, as judged by immunohistochemistry and Western blot analyses. Although hepatocytes also stained for Atp7b, localized intense staining of Atp7b was found on bile duct canaliculi. Inductive coupled plasma-mass spectrometry analysis of bile copper, iron, zinc, and manganese found a corresponding significant increase in biliary iron. In our attempt to determine if the increased biliary iron transport observed may be a result of altered bile flow, lysosomal trafficking, or glutathione biliary transport, we measured bile flow, bile acid phosphatase activity, and glutathione content. No significant difference was found in bile flow, bile acid phosphatase activity, and glutathione, between control livers and livers subjected to ischemia-reperfusion. Thus, we conclude that liver ischemia and ischemia-reperfusion induction and trafficking Atp7b to the bile duct canaliculi may contribute to preferential iron transport into bile.

Stroke onset time estimation from multispectral quantitative magnetic resonance imaging in a rat model of focal permanent cerebral ischemia.

PubMed

McGarry, Bryony L; Rogers, Harriet J; Knight, Michael J; Jokivarsi, Kimmo T; Sierra, Alejandra; Gröhn, Olli Hj; Kauppinen, Risto A

2016-08-01

Quantitative T2 relaxation magnetic resonance imaging allows estimation of stroke onset time. We aimed to examine the accuracy of quantitative T1 and quantitative T2 relaxation times alone and in combination to provide estimates of stroke onset time in a rat model of permanent focal cerebral ischemia and map the spatial distribution of elevated quantitative T1 and quantitative T2 to assess tissue status. Permanent middle cerebral artery occlusion was induced in Wistar rats. Animals were scanned at 9.4T for quantitative T1, quantitative T2, and Trace of Diffusion Tensor (Dav) up to 4 h post-middle cerebral artery occlusion. Time courses of differentials of quantitative T1 and quantitative T2 in ischemic and non-ischemic contralateral brain tissue (ΔT1, ΔT2) and volumes of tissue with elevated T1 and T2 relaxation times (f1, f2) were determined. TTC staining was used to highlight permanent ischemic damage. ΔT1, ΔT2, f1, f2, and the volume of tissue with both elevated quantitative T1 and quantitative T2 (V(Overlap)) increased with time post-middle cerebral artery occlusion allowing stroke onset time to be estimated. V(Overlap) provided the most accurate estimate with an uncertainty of ±25 min. At all times-points regions with elevated relaxation times were smaller than areas with Dav defined ischemia. Stroke onset time can be determined by quantitative T1 and quantitative T2 relaxation times and tissue volumes. Combining quantitative T1 and quantitative T2 provides the most accurate estimate and potentially identifies irreversibly damaged brain tissue. © 2016 World Stroke Organization.

The effects of warmed intravenous fluids, combined warming (warmed intravenous fluids with humid-warm oxygen), and pethidine on the severity of shivering in general anesthesia patients in the recovery room

PubMed Central

Nasiri, Ahmad; Akbari, Ayob; Sharifzade, GholamReza; Derakhshan, Pooya

2015-01-01

Background: Shivering is a common complication of general and epidural anesthesia. Warming methods and many drugs are used for control of shivering in the recovery room. The present study is a randomized clinical trial aimed to investigate the effects of two interventions in comparison with pethidine which is the routine treatment on shivering in patients undergoing abdominal surgery with general anesthesia. Materials and Methods: Eighty-seven patients undergoing abdominal surgery by general anesthesia were randomly assigned to three groups (two intervention groups in comparison with pethidine as routine). Patients in warmed intravenous fluids group received pre-warmed Ringer serum (38°C), patients in combined warming group received pre-warmed Ringer serum (38°C) accompanied by humid-warm oxygen, and patients in pethidine group received intravenous pethidine routinely. The elapsed time of shivering and some hemodynamic parameters of the participants were assessed for 20 min postoperatively in the recovery room. Then the collected data were analyzed by software SPSS (v. 16) with the significance level being P < 0.05. Results: The mean of elapsed time in the warmed intravenous serum group, the combined warming group, and the pethidine group were 7 (1.5) min, 6 (1.5) min, and 2.8 (0.7) min, respectively, which was statistically significant (P < 0.05). The body temperatures in both combined warming and pethidine groups were increased significantly (P < 0.05). Conclusions: Combined warming can be effective in controlling postoperative shivering and body temperature increase. PMID:26793258

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.

Adult mortality probability and nest predation rates explain parental effort in warming eggs with consequences for embryonic development time

USGS Publications Warehouse

Martin, Thomas E.; Oteyza, Juan C.; Boyce, Andy J.; Lloyd, Penn; Ton, Riccardo

2015-01-01

Parental behavior and effort vary extensively among species. Life-history theory suggests that age-specific mortality could cause this interspecific variation, but past tests have focused on fecundity as the measure of parental effort. Fecundity can cause costs of reproduction that confuse whether mortality is the cause or the consequence of parental effort. We focus on a trait, parental allocation of time and effort in warming embryos, that varies widely among species of diverse taxa and is not tied to fecundity. We conducted studies on songbirds of four continents and show that time spent warming eggs varies widely among species and latitudes and is not correlated with clutch size. Adult and offspring (nest) mortality explained most of the interspecific variation in time and effort that parents spend warming eggs, measured by average egg temperatures. Parental effort in warming eggs is important because embryonic temperature can influence embryonic development period and hence exposure time to predation risk. We show through correlative evidence and experimental swapping of embryos between species that parentally induced egg temperatures cause interspecific variation in embryonic development period. The strong association of age-specific mortality with parental effort in warming eggs and the subsequent effects on embryonic development time are unique results that can advance understanding of broad geographic patterns of life-history variation.

Time-resolved X-ray Absorption Spectroscopy for Electron Transport Study in Warm Dense Gold

NASA Astrophysics Data System (ADS)

Lee, Jong-Won; Bae, Leejin; Engelhorn, Kyle; Heimann, Philip; Ping, Yuan; Barbrel, Ben; Fernandez, Amalia; Beckwith, Martha Anne; Cho, Byoung-Ick; GIST Team; IBS Team; LBNL Collaboration; SLAC Collaboration; LLNL Collaboration

2015-11-01

The warm dense Matter represents states of which the temperature is comparable to Fermi energy and ions are strongly coupled. One of the experimental techniques to create such state in the laboratory condition is the isochoric heating of thin metal foil with femtosecond laser pulses. This concept largely relies on the ballistic transport of electrons near the Fermi-level, which were mainly studied for the metals in ambient conditions. However, they were barely investigated in warm dense conditions. We present a time-resolved x-ray absorption spectroscopy measured for the Au/Cu dual layered sample. The front Au layer was isochorically heated with a femtosecond laser pulse, and the x-ray absorption changes around L-edge of Cu, which was attached on the backside of Au, was measured with a picosecond resolution. Time delays between the heating of the `front surface' of Au layer and the alternation of x-ray spectrum of Cu attached on the `rear surface' of Au indicate the energetic electron transport mechanism through Au in the warm dense conditions. IBS (IBS-R012-D1) and the NRF (No. 2013R1A1A1007084) of Korea.

In vivo characterization of acute myocardial ischemia using photoacoustic imaging with a focused transducer

NASA Astrophysics Data System (ADS)

Li, Zhifang; Chen, Haiyu; Xie, Wengming; Li, Hui

2011-03-01

We explore the feasibility of using photoacoustic imaging based on a focused transducer to characterizing acute myocardial ischemia at different stage. In this study, we blocked rat left anterior coronary descending artery (LAD) to induce the acute myocardial ischemia. The results show that the intensity and areas of photoacoustic images of myocardial decrease with the LAD time increasing, which suggests that photoacoustic imaging has a potential for diagnosis of acute myocardial ischemia.

Warm-adapted microbial communities enhance their carbon-use efficiency in warmed soils

NASA Astrophysics Data System (ADS)

Rousk, Johannes; Frey, Serita

2017-04-01

Ecosystem models predict that climate warming will stimulate microbial decomposition of soil carbon (C), resulting in a positive feedback to increasing temperatures. The current generation of models assume that the temperature sensitivities of microbial processes do not respond to warming. However, recent studies have suggested that the ability of microbial communities to adapt to warming can lead both strengthened and weakened feedbacks. A further complication is that the balance between microbial C used for growth to that used for respiration - the microbial carbon-use efficiency (CUE) - also has been shown through both modelling and empirical study to respond to warming. In our study, we set out to assess how chronic warming (+5°C over ambient during 9 years) of a temperate hardwood forest floor (Harvard Forest LTER, USA) affected temperature sensitivities of microbial processes in soil. To do this, we first determined the temperature relationships for bacterial growth, fungal growth, and respiration in plots exposed to warmed or ambient conditions. Secondly, we parametrised the established temperature functions microbial growth and respiration with plot-specific measured soil temperature data at a hourly time-resolution over the course of 3 years to estimate the real-time variation of in situ microbial C production and respiration. To estimate the microbial CUE, we also divided the microbial C production with the sum of microbial C production and respiration as a proxy for substrate use. We found that warm-adapted bacterial and fungal communities both shifted their temperature relationships to grow at higher rates in warm conditions which coincided with reduced rates at cool conditions. As such, their optimal temperature (Topt), minimum temperature (Tmin) and temperature sensitivity (Q10) were all increased. The temperature relationship for temperature, in contrast, was only marginally shifted in the same direction, but at a much smaller effect size, with

Ionizing radiation as preconditioning against transient cerebral ischemia in rats.

PubMed

Kokošová, Natália; Danielisová, Viera; Smajda, Beňadik; Burda, Jozef

2014-01-01

Induction of ischemic tolerance (IT), the ability of an organism to survive an otherwise lethal ischemia, is the most effective known approach to preventing postischemic damage. IT can be induced by exposing animals to a broad range of stimuli. In this study we tried to induce IT of brain neurons using ionizing radiation (IR). A preconditioning (pre-C) dose of 10, 20, 30 or 50 Gy of gamma rays was used 2 days before an 8 min ischemia in adult male rats. Ischemia alone caused the degeneration of almost one half of neurons in CA1 region of hippocampus. However, a significant decrease of the number of degenerating neurons was observed after higher doses of radiation (30 and 50 Gy). Moreover, ischemia significantly impaired the spatial memory of rats as tested in Morris's water maze. In rats with a 50 Gy pre-C dose, the latency times were reduced to values close to the control level. Our study is the first to reveal that IR applied in sufficient doses can induce IT and thus allow pyramidal CA1 neurons to survive ischemia. In addition, we show that the beneficial effect of IR pre-C is proportional to the radiation dose.

Gene expression in cerebral ischemia: a new approach for neuroprotection.

PubMed

Millán, Mónica; Arenillas, Juan

2006-01-01

Cerebral ischemia is one of the strongest stimuli for gene induction in the brain. Hundreds of genes have been found to be induced by brain ischemia. Many genes are involved in neurodestructive functions such as excitotoxicity, inflammatory response and neuronal apoptosis. However, cerebral ischemia is also a powerful reformatting and reprogramming stimulus for the brain through neuroprotective gene expression. Several genes may participate in both cellular responses. Thus, isolation of candidate genes for neuroprotection strategies and interpretation of expression changes have been proven difficult. Nevertheless, many studies are being carried out to improve the knowledge of the gene activation and protein expression following ischemic stroke, as well as in the development of new therapies that modify biochemical, molecular and genetic changes underlying cerebral ischemia. Owing to the complexity of the process involving numerous critical genes expressed differentially in time, space and concentration, ongoing therapeutic efforts should be based on multiple interventions at different levels. By modification of the acute gene expression induced by ischemia or the apoptotic gene program, gene therapy is a promising treatment but is still in a very experimental phase. Some hurdles will have to be overcome before these therapies can be introduced into human clinical stroke trials. Copyright 2006 S. Karger AG, Basel.

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.

Time-dependent postural control adaptations following a neuromuscular warm-up in female handball players: a randomized controlled trial.

PubMed

Steib, Simon; Zahn, Peter; Zu Eulenburg, Christine; Pfeifer, Klaus; Zech, Astrid

2016-01-01

Female handball athletes are at a particular risk of sustaining lower extremity injuries. The study examines time-dependent adaptations of static and dynamic balance as potential injury risk factors to a specific warm-up program focusing on neuromuscular control. Fourty one (24.0 ± 5.9 years) female handball athletes were randomized to an intervention or control group. The intervention group implemented a 15-min specific neuromuscular warm-up program, three times per week for eleven weeks, whereas the control group continued with their regular warm-up. Balance was assessed at five time points. Measures included the star excursion balance test (SEBT), and center of pressure (COP) sway velocity during single-leg standing. No baseline differences existed between groups in demographic data. Adherence to neuromuscular warm-up was 88.7 %. Mean COP sway velocity decreased significantly over time in the intervention group (-14.4 %; p  < .001), but not in the control group (-6.2 %; p  = 0.056). However, these effects did not differ significantly between groups ( p  = .098). Mean changes over time in the SEBT score were significantly greater ( p  = .014) in the intervention group (+5.48) compared to the control group (+3.45). Paired t-tests revealed that the first significant balance improvements were observed after 6 weeks of training. A neuromuscular warm-up positively influences balance variables associated with an increased risk of lower extremity injuries in female handball athletes. The course of adaptations suggests that a training volume of 15 min, three times weekly over at least six weeks produces measurable changes. Retrospectively registered on 4th October 2016. Registry: clinicaltrials.gov. Trial number: NCT02925377.

Impact of Ischemia and Procurement Conditions on Gene Expression in Renal Cell Carcinoma

PubMed Central

Liu, Nick W.; Sanford, Thomas; Srinivasan, Ramaprasad; Liu, Jack L.; Khurana, Kiranpreet; Aprelikova, Olga; Valero, Vladimir; Bechert, Charles; Worrell, Robert; Pinto, Peter A.; Yang, Youfeng; Merino, Maria; Linehan, W. Marston; Bratslavsky, Gennady

2013-01-01

Purpose Previous studies have shown that ischemia alters gene expression in normal and malignant tissues. There are no studies that evaluated effects of ischemia in renal tumors. This study examines the impact of ischemia and tissue procurement conditions on RNA integrity and gene expression in renal cell carcinoma. Experimental Design Ten renal tumors were resected without renal hilar clamping from 10 patients with renal clear cell carcinoma. Immediately after tumor resection, a piece of tumor was snap frozen. Remaining tumor samples were stored at 4C, 22C and 37C and frozen at 5, 30, 60, 120, and 240 minutes. Histopathologic evaluation was performed on all tissue samples, and only those with greater than 80% tumor were selected for further analysis. RNA integrity was confirmed by electropherograms and quantitated using RIN index. Altered gene expression was assessed by paired, two-sample t-test between the zero time point and aliquots from various conditions obtained from the same tumor. Results One hundred and forty microarrays were performed. Some RNA degradation was observed 240 mins after resection at 37C. The expression of over 4,000 genes was significantly altered by ischemia times or storage conditions. The greatest gene expression changes were observed with longer ischemia time and warmer tissue procurement conditions. Conclusion RNA from kidney cancer remains intact for up to 4 hours post surgical resection regardless of storage conditions. Despite excellent RNA preservation, time after resection and procurement conditions significantly influence gene expression profiles. Meticulous attention to pre-acquisition variables is of paramount importance for accurate tumor profiling. PMID:23136194

Current spring warming as a driver of selection on reproductive timing in a wild passerine.

PubMed

Marrot, Pascal; Charmantier, Anne; Blondel, Jacques; Garant, Dany

2018-05-01

Evolutionary adaptation as a response to climate change is expected for fitness-related traits affected by climate and exhibiting genetic variance. Although the relationship between warmer spring temperature and earlier timing of reproduction is well documented, quantifications and predictions of the impact of global warming on natural selection acting on phenology in wild populations remain rare. If global warming affects fitness in a similar way across individuals within a population, or if fitness consequences are independent of phenotypic variation in key-adaptive traits, then no evolutionary response is expected for these traits. Here, we quantified the selection pressures acting on laying date during a 24-year monitoring of blue tits in southern Mediterranean France, a hot spot of climate warming. We explored the temporal fluctuation in annual selection gradients and we determined its temperature-related drivers. We first investigated the month-specific warming since 1970 in our study site and tested its influence on selection pressures, using a model averaging approach. Then, we quantified the selection strength associated with temperature anomalies experienced by the blue tit population. We found that natural selection acting on laying date significantly fluctuated both in magnitude and in sign across years. After identifying a significant warming in spring and summer, we showed that warmer daily maximum temperatures in April were significantly associated with stronger selection pressures for reproductive timing. Our results indicated an increase in the strength of selection by 46% for every +1°C anomaly. Our results confirm the general assumption that recent climate change translates into strong selection favouring earlier breeders in passerine birds. Our findings also suggest that differences in fitness among individuals varying in their breeding phenology increase with climate warming. Such climate-driven influence on the strength of directional

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 prior warm-up duration on the time limit at peak speed in untrained men.

PubMed

da Cruz, Victor H; Peserico, Cecília S; Machado, Fabiana A

2017-10-01

The peak speed (Vpeak) and its time limit (tlim) are variables used to prescribe training loads and the intervals durations during interval training, respectively. The aim of this study was to test different warm-up durations (5, 10 and 15 minutes), adapted from the protocol proposed by Billat et al.,1 to determine tlim in untrained men. Fifteen untrained men were submitted to the following laboratory evaluations: 1) an incremental running exercise test on a treadmill starting with a speed of 8 km/h, after a warm-up of walking at 6 km/h for three minutes, and increased by 1 km/h between each successive 3-minute stage until volitional exhaustion to determine Vpeak; 2) three rectangular tests, performed in randomized order, with warm-up durations of 5, 10, and 15 minutes at 60% of Vpeak to determine the tlim5, tlim10, and tlim15; after the warm-up the tests were performed at the speed of the individual Vpeak until volitional exhaustion. It was demonstrated that the duration of the warm-up affected the test duration (tlim). Significant differences were observed between tlim5 and tlim15, and between tlim10 and tlim15. However, tlim15 and tlim10 did not differ. Additionally, duration of the warm-up did not influence other variables (HRmax, RPEmax and post lactate concentrations). Therefore, it was concluded that the duration of the warm-up in tlim tests modifies the test duration in untrained men.

Impact of upper body precooling during warm-up on subsequent time trial paced cycling in the heat.

PubMed

Katica, Charles P; Wingo, Jonathan E; Herron, Robert L; Ryan, Greg A; Bishop, Stacy H; Richardson, Mark

2018-06-01

The purpose of this study was to test the hypothesis that cooling the upper body during a warm-up enhances performance during a subsequent 16.1-km simulated cycling time trial in a hot environment. Counterbalanced, repeated measures design. Eight trained, male cyclists (peak oxygen uptake=57.8±5.0mLkg -1 min -1 ) completed two simulated 16.1-km time trials in a hot environment (35.0±0.5°C, 43.8±2.0% relative humidity) each separated by 72h. Treatments were counterbalanced; participants warmed up for 20min while either wearing head and neck ice wraps and an ice vest (COOLING) or no cooling apparatus (CONTROL). Following the warm-up mean skin temperature (T¯ sk ), mean body temperature (T¯ b ) and rating of thermal comfort were significantly lower than baseline following the COOLING trial (all P<0.05); however, rectal temperature was unaffected (P=0.35). Because the effects of precooling on T¯ sk and T¯ b were not sustained during exercise, values for COOLING and CONTROL were not different throughout the time trial (P=0.38). Nonetheless, time to completion was significantly faster following the COOLING intervention when compared to the CONTROL (29.3±3.6min, vs. 30.3±3.1min; P=0.04). These data suggest that in short distance time trials in hot conditions cyclists may benefit from utilizing a cooling modality during the warm-up. Copyright © 2017 Sports Medicine Australia. Published by Elsevier Ltd. All rights reserved.

Warm Up to a Good Sound

ERIC Educational Resources Information Center

Tovey, David C.

1977-01-01

Most choral directors in schools today have been exposed to a variety of warm-up procedures. Yet, many do not use the warm-up time effectively as possible. Considers the factors appropriate to a warm-up exercise and three basic warm-up categories. (Author/RK)

Elevated CO2 and warming effects on grassland plant mortality are determined by the timing of rainfall

PubMed Central

Newton, Paul C. D.; Porter, Meagan

2017-01-01

Abstract Background and aims Global warming is expected to increase the mortality rate of established plants in water-limited systems because of its effect on evapotranspiration. The rising CO2 concentration ([CO2]), however, should have the opposite effect because it reduces plant transpiration, delaying the onset of drought. This potential for elevated [CO2] (eCO2) to modify the warming effect on mortality should be related to prevailing moisture conditions. This study aimed to determine the impacts of warming by 2 °C and eCO2 (550 μmol mol−1) on plant mortality in an Australian temperate grassland over a 6-year period and to test how interannual variation in rainfall influenced treatment effects. Methods Analyses were based on results from a field experiment, TasFACE, in which grassland plots were exposed to a combination of eCO2 by free air CO2 enrichment (FACE) and warming by infrared heaters. Using an annual census of established plants and detailed estimates of recruitment, annual mortality of all established plants was calculated. The influence of rainfall amount and timing on the relative impact of treatments on mortality in each year was analysed using multiple regression techniques. Key Results Warming and eCO2 effects had an interactive influence on mortality which varied strongly from year to year and this variation was determined by temporal rainfall patterns. Warming tended to increase density-adjusted mortality and eCO2 moderated that effect, but to a greater extent in years with fewer dry periods. Conclusions These results show that eCO2 reduced the negative effect of warming but this influence varied strongly with rainfall timing. Importantly, indices involving the amount of rainfall were not required to explain interannual variation in mortality or treatment effects on mortality. Therefore, predictions of global warming effects on plant mortality will be reliant not only on other climate change factors, but also on the temporal

Inflammatory Responses in Brain Ischemia

PubMed Central

Kawabori, Masahito; Yenari, Midori A.

2017-01-01

Brain infarction causes tissue death by ischemia due to occlusion of the cerebral vessels and recent work has shown that post stroke inflammation contributes significantly to the development of ischemic pathology. Because secondary damage by brain inflammation may have a longer therapeutic time window compared to the rescue of primary damage following arterial occlusion, controlling inflammation would be an obvious therapeutic target. A substantial amount of experimentall progress in this area has been made in recent years. However, it is difficult to elucidate the precise mechanisms of the inflammatory responses following ischemic stroke because inflammation is a complex series of interactions between inflammatory cells and molecules, all of which could be either detrimental or beneficial. We review recent advances in neuroinflammation and the modulation of inflammatory signaling pathways in brain ischemia. Potential targets for treatment of ischemic stroke will also be covered. The roles of the immune system and brain damage versus repair will help to clarify how immune modulation may treat stroke. PMID:25666795

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.

Therapeutic time window and underlying therapeutic mechanism of breviscapine injection against cerebral ischemia/reperfusion injury in rats.

PubMed

Guo, Chao; Zhu, Yanrong; Weng, Yan; Wang, Shiquan; Guan, Yue; Wei, Guo; Yin, Ying; Xi, Miaomaio; Wen, Aidong

2014-01-01

Breviscapine injection is a Chinese herbal medicine standardized product extracted from Erigeron breviscapus (Vant.) Hand.-Mazz. It has been widely used for treating cardiovascular and cerebrovascular diseases. However, the therapeutic time window and the action mechanism of breviscapine are still unclear. The present study was designed to investigate the therapeutic time window and underlying therapeutic mechanism of breviscapine injection against cerebral ischemic/reperfusion injury. Sprague-Dawley rats were subjected to middle cerebral artery occlusion for 2h followed by 24h of reperfusion. Experiment part 1 was used to investigate the therapeutic time window of breviscapine. Rats were injected intravenously with 50mg/kg breviscapine at different time-points of reperfusion. After 24h of reperfusion, neurologic score, infarct volume, brain water content and serum level of neuron specific enolase (NSE) were measured in a masked fashion. Part 2 was used to explore the therapeutic mechanism of breviscapine. 4-Hydroxy-2-nonenal (4-HNE), 8-hydroxyl-2'- deoxyguanosine (8-OHdG) and the antioxidant capacity of ischemia cortex were measured by ELISA and ferric-reducing antioxidant power (FRAP) assay, respectively. Immunofluorescence and western blot analysis were used to analyze the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1). Part 1: breviscapine injection significantly ameliorated neurologic deficit, reduced infarct volume and water content, and suppressed the levels of NSE in a time-dependent manner. Part 2: breviscapine inhibited the increased levels of 4-HNE and 8-OHdG, and enhanced the antioxidant capacity of cortex tissue. Moreover, breviscapine obviously raised the expression of Nrf2 and HO-1 proteins after 24h of reperfusion. The therapeutic time window of breviscapine injection for cerebral ischemia/reperfusion injury seemed to be within 5h after reperfusion. By up-regulating the expression of Nrf2/HO-1 pathway

Myocardial Ischemia Induces SDF-1α Release in Cardiac Surgery Patients.

PubMed

Kim, Bong-Sung; Jacobs, Denise; Emontzpohl, Christoph; Goetzenich, Andreas; Soppert, Josefin; Jarchow, Mareike; Schindler, Lisa; Averdunk, Luisa; Kraemer, Sandra; Marx, Gernot; Bernhagen, Jürgen; Pallua, Norbert; Schlemmer, Heinz-Peter; Simons, David; Stoppe, Christian

2016-06-01

In the present observational study, we measured serum levels of the chemokine stromal cell-derived factor-1α (SDF-1α) in 100 patients undergoing cardiac surgery with cardiopulmonary bypass at seven distinct time points including preoperative values, myocardial ischemia, reperfusion, and the postoperative course. Myocardial ischemia triggered a marked increase of SDF-1α serum levels whereas cardiac reperfusion had no significant influence. Perioperative SDF-1α serum levels were influenced by patients' characteristics (e.g., age, gender, aspirin intake). In an explorative analysis, we observed an inverse association between SDF-1α serum levels and the incidence of organ dysfunction. In conclusion, time of myocardial ischemia was identified as the key stimulus for a significant upregulation of SDF-1α, indicating its role as a marker of myocardial injury. The inverse association between SDF-1α levels and organ dysfunction association encourages further studies to evaluate its organoprotective properties in cardiac surgery patients.

Isolating the segment of the mitochondrial electron transport chain responsible for mitochondrial damage during cardiac ischemia

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

Chen, Qun; Yin, Guotian; Stewart, Sarah

2010-07-09

Ischemia damages the mitochondrial electron transport chain (ETC), mediated in part by damage generated by the mitochondria themselves. Mitochondrial damage resulting from ischemia, in turn, leads to cardiac injury during reperfusion. The goal of the present study was to localize the segment of the ETC that produces the ischemic mitochondrial damage. We tested if blockade of the proximal ETC at complex I differed from blockade distal in the chain at cytochrome oxidase. Isolated rabbit hearts were perfused for 15 min followed by 30 min stop-flow ischemia at 37 {sup o}C. Amobarbital (2.5 mM) or azide (5 mM) was used tomore » block proximal (complex I) or distal (cytochrome oxidase) sites in the ETC. Time control hearts were buffer-perfused for 45 min. Subsarcolemmal mitochondria (SSM) and interfibrillar mitochondria (IFM) were isolated. Ischemia decreased cytochrome c content in SSM but not in IFM compared to time control. Blockade of electron transport at complex I preserved the cytochrome c content in SSM. In contrast, blockade of electron transport at cytochrome oxidase with azide did not retain cytochrome c in SSM during ischemia. Since blockade of electron transport at complex III also prevented cytochrome c loss during ischemia, the specific site that elicits mitochondrial damage during ischemia is likely located in the segment between complex III and cytochrome oxidase.« less

"Zero ischemia" partial nephrectomy: novel laparoscopic and robotic technique.

PubMed

Gill, Inderbir S; Eisenberg, Manuel S; Aron, Monish; Berger, Andre; Ukimura, Osamu; Patil, Mukul B; Campese, Vito; Thangathurai, Duraiyah; Desai, Mihir M

2011-01-01

Ischemic injury impacts renal function outcomes following partial nephrectomy. Efforts to minimize, better yet, eliminate renal ischemia are imperative. Describe a novel technique of "zero ischemia" laparoscopic (LPN) and robotic-assisted (RAPN) partial nephrectomy. Data were prospectively collected into an institutional review board-approved database. Fifteen consecutive patients underwent zero ischemia procedures: LPN (n=12), RAPN (n=3). Included were all candidates for LPN or RAPN, irrespective of tumor complexity, including tumors that were central (n=9; 60%), hilar (n=1), in solitary kidney (n=1), in patients with chronic kidney disease grade 3 or greater (n=3). Anesthesia-related monitoring included pulmonary artery catheter (ie, Swan-Ganz), transesophageal echocardiography, cerebral oximetry, electroencephalographic bispectral index, mixed venous oxygen measurements, and vigorous hydration/diuresis. Pharmacologically induced hypotension was carefully timed to correspond with excision of the deepest aspect of the tumor. Renal parenchymal reconstruction was completed under normotension, ensuring complete hemostasis. Intraoperative and early postoperative data were collected prospectively. All cases were successfully completed without hilar clamping. Ischemia time was zero in all cases. Median tumor size was 2.5 cm (range: 1-4); operative time was 3 h (range: 1.3-6); blood loss was 150 ml (range: 20-400); and hospital stay was 3 d (range: 2-19). Nadir mean arterial pressure ranged from 52-65 mm Hg (median: 60), typically for 1-5 min. No patient had intraoperative transfusion or complication, acute or delayed renal hemorrhage, or hypotension-related sequelae. Postoperative complications (n=5) included urine retention (n=1), septicemia from presumed prostatitis (n=1), atrial fibrillation (n=1), urine leak (n=2). Pathology confirmed renal cell carcinoma in 13 patients (87%), all with negative margins. Median pre- and postoperative serum creatinine (0.9 mg/dl and 0

The route and timing of hydrogen sulfide therapy critically impacts intestinal recovery following ischemia and reperfusion injury.

PubMed

Jensen, Amanda R; Drucker, Natalie A; Te Winkel, Jan P; Ferkowicz, Michael J; Markel, Troy A

2018-06-01

Hydrogen sulfide (H 2 S) has many beneficial properties and may serve as a novel treatment in patients suffering from intestinal ischemia-reperfusion injury (I/R). The purpose of this study was to examine the method of delivery and timing of administration of H 2 S for intestinal therapy during ischemic injury. We hypothesized that 1) route of administration of hydrogen sulfide would impact intestinal recovery following acute mesenteric ischemia and 2) preischemic H 2 S conditioning using the optimal mode of administration as determined above would provide superior protection compared to postischemic application. Male C57BL/6J mice underwent intestinal ischemia by temporary occlusion of the superior mesenteric artery. Following ischemia, animals were treated according to one of the following (N=6 per group): intraperitoneal or intravenous injection of GYY4137 (H 2 S-releasing donor, 50mg/kg in PBS), vehicle, inhalation of oxygen only, inhalation of 80ppm hydrogen sulfide gas. Following 24-h recovery, perfusion was assessed via laser Doppler imaging, and animals were euthanized. Perfusion and histology data were assessed, and terminal ileum samples were analyzed for cytokine production following ischemia. Once the optimal route of administration was determined, preischemic conditioning with H 2 S was undertaken using that route of administration. All data were analyzed using Mann-Whitney. P-values <0.05 were significant. Mesenteric perfusion following intestinal I/R was superior in mice treated with intraperitoneal (IP) GYY4137 (IP vehicle: 25.6±6.0 vs. IP GYY4137: 79.7±15.1; p=0.02) or intravenous (IV) GYY4137 (IV vehicle: 36.3±5.9 vs. IV GYY4137: 100.7±34.0; p=0.03). This benefit was not observed with inhaled H 2 S gas (O2 vehicle: 66.6±11.4 vs. H 2 S gas: 81.8±6.0; p=0.31). However, histological architecture was only preserved with intraperitoneal administration of GYY4127 (IP vehicle: 3.4±0.4 vs. IP GYY4137: 2±0.3; p=0.02). Additionally, IP GYY4137

The protective effect of fasudil pretreatment combined with ischemia postconditioning on myocardial ischemia/reperfusion injury in rats.

PubMed

Li, W-N; Wu, N; Shu, W-Q; Guan, Y-E; Jia, D-L

2014-01-01

Ischemic postconditioning (IPO) and pharmacological pretreatment may reduce myocardial necrosis and apoptosis during ischemia/reperfusion. This study aimed to determine the protective effect of fasudil pretreatment combined with IPO on myocardial ischemia/reperfusion injury in rats and explore the possible mechanisms. The SD rats were induced by intraperitoneal injection of fasudil hydrochloride (1 or 10 mg/kg) 60 min before the initiation of ischemia, while the control rats were given the same volume of saline. The hearts were hung on the Langendorff perfusion apparatus and underwent 30 min global ischemia and 120 min reperfusion. The IPO protocol was induced by six cycles of 10 sec ischemia and 10 sec reperfusion at the onset of reperfusion. The hemodynamic changes were measured, myocardial infarct size was determined by triphenyltetrazolium chloride (TTC) staining, cardiomyocyte apoptosis was detected by TUNEL staining, lactate dehydrogenase (LDH) was analyzed from coronary effluents, phosphorylation of Akt and eNOS, as well as expression of Bcl-2 and Bax were measured by western blotting analysis. The high-dose fasudil (10 mg/kg) pretreatment group and IPO group significantly improved post-ischemia cardiac function, reduced myocardial infarct size, attenuated cardiomyocyte apoptosis, decreased the release of LDH, increased expression of phospho-Akt, phospho-eNOS and Bcl-2, and reduced expression of Bax compared with the control group (p < 0.05). In addition, the high-dose fasudil pretreatment combined with IPO group could further improved post-ischemia cardiac function, reduced myocardial infarct size, attenuated cardiomyocyte apoptosis, decreased the release of LDH, increased expression of phospho-Akt, phospho-eNOS and Bcl-2, and reduced expression of Bax compared with the single treatment groups (p < 0.05). The combination of high-dose fasudil pretreatment and IPO had a synergistic protective effect on myocardial ischemia/reperfusion injury, which was

Heart failure hospitalization in women with signs and symptoms of ischemia: A report from the women's ischemia syndrome evaluation study.

PubMed

Bakir, May; Nelson, Michael D; Jones, Erika; Li, Quanlin; Wei, Janet; Sharif, Behzad; Minissian, Margo; Shufelt, Chrisandra; Sopko, George; Pepine, Carl J; Merz, C Noel Bairey

2016-11-15

Women with signs and symptoms of ischemia, no obstructive coronary artery disease, and preserved left ventricular ejection fraction enrolled in the National Heart Lung and Blood Institute (NHLBI) sponsored Women's Ischemia Syndrome Evaluation (WISE) study have an unexpectedly high rate of subsequent heart failure (HF) hospitalization. We sought to verify and characterize the HF hospitalizations. A retrospective chart review was performed on 223 women with signs and symptoms of ischemia, undergoing coronary angiography for suspected coronary artery disease followed for 6±2.6years. Data were collected from a single site in the WISE study. At the time of study enrollment, the women were 57±11years of age, all had preserved left ventricular ejection fraction, and 81 (36%) had obstructive CAD (defined as >50% stenosis in at least one epicardial artery). Among the 223 patients, 25 (11%) reported HF hospitalizations, of which 14/25 (56%) had recurrent HF hospitalizations (>2 hospitalizations). Medical records were available in 13/25 (52%) women. Left ventricular ejection fraction was measured in all verified cases and was found to be preserved in 12/13 (92%). HF hospitalization was not related to obstructive CAD. Among women with signs and symptoms of ischemia undergoing coronary angiography for suspected obstructive CAD, HF hospitalization at 6-year follow-up was predominantly characterized by a preserved ejection fraction and not associated with obstructive CAD. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Liver injury following small intestinal ischemia reperfusion in rats is attenuated by Pistacia lentiscus oil: antioxidant and anti-inflammatory effects.

PubMed

Saidi, Saber Abdelkader; Ncir, Marwa; Chaaben, Rim; Jamoussi, Kamel; van Pelt, Jos; Elfeki, Abdelfattah

2017-10-01

Intestinal ischemia-reperfusion (IIR) not only leads to severe intestine damage but also induced subsequent destruction of remote organs. We investigated the protective effect of Pistascia lentiscus L. (Anacardiaceae) oil on IIR. Wistar rats were divided into three groups: sham, intestinal IR and P. lentiscus pretreatment (n = 18 each). In the pretreatment group, oil was administered 1 h before induction of warm ischemia. IIR led to severe liver damage manifested as a significant (p < .05) increase of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels. Pistacia lentiscus oil decreased the visible intestinal damage, as well as a significant decrease in serum AST and ALT levels. In addition, Pistacia lentiscus reduce liver injury, as evidenced by the decrease in liver tissue myeloperoxidase activity and lipoperoxidation (MDA) level. Pistascia lentiscus attenuates liver injury induced by IIR, attributable to the antioxidant and anti-inflammatory effect.

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 ...

Elevated CO2 and warming effects on grassland plant mortality are determined by the timing of rainfall.

PubMed

Hovenden, Mark J; Newton, Paul C D; Porter, Meagan

2017-05-01

Global warming is expected to increase the mortality rate of established plants in water-limited systems because of its effect on evapotranspiration. The rising CO 2 concentration ([CO 2 ]), however, should have the opposite effect because it reduces plant transpiration, delaying the onset of drought. This potential for elevated [CO 2 ] (eCO 2 ) to modify the warming effect on mortality should be related to prevailing moisture conditions. This study aimed to determine the impacts of warming by 2 °C and eCO 2 (550 μmol mol -1 ) on plant mortality in an Australian temperate grassland over a 6-year period and to test how interannual variation in rainfall influenced treatment effects. Analyses were based on results from a field experiment, TasFACE, in which grassland plots were exposed to a combination of eCO 2 by free air CO 2 enrichment (FACE) and warming by infrared heaters. Using an annual census of established plants and detailed estimates of recruitment, annual mortality of all established plants was calculated. The influence of rainfall amount and timing on the relative impact of treatments on mortality in each year was analysed using multiple regression techniques. Warming and eCO 2 effects had an interactive influence on mortality which varied strongly from year to year and this variation was determined by temporal rainfall patterns. Warming tended to increase density-adjusted mortality and eCO 2 moderated that effect, but to a greater extent in years with fewer dry periods. These results show that eCO 2 reduced the negative effect of warming but this influence varied strongly with rainfall timing. Importantly, indices involving the amount of rainfall were not required to explain interannual variation in mortality or treatment effects on mortality. Therefore, predictions of global warming effects on plant mortality will be reliant not only on other climate change factors, but also on the temporal distribution of rainfall. © The Author 2017. Published by

Effects of exercise preconditioning on intestinal ischemia-reperfusion injury.

PubMed

Gokbel, H; Oz, M; Okudan, N; Belviranli, M; Esen, H

2014-01-01

To investigate the effects of exercise preconditioning on oxidative injury in the intestinal tissue of rats. Sixty male Wistar rats were randomly divided into six groups as sham (n = 10), ischemia-reperfusion (n = 10), exercise (n = 10), exercise plus ischemia-reperfusion (n = 10), ischemic preconditioning (n = 10), and ischemic preconditioning plus ischemia-reperfusion groups (n = 10). Tissue levels of malondialdehyde and activities of myeloperoxidase and superoxide dismutase, and serum levels of tumor necrosis factor-alpha and interleukin-6 were measured. Intestinal tissue histopathology was also evaluated by light microscopy. Tumor necrosis factor-alpha concentrations significantly decreased in the exercise group compared to the sham group (p < 0.05). Myeloperoxidase activity significantly increased and superoxide dismutase activity significantly decreased in ischemia-reperfusion group compared to the sham group (p < 0.05). Superoxide dismutase activity in the ischemic preconditioning and ischemic preconditioning plus ischemia-reperfusion groups were significantly higher compared to the ischemia-reperfusion and exercise groups (p < 0.05). Histopathologically, intestinal injury significantly attenuated in the exercise plus ischemia-reperfusion group compared to the ischemia-reperfusion group. The results of the present study indicate that exercise training seems to have a protective role against intestinal ischemia-reperfusion injury (Tab. 3, Fig. 1, Ref. 35).

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.

Dipeptidyl peptidase IV, aminopeptidase N and DPIV/APN-like proteases in cerebral ischemia

PubMed Central

2012-01-01

Background Cerebral inflammation is a hallmark of neuronal degeneration. Dipeptidyl peptidase IV, aminopeptidase N as well as the dipeptidyl peptidases II, 8 and 9 and cytosolic alanyl-aminopeptidase are involved in the regulation of autoimmunity and inflammation. We studied the expression, localisation and activity patterns of these proteases after endothelin-induced occlusion of the middle cerebral artery in rats, a model of transient and unilateral cerebral ischemia. Methods Male Sprague-Dawley rats were used. RT-PCR, immunohistochemistry and protease activity assays were performed at different time points, lasting from 2 h to 7 days after cerebral ischemia. The effect of protease inhibitors on ischemia-dependent infarct volumes was quantified 7 days post middle cerebral artery occlusion. Statistical analysis was conducted using the t-test. Results Qualitative RT-PCR revealed these proteases in ipsilateral and contralateral cortices. Dipeptidyl peptidase II and aminopeptidase N were up-regulated ipsilaterally from 6 h to 7 days post ischemia, whereas dipeptidyl peptidase 9 and cytosolic alanyl-aminopeptidase were transiently down-regulated at day 3. Dipeptidyl peptidase 8 and aminopeptidase N immunoreactivities were detected in cortical neurons of the contralateral hemisphere. At the same time point, dipeptidyl peptidase IV, 8 and aminopeptidase N were identified in activated microglia and macrophages in the ipsilateral cortex. Seven days post artery occlusion, dipeptidyl peptidase IV immunoreactivity was found in the perikarya of surviving cortical neurons of the ipsilateral hemisphere, whereas their nuclei were dipeptidyl peptidase 8- and amino peptidase N-positive. At the same time point, dipeptidyl peptidase IV, 8 and aminopeptidase N were targeted in astroglial cells. Total dipeptidyl peptidase IV, 8 and 9 activities remained constant in both hemispheres until day 3 post experimental ischemia, but were increased (+165%) in the ipsilateral cortex at day 7

Blood modulates the kinetics of reactive oxygen release in pancreatic ischemia-reperfusion injury.

PubMed

Neeff, Hannes P; Sommer, Olaf; Meyer, Sebastian; Tinelli, Anja; Scholtes, Moritz; Hopt, Ulrich T; Drognitz, Oliver; von Dobschuetz, Ernst

2012-10-01

Reason for the unsuccessful use of antioxidants in transplantation might be the unknown kinetics of reactive oxygen species (ROS) release. In this study, we compared the kinetics of ROS release from rat pancreata in the presence and absence of blood. In vivo, ischemia-reperfusion injury (IRI) was induced in pancreata of male Wistar rats by occlusion of the arterial blood supply for 1 or 2 hours. In vitro, isolated pancreata were single-pass perfused with Krebs-Henseleit bicarbonate solution. Reactive oxygen species were quantified by electron spin resonance spectroscopy using CMH (1-hydroxy-3-methoxycarbonyl-2,2,5,5-tetramethylpyrrolidine) as spin label. Thiols (glutathione), nicotinamide adenine dinucleotide phosphate-oxidase activity, myeloperoxidase activity, and adenosine triphosphate content were measured. During reperfusion, an increase in IRI-induced ROS in arterial blood was noted after 2 hours of warm ischemia. In sharp contrast, ROS release was immediate and short lived in blood-free perfused organs. The degree of tissue damage correlated with nicotinamide adenine dinucleotide phosphate-oxidase activity and adenosine triphosphate content. Antioxidative capacity of tissues was reduced. Electron spin resonance spectroscopy in conjunction with spin labels allows for the detection of ROS kinetics in pancreatic IRI. Reactive oxygen species kinetics are dependent on the length of the ischemic period and the presence or absence of blood.

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.

The seasonal timing of warming that controls onset of the growing season.

PubMed

Clark, James S; Melillo, Jerry; Mohan, Jacqueline; Salk, Carl

2014-04-01

Forecasting how global warming will affect onset of the growing season is essential for predicting terrestrial productivity, but suffers from conflicting evidence. We show that accurate estimates require ways to connect discrete observations of changing tree status (e.g., pre- vs. post budbreak) with continuous responses to fluctuating temperatures. By coherently synthesizing discrete observations with continuous responses to temperature variation, we accurately quantify how increasing temperature variation accelerates onset of growth. Application to warming experiments at two latitudes demonstrates that maximum responses to warming are concentrated in late winter, weeks ahead of the main budbreak period. Given that warming will not occur uniformly over the year, knowledge of when temperature variation has the most impact can guide prediction. Responses are large and heterogeneous, yet predictable. The approach has immediate application to forecasting effects of warming on growing season length, requiring only information that is readily available from weather stations and generated in climate models. © 2013 John Wiley & Sons Ltd.

[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.

Respiratory muscle specific warm-up and elite swimming performance.

PubMed

Wilson, Emma E; McKeever, Tricia M; Lobb, Claire; Sherriff, Tom; Gupta, Luke; Hearson, Glenn; Martin, Neil; Lindley, Martin R; Shaw, Dominick E

2014-05-01

Inspiratory muscle training has been shown to improve performance in elite swimmers, when used as part of routine training, but its use as a respiratory warm-up has yet to be investigated. To determine the influence of inspiratory muscle exercise (IME) as a respiratory muscle warm-up in a randomised controlled cross-over trial. A total of 15 elite swimmers were assigned to four different warm-up protocols and the effects of IME on 100 m freestyle swimming times were assessed.Each swimmer completed four different IME warm-up protocols across four separate study visits: swimming-only warm-up; swimming warm-up plus IME warm-up (2 sets of 30 breaths with a 40% maximum inspiratory mouth pressure load using the Powerbreathe inspiratory muscle trainer); swimming warm-up plus sham IME warm-up (2 sets of 30 breaths with a 15% maximum inspiratory mouth pressure load using the Powerbreathe inspiratory muscle trainer); and IME-only warm-up. Swimmers performed a series of physiological tests and scales of perception (rate of perceived exertion and dyspnoea) at three time points (pre warm-up, post warm-up and post time trial). The combined standard swimming warm-up and IME warm-up were the fastest of the four protocols with a 100 m time of 57.05 s. This was significantly faster than the IME-only warm-up (mean difference=1.18 s, 95% CI 0.44 to 1.92, p<0.01) and the swim-only warm-up (mean difference=0.62 s, 95% CI 0.001 to 1.23, p=0.05). Using IME combined with a standard swimming warm-up significantly improves 100 m freestyle swimming performance in elite swimmers.

Hyperbaric oxygen in skeletal muscle of rats submitted to total acute left hindlimb ischemia: A research report.

PubMed

da Silva, Luis Gustavo Campos; Dalio, Marcelo Bellini; Joviliano, Edwaldo Edner; Feres, Omar; Piccinato, Carlos Eli

2015-01-01

Determine the effect of hyperbaric oxygen treatment in skeletal muscle of rats submitted to total acute left hindlimb ischemia. An experimental study was designed using 48 Wistar rats divided into four groups (n = 12): Control; Ischemia (I)--total hindlimb ischemia for 270 minutes; Hyperbaric oxygen treatment during ischemia (HBO2)--total hindlimb ischemia for 270 minutes and hyperbaric oxygen during the first 90 minutes; Pre-treatment with hyperbaric oxygen (PHBO2)--90 minutes of hyperbaric oxygen treatment before total hindlimb ischemia for 270 minutes. Skeletal muscle injury was evaluated by measuring levels of aspartate aminotransferase (AST), lactate dehydrogenase (LDH), total creatine phosphokinase (CPK); muscular malondialdehyde (MDA), muscular glycogen, and serum ischemia-modified albumin (IMA). AST was significantly higher in I, HBO2 and PHBO2 compared with control (P = .001). There was no difference in LDH. CPK was significantly higher in I, HBO2 and PHBO2, compared with control (p = .014). MDA was significantly higher in PHBO2, compared with other groups (p = .042). Glycogen was significantly decreased in I, HBO2 and PHBO2, compared with control (p < .001). Hyperbaric oxygen treatment in acute total hindlimb ischemia exerted no protective effect on muscle injury, regardless of time of application. When applied prior to installation of total ischemia, hyperbaric oxygen treatment aggravated muscle injury.

CXCL12 Gene Therapy Ameliorates Ischemia-Induced White Matter Injury in Mouse Brain.

PubMed

Li, Yaning; Tang, Guanghui; Liu, Yanqun; He, Xiaosong; Huang, Jun; Lin, Xiaojie; Zhang, Zhijun; Yang, Guo-Yuan; Wang, Yongting

2015-10-01

Remyelination is an important repair process after ischemic stroke-induced white matter injury. It often fails because of the insufficient recruitment of oligodendrocyte progenitor cells (OPCs) to the demyelinated site or the inefficient differentiation of OPCs to oligodendrocytes. We investigated whether CXCL12 gene therapy promoted remyelination after middle cerebral artery occlusion in adult mice. The results showed that CXCL12 gene therapy at 1 week after ischemia could protect myelin sheath integrity in the perifocal region, increase the number of platelet-derived growth factor receptor-α (PDGFRα)-positive and PDGFRα/bromodeoxyuridine-double positive OPCs in the subventricular zone, and further enhance their migration to the ischemic lesion area. Coadministration of AMD3100, the antagonist for CXCL12 receptor CXCR4, eliminated the beneficial effect of CXCL12 on myelin sheath integrity and negatively influenced OPC proliferation and migration. At 5 weeks after ischemia, CXCR4 was found on the PDGFRα- and/or neuron/glia type 2 (NG2)-positive OPCs but not on the myelin basic protein-positive mature myelin sheaths, and CXCR7 was only expressed on the mature myelin sheath in the ischemic mouse brain. Our data indicated that CXCL12 gene therapy effectively protected white matter and promoted its repair after ischemic injury. The treatment at 1 week after ischemia is effective, suggesting that this strategy has a longer therapeutic time window than the treatments currently available. This study has demonstrated for the first time that CXCL12 gene therapy significantly ameliorates brain ischemia-induced white matter injury and promotes oligodendrocyte progenitor cell proliferation in the subventricular zone and migration to the perifocal area in the ischemic mouse brain. Additional data showed that CXCR4 receptor plays an important role during the proliferation and migration of oligodendrocyte progenitor cells, and CXCR7 might play a role during maturation. In

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.

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.

Lung Matrix Metalloproteinase Activation following Partial Hepatic Ischemia/Reperfusion Injury in Rats

PubMed Central

Ferrigno, Andrea; Rizzo, Vittoria; Tarantola, Eleonora

2014-01-01

Purpose. Warm hepatic ischemia-reperfusion (I/R) injury can lead to multiorgan dysfunction. The aim of the present study was to investigate whether acute liver I/R does affect the function and/or structure of remote organs such as lung, kidney, and heart via modulation of extracellular matrix remodelling. Methods. Male Sprague-Dawley rats were subjected to 30 min partial hepatic ischemia by clamping the hepatic artery and the portal vein. After a 60 min reperfusion, liver, lung, kidney, and heart biopsies and blood samples were collected. Serum hepatic enzymes, creatinine, urea, Troponin I and TNF-alpha, and tissue matrix metalloproteinases (MMP-2, MMP-9), myeloperoxidase (MPO), malondialdehyde (MDA), and morphology were monitored. Results. Serum levels of hepatic enzymes and TNF-alpha were concomitantly increased during hepatic I/R. An increase in hepatic MMP-2 and MMP-9 activities was substantiated by tissue morphology alterations. Notably, acute hepatic I/R affect the lung inasmuch as MMP-9 activity and MPO levels were increased. No difference in MMPs and MPO was observed in kidney and heart. Conclusions. Although the underlying mechanism needs further investigation, this is the first study in which the MMP activation in a distant organ is reported; this event is probably TNF-alpha-mediated and the lung appears as the first remote organ to be involved in hepatic I/R injury. PMID:24592193

Influences of spawning timing, water temperature, and climatic warming on early life history phenology in western Alaska sockeye salmon

USGS Publications Warehouse

Sparks, Morgan M.; Falke, Jeffrey A.; Quinn, Thomas P.; Adkison, Milo D.; Schindler, Daniel E.; Bartz, Krista K.; Young, Daniel B.; Westley, Peter A. H.

2018-01-01

We applied an empirical model to predict hatching and emergence timing for 25 western Alaska sockeye salmon (Oncorhynchus nerka) populations in four lake-nursery systems to explore current patterns and potential responses of early life history phenology to warming water temperatures. Given experienced temperature regimes during development, we predicted hatching to occur in as few as 58 d to as many as 260 d depending on spawning timing and temperature. For a focal lake spawning population, our climate-lake temperature model predicted a water temperature increase of 0.7 to 1.4 °C from 2015 to 2099 during the incubation period, which translated to a 16 d to 30 d earlier hatching timing. The most extreme scenarios of warming advanced development by approximately a week earlier than historical minima and thus climatic warming may lead to only modest shifts in phenology during the early life history stage of this population. The marked variation in the predicted timing of hatching and emergence among populations in close proximity on the landscape may serve to buffer this metapopulation from climate change.

Huperzine A attenuates cognitive deficits and hippocampal neuronal damage after transient global ischemia in gerbils.

PubMed

Zhou, J; Zhang, H Y; Tang, X C

2001-11-09

The protective effects of huperzine A on transient global ischemia in gerbils were investigated. Five min of global ischemia in gerbils results in working memory impairments shown by increased escape latency in a water maze and reduced time spent in the target quadrant. These signs of dysfunction are accompanied by delayed degeneration of pyramidal hippocampal CA1 neurons and by decrease in acetylcholinesterase activity in the hippocampus. Subchronic oral administration of huperzine A (0.1 mg/kg, twice per day for 14 days) after ischemia significantly reduced the memory impairment, reduced neuronal degeneration in the CA1 region, and partially restored hippocampal choline acetyltransferase activity. The ability of huperzine A to attenuate memory deficits and neuronal damage after ischemia might be beneficial in cerebrovascular type dementia.

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.

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

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.

Diagnosis and treatment of limb fractures associated with acute peripheral ischemia.

PubMed

Popescu, G I; Lupescu, O; Nagea, M; Patru, C

2013-01-01

Acute Peripheral Ischemia (API) is the most severe acute complication after both open and closed fractures, as ischemia compromises not only the vitality of the affected limb, but also the patient's life, because metabolic anaerobic changes following ischemia have serious local and general consequences. These explain why early diagnosis of API is very important for the prognosis of the traumatized limb.The authors analyse cases when API was not diagnosed immediately after trauma, but some time after the first examination, due to either low systolic BP or to late onset of API. The patients were analysed concerning the type of the fracture, the reason for delayed diagnosis of API, the moment of API diagnosis and the arterial injury. In all those cases, surgery was performed immediately after API diagnosis, in order to identify and treat the complex injuries(bone and vascular). Celsius.

Grade III ischemia on presentation with acute myocardial infarction predicts rapid progression of necrosis and less myocardial salvage with thrombolysis.

PubMed

Birnbaum, Yochai; Mahaffey, Kenneth W; Criger, Douglas A; Gates, Kathy B; Barbash, Gabriel I; Barbagelata, Alejandro; Clemmensen, Peter; Sgarbossa, Elena B; Gibbons, Raymond J; Rahman, M Atiar; Califf, Robert M; Granger, Chistopher B; Wagner, Galen S

2002-01-01

We assessed the relation between baseline electrocardiographic ischemia grades and initial myocardial area at risk (AR) and final infarct size (IS) in 49 patients who had undergone (99m)Tc sestamibi single-photon emission computed tomography before and 6 +/- 1 days after thrombolysis. Patients were classed as having grade III ischemia (ST segment elevation with terminal QRS distortion, n = 19) or grade II ischemia (ST elevation but no terminal QRS distortion, n = 30). We compared AR and IS by baseline ischemia grade and treatment (adenosine vs. placebo) and assessed relations of infarction index (IS/AR ratio x100) to time to thrombolysis, baseline ischemia grade, and adenosine therapy. Time to thrombolysis was similar for grade II and grade III. For placebo- treated patients, the median AR did not differ significantly between grade II (38%) and grade III patients (46%, p = 0.47), nor did median IS (16 vs. 40%, p = 0.096), but the median infarction index was 66 vs. 90% (p = 0.006). For adenosine-treated patients, median AR (21 vs. 26%, p = 0.44), median IS (5 vs. 17%, p = 0.15), and their ratio (31 vs. 67%, p = 0.23) did not differ significantly between grade II and grade III patients. The infarction index independently related to grade III ischemia (p = 0.0121) and adenosine therapy (p = 0.045). Infarct size related to baseline ischemia grade and was reduced by adenosine treatment. Necrosis progressed slowlier with baseline grade II versus III ischemia, which could offer more time for myocardial salvage with reperfusion. Copyright 2002 S. Karger AG, Basel

Continuous monitoring of myocardial acid-base status during intermittent warm blood cardioplegia.

PubMed

Graffigna, A C L; Nollo, G; Pederzolli, C; Ferrari, P; Widesott, L; Antolini, R

2002-06-01

Intermittent warm blood cardioplegia (IWBC) is a well-established technique for myocardial protection during cardiac operations. According to standardized protocols, IWBC administration is currently performed every 15-20 min regardless of any individual variable and in the absence of any instrumental monitoring. We devised a new system for continuous measurement of the acid-base status of coronary sinus blood for on-line evaluation of myocardial oxygenation during IWBC. In 19 patients undergoing cardiac surgery for coronary artery bypass graft and/or valve surgery and receiving IWBC (34-37 degrees C) by antegrade induction (3 min) and retrograde or antegrade maintenance (2 min) every 15 min, continuous monitoring of myocardial oxygenation and acid/base status was performed by means of a multiparameter PO(2), PCO(2), pH, and temperature sensor (Paratrend7 (R), Philips Medical System) inserted into the coronary sinus. Mean cross-clamping time was 76+/-26 min; ischemic time was 13+/-0.2 min. pH decline was not linear, showing an initial fast decline, a point of flexus, and a progressive slow decline. After every ischemic period, the pH adaptation curve showed a complex pattern reaching step-by-step lower minimum levels (7.28+/-0.14 during the first ischemic period, to 7.16+/-0.19 during the third ischemic period - P=0.003). PO(2) decreased rapidly at 90% in 5.0+/-1.2 min after every reperfusion. During ischemia, PCO(2) increased steadily at 1.6+/-0.1 mmHg per minute, with progressively incomplete removal after successive reperfusion, and progressive increase of maximal level (42+/-12 mmHg during the first ischemic period, to 53+/-23 mmHg during the third ischemic period - P=0.05). Myocardial oxygen, carbon dioxide, and pH show marked changes after repeated IWBC. Myocardial ischemia is not completely reversed by standardized reperfusions, as reflected by steady deterioration of PCO(2) and pH after each reperfusion. Progressive increase of reperfusion durations or

Human primary CD34+ cells transplantation for critical limb ischemia.

PubMed

Lian, Weishuai; Hu, Xiaoxiao; Pan, Long; Han, Shilong; Cao, Chuanwu; Jia, Zhongzhi; Li, Maoquan

2018-06-11

The goal of this study was to characterize the properties of human CD34 + cells in culture and investigate the feasibility and efficacy of CD34 + transplantation in a mouse model of limb ischemia and in patients with no-option critical limb ischemia. Human CD34 + cells isolated from peripheral blood and grown in culture for up to four passages stained positively for the surface markers CD34 and CD133 and showed high viability after cryopreservation and recovery. Seven days after surgery to induce limb ischemia, ischemic muscles of nude mice were injected with CD34 + cells. Two weeks later, mice were scored for extent of ischemic injury, and muscle tissue was collected for immunohistochemical analysis of vascular endothelial cells and RT-PCR analysis of cytokine expression. Injury scores of CD34 + -treated, but not control, mice were significantly different before and after transplantation. Vascular density and expression of VEGF and bFGF mRNAs were also significantly increased in the treated mice. Patients with severe lower extremity arterial ischemia were injected with their own CD34 + cells in the affected calf, foot, or toe. Significant improvements were observed in peak pain-free walking time, ankle-brachial index, and transcutaneous partial oxygen pressure. These findings demonstrate that growth of human CD34 + cells in vitro and cryopreservations are feasible. Such cells may provide a renewable source of stem cells for transplantation, which appears to be a feasible, safe, and effective treatment for patients with critical limb ischemia. © 2018 Wiley Periodicals, Inc.

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

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.

Otoacoustic emission responses of the cochlea to acute and total ischemia.

PubMed

Yıldırım, Yavuz Selim; Aksoy, Fadlullah; Ozturan, Orhan; Veyseller, Bayram; Demirhan, Hasan

2013-12-01

In the present experimental study, we sought to monitor distortion product otoacoustic emissions (DPOAEs) as an indicator of cochlear function, after sudden, total, and irreversible interruption of cochlear blood flow, to provide information on the time course of cochlear response to ischemia. Twenty rats with normal hearing function were included. Complete and abrupt ischemia was provided by decapitation. DPOAEs at 3-8 kHz frequencies were recorded at baseline and exactly every consecutive minute after decapitation, until emissions in all frequencies disappeared completely. Mean DPOAE values decreased significantly and progressively after decapitation for all frequencies. The mean duration of emissions was 8.20 ± 1.96 min (minimum 3 min, maximum 11 min). The longest durations of DPOAEs were observed with 4 and 5 kHz frequencies, and 3 and 6 kHz had the shortest durations. The outer hair cells exposed to acute ischemia seem to exhibit a rapid functional loss; thus, cautious handling of the cochlear vasculature and surrounding structures is necessary in surgical interventions. Additionally, our results provide some idea of the normal tolerance range of the cochlea to ischemia, which could be useful for future studies.

How does warming affect carbon allocation, respiration and residence time in trees? An isotope tracer approach in a eucalypt

NASA Astrophysics Data System (ADS)

Pendall, E.; Drake, J. E.; Furze, M.; Barton, C. V.; Carillo, Y.; Richter, A.; Tjoelker, M. G.

2017-12-01

Climate warming has the potential to alter the balance between photosynthetic carbon assimilation and respiratory losses in forest trees, leading to uncertainty in predicting their future physiological functioning. In a previous experiment, warming decreased canopy CO2 assimilation (A) rates of Eucalyptus tereticornis trees, but respiration (R) rates were usually not significantly affected, due to physiological acclimation to temperature. This led to a slight increase in (R/A) and thus decrease in plant carbon use efficiency with climate warming. In contrast to carbon fluxes, the effect of warming on carbon allocation and residence time in trees has received less attention. We conducted a study to test the hypothesis that warming would decrease the allocation of C belowground owing to reduced cost of nutrient uptake. E. parramattensis trees were grown in the field in unique whole-tree chambers operated at ambient and ambient +3 °C temperature treatments (n=3 per treatment). We applied a 13CO2 pulse and followed the label in CO2 respired from leaves, roots, canopy and soil, in plant sugars, and in rhizosphere microbes over a 3-week period in conjunction with measurements of tree growth. The 9-m tall, 57 m3 whole-tree chambers were monitored for CO2 concentrations in independent canopy and below ground (root and soil) compartments; periodic monitoring of δ13C values in air in the compartments allowed us to quantify the amount of 13CO2 assimilated and respired by each tree. Warmed trees grew faster and assimilated more of the label than control trees, but the 13C allocation to canopy, root and soil respiration was not altered. However, warming appeared to reduce the residence time of carbon respired from leaves, and especially from roots and soil, indicating that autotrophic respiration has the potential to feedback to climate change. This experiment provides insights into how warming may affect the fate of assimilated carbon from the leaf to the ecosystem scale.

Real-Time Noninvasive Assessment of Pancreatic ATP Levels During Cold Preservation

PubMed Central

Scott, W.E.; Matsumoto, S.; Tanaka, T.; Avgoustiniatos, E.S.; Graham, M.L.; Williams, P.C.; Tempelman, L.A.; Sutherland, D.E.; Hering, B.J.; Hammer, B.E.; Papas, K.K.

2008-01-01

31P-NMR spectroscopy was utilized to investigate rat and porcine pancreatic ATP:Pi ratios to assess the efficacy of existing protocols for cold preservation (CP) in maintaining organ quality. Following sacrifice, rat pancreata were immediately excised or left enclosed in the body for 15 minutes of warm ischemia (WI). After excision, rat pancreata were stored at 6°C to 8°C using histidine-tryptophan-ketoglutarate solution (HTK) presaturated with air (S1), HTK presaturated with O2 (S2), or the HTK/perfluorodecalin two-layer method (TLM) with both liquids presaturated with O2 (S3). 31P-NMR spectra were sequentially collected at 3, 6, 9, 12, and 24 hours of CP from pancreata stored with each of the three protocols examined. The ATP:Pi ratio for rat pancreata exposed to 15 minutes of WI and stored with S3 increased during the first 9 hours of CP, approaching values observed for organs procured with no WI. A marked reduction in the ATP:Pi ratio was observed beyond 12 hours of CP with S3. After 6 hours of CP, the ATP:Pi ratio was highest for S3, substantially decreased for S2, and below detection for S1. In sharp contrast to the rat model, ATP was barely detectable in porcine pancreata exposed to minimal warm ischemia (<15 minutes) stored with the TLM regardless of CP time. We conclude that 31P-NMR spectroscopy is a powerful tool that can be used to (1) noninvasively evaluate pancreata prior to islet isolation, (2) assess the efficacy of different preservation protocols, (3) precisely define the timing of reversible versus irreversible damage, and (4) assess whether intervention will extend this timing. PMID:18374082

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.

Stochastic Modeling and Global Warming Trend Extraction For Ocean Acoustic Travel Times.

DTIC Science & Technology

1995-01-06

consideration and that these models can not currently be relied upon by themselves to predict global warming . Experimental data is most certainly needed, not...only to measure global warming itself, but to help improve the ocean model themselves. (AN)

Protective effects of mangiferin on cerebral ischemia-reperfusion injury and its mechanisms.

PubMed

Yang, Zhang; Weian, Chen; Susu, Huang; Hanmin, Wang

2016-01-15

The aim of our study was to investigate the protective properties of mangiferin, a natural glucosyl xanthone found in both mango and papaya on the cerebral ischemia-reperfusion injury and the underlying mechanism. Wistar male rats were subjected to middle cerebral artery occlusion for 2h followed by 24h of reperfusion. Mangiferin (25, 50, and 100mg/kg, ig) or 0.5% carboxymethyl cellulose sodium was administered three times before ischemia and once at 2h after the onset of ischemia. Neurological score, infarct volume, and brain water content, some oxidative stress markers and inflammatory cytokines were evaluated after 24h of reperfusion. Treatment with mangiferin significantly ameliorated neurologic deficit, infarct volume and brain water content after cerebral ischemia reperfusion. Mangiferin also reduced the content of malondialdehyde (MDA), IL-1β and TNF-α, and up-regulated the activities of superoxide dismutase (SOD), glutathione (GSH) and IL-10 levels in the brain tissue of rats with the cerebral ischemia-reperfusion injury. Moreover, mangiferin up-regulated the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and its downstream anti-oxidant protein heme oxygenase-1 (HO-1). The results indicate that mangiferin can play a certain protective role in the cerebral ischemia-reperfusion injury, and the protective effect of mangiferin may be related to the improvement on the antioxidant capacity of brain tissue and the inhibition of overproduction of inflammatory cytokines. The mechanisms are associated with enhancing the oxidant defense systems via the activation of Nrf2/HO-1 pathway. Copyright © 2015 Elsevier B.V. All rights reserved.

Autofluorescence of liver tissue and bile: organ functionality monitoring during ischemia and reoxygenation.

PubMed

Croce, Anna C; Ferrigno, Andrea; Santin, Giada; Piccolini, Valeria M; Bottiroli, Giovanni; Vairetti, Mariapia

2014-07-01

Autofluorescence (AF) based optical biopsy of liver tissue is a powerful approach for the real-time diagnosis of its functionality. Since increasing attention is given to the bile production and composition to monitor the liver metabolic engagement in surgery and transplantation, we have investigated the bile AF properties as a potential, additional diagnostic parameter. Spectrofluorometric analysis has been performed in real time on a rat liver model of warm ischemia and reperfusion-60 minutes partial portal vein and hepatic artery clamping and subsequent restoration of blood circulation-in comparison with sham operated rats. The AF spectra have been recorded through a single fiber optic probe (366 nm excitation) from both liver tissue and bile, collected from the cannulated bile duct, and analyzed by means of curve fitting procedures. Bile composition has been also analyzed through biochemical assays of bilirubin, total bile acids (TBA) and proteins. Both liver and bile AF signal amplitude and spectral shape undergo changes during induction of ischemia and subsequent reperfusion. The liver tissue response is mainly ascribable to changes in NAD(P)H and flavins and their redox state, largely dependent on oxygen supply, and to the decrease of both vitamin A and fatty acid AF contributions. During comparable times, sham operated rat livers undergo smaller alterations in AF spectral shape, indicating a continuous, slight increase in the oxidized state. Bile AF emission shows a region in the 510-600 nm range ascribable to bilirubin, and resulting from the contribution of two bands, centered at about 515-523 and 570 nm, consistently with its bichromophore nature. Variations in the balance between these two bands depend on the influence of microenvironment on bilirubin intramolecular interchromophore energy transfer efficiency and are likely indicating alteration in a bile composition. This event is supported also by changes observed in the 400-500 nm emission

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.

Critical Ischemia Times and the Effect of Novel Preservation Solutions HTK-N and TiProtec on Tissues of a Vascularized Tissue Isograft.

PubMed

Messner, Franka; Hautz, Theresa; Blumer, Michael J F; Bitsche, Mario; Pechriggl, Elisabeth J; Hermann, Martin; Zelger, Bettina; Zelger, Bernhard; Öfner, Dietmar; Schneeberger, Stefan

2017-09-01

We herein investigate critical ischemia times and the effect of novel preservation solutions such as new histidine-tryptophan-ketoglutarate (HTK-N) and TiProtec on the individual tissues of a rat limb isograft. Orthotopic hind-limb transplantations were performed in male Lewis rats after 2 hours, 6 hours, or 10 hours of cold ischemia (CI). Limbs were flushed and stored in HTK-N, TiProtec, HTK, or saline solution. Muscle, nerve, vessel, skin, and bone samples were procured on day 10 for histology, immunohistochemistry, confocal and electron microscopy, and quantitative real-time polymerase chain reaction analysis. Histomorphology of the muscle showed a mainly perivascular inflammatory infiltrate, fibrotic degeneration, and neovascularization after 6 hours and 10 hours of CI. However, centrally aligned nuclei observed in muscle fibers suggest for muscle regeneration in these samples. In addition to Wallerian degeneration, nerve injury was significantly aggravated (P = 0.032) after prolonged CI. Proinflammatory and regulatory cytokines were most significantly upregulated after 2-hour CI. Our data suggest no superiority of novel perfusates HTK-N and TiProtec in terms of tissue preservation, compared with HTK and saline. Limiting CI time for less than 6 hours is the most significant factor to reduce tissue damage in vascularized tissue transplantation. Signs of muscle regeneration give rise that ischemic muscle damage in limb transplantation might be reversible to a certain extent.

Evaluation of hypoxic tissue dynamics with 18F-FMISO PET in a rat model of permanent cerebral ischemia.

PubMed

Rojas, Santiago; Herance, José Raul; Abad, Sergio; Jiménez, Xavier; Pareto, Deborah; Ruiz, Alba; Torrent, Èlia; Figueiras, Francisca P; Popota, Foteini; Fernández-Soriano, Francisco J; Planas, Anna M; Gispert, Juan D

2011-06-01

[¹⁸F]Fluoromisonidazole (¹⁸F-FMISO) is a nitroimidazole derivative that has been proposed as a positron emission tomography (PET) radiotracer to detect hypoxic tissue in vivo. This compound accumulates in hypoxic but viable tissue and may be a good candidate for evaluating the ischemic penumbra. We evaluated the time course of ¹⁸F-FMISO uptake using PET in a rat model of permanent cerebral ischemia and the correlation with histological changes. Rats (n = 14) were subjected to permanent ischemia by intraluminal occlusion of the middle cerebral artery in order to assess by PET the uptake of ¹⁸F-FMISO at various times over 24 h following ischemia. The PET results were compared to histological changes with Nissl and 2,3,5 triphenyltetrazolium chloride staining. Elevated uptake of ¹⁸F-FMISO was detected in the infarcted area up to 8 h after occlusion but was no longer detected at 24 h, a time point coincident with pan necrosis of the tissue. Our findings suggest that salvageable tissue persists for up to 8 h in this rat model of brain ischemia. We propose ¹⁸F-FMISO PET as a tool for evaluating the ischemic penumbra after cerebral ischemia.

Left ventricular energy model predicts adverse events in women with suspected myocardial ischemia: results from the NHLBI-sponsored women’s ischemia syndrome evaluation (WISE) study

PubMed Central

Weinberg, Nicole; Pohost, Gerald M.; Bairey Merz, C. Noel; Shaw, Leslee J.; Sopko, George; Fuisz, Anthon; Rogers, William J.; Walsh, Edward G.; Johnson, B. Delia; Sharaf, Barry L.; Pepine, Carl J.; Mankad, Sunil; Reis, Steven E.; Rayarao, Geetha; Vido, Diane A.; Bittner, Vera; Tauxe, Lindsey; Olson, Marian B.; Kelsey, Sheryl F.; Biederman, Robert WW

2013-01-01

Objectives To assess the prognostic value of a left ventricular energy-model in women with suspected myocardial ischemia. Background The prognostic value of internal energy utilization (IEU) of the left ventricle in women with suspected myocardial ischemia is unknown. Methods Women [n=227, mean age 59±12 years (range, 31-86 years)], with symptoms of myocardial ischemia, underwent myocardial perfusion imaging (MPI) assessment for regional perfusion defects along with measurement of ventricular volumes separately by gated Single Photon Emission Computed Tomography (SPECT) (n=207) and magnetic resonance imaging (MRI) (n=203). During follow-up (40±17 months), time to first major adverse cardiovascular event (MACE, death, myocardial infarction or hospitalization for congestive heart failure) was analyzed using MRI and gated SPECT variables. Results Adverse events occurred in 31 (14%). Multivariable Cox models were formed for each modality: IEU and wall thickness by MRI (Chi-squared 34, P<0.005) and IEU and systolic blood pressure by gated SEPCT (Chi-squared 34, P<0.005). The models remained predictive after adjustment for age, disease history and Framingham risk score. For each Cox model, patients were categorized as high-risk if the model hazard was positive and not high-risk otherwise. Kaplan-Meier analysis of time to MACE was performed for high-risk vs. not high-risk for MR (log rank 25.3, P<0.001) and gated SEPCT (log rank 18.2, P<0.001) models. Conclusions Among women with suspected myocardial ischemia a high internal energy utilization has higher prognostic value than either a low EF or the presence of a myocardial perfusion defect assessed using two independent modalities of MR or gated SPECT. PMID:24015377

Warming trends: Adapting to nonlinear change

DOE PAGES

Jonko, Alexandra K.

2015-01-28

As atmospheric carbon dioxide concentrations rise, some regions are expected to warm more than others. Research suggests that whether warming will intensify or slow down over time also depends on location.

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.

Lipidomics comparing DCD and DBD liver allografts uncovers lysophospholipids elevated in recipients undergoing early allograft dysfunction.

PubMed

Xu, Jin; Casas-Ferreira, Ana M; Ma, Yun; Sen, Arundhuti; Kim, Min; Proitsi, Petroula; Shkodra, Maltina; Tena, Maria; Srinivasan, Parthi; Heaton, Nigel; Jassem, Wayel; Legido-Quigley, Cristina

2015-12-04

Finding specific biomarkers of liver damage in clinical evaluations could increase the pool of available organs for transplantation. Lipids are key regulators in cell necrosis and hence this study hypothesised that lipid levels could be altered in organs suffering severe ischemia. Matched pre- and post-transplant biopsies from donation after circulatory death (DCD, n = 36, mean warm ischemia time = 2 min) and donation after brain death (DBD, n = 76, warm ischemia time = none) were collected. Lipidomic discovery and multivariate analysis (MVA) were applied. Afterwards, univariate analysis and clinical associations were conducted for selected lipids differentiating between these two groups. MVA grouped DCD vs. DBD (p = 6.20 × 10(-12)) and 12 phospholipids were selected for intact lipid measurements. Two lysophosphatidylcholines, LysoPC (16:0) and LysoPC (18:0), showed higher levels in DCD at pre-transplantation (q < 0.01). Lysophosphatidylcholines were associated with aspartate aminotransferase (AST) 14-day post-transplantation (q < 0.05) and were more abundant in recipients undergoing early allograft dysfunction (EAD) (p < 0.05). A receiver-operating characteristics (ROC) curve combining both lipid levels predicted EAD with 82% accuracy. These findings suggest that LysoPC (16:0) and LysoPC (18:0) might have a role in signalling liver tissue damage due to warm ischemia before transplantation.

The timing of bud break in warming conditions: variation among seven sympatric conifer species from Eastern Canada

NASA Astrophysics Data System (ADS)

Rossi, Sergio; Isabel, Nathalie

2017-11-01

Phenological changes are expected with the ongoing global warming, which could create mismatches in the growth patterns among sympatric species or create synchrony with insect herbivores. In this study, we performed a comparative assessment of the timings of bud break among seven conifer species of Eastern Canada by evaluating seedling development in growth chambers under different temperatures (16, 20 and 24 °C). Bud break occurred earliest in Larix laricina, while Pinus strobus and Pinus resinosa had the latest. Warmer conditions advanced bud break, with the greatest effects being observed at the lower temperatures. Mixed models estimated that one additional degree of temperature produced advancements of 5.3 and 2.1 days at 16 and 20 °C, respectively. The hypothesis of an asynchronous change between species under warming was demonstrated only for the last phenological phases (split buds and exposed shoots), and principally in pines. Abies balsamea showed changes in bud break comparable with the other species analysed, rejecting the hypothesis of mismatches under warmer conditions. The observed non-linear responses of the timings of bud break to warming suggest that the major changes in bud phenology should be expected at the lowest temperatures.

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.

Oxidative and inflammatory biomarkers of ischemia and reperfusion injuries.

PubMed

Halladin, Natalie Løvland

2015-04-01

Ischemia-reperfusion injuries occur when the blood supply to an organ or tissue is temporarily cut-off and then restored. Even though the restoration of blood flow is absolutely essential in preventing tissue death, the reperfusion of oxygenated blood to the oxygen-deprived areas may in itself augment the tissue damage in excess of that produced by the ischemia alone. The process of ischemia-reperfusion is multifactorial and there are several mechanisms involved in the pathogenesis. Ample evidence shows that the injury is in part caused by an excessive generation of reactive oxygen species or free radicals. The free radicals consequently initiate an inflammatory response, which in some cases may affect distant organs, thus causing remote organ injuries. Ischemia-reperfusion injuries are a common complication in many diseases (acute myocardial infarctions, stroke) or surgical settings (transplantations, tourniquet-related surgery) and they have potential detrimental and disabling consequences. The tolerance of ischemia-reperfusion has proven to be time-of-day-dependent and the size of myocardial infarctions has proven to be significantly higher when occurring in the dark-to-light period. This period is characterized by and coincides with a rapid decrease in the plasma levels of the hormone melatonin. Melatonin is the body's most potent antioxidant and is capable of both direct free radical scavenging and indirect optimization of other anti-oxidant enzymes. It also possesses anti-inflammatory properties and is known to inhibit the mitochondrial permeability transition pore during reperfusion. This inhibiting property has been shown to be of great importance in reducing ischemia-reperfusion injuries. Furthermore, melatonin is a relatively non-toxic molecule, which has proven to be safe for use in clinical trials. Thus, there is compelling evidence of melatonin's effect in reducing ischemia-reperfusion injuries in many experimental studies, but the number of human

Zero ischemia robotic-assisted partial nephrectomy in Alberta: Initial results of a novel approach.

PubMed

Forbes, Ellen; Cheung, Douglas; Kinnaird, Adam; Martin, Blair St

2015-01-01

Partial nephrectomy remains the standard of care in early stage, organ-confined renal tumours. Recent evidence suggests that minimally invasive surgery can proceed without segmental vessel clamping. In this study, we review our experience at a Canadian centre with zero ischemia robotic-assisted partial nephrectomy (RAPN). A retrospective chart review of zero ischemia RAPN was performed. All surgeries were consecutive partial nephrectomies performed by the same surgeon at a tertiary care centre in Northern Alberta. The mean follow-up period was 28 months. These outcomes were compared against the current standards for zero ischemia (as outlined by the University of Southern California Institute of Urology [USC]). We included 21 patients who underwent zero ischemia RAPN between January 2012 and June 2013. Baseline data were similar to contemporary studies. Twelve (57.1%) required no vascular clamping, 7 (33.3%) required clamping of a single segmental artery, and 2 (9.5%) required clamping of two segmental arteries. We achieved an average estimated blood loss of 158 cc, with a 9.2% average increase in creatinine postoperatively. Operating time and duration of hospital stay were short at 153 minutes and 2.2 days, respectively. Zero ischemia partial nephrectomy was a viable option at our institution with favourable results in terms of intra-operative blood loss and postoperative creatinine change compared to results from contemporary standard zero ischemia studies (USC). To our knowledge, this is the first study to review an initial experience with the zero ischemia protocol in robotic-assisted partial nephrectomies at a Canadian hospital.

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.

Protective effects of osthole on intestinal ischemia-reperfusion injury in mice.

PubMed

Zhang, Zhen; Pan, Chen; Wang, Hong-zhi; Li, Yong-xiang

2014-06-01

The purpose of this study was to evaluate the effect of intravenous injection of osthole on intestinal ischemia-reperfusion injury and parameters of oxidative stress. In 45 Kunming male mice, treatment included sham surgery (15 mice); intestinal ischemia-reperfusion injury (clamping of the superior mesenteric artery, 2 h; clamp release, 1 h; 15 mice); or osthole treatment before and after ischemia-reperfusion injury (15 mice). Evaluation included histopathology, determination of intestinal wet/dry weight ratio, and measurement of levels of diamine oxidase, superoxide dismutase, malondialdehyde, interleukin 1β, tumor necrosis factor α, and interleukin 2. Intestinal barrier permeability was evaluated with Evans blue test. The mean wet-to-dry weight ratio, Evans blue content, and Chiu score were significantly greater in the ischemia-reperfusion than in the sham group and lower in the osthole-treated than the ischemia-reperfusion group. The mean serum diamine oxidase, malondialdehyde, interleukin 1β, and tumor necrosis factor α levels were significantly greater in the ischemia-reperfusion than in the sham group and lower in the osthole-treated than in the ischemia-reperfusion group. The mean superoxide dismutase activity and interleukin 2 levels were lower in the ischemia-reperfusion than in the sham group and greater in the osthole-treated than in the ischemia-reperfusion group. Treatment with osthole may protect against oxidative stress and tissue damage from intestinal ischemia-reperfusion injury.

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.

Tezosentan, a Novel Endothelin Receptor Antagonist, Markedly Reduces Rat Hepatic Ischemia and Reperfusion Injury in Three Different Models

PubMed Central

Farmer, Douglas G.; Kaldas, Fady; Anselmo, Dean; Katori, Masamichi; Shen, Xiu-Da; Lassman, Charles; Kaldas, Marian; Clozel, Martine; Busuttil, Ronald W.; Kupiec-Weglinski, Jerzy

2010-01-01

This study investigated the effects of dual endothelin (ET) receptor blockade in rat models of liver ischemia and reperfusion injury (IRI). Three models of IRI were used: (1) in vivo total hepatic warm ischemia with portal shunting for 60 minutes with control (saline) and treatment groups (15 mg/kg tezosentan intravenously prior to reperfusion), (2) ex vivo hepatic perfusion after 24 hours of cold storage in University of Wisconsin solution with control and treatment groups (10 mg/kg tezosentan in the perfusate), and (3) syngeneic liver transplantation (LT) after 24 hours of cold storage in University of Wisconsin solution with control and treatment groups (10 mg/kg tezosentan intravenously prior to reperfusion). Tezosentan treatment significantly improved serum transaminase and histology after IRI in all 3 models. This correlated with reduced vascular resistance, improved bile production, and an improved oxygen extraction ratio. Treatment led to a reduction in neutrophil infiltration and interleukin-1 beta and macrophage inflammatory protein 2 production. A reduction in endothelial cell injury as measured by purine nucleoside phosphorylase was seen. Survival after LT was significantly increased with tezosentan treatment (90% versus 50%). In conclusion, this is the first investigation to examine dual receptor ET blockade in 3 models of hepatic IRI and the first to use the parenterally administered agent tezosentan. The results demonstrate that in both warm and cold IRI tezosentan administration improves sinusoidal hemodynamics and is associated with improved tissue oxygenation and reduced endothelial cell damage. In addition, reduced tissue inflammation, injury, and leukocyte chemotactic signaling were seen. These results provide compelling data for the further investigation of the use of tezosentan in hepatic IRI. PMID:19025917

Parecoxib reduces renal injury in an ischemia/reperfusion model in rats.

PubMed

Calistro Neto, José Pedro; Torres, Rômulo da Costa; Gonçalves, Giovanna Maria; Silva, Leopoldo Muniz da; Domingues, Maria Aparecida Custódio; Módolo, Norma Sueli Pinheiro; Barros, Guilherme Antonio Moreira de

2015-04-01

To evaluate the effect of parecoxib (an NSAID) on renal function by measuring plasma NGAL (serum neutrophil gelatinase-associated lipocalin) levels in an induced-ischemia rat model. Forty male Wistar rats were randomly assigned to one of four groups: Ischemia (I), Ischemia/parecoxib (IP), No-ischemia (NI), and No-ischemia/parecoxib (NIP). Body weight, mean arterial pressure, heart rate, body temperature, NGAL levels, and renal histology were compared across groups. The Ischemia (I) group, which did not receive parecoxib, showed the highest NGAL levels (p=0.001), while the IP group, which received the medication, had NGAL levels similar to those of the non-ischemic (NI and NIP) groups. Parecoxib resulted in renal protection in this experimental model.

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.

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

[Effects of sowing times on the spike differentiation of different wheat varieties under the climate of warm winter].

PubMed

Gao, Qinglu; Xue, Xiang; Wu, Yu; Ru, Zhengang

2003-10-01

Spike differentiation processes and freezing damage of three wheat varieties were studied by sowing in different stages. The results showed that under the condition of weather changing warm, the time of entering each stage of spike differentiation of wheat of strong spring variety was earlier than that of wheat of spring variety and semi-winter variety. Sowing times had more effects on durative time of the elongation stage, single-prism stage and two-prism stage of the spike differentiation. Under sowing early, the stronger the springness of wheat was, the quicker it developed, the higher spike differentiation phases it reached before winter, and the more serious freezing damage it suffered in wintering. According to this, the semi-winter varieties of wheat should be adopted first and arranged in pairs with spring varieties in wheat production, and the sowing times should not be too early as the weather becoming warm.

Steady-state and time-dependent thermodynamic modeling of the effect of intravenous infusion of warm and cold fluids.

PubMed

Barthel, Erik R; Pierce, James R

2012-06-01

Hypothermia results in vital sign lability, coagulopathy, wound infections, and other sequelae. Normothermia can be restored by several modalities, including passive blanket heating, warm forced-air devices, and active fluid warming (AFW). In AFW, intravenously administered fluids are heated to 40 to 45 °C to minimize net thermal losses and to raise body temperature. Clinical studies have demonstrated the efficacy of AFW as part of a strategy encompassing several methods, but the isolated contribution of AFW to warming has not been theoretically examined in detail. A calorimetric model is derived to determine the functional dependence of warming on patient weight, hypothermia severity, infusion temperature, and volume infused. A second heat transfer model is derived to describe the time-dependent temperature changes of the periphery and core after warmed-fluid infusion. There is an inverse linear relationship between the patient's initial temperature and the amount of warming achieved with a given volume. In contrast, as the temperature of the infusion approaches the desired final temperature, the volume required for a fixed temperature change increases nonlinearly. For weight-based boluses, the temperature change scales appropriately with patient mass. Infusion of 2 L of room-temperature crystalloid results in a decrease in body temperature of approximately one-third degree Celsius in the average normothermic adult. For the heat transfer model, previously reported rates of temperature drop and recovery after the intravenous infusion of cold fluids are qualitatively reproduced with a blood mixing time of approximately 15 minutes. Our calculations reveal that AFW has a larger measurable beneficial effect for patients with more severe hypothermia, but true rewarming of the patient with AFW alone would require prohibitively large fluid volumes (more than 10 L of 40 °C fluid) or dangerously hot fluid (20 mL/kg of 80 °C fluid for a 1 °C increase). The major

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.

Authropogenic Warming in North Alaska?.

NASA Astrophysics Data System (ADS)

Michaels, Patrick J.; Sappington, David E.; Stooksbury, David E.

1988-09-01

Using permafrost boreholes, Lachenbruch and Marshall recently reported evidence for a 2°-4°C warming in North Alaska occurring at some undetermined time during the last century. Popular accounts suggest their findings are evidence for anthropogenic warming caused by trace gases. Analyses of North Alaskan 1000-500 mb thickness onwards back to 1948 indicate that the warming was prior to that date. Relatively sparse thermometric data for the early twentieth century from Jones et al. are too noisy to support any trend since the data record begins in 1910, or to apply to any subperiod of climatic significance. Any warming detected from the permafrost record therefore occurred before the major emissions of thermally active trace gases.

Improvement of retinal functions after ischemia with L-arginine and its derivatives.

PubMed

Liu, S X; Chiou, G C; Varma, R S

1995-01-01

Retinal ischemia was created by occlusion of rat central retinal artery for 30 minutes. The loss of retinal function was indicated by the loss of b-wave of electroretinogram. The recovery of retinal function after reperfusion of central retinal artery was observed with the gradual recovery of b-wave amplitude to approximately 20% of original b-wave amplitude. When L-arginine (RVC-579) was administered at the time of retina ischemia, the b-wave amplitudes recovered up to 64% of original height and were significantly higher than corresponding controls at 120, 180, and 240 min after ischemia. When the derivative of L-arginine, N alpha-benzoyl-L-arginine ethyl ester (RVC-578), was administered, the b-wave recovery was significantly higher than corresponding controls at 90, 120, 180, and 240 min after ischemia; the recovery reached 51% of the original b-wave value. These results indicate that the L-arginine and its lipophilic derivatives could be used for the treatment of ischemic retinopathy. Since L-arginine is a natural amino acid, it is not expected to produce major side effects, if any, and could pave the way for the development of a safer drug to be used in the clinics. Compounds which increase the formation of NO in vivo, dilate blood vessels. Both L-arginine and RVC-578 can be placed in this category. They may improve effects of retinal ischemia by increasing NO production.

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.

Time-Space Position of Warm Dense Matter in Laser Plasma Interaction Process

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

Cao, L F; Uschmann, I; Forster, E

2006-09-25

Laser plasma interaction experiments have been perform performed using an fs Titanium Sapphire laser. Plasmas have been generated from planar PMMA targets using single laser pulses with 3.3 mJ pulse energy, 50 fs pulse duration at 800 nm wavelength. Electron density distributions of the plasmas in different delay times have been characterized by means of Nomarski Interferometry. Experimental data were cautiously compared with relevant 1D numerical simulation. Finally these results provide a first experience of searching for the time-space position of the so-called warm dense plasma in an ultra fast laser target interaction process. These experiments aim to prepare nearmore » solid-density plasmas for Thomson scattering experiments using the short wavelength free-electron laser FLASH, DESY Hamburg.« less

Protective response in renal transplantation: no clinical or molecular differences between open and laparoscopic donor nephrectomy.

PubMed

Machado, Christiano; Malheiros, Denise Maria Avancini Costa; Adamy, Ari; Santos, Luiz Sergio; Silva Filho, Agenor Ferreira da; Nahas, William Carlos; Lemos, Francine Brambate Carvalhinho

2013-04-01

Prolonged warm ischemia time and increased intra-abdominal pressure caused by pneumoperitoneum during a laparoscopic donor nephrectomy could enhance renal ischemia reperfusion injury. For this reason, laparoscopic donor nephrectomy may be associated with a slower graft function recovery. However, an adequate protective response may balance the ischemia reperfusion damage. This study investigated whether laparoscopic donor nephrectomy modified the protective response of renal tissue during kidney transplantation. Patients undergoing live renal transplantation were prospectively analyzed and divided into two groups based on the donor nephrectomy approach used: 1) the control group, recipients of open donor nephrectomy (n = 29), and 2) the study group, recipients of laparoscopic donor nephrectomy (n = 26). Graft biopsies were obtained at two time points: T-1 = after warm ischemia time and T+1 = 45 minutes after kidney reperfusion. The samples were analyzed by immunohistochemistry for the Bcl-2 and HO-1 proteins and by real-time polymerase chain reaction for the mRNA expression of Bcl-2, HO-1 and vascular endothelial growth factor. The area under the curve for creatinine and delayed graft function were similar in both the laparoscopic and open groups. There was no difference in the protective gene expression between the laparoscopic donor nephrectomy and open donor nephrectomy groups. The protein expression of HO-1 and Bcl-2 were similar between the open and laparoscopic groups. Furthermore, the gene expression of B-cell lymphoma 2 correlated with the warm ischemia time in the open group (p = 0.047) and that of vascular endothelial growth factor with the area under the curve for creatinine in the laparoscopic group (p = 0.01). The postoperative renal function and protective factor expression were similar between laparoscopic donor nephrectomy and open donor nephrectomy. These findings ensure laparoscopic donor nephrectomy utilization in renal transplantation.

Protective response in renal transplantation: no clinical or molecular differences between open and laparoscopic donor nephrectomy

PubMed Central

Machado, Christiano; Malheiros, Denise Maria Avancini Costa; Adamy, Ari; Santos, Luiz Sergio; da Silva Filho, Agenor Ferreira; Nahas, William Carlos; Lemos, Francine Brambate Carvalhinho

2013-01-01

OBJECTIVE: Prolonged warm ischemia time and increased intra-abdominal pressure caused by pneumoperitoneum during a laparoscopic donor nephrectomy could enhance renal ischemia reperfusion injury. For this reason, laparoscopic donor nephrectomy may be associated with a slower graft function recovery. However, an adequate protective response may balance the ischemia reperfusion damage. This study investigated whether laparoscopic donor nephrectomy modified the protective response of renal tissue during kidney transplantation. METHODS: Patients undergoing live renal transplantation were prospectively analyzed and divided into two groups based on the donor nephrectomy approach used: 1) the control group, recipients of open donor nephrectomy (n = 29), and 2) the study group, recipients of laparoscopic donor nephrectomy (n = 26). Graft biopsies were obtained at two time points: T-1 = after warm ischemia time and T+1 = 45 minutes after kidney reperfusion. The samples were analyzed by immunohistochemistry for the Bcl-2 and HO-1 proteins and by real-time polymerase chain reaction for the mRNA expression of Bcl-2, HO-1 and vascular endothelial growth factor. RESULTS: The area under the curve for creatinine and delayed graft function were similar in both the laparoscopic and open groups. There was no difference in the protective gene expression between the laparoscopic donor nephrectomy and open donor nephrectomy groups. The protein expression of HO-1 and Bcl-2 were similar between the open and laparoscopic groups. Furthermore, the gene expression of B-cell lymphoma 2 correlated with the warm ischemia time in the open group (p = 0.047) and that of vascular endothelial growth factor with the area under the curve for creatinine in the laparoscopic group (p = 0.01). CONCLUSION: The postoperative renal function and protective factor expression were similar between laparoscopic donor nephrectomy and open donor nephrectomy. These findings ensure laparoscopic

Histone deacetylase inhibition blunts ischemia/reperfusion injury by inducing cardiomyocyte autophagy.

PubMed

Xie, Min; Kong, Yongli; Tan, Wei; May, Herman; Battiprolu, Pavan K; Pedrozo, Zully; Wang, Zhao V; Morales, Cyndi; Luo, Xiang; Cho, Geoffrey; Jiang, Nan; Jessen, Michael E; Warner, John J; Lavandero, Sergio; Gillette, Thomas G; Turer, Aslan T; Hill, Joseph A

2014-03-11

Reperfusion accounts for a substantial fraction of the myocardial injury occurring with ischemic heart disease. Yet, no standard therapies are available targeting reperfusion injury. Here, we tested the hypothesis that suberoylanilide hydroxamic acid (SAHA), a histone deacetylase inhibitor approved for cancer treatment by the US Food and Drug Administration, will blunt reperfusion injury. Twenty-one rabbits were randomly assigned to 3 groups: (1) vehicle control, (2) SAHA pretreatment (1 day before and at surgery), and (3) SAHA treatment at the time of reperfusion only. Each arm was subjected to ischemia/reperfusion surgery (30 minutes coronary ligation, 24 hours reperfusion). In addition, cultured neonatal and adult rat ventricular cardiomyocytes were subjected to simulated ischemia/reperfusion to probe mechanism. SAHA reduced infarct size and partially rescued systolic function when administered either before surgery (pretreatment) or solely at the time of reperfusion. SAHA plasma concentrations were similar to those achieved in patients with cancer. In the infarct border zone, SAHA increased autophagic flux, assayed in both rabbit myocardium and in mice harboring an RFP-GFP-LC3 transgene. In cultured myocytes subjected to simulated ischemia/reperfusion, SAHA pretreatment reduced cell death by 40%. This reduction in cell death correlated with increased autophagic activity in SAHA-treated cells. RNAi-mediated knockdown of ATG7 and ATG5, essential autophagy proteins, abolished SAHA's cardioprotective effects. The US Food and Drug Administration-approved anticancer histone deacetylase inhibitor, SAHA, reduces myocardial infarct size in a large animal model, even when delivered in the clinically relevant context of reperfusion. The cardioprotective effects of SAHA during ischemia/reperfusion occur, at least in part, through the induction of autophagic flux.

Relaxin protects against myocardial injury caused by ischemia and reperfusion in rat heart.

PubMed Central

Bani, D.; Masini, E.; Bello, M. G.; Bigazzi, M.; Sacchi, T. B.

1998-01-01

Myocardial injury caused by ischemia and reperfusion comes from multiple pathogenic events, including endothelial damage, neutrophil extravasation into tissue, platelet and mast cell activation, and peroxidation of cell membrane lipids, which are followed by myocardial cell alterations resulting eventually in cell necrosis. The current study was designed to test the possible cardioprotective effect of the hormone relaxin, which has been found to cause coronary vessel dilation and to inhibit platelet and mast cell activation. Ischemia (for 30 minutes) was induced in rat hearts in vivo by ligature of the left anterior descending coronary artery; reperfusion (for 60 minutes or less if the rats died before this predetermined time) was induced by removal of the ligature. Relaxin (100 ng) was given intravenously 30 minutes before ischemia. The results obtained showed that relaxin strongly reduces 1) the extension of the myocardial areas affected by ischemia-reperfusion-induced damage, 2) ventricular arrhythmias, 3) mortality, 4) myocardial neutrophil number, 5) myeloperoxidase activity, a marker of neutrophil accumulation, 6) production of malonyldialdehyde, an end product of lipid peroxidation, 7) mast cell granule release, 8) calcium overload, and 9) morphological signs of myocardial cell injury. This study shows that relaxin can be regarded as an agent with a marked cardioprotective action against ischemia-reperfusion-induced myocardial injury. Images Figure 6 Figure 7 Figure 8 Figure 9 Figure 10 PMID:9588905

Analysis of data from spacecraft (stratospheric warmings)

NASA Technical Reports Server (NTRS)

1974-01-01

The details of the stratospheric warming processes as to time, area, and intensity were established, and the warmings with other terrestrial and solar phenomena occurring at satellite platform altitudes, or observable from satellite platforms, were correlated. Links were sought between the perturbed upper atmosphere (mesosphere and thermosphere) and the stratosphere that might explain stratospheric warmings.

Texture Analysis of Poly-Adenylated mRNA Staining Following Global Brain Ischemia and Reperfusion

PubMed Central

Szymanski, Jeffrey J.; Jamison, Jill T.; DeGracia, Donald J.

2011-01-01

Texture analysis provides a means to quantify complex changes in microscope images. We previously showed that cytoplasmic poly-adenylated mRNAs form mRNA granules in post-ischemic neurons and that these granules correlated with protein synthesis inhibition and hence cell death. Here we utilized the texture analysis software MaZda to quantify mRNA granules in photomicrographs of the pyramidal cell layer of rat hippocampal region CA3 around 1 hour of reperfusion after 10 min of normothermic global cerebral ischemia. At 1 hour reperfusion, we observed variations in the texture of mRNA granules amongst samples that were readily quantified by texture analysis. Individual sample variation was consistent with the interpretation that animal-to-animal variations in mRNA granules reflected the time-course of mRNA granule formation. We also used texture analysis to quantify the effect of cycloheximide, given either before or after brain ischemia, on mRNA granules. If administered before ischemia, cycloheximide inhibited mRNA granule formation, but if administered after ischemia did not prevent mRNA granulation, indicating mRNA granule formation is dependent on dissociation of polysomes. We conclude that texture analysis is an effective means for quantifying the complex morphological changes induced in neurons by brain ischemia and reperfusion. PMID:21477879

[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.

Quantified kidney echogenicity in mice with renal ischemia reperfusion injury: evaluation as a noninvasive biomarker of acute kidney injury.

PubMed

Murata, Shinya; Sugiyama, Noriyuki; Maemura, Kentaro; Otsuki, Yoshinori

2017-09-01

The purpose is to evaluate quantified kidney echogenicity as a biomarker for the early diagnosis of acute kidney injury (AKI) and predicting progression to chronic kidney disease (CKD) in a mouse model of ischemia-reperfusion injury (IRI). Two separate protocols of murine models of IRI were used: (1) 10, 30, and 40 min of bilateral ischemia duration and (2) 45 and 60 min of unilateral ischemia duration. Renal echogenicity was measured with ultrasound and compared with serum creatinine or urine neutrophil gelatinase-associated lipocalin (NGAL) at various timepoints after IRI. In mice subjected to 10, 30, and 40 min of bilateral ischemia, renal echogenicity increased about 2 h after IRI for all ischemia times, earlier than serum creatinine or urine NGAL. In those subjected to 45 and 60 min of unilateral ischemia, 60 min of unilateral ischemia, which represents atrophic changes 28 days after IRI, resulted in a sustained high level of echogenicity and was significantly different 24 h after IRI, while 45 min of unilateral ischemia resulted in trivial levels of histological damage 28 days after IRI. Renal echogenicity might have the potential to be a biomarker for the early diagnosis of AKI and the prognosis of CKD.

Average-atom treatment of relaxation time in x-ray Thomson scattering from warm dense matter.

PubMed

Johnson, W R; Nilsen, J

2016-03-01

The influence of finite relaxation times on Thomson scattering from warm dense plasmas is examined within the framework of the average-atom approximation. Presently most calculations use the collision-free Lindhard dielectric function to evaluate the free-electron contribution to the Thomson cross section. In this work, we use the Mermin dielectric function, which includes relaxation time explicitly. The relaxation time is evaluated by treating the average atom as an impurity in a uniform electron gas and depends critically on the transport cross section. The calculated relaxation rates agree well with values inferred from the Ziman formula for the static conductivity and also with rates inferred from a fit to the frequency-dependent conductivity. Transport cross sections determined by the phase-shift analysis in the average-atom potential are compared with those evaluated in the commonly used Born approximation. The Born approximation converges to the exact cross sections at high energies; however, differences that occur at low energies lead to corresponding differences in relaxation rates. The relative importance of including relaxation time when modeling x-ray Thomson scattering spectra is examined by comparing calculations of the free-electron dynamic structure function for Thomson scattering using Lindhard and Mermin dielectric functions. Applications are given to warm dense Be plasmas, with temperatures ranging from 2 to 32 eV and densities ranging from 2 to 64 g/cc.

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.

Ocular Blood Flow in Rabbits under Deep Anesthesia: A Real-Time Measurement Technique and Its Application in Characterizing Retinal Ischemia.

PubMed

Bhatti, Mehwish Saba; Tang, Tong Boon; Chen, Hui Cheng

2018-04-09

In this study, we reported a new technique based on laser speckle flowgraphy to record the ocular blood flow in rabbits under deep anesthesia, and proposed parameters to characterize retinal ischemia. We applied the proposed technique to study the correlation of blood flow between the eyes of normal non-anesthetized animals, and to characterize the occlusion of the internal carotid artery (ICA) and external carotid artery (ECA). We established a correlation in blood flow between the eyes of non-anesthetized animals, and derived two new parameters, namely, the laterality index and vascular perfusion estimate (VPE). Our experimental results from 16 eyes (of 13 New Zealand white rabbits) showed a reduction in ocular blood flow with a significant decrease in the VPE after the occlusion of the ECA (p < 0.001). A low/minimal effect on blood flow was observed with the occlusion of the ICA. In conclusion, we demonstrated a means for the real-time measurement of the ocular blood flow in rabbits under deep anesthesia by using laser speckle flowgraphy and the VPE as an indicator of successful occlusion. The proposed technique might be applicable in quantifying the efficacy of new drugs and interventions for the treatment of retinal ischemia.

Warm Hands and Feet

NASA Technical Reports Server (NTRS)

1976-01-01

Comfort Products, Inc. was responsible for the cold weather glove and thermal boots, adapted from a spacesuit design that kept astronauts warm or cool in the temperature extremes of the Apollo Moon Mission. Gloves and boots are thermally heated. Batteries are worn inside wrist of glove or sealed in sole of skiboot and are rechargeable hundreds of times. They operate flexible resistance circuit which is turned on periodically when wearer wants to be warm.

Real-time digital imaging of leukocyte-endothelial interaction in ischemia-reperfusion injury (IRI) of the rat cremaster muscle.

PubMed

Thiele, Jan R; Goerendt, Kurt; Stark, G Bjoern; Eisenhardt, Steffen U

2012-08-05

Ischemia-reperfusion injury (IRI) has been implicated in a large array of pathological conditions such as cerebral stroke, myocardial infarction, intestinal ischemia as well as following transplant and cardiovascular surgery. Reperfusion of previously ischemic tissue, while essential for the prevention of irreversible tissue injury, elicits excessive inflammation of the affected tissue. Adjacent to the production of reactive oxygen species, activation of the complement system and increased microvascular permeability, the activation of leukocytes is one of the principle actors in the pathological cascade of inflammatory tissue damage during reperfusion. Leukocyte activation is a multistep process consisting of rolling, firm adhesion and transmigration and is mediated by a complex interaction between adhesion molecules in response to chemoattractants such as complement factors, chemokines, or platelet-activating factor. While leukocyte rolling in postcapillary venules is predominantly mediated by the interaction of selectins with their counter ligands, firm adhesion of leukocytes to the endothelium is selectin-controlled via binding to intercellular adhesion molecules (ICAM) and vascular cellular adhesion molecules (VCAM). Gold standard for the in vivo observation of leukocyte-endothelial interaction is the technique of intravital microscopy, first described in 1968. Though various models of IRI (ischemia-reperfusion injury) have been described for various organs, only few are suitable for direct visualization of leukocyte recruitment in the microvascular bed on a high level of image quality. We here promote the digital intravital epifluorescence microscopy of the postcapillary venule in the cremasteric microcirculation of the rat as a convenient method to qualitatively and quantitatively analyze leukocyte recruitment for IRI-research in striated muscle tissue and provide a detailed manual for accomplishing the technique. We further illustrate common pitfalls and

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.

Cromoglycate, not ketotifen, ameliorated the injured effect of warm ischemia/reperfusion in rat liver: role of mast cell degranulation, oxidative stress, proinflammatory cytokine, and inducible nitric oxide synthase

PubMed Central

El-Shitany, Nagla A; El-Desoky, Karema

2015-01-01

Hepatic ischemia/reperfusion (ISCH/REP) is a major clinical problem that is considered to be the most common cause of postoperative liver failure. Recently, mast cells have been proposed to play an important role in the pathophysiology of ISCH/REP in many organs. In contrast, the role played by mast cells during ISCH/REP-induced liver damage has remained an issue of debate. This study aimed to investigate the protective role of mast cells in order to search for an effective therapeutic agent that could protect against fatal ISCH/REP-induced liver damage. A model of warm ISCH/REP was induced in the liver of rats. Four groups of rats were used in this study: Group I: SHAM (normal saline, intravenously [iv]); Group II: ISCH/REP; Group III: sodium cromoglycate + ISCH/REP (CROM + ISCH/REP), and Group IV: ketotifen (KET) + ISCH/REP (KET + ISCH/REP). Liver damage was assessed both histopathologically and biochemically. Mast cell degranulation was assessed histochemically. Lipid peroxidation (malondialdehyde [MDA]) as well as the levels of glutathione (GSH), interleukin-6 (IL-6), and tumor necrosis factor alpha (TNF-α), the formation of nitric oxide (NO), and the expression of inducible NO synthase (iNOS) were determined. The results of this study revealed increased mast cell degranulation in the liver during the acute phase of ISCH/REP. Moreover, CROM, but not KET, decreased the activity of alanine aminotransferase, aspartate aminotransferase, and lactic dehydrogenase and maintained normal liver tissue histology. Both CROM and KET protected against mast cell degranulation in the liver. In addition, both CROM and KET decreased IL-6 and TNF-α. However, CROM, but not KET, decreased MDA formation and increased GSH. Furthermore, KET, but not CROM, increased both NO formation and iNOS expression. In conclusion, this study clearly demonstrated mast cell degranulation in warm ISCH/REP in the liver of rats. More importantly, CROM, but not KET, ameliorated the effect of ISCH

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.

Salutary effect of pre-treatment with an Nrf2 inducer on ischemia reperfusion injury in the rat liver.

PubMed

Masuda, Yuichi; Vaziri, Nosratola D; Takasu, Chie; Li, Shiri; Robles, Lourdes; Pham, Christine; Le, Aimee; Vo, Kelly; Farzaneh, Seyed H; Stamos, Michael J; Ichii, Hirohito

2014-01-01

Ischemia-reperfusion injury (IRI) is a common phenomenon occurring during liver surgery, transplantation, and trauma. IRI causes oxidative stress which plays a critical role in causing organ damage. The Nrf2 is the master regulator of numerous genes, encoding antioxidant, detoxifying, and cytoprotective molecules. Nrf2 dysfunction has been implicated in the pathogenesis of several inflammatory disorders, cancer, and aging. This study was undertaken to investigate the effect of Nrf2 pathway activator (dh404) on warm liver IRI in a rodent model. Ten Sprague-Dawley rats were treated with dh404 or vehicle. Dh404 was dissolved in sesame oil and was given orally (1.5mg/kg) the night before and 5 hours before procedures. Rat livers were subjected to 60 minutes of 70% ischemia followed by 3 hours of reperfusion. Serum ALT and Malondialdehyde (MDA) were determined and liver tissue was processed for histological examination, and determination of apoptosis, myeloperoxidase (MPO) activity, ADP/ATP ratio, and expressions of Nrf2, eNOS, anti-oxidant enzymes, and inflammatory mediators. Serum ALT and MDA levels and tissue MPO activity were significantly lower, expression of the anti-oxidant enzyme, glutamate cysteine ligase were significantly higher, whereas expression of NFkB and COX-2 was unchanged in the dh404-treated group. Although the total Suzuki histology score did not differ significantly, the extent of sinusoidal congestion, vacuolization, and apoptosis was significantly reduced in the dh404 treated compared to the untreated group (P<0.01). Pre-treatment with dh404 resulted in partial attenuation of hepatic ischemia reperfusion injury in rats.

Downregulation of potassium chloride cotransporter KCC2 after transient focal cerebral ischemia.

PubMed

Jaenisch, Nadine; Witte, Otto W; Frahm, Christiane

2010-03-01

The potassium chloride cotransporter 2 (KCC2) is the main neuronal chloride extruder in the adult nervous system. Therefore, KCC2 is responsible for an inwardly directed electrochemical gradient of chloride that leads to hyperpolarizing GABA-mediated responses. Under some pathophysiological conditions, GABA has been reported to be depolarizing because of a downregulation of KCC2. This is the first study to our knowledge analyzing the expression of KCC2 after a focal cerebral ischemia. Mild and severe ischemia were induced in rats by a transient occlusion of the middle cerebral artery for 30 and 120 minutes, respectively. KCC2 mRNA and protein expression were studied in the ischemic hemisphere after different reperfusion times (2 hour, 1 day, 7 days, 30 days, 168 days) by using quantitative polymerase chain reaction, Western blotting, and immunohistological staining. We found a substantial decrease of KCC2 mRNA and protein levels in the ischemic hemisphere, with a stronger downregulation of KCC2 after severe vs mild ischemia. Long-term surviving cells expressing KCC2 could be detected in the infarct core. These cells were identified as GABAergic interneurons mainly expressing parvalbumin. Our study revealed a substantial neuron-specific downregulation of KCC2 after focal cerebral ischemia.

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

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

Testicular Ischemia Caused by Incarcerated Inguinal Hernia in Infants: Incidence, Conservative treatment procedure, and Follow-up.

PubMed

Ozdamar, Mustafa Yasar; Karakus, Osman Zeki

2017-07-02

Testicular ischemia and necrosis, especially in the infant age, may result from incarcerated inguinal hernia. Duration of ischemia is a significant factor for the affected testicle. We aimed to present a case series on the conservative management in the testicular ischemia caused by incarcerated inguinal hernia. Inguinal hernia repairs performed in between March 2009 and December 2014 were investigated retrospectively. Patients' characteristics, hernia side, incarceration, testicular ischemia and complications were recorded. Color Doppler ultrasonography was performed in the incarcerated inguinal hernia patients preoperatively and was repeated on 3 and 7 days and then at 1, 3 and 6 months postoperatively. The testicle sizes, volumes, and arterial flow patterns of them were recorded at the same time. Total 785 inguinal hernias were treated in 738 male patients, ranging from 18 days to 16 years. From all male patients, 44 (5.9%) had the IIH. There were 16 (36.3%) irreducible hernias in 44 incarcerated hernia patients. Of these 16, testicular ischemia was determined in 9 (56.2%) infants with the irreducible incarcerated hernia. Orchidopexyprocedure was performed in these patients. Testicular atrophy was occurred in two patients (22.2%). In the others, testicular volumes and perfusions were normal during follow-up (mean 8.3 ± 2.2 months). Testicular ischemia resulting from incarcerated inguinal hernia may be treated conservatively without orchiectomy for the ischemic testicle and testicular ischemia may be followed with color Doppler ultrasound for atleast 6 months. The inguinal hernia repair in infants should be subject to urgent surgery rather than elective surgery. So, the testicular ischemia in infants with the inguinal hernia will be an avoidable complication.

Seasonally different response of photosynthetic activity to daytime and night-time warming in the Northern Hemisphere

DOE PAGES

Tan, Jianguang; Piao, Shilong; Chen, Anping; ...

2014-08-27

Over the last century the Northern Hemisphere has experienced rapid climate warming, but this warming has not been evenly distributed seasonally, as well as diurnally. The implications of such seasonal and diurnal heterogeneous warming on regional and global vegetation photosynthetic activity, however, are still poorly understood. Here, we investigated for different seasons how photosynthetic activity of vegetation correlates with changes in seasonal daytime and night-time temperature across the Northern Hemisphere (>30°N), using Normalized Difference Vegetation Index (NDVI) data from 1982 to 2011 obtained from the Advanced Very High Resolution Radiometer (AVHRR). Our analysis revealed some striking seasonal differences in themore » response of NDVI to changes in day- versus night-time temperatures. For instance, while higher daytime temperature (T max) is generally associated with higher NDVI values across the boreal zone, the area exhibiting a statistically significant positive correlation between T max and NDVI is much larger in spring (41% of area in boreal zone – total area 12.6 × 10 6 km 2) than in summer and autumn (14% and 9%, respectively). In contrast to the predominantly positive response of boreal ecosystems to changes in T max, increases in T max tended to negatively influence vegetation growth in temperate dry regions, particularly during summer. Changes in night-time temperature (T min) correlated negatively with autumnal NDVI in most of the Northern Hemisphere, but had a positive effect on spring and summer NDVI in most temperate regions (e.g., Central North America and Central Asia). Such divergent covariance between the photosynthetic activity of Northern Hemispheric vegetation and day- and night-time temperature changes among different seasons and climate zones suggests a changing dominance of ecophysiological processes across time and space. Lastly, understanding the seasonally different responses of vegetation photosynthetic activity to

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.

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

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.

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.

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.

Silent myocardial ischemia in patients with stable coronary artery disease receiving conventional antianginal drug therapy.

PubMed

Ferreira, João Fernando Monteiro; César, Luiz Antonio Machado; Gruppi, César J; Giorgi, Dante M A; Hueb, Whady A; Mansur, Antonio P; Ramires, José A F

2007-11-01

Few data are available on the behavior of myocardial ischemia during daily activities in patients with coronary artery disease receiving antianginal drug therapy. To study the mechanism generating myocardial ischemia by evaluating blood pressure and heart rate changes in patients with stable atherosclerotic disease receiving drug therapy and with evidence of myocardial ischemia. Fifty non-hospitalized patients (40 males) underwent 24-hour electrocardiographic monitoring synchronized with blood pressured monitoring. Thirty five episodes of myocardial ischemia were detected in 17 patients, with a total duration of 146.3 minutes; angina was reported in five cases. Twenty nine episodes (100.3 minutes) occurred during wakefulness, with 11 episodes (35.3 + 3.7 min) in the period from 11 a.m. to 3 p.m. Blood pressure and heart rate evaluation in the three ten-minute intervals following the ischemic episodes showed a statistically significant difference (p< 0.05), unlike that shown for the three intervals preceding the episodes. However, during the ischemic episode, a higher than 10-mmHg elevation in blood pressure and 5 beats per minute in heart rate were observed when compared with the time interval between 20 and 10 minutes before the episode. The mean heart rate at the onset of ischemia during the exercise test performed before the study was 118.2 + 14.0, and 81.1 + 20.8 beats per minute on the 24-hour electrocardiogram (p < 0.001). The incidence of silent myocardial ischemia is high in stable coronary artery disease and is related to alterations in blood pressure and heart rate, with different thresholds for ischemia for the same patient.

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.

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

Characterization of Microparticles after Hepatic Ischemia-Reperfusion Injury

PubMed Central

Freeman, Christopher M.; Quillin, Ralph C.; Wilson, Gregory C.; Nojima, Hiroyuki; Johnson, Bobby L.; Sutton, Jeffrey M.; Schuster, Rebecca M.; Blanchard, John; Edwards, Michael J.; Caldwell, Charles C.; Lentsch, Alex B.

2014-01-01

Background Hepatic ischemia-reperfusion (I/R) is a well-studied model of liver injury and has demonstrated a biphasic injury followed by recovery and regeneration. Microparticles (MPs) are a developing field of study and these small membrane bound vesicles have been shown to have effector function in other physiologic and pathologic states. This study was designed to quantify the levels of MPs from various cell origins–platelets, neutrophils, and endolethial cells–following hepatic ischemia-reperfusion injury. Methods A murine model was used with mice undergoing 90 minutes of partial hepatic ischemia followed by various times of reperfusion. Following reperfusion, plasma samples were taken and MPs of various cell origins were labeled and levels were measured using flow cytometry. Additionally, cell specific MPs were further assessed by Annexin V, which stains for the presence of phosphatidylserine, a cell surface marker linked to apoptosis. Statistical analysis was performed using one-way analysis of variance with subsequent Student-Newman-Keuls test with data presented as the mean and standard error of the mean. Results MPs from varying sources show an increase in circulating levels following hepatic I/R injury. However, the timing of the appearance of different MP subtypes differs for each cell type. Platelet and neutrophil-derived MP levels demonstrated an acute elevation following injury whereas endothelial-derived MP levels demonstrated a delayed elevation. Conclusion This is the first study to characterize circulating levels of cell-specific MPs after hepatic I/R injury and suggests that MPs derived from platelets and neutrophils serve as markers of inflammatory injury and may be active participants in this process. In contrast, MPs derived from endothelial cells increase after the injury response during the reparative phase and may be important in angiogenesis that occurs in the regenerating liver. PMID:24879335

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.

Ischemia-reperfusion injury and pregnancy initiate time-dependent and robust signs of up-regulation of cardiac progenitor cells.

PubMed

Genead, Rami; Fischer, Helene; Hussain, Alamdar; Jaksch, Marie; Andersson, Agneta B; Ljung, Karin; Bulatovic, Ivana; Franco-Cereceda, Anders; Elsheikh, Elzafir; Corbascio, Matthias; Smith, C I Edvard; Sylvén, Christer; Grinnemo, Karl-Henrik

2012-01-01

To explore how cardiac regeneration and cell turnover adapts to disease, different forms of stress were studied for their effects on the cardiac progenitor cell markers c-Kit and Isl1, the early cardiomyocyte marker Nkx2.5, and mast cells. Adult female rats were examined during pregnancy, after myocardial infarction and ischemia-reperfusion injury with/out insulin like growth factor-1(IGF-1) and hepatocyte growth factor (HGF). Different cardiac sub-domains were analyzed at one and two weeks post-intervention, both at the mRNA and protein levels. While pregnancy and myocardial infarction up-regulated Nkx2.5 and c-Kit (adjusted for mast cell activation), ischemia-reperfusion injury induced the strongest up-regulation which occurred globally throughout the entire heart and not just around the site of injury. This response seems to be partly mediated by increased endogenous production of IGF-1 and HGF. Contrary to c-Kit, Isl1 was not up-regulated by pregnancy or myocardial infarction while ischemia-reperfusion injury induced not a global but a focal up-regulation in the outflow tract and also in the peri-ischemic region, correlating with the up-regulation of endogenous IGF-1. The addition of IGF-1 and HGF did boost the endogenous expression of IGF and HGF correlating to focal up-regulation of Isl1. c-Kit expression was not further influenced by the exogenous growth factors. This indicates that there is a spatial mismatch between on one hand c-Kit and Nkx2.5 expression and on the other hand Isl1 expression. In conclusion, ischemia-reperfusion injury was the strongest stimulus with both global and focal cardiomyocyte progenitor cell marker up-regulations, correlating to the endogenous up-regulation of the growth factors IGF-1 and HGF. Also pregnancy induced a general up-regulation of c-Kit and early Nkx2.5+ cardiomyocytes throughout the heart. Utilization of these pathways could provide new strategies for the treatment of cardiac disease.

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.

The Neuroprotective Effect of Kefir on Spinal Cord Ischemia/Reperfusion Injury in Rats.

PubMed

Guven, Mustafa; Akman, Tarik; Yener, Ali Umit; Sehitoglu, Muserref Hilal; Yuksel, Yasemin; Cosar, Murat

2015-05-01

The main causes of spinal cord ischemia are a variety of vascular pathologies causing acute arterial occlusions. We investigated neuroprotective effects of kefir on spinal cord ischemia injury in rats. Rats were divided into three groups : 1) sham operated control rats; 2) spinal cord ischemia group fed on a standard diet without kefir pretreatment; and 3) spinal cord ischemia group fed on a standard diet plus kefir. Spinal cord ischemia was performed by the infrarenal aorta cross-clamping model. The spinal cord was removed after the procedure. The biochemical and histopathological changes were observed within the samples. Functional assessment was performed for neurological deficit scores. The kefir group was compared with the ischemia group, a significant decrease in malondialdehyde levels was observed (p<0.05). Catalase and superoxide dismutase levels of the kefir group were significantly higher than ischemia group (p<0.05). In histopathological samples, the kefir group is compared with ischemia group, there was a significant decrease in numbers of dead and degenerated neurons (p<0.05). In immunohistochemical staining, hipoxia-inducible factor-1α and caspase 3 immunopositive neurons were significantly decreased in kefir group compared with ischemia group (p<0.05). The neurological deficit scores of kefir group were significantly higher than ischemia group at 24 h (p<0.05). Our study revealed that kefir pretreatment in spinal cord ischemia/reperfusion reduced oxidative stress and neuronal degeneration as a neuroprotective agent. Ultrastructural studies are required in order for kefir to be developed as a promising therapeutic agent to be utilized for human spinal cord ischemia in the future.

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.

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

Average-atom treatment of relaxation time in x-ray Thomson scattering from warm dense matter

DOE PAGES

Johnson, W. R.; Nilsen, J.

2016-03-14

Here, the influence of finite relaxation times on Thomson scattering from warm dense plasmas is examined within the framework of the average-atom approximation. Presently most calculations use the collision-free Lindhard dielectric function to evaluate the free-electron contribution to the Thomson cross section. In this work, we use the Mermin dielectric function, which includes relaxation time explicitly. The relaxation time is evaluated by treating the average atom as an impurity in a uniform electron gas and depends critically on the transport cross section. The calculated relaxation rates agree well with values inferred from the Ziman formula for the static conductivity andmore » also with rates inferred from a fit to the frequency-dependent conductivity. Transport cross sections determined by the phase-shift analysis in the average-atom potential are compared with those evaluated in the commonly used Born approximation. The Born approximation converges to the exact cross sections at high energies; however, differences that occur at low energies lead to corresponding differences in relaxation rates. The relative importance of including relaxation time when modeling x-ray Thomson scattering spectra is examined by comparing calculations of the free-electron dynamic structure function for Thomson scattering using Lindhard and Mermin dielectric functions. Applications are given to warm dense Be plasmas, with temperatures ranging from 2 to 32 eV and densities ranging from 2 to 64 g/cc.« less

Effects of in situ climate warming on monarch caterpillar (Danaus plexippus) development.

PubMed

Lemoine, Nathan P; Capdevielle, Jillian N; Parker, John D

2015-01-01

Climate warming will fundamentally alter basic life history strategies of many ectothermic insects. In the lab, rising temperatures increase growth rates of lepidopteran larvae but also reduce final pupal mass and increase mortality. Using in situ field warming experiments on their natural host plants, we assessed the impact of climate warming on development of monarch (Danaus plexippus) larvae. Monarchs were reared on Asclepias tuberosa grown under 'Ambient' and 'Warmed' conditions. We quantified time to pupation, final pupal mass, and survivorship. Warming significantly decreased time to pupation, such that an increase of 1 °C corresponded to a 0.5 day decrease in pupation time. In contrast, survivorship and pupal mass were not affected by warming. Our results indicate that climate warming will speed the developmental rate of monarchs, influencing their ecological and evolutionary dynamics. However, the effects of climate warming on larval development in other monarch populations and at different times of year should be investigated.

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

according to CMR timing, ischemia duration, and cardioprotective strategy. Conclusions: Cardioprotective therapies, duration of index ischemia, and the interplay between these greatly influence temporal dynamics and extent of tissue composition changes after I/R. Consequently, imaging techniques and protocols for assessing edema, myocardium at risk, infarct size, salvage, intramyocardial hemorrhage, and microvascular obstruction should be standardized accordingly. PMID:28596216

Recent Warming of Lake Kivu

PubMed Central

Katsev, Sergei; Aaberg, Arthur A.; Crowe, Sean A.; Hecky, Robert E.

2014-01-01

Lake Kivu in East Africa has gained notoriety for its prodigious amounts of dissolved methane and dangers of limnic eruption. Being meromictic, it is also expected to accumulate heat due to rising regional air temperatures. To investigate the warming trend and distinguish between atmospheric and geothermal heating sources, we compiled historical temperature data, performed measurements with logging instruments, and simulated heat propagation. We also performed isotopic analyses of water from the lake's main basin and isolated Kabuno Bay. The results reveal that the lake surface is warming at the rate of 0.12°C per decade, which matches the warming rates in other East African lakes. Temperatures increase throughout the entire water column. Though warming is strongest near the surface, warming rates in the deep waters cannot be accounted for solely by propagation of atmospheric heat at presently assumed rates of vertical mixing. Unless the transport rates are significantly higher than presently believed, this indicates significant contributions from subterranean heat sources. Temperature time series in the deep monimolimnion suggest evidence of convection. The progressive deepening of the depth of temperature minimum in the water column is expected to accelerate the warming in deeper waters. The warming trend, however, is unlikely to strongly affect the physical stability of the lake, which depends primarily on salinity gradient. PMID:25295730

Recent warming of lake Kivu.

PubMed

Katsev, Sergei; Aaberg, Arthur A; Crowe, Sean A; Hecky, Robert E

2014-01-01

Lake Kivu in East Africa has gained notoriety for its prodigious amounts of dissolved methane and dangers of limnic eruption. Being meromictic, it is also expected to accumulate heat due to rising regional air temperatures. To investigate the warming trend and distinguish between atmospheric and geothermal heating sources, we compiled historical temperature data, performed measurements with logging instruments, and simulated heat propagation. We also performed isotopic analyses of water from the lake's main basin and isolated Kabuno Bay. The results reveal that the lake surface is warming at the rate of 0.12°C per decade, which matches the warming rates in other East African lakes. Temperatures increase throughout the entire water column. Though warming is strongest near the surface, warming rates in the deep waters cannot be accounted for solely by propagation of atmospheric heat at presently assumed rates of vertical mixing. Unless the transport rates are significantly higher than presently believed, this indicates significant contributions from subterranean heat sources. Temperature time series in the deep monimolimnion suggest evidence of convection. The progressive deepening of the depth of temperature minimum in the water column is expected to accelerate the warming in deeper waters. The warming trend, however, is unlikely to strongly affect the physical stability of the lake, which depends primarily on salinity gradient.

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.

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.

Preclinical Evidence for the Efficacy of Ischemic Postconditioning against Renal Ischemia-Reperfusion Injury, a Systematic Review and Meta-Analysis

PubMed Central

Jonker, Simone J.; Menting, Theo P.; Warlé, Michiel C.; Ritskes-Hoitinga, Merel; Wever, Kimberley E.

2016-01-01

Background Renal ischemia-reperfusion injury (IRI) is a major cause of kidney damage after e.g. renal surgery and transplantation. Ischemic postconditioning (IPoC) is a promising treatment strategy for renal IRI, but early clinical trials have not yet replicated the promising results found in animal studies. Method We present a systematic review, quality assessment and meta-analysis of the preclinical evidence for renal IPoC, and identify factors which modify its efficacy. Results We identified 39 publications studying >250 control animals undergoing renal IRI only and >290 animals undergoing renal IRI and IPoC. Healthy, male rats undergoing warm ischemia were used in the vast majority of studies. Four studies applied remote IPoC, all others used local IPoC. Meta-analysis showed that both local and remote IPoC ameliorated renal damage after IRI for the outcome measures serum creatinine, blood urea nitrogen and renal histology. Subgroup analysis indicated that IPoC efficacy increased with the duration of index ischemia. Measures to reduce bias were insufficiently reported. Conclusion High efficacy of IPoC is observed in animal models, but factors pertaining to the internal and external validity of these studies may hamper the translation of IPoC to the clinical setting. The external validity of future animal studies should be increased by including females, comorbid animals, and transplantation models, in order to better inform clinical trial design. The severity of renal damage should be taken into account in the design and analysis of future clinical trials. PMID:26963819

The Neuroprotective Effect of Kefir on Spinal Cord Ischemia/Reperfusion Injury in Rats

PubMed Central

Akman, Tarik; Yener, Ali Umit; Sehitoglu, Muserref Hilal; Yuksel, Yasemin; Cosar, Murat

2015-01-01

Objective The main causes of spinal cord ischemia are a variety of vascular pathologies causing acute arterial occlusions. We investigated neuroprotective effects of kefir on spinal cord ischemia injury in rats. Methods Rats were divided into three groups : 1) sham operated control rats; 2) spinal cord ischemia group fed on a standard diet without kefir pretreatment; and 3) spinal cord ischemia group fed on a standard diet plus kefir. Spinal cord ischemia was performed by the infrarenal aorta cross-clamping model. The spinal cord was removed after the procedure. The biochemical and histopathological changes were observed within the samples. Functional assessment was performed for neurological deficit scores. Results The kefir group was compared with the ischemia group, a significant decrease in malondialdehyde levels was observed (p<0.05). Catalase and superoxide dismutase levels of the kefir group were significantly higher than ischemia group (p<0.05). In histopathological samples, the kefir group is compared with ischemia group, there was a significant decrease in numbers of dead and degenerated neurons (p<0.05). In immunohistochemical staining, hipoxia-inducible factor-1α and caspase 3 immunopositive neurons were significantly decreased in kefir group compared with ischemia group (p<0.05). The neurological deficit scores of kefir group were significantly higher than ischemia group at 24 h (p<0.05). Conclusion Our study revealed that kefir pretreatment in spinal cord ischemia/reperfusion reduced oxidative stress and neuronal degeneration as a neuroprotective agent. Ultrastructural studies are required in order for kefir to be developed as a promising therapeutic agent to be utilized for human spinal cord ischemia in the future. PMID:26113960

The effect of high intensity interval training on cardioprotection against ischemia-reperfusion injury in wistar rats

PubMed Central

Rahimi, Mostafa; Shekarforoush, Shahnaz; Asgari, Ali Reza; Khoshbaten, Ali; Rajabi, Hamid; Bazgir, Behzad; Mohammadi, Mohammad Taghi; Sobhani, Vahid; Shakibaee, Abolfazl

2015-01-01

The aims of the present study were to determine whether short term high intensity interval training (HIIT) could protect the heart against ischemia reperfusion (IR) injury; and if so, to evaluate how long the exercise-associated protection can be lasted. Sixty-three rats were randomly assigned into sedentary (n = 15), sham (n = 7), and exercise groups (n = 41). Rats in the exercise groups performed 5 consecutive days of HIIT on treadmill: 5 min warm up with 50 % VO2max, 6×2 min with 95-105 % VO2max (about 40 to 45 m/min), 5×2 min recovery with 65-75 % VO2max (about 28 to 32 m/min), and 3 min cool down with 50 % VO2max, all at 0 % grade. Animals exposed to an in vivo cardiac IR surgery, performed at days 1, 7, and 14 following the final exercise session. Ischemia-induced arrhythmias, myocardial infarct size (IS), plasma lactate dehydrogenase (LDH) and creatine kinase (CK) activities were measured in all animals. Compared to sedentary rats, exercised animals sustained less IR injury as evidenced by a lower size of infarction and lower levels of LDH and CK at day one and day 7 post exercise. In comparison of sedentary group, IS significantly decreased in EX-IR1 and EX-IR7 groups (50 and 35 %, respectively), but not in EX-IR14 group (19 %). The exercise-induced cardioprotection disappeared 14 days following exercise cessation. There were no significant changes in ischemia-induced arrhythmia between exercised and sedentary rats. The results clearly demonstrate that HIIT protects the heart against myocardial IR injury. This protective effect can be sustained for at least one week following the cessation of the training. PMID:26417361

Exploration of warm-up period in conceptual hydrological modelling

NASA Astrophysics Data System (ADS)

Kim, Kue Bum; Kwon, Hyun-Han; Han, Dawei

2018-01-01

One of the important issues in hydrological modelling is to specify the initial conditions of the catchment since it has a major impact on the response of the model. Although this issue should be a high priority among modelers, it has remained unaddressed by the community. The typical suggested warm-up period for the hydrological models has ranged from one to several years, which may lead to an underuse of data. The model warm-up is an adjustment process for the model to reach an 'optimal' state, where internal stores (e.g., soil moisture) move from the estimated initial condition to an 'optimal' state. This study explores the warm-up period of two conceptual hydrological models, HYMOD and IHACRES, in a southwestern England catchment. A series of hydrologic simulations were performed for different initial soil moisture conditions and different rainfall amounts to evaluate the sensitivity of the warm-up period. Evaluation of the results indicates that both initial wetness and rainfall amount affect the time required for model warm up, although it depends on the structure of the hydrological model. Approximately one and a half months are required for the model to warm up in HYMOD for our study catchment and climatic conditions. In addition, it requires less time to warm up under wetter initial conditions (i.e., saturated initial conditions). On the other hand, approximately six months is required for warm-up in IHACRES, and the wet or dry initial conditions have little effect on the warm-up period. Instead, the initial values that are close to the optimal value result in less warm-up time. These findings have implications for hydrologic model development, specifically in determining soil moisture initial conditions and warm-up periods to make full use of the available data, which is very important for catchments with short hydrological records.

Scaling Potential Evapotranspiration with Greenhouse Warming (Invited)

NASA Astrophysics Data System (ADS)

Scheff, J.; Frierson, D. M.

2013-12-01

Potential evapotranspiration (PET) is a supply-independent measure of the evaporative demand of a terrestrial climate, of basic importance in climatology, hydrology, and agriculture. Future increases in PET from greenhouse warming are often cited as key drivers of global trends toward drought and aridity. The present work computes recent and business-as-usual-future Penman-Monteith (i.e. physically-based) PET fields at 3-hourly resolution in 14 modern global climate models. The %-change in local annual-mean PET over the upcoming century is almost always positive, modally low double-digit in magnitude, usually increasing with latitude, yet quite divergent between models. These patterns are understood as follows. In every model, the global field of PET %-change is found to be dominated by the direct, positive effects of constant-relative-humidity warming (via increasing vapor pressure deficit and increasing Clausius-Clapeyron slope.) This direct-warming term very accurately scales as the PET-weighted (warm-season daytime) local warming, times 5-6% per degree (related to the Clausius-Clapeyron equation), times an analytic factor ranging from about 0.25 in warm climates to 0.75 in cold climates, plus a small correction. With warming of several degrees, this product is of low double-digit magnitude, and the strong temperature dependence gives the latitude dependence. Similarly, the inter-model spread in the amount of warming gives most of the spread in this term. Additional spread in the total change comes from strong disagreement on radiation, relative-humidity, and windspeed changes, which make smaller yet substantial contributions to the full PET %-change fields.

Delayed Administration of Bone Marrow Mesenchymal Stem Cell Conditioned Medium Significantly Improves Outcome After Retinal Ischemia in Rats

PubMed Central

Dreixler, John C.; Poston, Jacqueline N.; Balyasnikova, Irina; Shaikh, Afzhal R.; Tupper, Kelsey Y.; Conway, Sineadh; Boddapati, Venkat; Marcet, Marcus M.; Lesniak, Maciej S.; Roth, Steven

2014-01-01

Purpose. Delayed treatment after ischemia is often unsatisfactory. We hypothesized that injection of bone marrow stem cell (BMSC) conditioned medium after ischemia could rescue ischemic retina, and in this study we characterized the functional and histological outcomes and mechanisms of this neuroprotection. Methods. Retinal ischemia was produced in adult Wistar rats by increasing intraocular pressure for 55 minutes. Conditioned medium (CM) from rat BMSCs or unconditioned medium (uCM) was injected into the vitreous 24 hours after the end of ischemia. Recovery was assessed 7 days after ischemia using electroretinography, at which time we euthanized the animals and then prepared 4-μm-thick paraffin-embedded retinal sections. TUNEL and Western blot were used to identify apoptotic cells and apoptosis-related gene expression 24 hours after injections; that is, 48 hours after ischemia. Protein content in CM versus uCM was studied using tandem mass spectrometry, and bioinformatics methods were used to model protein interactions. Results. Intravitreal injection of CM 24 hours after ischemia significantly improved retinal function and attenuated cell loss in the retinal ganglion cell layer. CM attenuated postischemic apoptosis and apoptosis-related gene expression. By spectral counting, 19 proteins that met stringent identification criteria were increased in the CM compared to uCM; the majority were extracellular matrix proteins that mapped into an interactional network together with other proteins involved in cell growth and adhesion. Conclusions. By restoring retinal function, attenuating apoptosis, and preventing retinal cell loss after ischemia, CM is a robust means of delayed postischemic intervention. We identified some potential candidate proteins for this effect. PMID:24699381

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

Reduced cerebral ischemia-reperfusion injury in Toll-like receptor 4 deficient mice

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

Cao Canxiang; Yang Qingwu; Lv Fenglin

Inflammatory reaction plays an important role in cerebral ischemia-reperfusion injury, however, its mechanism is still unclear. Our study aims to explore the function of Toll-like receptor 4 (TLR4) in the process of cerebral ischemia-reperfusion. We made middle cerebral artery ischemia-reperfusion model in mice with line embolism method. Compared with C3H/OuJ mice, scores of cerebral water content, cerebral infarct size and neurologic impairment in C3H/Hej mice were obviously lower after 6 h ischemia and 24 h reperfusion. Light microscopic and electron microscopic results showed that cerebral ischemia-reperfusion injury in C3H/Hej mice was less serious than that in C3H/OuJ mice. TNF-{alpha} andmore » IL-6 contents in C3H/HeJ mice were obviously lower than that in C3H/OuJ mice with ELISA. The results showed that TLR4 participates in the process of cerebral ischemia-reperfusion injury probably through decrease of inflammatory cytokines. TLR4 may become a new target for prevention of cerebral ischemia-reperfusion injury. Our study suggests that TLR4 is one of the mechanisms of cerebral ischemia-reperfusion injury besides its important role in innate immunity.« less

Unabated global surface temperature warming: evaluating the evidence

NASA Astrophysics Data System (ADS)

Karl, T. R.; Arguez, A.

2015-12-01

New insights related to time-dependent bias corrections in global surface temperatures have led to higher rates of warming over the past few decades than previously reported in the IPCC Fifth Assessment Report (2014). Record high global temperatures in the past few years have also contributed to larger trends. The combination of these factors and new analyses of the rate of temperature change show unabated global warming since at least the mid-Twentieth Century. New time-dependent bias corrections account for: (1) differences in temperatures measured from ships and drifting buoys; (2) improved corrections to ship measured temperatures; and (3) the larger rates of warming in polar regions (particularly the Arctic). Since 1951, the period over which IPCC (2014) attributes over half of the observed global warming to human causes, it is shown that there has been a remarkably robust and sustained warming, punctuated with inter-annual and decadal variability. This finding is confirmed through simple trend analysis and Empirical Mode Decomposition (EMD). Trend analysis however, especially for decadal trends, is sensitive to selection bias of beginning and ending dates. EMD has no selection bias. Additionally, it can highlight both short- and long-term processes affecting the global temperature times series since it addresses both non-linear and non-stationary processes. For the new NOAA global temperature data set, our analyses do not support the notion of a hiatus or slowing of long-term global warming. However, sub-decadal periods of little (or no warming) and rapid warming can also be found, clearly showing the impact of inter-annual and decadal variability that previously has been attributed to both natural and human-induced non-greenhouse forcings.

Minoxidil attenuates ischemia-induced apoptosis in cultured neonatal rat cardiomyocytes.

PubMed

Takatani, Tomoka; Takahashi, Kyoko; Jin, Chengshi; Matsuda, Takahisa; Cheng, Xinyao; Ito, Takashi; Azuma, Junichi

2004-06-01

The effects of minoxidil (a mitochondrial K+(ATP) channel opener) on ischemia-induced necrosis and apoptosis were examined using a cardiomyocyte model of simulated ischemia, since mitochondrial K+(ATP) channel openers have been suggested to be involved in the mechanisms of cardioprotective action against ischemia/reperfusion injury. In the absence of minoxidil, simulated ischemia led to cellular release of creatine phosphokinase (CPK), morphologic degeneration, and beating cessation within 24 to 72 hours. Based on the Hoechst 33258 staining pattern, a significant number of cells placed in sealed flasks underwent apoptosis. Myocytes treated with 5 microM of minoxidil failed to alter the degree of ischemia-induced CPK loss for 48 to 72 hours. However, minoxidil treatment prevented the loss of beating function in many of the ischemic cells, and attenuated the decline in intracellular ATP content after a 48-hour ischemic incubation. The number of nuclear fragmentation was significantly reduced in minoxidil-treated cells after a 72-hour ischemic insult compared with untreated ischemic cells. This effect was blocked by the mitochondrial K+(ATP) channel antagonist 5-HD. The data suggest that minoxidil renders the cell resistant to ischemia-induced necrosis and apoptosis. The beneficial effects of minoxidil appear to be related to the opening of mitochondrial K+(ATP) channels.

[Ischemic postconditioning attenuates ischemia/reperfusion injury in isolated hypertrophied rat heart].

PubMed

Peng, Long-yun; Ma, Hong; He, Jian-gui; Gao, Xiu-ren; Zhang, Yan; He, Xiao-hong; Zhai, Yuan-sheng; Zhang, Xue-jiao

2006-08-01

To explore the effects of ischemic postconditioning on ischemia/reperfusion injury in isolated hypertrophied rat heart and investigate the signal transduction pathway changes induced by ischemia postconditioning. Cardiac hypertrophy was induced in rats by abdominal aortic banding, and isolated hypertrophied rat heart ischemia/reperfusion model was made by Langendorff technique to evaluate the effects of ischemia postconditioning on left ventricular systole pressure, coronary artery flow, creatine phosphokinase (CPK) and lactate dehydrogenase (LDH) release, myocardial infarction size, and the level of myocardial phospho-protein kinase B/Akt (Ser473), phospho-glycogen synthase kinase-3beta (Ser9). Following groups were studied (n = 12 each group): IR, 30 min ischemia (I)/60 min Reperfusion (R); Post: 30 min ischemia, 6 circles of 10 s I/10 s R followed by 60 min R; Post Wort: 30 min ischemia, 6 circles of 10 s I/10 s R, wortmannin (10(-7) mol/L) followed by 60 min R; Wort: 30 min ischemia, wortmannin (10(-7) mol/L) followed by 60 min R. Left ventricular systolic pressure and coronary artery flow were significantly increased, myocardial infarction size and the release of CPK, LDH significantly reduced in Post group compared to that in IR group. Phospho-protein kinase B/Akt (Ser473) and phospho-glycogen synthase kinase-3beta (Ser9) levels were also significantly higher in Post group than that in IR group. Phosphatidylinositol 3-kinase (PI3K) inhibitor wortmannin prevented the increase of phospho-protein kinase B/Akt (Ser473) and phospho-glycogen synthase kinase-3beta (Ser9) induced by ischemic postconditioning, but only partly abolished the cardioprotection of ischemic postconditioning. Ischemic postconditioning attenuates ischemia/reperfusion injury in isolated hypertrophied rat heart. The cardioprotective effects of ischemic postconditioning were partly mediated through PI3K/Akt/GSK-3beta signaling pathway.

Blue light reduces organ injury from ischemia and reperfusion

PubMed Central

Yuan, Du; Collage, Richard D.; Huang, Hai; Zhang, Xianghong; Kautza, Benjamin C.; Lewis, Anthony J.; Zuckerbraun, Brian S.; Tsung, Allan; Angus, Derek C.; Rosengart, Matthew R.

2016-01-01

Evidence suggests that light and circadian rhythms profoundly influence the physiologic capacity with which an organism responds to stress. However, the ramifications of light spectrum on the course of critical illness remain to be determined. Here, we show that acute exposure to bright blue spectrum light reduces organ injury by comparison with bright red spectrum or ambient white fluorescent light in two murine models of sterile insult: warm liver ischemia/reperfusion (I/R) and unilateral renal I/R. Exposure to bright blue light before I/R reduced hepatocellular injury and necrosis and reduced acute kidney injury and necrosis. In both models, blue light reduced neutrophil influx, as evidenced by reduced myeloperoxidase (MPO) within each organ, and reduced the release of high-mobility group box 1 (HMGB1), a neutrophil chemotactant and key mediator in the pathogenesis of I/R injury. The protective mechanism appeared to involve an optic pathway and was mediated, in part, by a sympathetic (β3 adrenergic) pathway that functioned independent of significant alterations in melatonin or corticosterone concentrations to regulate neutrophil recruitment. These data suggest that modifying the spectrum of light may offer therapeutic utility in sterile forms of cellular injury. PMID:27114521

Clinical Trial Research on Mongolian Medical Warm Acupuncture in Treating Insomnia.

PubMed

Bo, Agula; Si, Lengge; Wang, Yuehong; Xiu, Lan; Wu, Rihan; Li, Yutang; Mu, Rigenjiya; Ga, Latai; Miao, Mei; Shuang, Fu; Wu, Yunhua; Jin, Qiu; Tong, Suocai; Wuyun, Gerile; Guan, Wurihan; Mo, Rigen; Hu, Sileng; Zhang, Lixia; Peng, Rui; Bao, Lidao

2016-01-01

Objective. Insomnia is one of the most common sleep disorders. Hypnotics have poor long-term efficacy. Mongolian medical warm acupuncture has significant efficacy in treating insomnia. The paper evaluates the role of Mongolian medical warm acupuncture in treating insomnia by investigating the Mongolian medicine syndromes and conditions, Pittsburgh sleep quality index, and polysomnography indexes. Method. The patients were diagnosed in accordance with International Classification of Sleep Disorders (ICSD-2). The insomnia patients were divided into the acupuncture group (40 cases) and the estazolam group (40 cases). The patients underwent intervention of Mongolian medical warm acupuncture and estazolam. The indicators of the Mongolian medicine syndromes and conditions, Pittsburgh sleep quality index (PSQI), and polysomnography indexes (PSG) have been detected. Result. Based on the comparison of the Mongolian medicine syndrome scores between the warm acupuncture group and the drug treatment group, the result indicated P < 0.01. The clinical efficacy result showed that the effective rate (85%) in the warm acupuncture group was higher than that (70%) in the drug group. The total scores of PSQI of both groups were approximated. The sleep quality indexes of both groups decreased significantly ( P < 0.05). The sleep quality index in the Mongolian medical warm acupuncture group decreased significantly ( P < 0.01) and was better than that in the estazolam group. The sleep efficiency and daytime functions of the patients in the Mongolian medical warm acupuncture group improved significantly ( P < 0.01). The sleep time was significantly extended ( P < 0.01) in the Mongolian medical warm acupuncture group following PSG intervention. The sleep time during NREM in the Mongolian warm acupuncture group increased significantly ( P < 0.01). The sleep time exhibited a decreasing trend during REM and it decreased significantly in the Mongolian warm acupuncture group ( P < 0.01). The

The effects of deformation, ischemia, and reperfusion on the development of muscle damage during prolonged loading.

PubMed

Loerakker, S; Manders, E; Strijkers, G J; Nicolay, K; Baaijens, F P T; Bader, D L; Oomens, C W J

2011-10-01

Deep tissue injury (DTI) is a severe form of pressure ulcer where tissue damage starts in deep tissues underneath intact skin. In the present study, the contributions of deformation, ischemia, and reperfusion to skeletal muscle damage development were examined in a rat model during a 6-h period. Magnetic resonance imaging (MRI) was used to study perfusion (contrast-enhanced MRI) and tissue integrity (T2-weighted MRI). The levels of tissue deformation were estimated using finite element models. Complete ischemia caused a gradual homogeneous increase in T2 (∼20% during the 6-h period). The effect of reperfusion on T2 was highly variable, depending on the anatomical location. In experiments involving deformation, inevitably associated with partial ischemia, a variable T2 increase (17-66% during the 6-h period) was observed reflecting the significant variation in deformation (with two-dimensional strain energies of 0.60-1.51 J/mm) and ischemia (50.8-99.8% of the leg) between experiments. These results imply that deformation, ischemia, and reperfusion all contribute to the damage process during prolonged loading, although their importance varies with time. The critical deformation threshold and period of ischemia that cause muscle damage will certainly vary between individuals. These variations are related to intrinsic factors, such as pathological state, which partly explain the individual susceptibility to the development of DTI and highlight the need for regular assessments of individual subjects.

Culture time of vitrified/warmed zygotes before microinjection affects the production efficiency of CRISPR-Cas9-mediated knock-in mice.

PubMed

Nakagawa, Yoshiko; Sakuma, Tetsushi; Nishimichi, Norihisa; Yokosaki, Yasuyuki; Takeo, Toru; Nakagata, Naomi; Yamamoto, Takashi

2017-05-15

Robust reproductive engineering techniques are required for the efficient and rapid production of genetically modified mice. We have reported the efficient production of genome-edited mice using reproductive engineering techniques, such as ultra-superovulation, in vitro fertilization (IVF) and vitrification/warming of zygotes. We usually use vitrified/warmed fertilized oocytes created by IVF for microinjection because of work efficiency and flexible scheduling. Here, we investigated whether the culture time of zygotes before microinjection influences the efficiency of producing knock-in mice. Knock-in mice were generated using clustered regularly interspaced short palindromic repeats (CRISPR)-CRISPR-associated protein 9 (Cas9) system and single-stranded oligodeoxynucleotide (ssODN) or PITCh (Precise Integration into Target Chromosome) system, a method of integrating a donor vector assisted by microhomology-mediated end-joining. The cryopreserved fertilized oocytes were warmed, cultured for several hours and microinjected at different timings. Microinjection was performed with Cas9 protein, guide RNA(s), and an ssODN or PITCh donor plasmid for the ssODN knock-in and the PITCh knock-in, respectively. Different production efficiencies of knock-in mice were observed by changing the timing of microinjection. Our study provides useful information for the CRISPR-Cas9-based generation of knock-in mice. © 2017. Published by The Company of Biologists Ltd.

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

Acute retinal ischemia inhibits endothelium-dependent nitric oxide-mediated dilation of retinal arterioles via enhanced superoxide production.

PubMed

Hein, Travis W; Ren, Yi; Potts, Luke B; Yuan, Zhaoxu; Kuo, Enoch; Rosa, Robert H; Kuo, Lih

2012-01-03

Because retinal vascular disease is associated with ischemia and increased oxidative stress, the vasodilator function of retinal arterioles was examined after retinal ischemia induced by elevated intraocular pressure (IOP). The role of superoxide anions in the development of vascular dysfunction was assessed. IOP was increased and maintained at 80 to 90 mm Hg for 30, 60, or 90 minutes by infusing saline into the anterior chamber of a porcine eye. The fellow eye with normal IOP (10-20 mm Hg) served as control. In some pigs, superoxide dismutase mimetic TEMPOL (1 mM) or vehicle (saline) was injected intravitreally before IOP elevation. After enucleation, retinal arterioles were isolated and pressurized without flow for functional analysis by recording diameter changes using videomicroscopic techniques. Dihydroethidium (DHE) was used to detect superoxide production in isolated retinal arterioles. Isolated retinal arterioles developed stable basal tone and the vasodilations to endothelium-dependent nitric oxide (NO)-mediated agonists bradykinin and L-lactate were significantly reduced only by 90 minutes of ischemia. However, vasodilation to endothelium-independent NO donor sodium nitroprusside was unaffected after all time periods of ischemia. DHE staining showed that 90 minutes of ischemia significantly increased superoxide levels in retinal arterioles. Intravitreal injection of membrane-permeable radical scavenger but not vehicle before ischemia prevented elevation of vascular superoxide and preserved bradykinin-induced dilation. Endothelium-dependent NO-mediated dilation of retinal arterioles is impaired by 90 minutes of ischemia induced by elevated IOP. The inhibitory effect appears to be mediated by the alteration of NO signaling via vascular superoxide.

Green tea polyphenols alleviate early BBB damage during experimental focal cerebral ischemia through regulating tight junctions and PKCalpha signaling.

PubMed

Liu, Xiaobai; Wang, Zhenhua; Wang, Ping; Yu, Bo; Liu, Yunhui; Xue, Yixue

2013-07-21

It has been supposed that green tea polyphenols (GTPs) have neuroprotective effects on brain damage after brain ischemia in animal experiments. Little is known regarding GTPs' protective effects against the blood-brain barrier (BBB) disruption after ischemic stroke. We investigated the effects of GTPs on the expression of claudin-5, occludin, and ZO-1, and the corresponding cellular mechanisms involved in the early stage of cerebral ischemia. Male Wistar rats were subjected to a middle cerebral artery occlusion (MCAO) for 0, 30, 60, and 120 min. GTPs (400 mg/kg/day) or vehicle was administered by intragastric gavage twice a day for 30 days prior to MCAO. At different time points, the expression of claudin-5, occludin, ZO-1, and PKCα signaling pathway in microvessel fragments of cerebral ischemic tissue were evaluated. GTPs reduced BBB permeability at 60 min and 120 min after ischemia as compared with the vehicle group. Transmission electron microscopy also revealed that GTPs could reverse the opening of tight junction (TJ) barrier at 60 min and 120 min after MACO. The decreased mRNA and protein expression levels of claudin-5, occludin, and ZO-1 in microvessel fragments of cerebral ischemic tissue were significantly prevented by treatment with GTPs at the same time points after ischemia in rats. Furthermore, GTPs could attenuate the increase in the expression levels of PKCα mRNA and protein caused by cerebral ischemia. These results demonstrate that GTPs may act as a potential neuroprotective agent against BBB damage at the early stage of focal cerebral ischemia through the regulation of TJ and PKCα signaling.

Warm water and cool nests are best. How global warming might influence hatchling green turtle swimming performance.

PubMed

Booth, David T; Evans, Andrew

2011-01-01

For sea turtles nesting on beaches surrounded by coral reefs, the most important element of hatchling recruitment is escaping predation by fish as they swim across the fringing reef, and as a consequence hatchlings that minimize their exposure to fish predation by minimizing the time spent crossing the fringing reef have a greater chance of surviving the reef crossing. One way to decrease the time required to cross the fringing reef is to maximize swimming speed. We found that both water temperature and nest temperature influence swimming performance of hatchling green turtles, but in opposite directions. Warm water increases swimming ability, with hatchling turtles swimming in warm water having a faster stroke rate, while an increase in nest temperature decreases swimming ability with hatchlings from warm nests producing less thrust per stroke.

Imaging of acute mesenteric ischemia using multidetector CT and CT angiography in a porcine model.

PubMed

Rosow, David E; Sahani, Dushyant; Strobel, Oliver; Kalva, Sanjeeva; Mino-Kenudson, Mari; Holalkere, Nagaraj S; Alsfasser, Guido; Saini, Sanjay; Lee, Susanna I; Mueller, Peter R; Fernández-del Castillo, Carlos; Warshaw, Andrew L; Thayer, Sarah P

2005-12-01

Acute mesenteric ischemia, a frequently lethal disease, requires prompt diagnosis and intervention for favorable clinical outcomes. This goal remains elusive due, in part, to lack of a noninvasive and accurate imaging study. Traditional angiography is the diagnostic gold standard but is invasive and costly. Computed tomography (CT) is readily available and noninvasive but has shown variable success in diagnosing this disease. The faster scanning time of multidetector row CT (M.D.CT) greatly facilitates the use of CT angiography (CTA) in the clinical setting. We sought to determine whether M.D.CT-CTA could accurately demonstrate vascular anatomy and capture the earliest stages of mesenteric ischemia in a porcine model. Pigs underwent embolization of branches of the superior mesenteric artery, then imaging by M.D.CT-CTA with three-dimensional reconstruction protocols. After scanning, diseased bowel segments were surgically resected and pathologically examined. Multidetector row CT and CT angiography reliably defined normal and occluded mesenteric vessels in the pig. It detected early changes of ischemia including poor arterial enhancement and venous dilatation, which were seen in all ischemic animals. The radiographic findings--compared with pathologic diagnoses-- predicted ischemia, with a positive predictive value of 92%. These results indicate that M.D.CT-CTA holds great promise for the early detection necessary for successful treatment of acute mesenteric ischemia.

[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.

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.

Warm-up and performance in competitive swimming.

PubMed

Neiva, Henrique P; Marques, Mário C; Barbosa, Tiago M; Izquierdo, Mikel; Marinho, Daniel A

2014-03-01

Warm-up before physical activity is commonly accepted to be fundamental, and any priming practices are usually thought to optimize performance. However, specifically in swimming, studies on the effects of warm-up are scarce, which may be due to the swimming pool environment, which has a high temperature and humidity, and to the complexity of warm-up procedures. The purpose of this study is to review and summarize the different studies on how warming up affects swimming performance, and to develop recommendations for improving the efficiency of warm-up before competition. Most of the main proposed effects of warm-up, such as elevated core and muscular temperatures, increased blood flow and oxygen delivery to muscle cells and higher efficiency of muscle contractions, support the hypothesis that warm-up enhances performance. However, while many researchers have reported improvements in performance after warm-up, others have found no benefits to warm-up. This lack of consensus emphasizes the need to evaluate the real effects of warm-up and optimize its design. Little is known about the effectiveness of warm-up in competitive swimming, and the variety of warm-up methods and swimming events studied makes it difficult to compare the published conclusions about the role of warm-up in swimming. Recent findings have shown that warm-up has a positive effect on the swimmer's performance, especially for distances greater than 200 m. We recommend that swimmers warm-up for a relatively moderate distance (between 1,000 and 1,500 m) with a proper intensity (a brief approach to race pace velocity) and recovery time sufficient to prevent the early onset of fatigue and to allow the restoration of energy reserves (8-20 min).

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

Efficacy of external warming in attenuation of hypothermia in surgical patients.

PubMed

Zeba, Snjezana; Surbatović, Maja; Marjanović, Milan; Jevdjić, Jasna; Hajduković, Zoran; Karkalić, Radovan; Jovanović, Dalibor; Radaković, Sonja

2016-06-01

Hypothermia in surgical patients can be the consequence of long duration of surgical intervention, general anaesthesia and low temperature in operating room. Postoperative hypothermia contributes to a number of postoperative complications such as arrhythmia, myocardial ischemia, hypertension, bleeding, wound infection, coagulopathy, and prolonged effect of muscle relaxants. External heating procedures are used to prevent this condition. The aim of this study was to evaluate the efficiency of external warming system in alleviation of cold stress and hypothermia in patients who underwent major surgical procedures. The study was conducted in the Military Medical Academy in Belgrade. A total of 30 patients of both genders underwent abdominal surgical procedures, randomly divided into two equal groups: the one was externally warmed using warm air mattress (W), while in the control group (C) surgical procedure was performed in regular conditions, without additional warming. Oesophageal temperature (Te) was used as indicator of changes in core temperature, during surgery and awakening postoperative period, and temperature of control sites on the right hand (Th) and the right foot (Tf) reflected the changes in skin temperatures during surgery. Te and skin temperatures were monitored during the intraoperative period, with continuous measurement of Te during the following 90 minutes of the postoperative period. Heart rates and blood pressures were monitored continuously during the intraoperative and awakening period. In the W group, the average Te, Tf and Th did not change significantly during the intraoperative as well as the postoperative period. In the controls, the average Te significantly decreased during the intraoperative period (from 35.61 ± 0.35 °C at 0 minute to 33.86 ± 0.51°C at 120th minute). Compared to the W group, Te in the C group was significantly lower in all the observed periods. Average values of Tf and Th significantly decreased in the C group (from

Climatic warming destabilizes forest ant communities

PubMed Central

Diamond, Sarah E.; Nichols, Lauren M.; Pelini, Shannon L.; Penick, Clint A.; Barber, Grace W.; Cahan, Sara Helms; Dunn, Robert R.; Ellison, Aaron M.; Sanders, Nathan J.; Gotelli, Nicholas J.

2016-01-01

How will ecological communities change in response to climate warming? Direct effects of temperature and indirect cascading effects of species interactions are already altering the structure of local communities, but the dynamics of community change are still poorly understood. We explore the cumulative effects of warming on the dynamics and turnover of forest ant communities that were warmed as part of a 5-year climate manipulation experiment at two sites in eastern North America. At the community level, warming consistently increased occupancy of nests and decreased extinction and nest abandonment. This consistency was largely driven by strong responses of a subset of thermophilic species at each site. As colonies of thermophilic species persisted in nests for longer periods of time under warmer temperatures, turnover was diminished, and species interactions were likely altered. We found that dynamical (Lyapunov) community stability decreased with warming both within and between sites. These results refute null expectations of simple temperature-driven increases in the activity and movement of thermophilic ectotherms. The reduction in stability under warming contrasts with the findings of previous studies that suggest resilience of species interactions to experimental and natural warming. In the face of warmer, no-analog climates, communities of the future may become increasingly fragile and unstable. PMID:27819044

Climatic warming destabilizes forest ant communities.

PubMed

Diamond, Sarah E; Nichols, Lauren M; Pelini, Shannon L; Penick, Clint A; Barber, Grace W; Cahan, Sara Helms; Dunn, Robert R; Ellison, Aaron M; Sanders, Nathan J; Gotelli, Nicholas J

2016-10-01

How will ecological communities change in response to climate warming? Direct effects of temperature and indirect cascading effects of species interactions are already altering the structure of local communities, but the dynamics of community change are still poorly understood. We explore the cumulative effects of warming on the dynamics and turnover of forest ant communities that were warmed as part of a 5-year climate manipulation experiment at two sites in eastern North America. At the community level, warming consistently increased occupancy of nests and decreased extinction and nest abandonment. This consistency was largely driven by strong responses of a subset of thermophilic species at each site. As colonies of thermophilic species persisted in nests for longer periods of time under warmer temperatures, turnover was diminished, and species interactions were likely altered. We found that dynamical (Lyapunov) community stability decreased with warming both within and between sites. These results refute null expectations of simple temperature-driven increases in the activity and movement of thermophilic ectotherms. The reduction in stability under warming contrasts with the findings of previous studies that suggest resilience of species interactions to experimental and natural warming. In the face of warmer, no-analog climates, communities of the future may become increasingly fragile and unstable.

Amplified Arctic warming by phytoplankton under greenhouse warming.

PubMed

Park, Jong-Yeon; Kug, Jong-Seong; Bader, Jürgen; Rolph, Rebecca; Kwon, Minho

2015-05-12

Phytoplankton have attracted increasing attention in climate science due to their impacts on climate systems. A new generation of climate models can now provide estimates of future climate change, considering the biological feedbacks through the development of the coupled physical-ecosystem model. Here we present the geophysical impact of phytoplankton, which is often overlooked in future climate projections. A suite of future warming experiments using a fully coupled ocean-atmosphere model that interacts with a marine ecosystem model reveals that the future phytoplankton change influenced by greenhouse warming can amplify Arctic surface warming considerably. The warming-induced sea ice melting and the corresponding increase in shortwave radiation penetrating into the ocean both result in a longer phytoplankton growing season in the Arctic. In turn, the increase in Arctic phytoplankton warms the ocean surface layer through direct biological heating, triggering additional positive feedbacks in the Arctic, and consequently intensifying the Arctic warming further. Our results establish the presence of marine phytoplankton as an important potential driver of the future Arctic climate changes.

Amplified Arctic warming by phytoplankton under greenhouse warming

PubMed Central

Park, Jong-Yeon; Kug, Jong-Seong; Bader, Jürgen; Rolph, Rebecca; Kwon, Minho

2015-01-01

Phytoplankton have attracted increasing attention in climate science due to their impacts on climate systems. A new generation of climate models can now provide estimates of future climate change, considering the biological feedbacks through the development of the coupled physical–ecosystem model. Here we present the geophysical impact of phytoplankton, which is often overlooked in future climate projections. A suite of future warming experiments using a fully coupled ocean−atmosphere model that interacts with a marine ecosystem model reveals that the future phytoplankton change influenced by greenhouse warming can amplify Arctic surface warming considerably. The warming-induced sea ice melting and the corresponding increase in shortwave radiation penetrating into the ocean both result in a longer phytoplankton growing season in the Arctic. In turn, the increase in Arctic phytoplankton warms the ocean surface layer through direct biological heating, triggering additional positive feedbacks in the Arctic, and consequently intensifying the Arctic warming further. Our results establish the presence of marine phytoplankton as an important potential driver of the future Arctic climate changes. PMID:25902494

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.

Precompetition warm-up in elite and subelite rhythmic gymnastics.

PubMed

Guidetti, Laura; Di Cagno, Alessandra; Gallotta, Maria Chiara; Battaglia, Claudia; Piazza, Marina; Baldari, Carlo

2009-09-01

The aim of this study was to investigate which precompetition warm-up methodologies resulted in the best overall performance in rhythmic gymnastics. The coaches of national and international clubs (60 elite and 90 subelite) were interviewed. The relationship between sport performance and precompetition warm-up routines was examined. A total of 49% of the coaches interviewed spent more than 1 hour to prepare their athletes for the competition, including 45 minutes dedicated to warm-up exercises. In spite of previous studies' suggestions, the time between the end of warm-up and the beginning of competition was more than 5 minutes for 68% of those interviewed. A slow run was the activity of choice used to begin the warm-up (96%). Significant differences between elite and subelite gymnasts were found concerning the total duration of warm-up, duration of slow running, utilization of rhythmic steps and leaps during the warm-up, the use of dynamic flexibility exercises, competition performances repetition (p < 0.01), and utilization of imagery (p < 0.05). A precompetition warm-up in rhythmic gymnastics would include static stretching exercises at least 60 minutes prior to the competition starting time and the active stretching exercises alternated with analytic muscle strengthening aimed at increasing muscle temperature. Rhythmic gymnastics coaches at all levels can use this data as a review of precompetition warm-up practices and a possible source of new ideas.

Normothermic perfusion: a new paradigm for organ preservation.

PubMed

Brockmann, Jens; Reddy, Srikanth; Coussios, Constantin; Pigott, David; Guirriero, Dino; Hughes, David; Morovat, Alireza; Roy, Debabrata; Winter, Lucy; Friend, Peter J

2009-07-01

Transplantation of organs retrieved after cardiac arrest could increase the donor organ supply. However, the combination of warm ischemia and cold preservation is highly detrimental to the reperfused organ. Our objective was to maintain physiological temperature and organ function during preservation and thereby alleviate this injury and allow successful transplantation. We have developed a liver perfusion device that maintains physiological temperature with provision of oxygen and nutrition. Reperfusion experiments suggested that this allows recovery of ischemic damage. In a pig liver transplant model, we compared the outcome following either conventional cold preservation or warm preservation. Preservation periods of 5 and 20 hours and durations of warm ischemia of 40 and 60 minutes were tested. After 20 hours preservation without warm ischemia, post-transplant survival was improved (27%-86%, P = 0.026), with corresponding differences in transaminase levels and histological analysis. With the addition of 40 minutes warm ischemia, the differences were even more marked (cold vs. warm groups 0% vs. 83%, P = 0.001). However, with 60 minutes warm ischemia and 20 hours preservation, there were no survivors. Analysis of hemodynamic and liver function data during perfusion showed several factors to be predictive of posttransplant survival, including bile production, base excess, portal vein flow, and hepatocellular enzymes. Organ preservation by warm perfusion, maintaining physiological pressure and flow parameters, has enabled prolonged preservation and successful transplantation of both normal livers and those with substantial ischemic damage. This technique has the potential to address the shortage of organs for transplantation.

Effect of hydrogen sulfide on inflammatory cytokines in acute myocardial ischemia injury in rats

PubMed Central

LIU, FANG; LIU, GUANG-JIE; LIU, NA; ZHANG, GANG; ZHANG, JIAN-XIN; LI, LAN-FANG

2015-01-01

Hydrogen sulfide (H2S) is believed to be involved in numerous physiological and pathophysiological processes, and now it is recognized as the third endogenous signaling gasotransmitter, following nitric oxide and carbon monoxide; however, the effects of H2S on inflammatory factors in acute myocardial ischemia injury in rats have not been clarified. In the present study, sodium hydrosulfide (NaHS) was used as the H2S donor. Thirty-six male Sprague Dawley rats were randomly divided into five groups: Sham, ischemia, ischemia + low-dose (0.78 mg/kg) NaHS, ischemia + medium-dose (1.56 mg/kg) NaHS, ischemia + high-dose (3.12 mg/kg) NaHS and ischemia + propargylglycine (PPG) (30 mg/kg). The rats in each group were sacrificed 6 h after the surgery for sample collection. Compared with the ischemia group, the cardiac damage in the rats in the ischemia + NaHS groups was significantly reduced, particularly in the high-dose group; in the ischemia + PPG group, the myocardial injury was aggravated compared with that in the ischemia group. Compared with the ischemia group, the levels of interleukin (IL)-1β, IL-6 and tumor necrosis factor-α (TNF-α) in the serum of rats in the ischemia + medium- and high-dose NaHS groups were significantly reduced, and the expression of intercellular adhesion molecule-1 (ICAM-1) mRNA and nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB) protein in the myocardial tissues of rats was significantly reduced. In the ischemia + PPG group, the TNF-α, IL-1β and IL-6 levels in the serum were significantly increased, the expression of ICAM-1 mRNA was increased, although without a significant difference, and the expression of NF-κB was increased. The findings of the present study provide novel evidence for the dual effects of H2S on acute myocardial ischemia injury via the modulation of inflammatory factors. PMID:25667680

Controls on SOC across space and time: Models with different acclimation schemes make similar spatial predictions but divergent warming predictions

NASA Astrophysics Data System (ADS)

Abramoff, R. Z.; Torn, M. S.; Georgiou, K.; Tang, J.; Riley, W. J.

2017-12-01

Researchers use spatial gradients to estimate long-term ecosystem responses to perturbations. This approach is commonly applied to soil organic carbon (SOC) stocks which change slowly but store the majority of terrestrial carbon. Climate warming may reduce SOC stocks if higher temperatures increase decomposition rates. Yet, it is uncertain how vulnerable SOC is to warming, and whether the same factors - such as organo-mineral associations, climate, or plant inputs - determine SOC stocks across space and time. In order to test the "space for time" concept, we developed two versions of the Substrate-Mineral-Microbe Soil (SuMMS) model - one with microbial temperature acclimation and one without - to analyze observed SOC stocks at 24 sites spanning a wide range of soil types and climate. Both model predictions of SOC were strongly correlated with observations (R2 > 0.9), because mineral sorption capacity was the dominant control over steady-state SOC stock as determined by a Random Forest model. However, the two model versions made fundamentally different predictions of the change in SOC following 5°C soil warming from 2016 to 2100 because the initial mean annual temperature (MAT) was the dominant control over the SOC response. The model with microbial acclimation predicted that SOC would decline 10% at all sites along the transect, while the model with no acclimation predicted large surface SOC losses at high latitude sites and SOC gains at low latitude sites where microbial exoenzymes were already at or near their temperature optimum. These simulations suggest that gradient studies cannot be used to infer site-level responses to warming, because the dominant controls on SOC at steady state (i.e., mineral sorption capacity) are different than the dominant controls on the SOC response to a warming perturbation (i.e., initial MAT, capacity for acclimation).

Postconditioning: "Toll-erating" mesenteric ischemia-reperfusion injury?

PubMed

Rosero, Olivér; Ónody, Péter; Kovács, Tibor; Molnár, Dávid; Fülöp, András; Lotz, Gábor; Harsányi, László; Szijártó, Attila

2017-04-01

Postconditioning may prove to be a suitable method to decrease ischemia-reperfusion injury of intestine after mesenteric arterial occlusion. Toll-like-receptor-4 is involved in the pathophysiology of organ damage after ischemia-reperfusion; therefore, the aim of our study was to investigate the effect of postconditioning on the mucosal expression of toll-like-receptor-4. Male Wistar rats (n = 10/group) underwent 60 minutes of superior mesenteric artery occlusion followed by 6 hours of reperfusion in 3 groups: sham-operated, ischemia-reperfusion, and a postconditioned group. Postconditioning was performed by 6 alternating cycles of 10 seconds of reperfusion/reocclusion. Blood and tissue samples were collected at the end of reperfusion. Intestinal histopathologic changes and immunohistochemical expression of mucosal caspase-3, antioxidant status, and protein levels of high-mobility group box-1 and toll-like-receptor-4 were assessed. Immunofluorescent labeling and confocal microscopic analysis of toll-like-receptor-4 were performed. Mucosal and serum levels of interleukin-6 and tumor necrosis factor-α protein were measured. Histologic alterations in the postconditioned group were associated with decreased caspase-3 positivity, less toll-like-receptor-4 mRNA, and less protein expression of high-mobility group box-1 and toll-like-receptor-4 in the intestinal villi compared with the ischemia-reperfusion group. Furthermore, a significantly improved antioxidant state of the intestinal mucosa and less mucosal and serum protein levels of interleukin-6 and tumor necrosis factor-α were detected in the postconditioned group. Small intestinal ischemia-reperfusion injury in male Wistar rats caused by the occlusion of the superior mesenteric artery was ameliorated by the use of postconditioning, showing a more favorable inflammatory response, which may be attributed to the decreased mucosal expression of toll-like-receptor-4. Copyright © 2016 Elsevier Inc. All rights

Reparative neurogenesis after cerebral ischemia: Clinical application prospects

NASA Astrophysics Data System (ADS)

Khodanovich, M. Yu.

2015-11-01

At the present time two main approaches are in the focus of neurobiological studies of brain recovery after a stroke. One of them is concerned with the infusion of stem cells in damaged brain. The second approach is directed at the stimulation of endogenous reparative processes, in particular, adult neurogenesis. This review considers alterations of adult neurogenesis caused by cerebral ischemia and possible pathways of its regulation. Multiple studies on animal models have shown that adult neurogenesis is mostly increased by cerebral ischemia. In spite of increasing proliferation and moving neural progenitors to infarct zone, most newborn neurons die before reaching maturity. Besides, an increase of neurogenesis in pathological conditions is mainly due to recruitment of new stem cells, but not due to an additional precursor-cells division that results in an overall decline of the regeneration capacity. Thus, the endogenous reparative mechanisms are not sufficient, and the search for new targets to promote proliferation, survival, and maturation of new neurons after a stroke is needed. Neurotransmitter systems and anti-inflammatory drugs are considered as potential regulators of post-ischemic neurogenesis growth factors.

Intermediate-term follow-up of chronically ill patients with digital ischemia treated with peripheral digital sympathectomy.

PubMed

Soberón, José R; Greengrass, Roy A; Davis, William E; Murray, Peter M; Feinglass, Neil

2016-02-01

Digital ischemia is commonly found in patients with scleroderma and has been shown to respond to peripheral digital sympathectomy. While favorable long- and intermediate-term results have been documented in the literature, minimal objective data are available and the mechanism of surgical sympathectomy has not been entirely elucidated. Patients with digital ischemia secondary to Raynaud's phenomenon that had undergone peripheral sympathectomy surgery between 2001 and 2009 were identified and contacted for participation. Radial artery Doppler ultrasound studies were performed and compared to those done at the time of their sympathectomy. Of 11 patients treated over a 9-year period, only two patients were available for detailed follow-up analysis. Four patients were deceased, and two were lost to follow-up. Four of the five remaining patients reported excellent use of the hand and no significant episodes of digital ischemia. Of the two patients studied, functional results were favorable and pain was markedly improved despite worsening of the digital flow resistance over time. We conclude that peripheral digital sympathectomy may provide favorable long-term results in patients with digital ischemia from autoimmune causes, although this intervention should be considered in the early stages once ischemic symptoms manifest. Interestingly, Doppler data did not appear to correlate with functional status and symptom severity in these two patients. Further research, particularly prospective studies, is warranted to guide clinical decisions in this patient population.

Global warming 2007. An update to global warming: the balance of evidence and its policy implications.

PubMed

Keller, Charles F

2007-03-09

In the four years since my original review (Keller[25]; hereafter referred to as CFK03), research has clarified and strengthened our understanding of how humans are warming the planet. So many of the details highlighted in the IPCC's Third Assessment Report[21] and in CFK03 have been resolved that I expect many to be a bit overwhelmed, and I hope that, by treating just the most significant aspects of the research, this update may provide a road map through the expected maze of new information. In particular, while most of CFK03 remains current, there are important items that have changed: Most notable is the resolution of the conundrum that mid-tropospheric warming did not seem to match surface warming. Both satellite and radiosonde (balloon-borne sensors) data reduction showed little warming in the middle troposphere (4-8 km altitude). In the CFK03 I discussed potential solutions to this problem, but at that time there was no clear resolution. This problem has now been solved, and the middle troposphere is seen to be warming apace with the surface. There have also been advances in determinations of temperatures over the past 1,000 years showing a cooler Little Ice Age (LIA) but essentially the same warming during medieval times (not as large as recent warming). The recent uproar over the so-called "hockey stick" temperature determination is much overblown since at least seven other groups have made relatively independent determinations of northern hemisphere temperatures over the same time period and derived essentially the same results. They differ on how cold the LIA was but essentially agree with the Mann's hockey stick result that the Medieval Warm Period was not as warm as the last 25 years. The question of the sun's influence on climate continues to generate controversy. It appears there is a growing consensus that, while the sun was a major factor in earlier temperature variations, it is incapable of having caused observed warming in the past quarter

Depolarization changes during acute myocardial ischemia by evaluation of QRS slopes: standard lead and vectorial approach.

PubMed

Romero, Daniel; Ringborn, Michael; Laguna, Pablo; Pahlm, Olle; Pueyo, Esther

2011-01-01

Diagnosis and risk stratification of patients with acute coronary syndromes can be improved by adding information from the depolarization phase (QRS complex) to the conventionally used ST-T segment changes. In this study, ischemia-induced changes in the main three slopes of the QRS complex, upward ( ℑ(US)) and downward ( ℑ(DS) ) slopes of the R wave as well as the upward ( ℑ(TS)) slope of the terminal S wave, were evaluated as to represent a robust measure of pathological changes within the depolarization phase. From ECG recordings both in a resting state (control recordings) and during percutaneous coronary intervention (PCI)-induced transmural ischemia, we developed a method for quantification of ℑ(US), ℑ(DS), and ℑ(TS) that incorporates dynamic ECG normalization so as to improve the sensitivity in the detection of ischemia-induced changes. The same method was also applied on leads obtained by projection of QRS loops onto their dominant directions. We show that ℑ(US), ℑ(DS), and ℑ(TS) present high stability in the resting state, thus providing a stable reference for ischemia characterization. Maximum relative factors of change ( ℜ(ℑ)) during PCI were found in leads derived from the QRS loop, reaching 10.5 and 13.7 times their normal variations in the control for ℑ(US) and ℑ(DS), respectively. For standard leads, the relative factors of change were 6.01 and 9.31. The ℑ(TS) index presented a similar behavior to that of ℑ(DS). The timing for the occurrence of significant changes in ℑ(US) and ℑ(DS) varied with lead, ranging from 30 s to 2 min after initiation of coronary occlusion. In the present ischemia model, relative ℑ(DS) changes were smaller than ST changes in most leads, however with only modest correlation between the two indices, suggesting they present different information about the ischemic process. We conclude that QRS slopes offer a robust tool for evaluating depolarization changes during myocardial ischemia.

Independent cellular effects of cold ischemia and reperfusion: experimental molecular study.

PubMed

Lledó-García, E; Humanes-Sánchez, B; Mojena-Sánchez, M; Rodrígez, J C J; Hernández-Fernández, C; Tejedor-Jorge, A; Fernández, A L

2013-04-01

There is less information available on cell cultures on the exclusive effects of either duration of cold ischemia (CI) or rewarming-reperfusion in the kidney subjected to initial warm ischemia (WI). Therefore, the goals of our work were: (1) to evaluate the consequences on tubular cellular viability of different durations of CI on a kidney after an initial period of WI, and (2) to analyze the additional effect on tubular cell viability of rewarming of the same kidney. Sixteen mini-pig were used. All the animals were performed a right nephrectomy after 45-minute occlusion of the vascular pedicle. The kidneys were then divided into 2 groups (phase 1): cold storage in university of wisconsin (UW) solution for 3 hours (group A, n = 8) at 4°C, or cold storage in UW for 12 hours (group B, n = 8) at 4°C. Four organs of group A and four organs of group B were autotrasplanted (AT) and reperfused for 1 hour (phase 2). Nephrectomy was finally done. Biopsies were taken from all groups to perform cultures of proximal tubule epithelium cells. The biopsies were subjected to studies of cellular morphological viability (contrast phase microscopy [CPM]) and quantitative (confluence cell [CC]) parameters. Phase of pure CI effects (phase 1): Both CC rate and CPM parameters were significantly lower in group B compared with group A, where cell activity reached almost normal results. Phase of CI + AT (phase 2): At produced additional harmful effects in cell cultures compared with those obtained in phase 1, more evident in group B cells. The presence of cold storage followed by rewarming-reperfusion induces independent and cumulative detrimental effects in viability of renal proximal tubule cells. CI periods ≤ 3 hours may ameliorate the injuries secondary to reperfusion in comparison with longer CI periods. Copyright © 2013 Elsevier Inc. All rights reserved.

Warming trends of perialpine lakes from homogenised time series of historical satellite and in-situ data.

PubMed

Pareeth, Sajid; Bresciani, Mariano; Buzzi, Fabio; Leoni, Barbara; Lepori, Fabio; Ludovisi, Alessandro; Morabito, Giuseppe; Adrian, Rita; Neteler, Markus; Salmaso, Nico

2017-02-01

The availability of more than thirty years of historical satellite data is a valuable source which could be used as an alternative to the sparse in-situ data. We developed a new homogenised time series of daily day time Lake Surface Water Temperature (LSWT) over the last thirty years (1986-2015) at a spatial resolution of 1km from thirteen polar orbiting satellites. The new homogenisation procedure implemented in this study corrects for the different acquisition times of the satellites standardizing the derived LSWT to 12:00 UTC. In this study, we developed new time series of LSWT for five large lakes in Italy and evaluated the product with in-situ data from the respective lakes. Furthermore, we estimated the long-term annual and summer trends, the temporal coherence of mean LSWT between the lakes, and studied the intra-annual variations and long-term trends from the newly developed LSWT time series. We found a regional warming trend at a rate of 0.017°Cyr -1 annually and 0.032°Cyr -1 during summer. Mean annual and summer LSWT temporal patterns in these lakes were found to be highly coherent. Amidst the reported rapid warming of lakes globally, it is important to understand the long-term variations of surface temperature at a regional scale. This study contributes a new method to derive long-term accurate LSWT for lakes with sparse in-situ data thereby facilitating understanding of regional level changes in lake's surface temperature. Copyright © 2016 Elsevier B.V. All rights reserved.

PARP inhibition attenuates histopathological lesion in ischemia/reperfusion renal mouse model after cold prolonged ischemia.

PubMed

del Moral, Raimundo M G; Gómez-Morales, Mercedes; Hernández-Cortés, Pedro; Aguilar, David; Caballero, Trinidad; Aneiros-Fernández, Jose; Caba-Molina, Mercedes; Rodríguez-Martínez, M Dolores; Peralta, Andreina; Galindo-Moreno, Pablo; Osuna, Antonio; Oliver, F Javier; del Moral, Raimundo G; O'Valle, Francisco

2013-01-01

We test the hypothesis that PARP inhibition can decrease acute tubular necrosis (ATN) and other renal lesions related to prolonged cold ischemia/reperfusion (IR) in kidneys preserved at 4°C in University of Wisconsin (UW) solution. Material and Methods. We used 30 male Parp1(+/+) wild-type and 15 male Parp1(0/0) knockout C57BL/6 mice. Fifteen of these wild-type mice were pretreated with 3,4-dihydro-5-[4-(1-piperidinyl)butoxyl]-1(2H)-isoquinolinone (DPQ) at a concentration of 15 mg/kg body weight, used as PARP inhibitor. Subgroups of mice were established (A: IR 45 min/6 h; B: IR + 48 h in UW solution; and C: IR + 48 h in UW solution plus DPQ). We processed samples for morphological, immunohistochemical, ultrastructural, and western-blotting studies. Results. Prolonged cold ischemia time in UW solution increased PARP-1 expression and kidney injury. Preconditioning with PARP inhibitor DPQ plus DPQ supplementation in UW solution decreased PARP-1 nuclear expression in renal tubules and renal damage. Parp1(0/0) knockout mice were more resistant to IR-induced renal lesion. In conclusion, PARP inhibition attenuates ATN and other IR-related renal lesions in mouse kidneys under prolonged cold storage in UW solution. If confirmed, these data suggest that pharmacological manipulation of PARP activity may have salutary effects in cold-stored organs at transplantation.

Global assessment of experimental climate warming on tundra vegetation: heterogeneity over space and time

Treesearch

Sarah C. Elmendorf; Gregory H.R. Henry; Robert D. Hollister; Robert G. Björk; Anne D. Bjorkman; Terry V. Callaghan; [and others] NO-VALUE; William Gould; Joel Mercado

2012-01-01

Understanding the sensitivity of tundra vegetation to climate warming is critical to forecasting future biodiversity and vegetation feedbacks to climate. In situ warming experiments accelerate climate change on a small scale to forecast responses of local plant communities. Limitations of this approach include the apparent site-specificity of results and uncertainty...

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.

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

Positron emission tomography imaging of angiogenesis in a murine hindlimb ischemia model with 64Cu-labeled TRC105.

PubMed

Orbay, Hakan; Zhang, Yin; Hong, Hao; Hacker, Timothy A; Valdovinos, Hector F; Zagzebski, James A; Theuer, Charles P; Barnhart, Todd E; Cai, Weibo

2013-07-01

The goal of this study was to assess ischemia-induced angiogenesis with (64)Cu-NOTA-TRC105 positron emission tomography (PET) in a murine hindlimb ischemia model of peripheral artery disease (PAD). CD105 binding affinity/specificity of NOTA-conjugated TRC105 (an anti-CD105 antibody) was evaluated by flow cytometry, which exhibited no difference from unconjugated TRC105. BALB/c mice were anesthetized, and the right femoral artery was ligated to induce hindlimb ischemia, with the left hindlimb serving as an internal control. Laser Doppler imaging showed that perfusion in the ischemic hindlimb plummeted to ∼ 20% of the normal level after surgery and gradually recovered to near normal level on day 24. Ischemia-induced angiogenesis was noninvasively monitored and quantified with (64)Cu-NOTA-TRC105 PET on postoperative days 1, 3, 10, 17, and 24. (64)Cu-NOTA-TRC105 uptake in the ischemic hindlimb increased significantly from the control level of 1.6 ± 0.2 %ID/g to 14.1 ± 1.9 %ID/g at day 3 (n = 3) and gradually decreased with time (3.4 ± 1.9 %ID/g at day 24), which correlated well with biodistribution studies performed on days 3 and 24. Blocking studies confirmed the CD105 specificity of tracer uptake in the ischemic hindlimb. Increased CD105 expression on days 3 and 10 following ischemia was confirmed by histology and reverse transcription polymerase chain reaction (RT-PCR). This is the first report of PET imaging of CD105 expression during ischemia-induced angiogenesis. (64)Cu-NOTA-TRC105 PET may play multiple roles in future PAD-related research and improve PAD patient management by identifying the optimal timing of treatment and monitoring the efficacy of therapy.

[Activity of antioxidative enzymes of the myocardium during ischemia].

PubMed

Gutkin, D V; Petrovich, Iu A

1982-01-01

Activation of lipid peroxidation during myocardial ischemia may be determined by the reduction of the enzymatic antioxidant cell protection. Such a conclusion has been drawn on the basis of an analysis of variation in the activity of superoxide dismutase, glutathion peroxidase and catalase in experimental myocardial ischemia in rats, induced by ligation of the left descending artery of the heart. In the early period of ischemia (1-3 h) the activity of superoxide dismutase and glutation peroxidase markedly decreases. In the periischemic zone, the fall in the enzymatic activity is not so pronounced. The activity of the enzymes does not reach the basic level 5 days after the operation.

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.

Global Warming.

ERIC Educational Resources Information Center

Hileman, Bette

1989-01-01

States the foundations of the theory of global warming. Describes methodologies used to measure the changes in the atmosphere. Discusses steps currently being taken in the United States and the world to slow the warming trend. Recognizes many sources for the warming and the possible effects on the earth. (MVL)

Usefulness of warm water and oil assistance in colonoscopy by trainees.

PubMed

Park, Sung Chul; Keum, Bora; Kim, Eun Sun; Jung, Eun Suk; Lee, Sehe Dong; Park, Sanghoon; Seo, Yeon Seok; Kim, Yong Sik; Jeen, Yoon Tae; Chun, Hoon Jai; Um, Soon Ho; Kim, Chang Duck; Ryu, Ho Sang

2010-10-01

Success rate of cecal intubation, endoscopist's difficulty, and procedure-related patient pain are still problems for beginners performing colonoscopy. New methods to aid colonoscopic insertion such as warm water instillation and oil lubrication have been proposed. The aim of this study is to evaluate the feasibility of using warm water or oil in colonoscopy. Colonoscopy was performed in 117 unsedated patients by three endoscopists-in-training. Patients were randomly allocated to three groups, using a conventional method with administration of antispasmodics, warm water instillation, and oil lubrication, respectively. Success rate of total intubation within time limit (15 min), cecal intubation time, degree of endoscopist's difficulty, and level of patient discomfort were compared among the three groups. Cecal intubation time was shorter in the warm water group than in the conventional and oil groups. Degree of procedural difficulty was lower in the warm water group, and patient pain score was higher in the oil lubrication group, compared with the other groups. However, there was no significant difference in success rate of intubation within time limit among the three groups. The warm water method is a simple, safe, and feasible method for beginners. Oil lubrication may not be a useful method compared with conventional and warm water method.

Reconciling controversies about the 'global warming hiatus'.

PubMed

Medhaug, Iselin; Stolpe, Martin B; Fischer, Erich M; Knutti, Reto

2017-05-03

Between about 1998 and 2012, a time that coincided with political negotiations for preventing climate change, the surface of Earth seemed hardly to warm. This phenomenon, often termed the 'global warming hiatus', caused doubt in the public mind about how well anthropogenic climate change and natural variability are understood. Here we show that apparently contradictory conclusions stem from different definitions of 'hiatus' and from different datasets. A combination of changes in forcing, uptake of heat by the oceans, natural variability and incomplete observational coverage reconciles models and data. Combined with stronger recent warming trends in newer datasets, we are now more confident than ever that human influence is dominant in long-term warming.

The whole-soil carbon flux in response to warming

NASA Astrophysics Data System (ADS)

Hicks Pries, Caitlin E.; Castanha, C.; Porras, R. C.; Torn, M. S.

2017-03-01

Soil organic carbon harbors three times as much carbon as Earth’s atmosphere, and its decomposition is a potentially large climate change feedback and major source of uncertainty in climate projections. The response of whole-soil profiles to warming has not been tested in situ. In a deep warming experiment in mineral soil, we found that CO2 production from all soil depths increased with 4°C warming; annual soil respiration increased by 34 to 37%. All depths responded to warming with similar temperature sensitivities, driven by decomposition of decadal-aged carbon. Whole-soil warming reveals a larger soil respiration response than many in situ experiments (most of which only warm the surface soil) and models.

Global Warming, Africa and National Security

DTIC Science & Technology

2008-01-15

African populations. This includes awareness from a global perspective in line with The Army Strategy for the Environment, the UN’s Intergovernmental...2 attention. At the time, computer models did not indicate a significant issue with global warming suggesting only a modest increase of 2°C9...projected climate changes. Current Science The science surrounding climate change and global warming was, until recently, a point of

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.

Stress Perfusion Cardiac Magnetic Resonance Imaging Effectively Risk Stratifies Diabetic Patients With Suspected Myocardial Ischemia.

PubMed

Heydari, Bobak; Juan, Yu-Hsiang; Liu, Hui; Abbasi, Siddique; Shah, Ravi; Blankstein, Ron; Steigner, Michael; Jerosch-Herold, Michael; Kwong, Raymond Y

2016-04-01

Diabetics remain at high risk of cardiovascular disease and mortality despite advancements in medical therapy. Noninvasive cardiac risk profiling is often more difficult in diabetics owing to the prevalence of silent ischemia with unrecognized myocardial infarction, reduced exercise capacity, nondiagnostic electrocardiographic changes, and balanced ischemia from diffuse epicardial coronary atherosclerosis and microvascular dysfunction. A consecutive cohort of 173 patients with diabetes mellitus (mean age, 61.7±11.9 years; 37% women) with suspected myocardial ischemia underwent stress perfusion cardiac magnetic resonance imaging. Patients were evaluated for adverse cardiac events after cardiac magnetic resonance imaging with mean follow-up time of 2.9±2.5 years. Mean hemoglobin A1c for the population was 7.9±1.8%. Primary end point was a composite of cardiac death and nonfatal myocardial infarction. Diabetics with no inducible ischemia (n=94) experienced an annualized event rate of 1.4% compared with 8.2% (P=0.0003) in those with inducible ischemia (n=79). Diabetics without late gadolinium enhancement or inducible ischemia had a low annual cardiac event rate (0.5% per year). The presence of inducible ischemia was the strongest unadjusted predictor (hazard ratio, 4.86; P<0.01) for cardiac death and nonfatal myocardial infarction. This association remained robust in adjusted stepwise multivariable Cox regression analysis (hazard ratio, 4.28; P=0.02). In addition, categorical net reclassification index using 5-year risk cutoffs of 5% and 10% resulted in reclassification of 43.4% of the diabetic cohort with net reclassification index of 0.38 (95% confidence interval, 0.20-0.56; P<0.0001). Stress perfusion cardiac magnetic resonance imaging provided independent prognostic utility and effectively reclassified risk in patients with diabetes mellitus referred for ischemic assessment. Further evaluation is required to determine whether a noninvasive imaging strategy with

Exertional headache and coronary ischemia despite normal electrocardiographic stress testing.

PubMed

Cutrer, F Michael; Huerter, Karina

2006-01-01

Exertional headaches may under certain conditions reflect coronary ischemia. We report the case of a patient seen in a neurology referral practice whose exertional headaches, even in the face of two normal electrocardiographic stress tests and in the absence of underlying chest pain were the sole symptoms of coronary ischemia as detected by Tc-99m Sestamibi testing SPECT stress testing. Stent placement resulted in complete resolution of headaches. Exertional headache in the absence of chest pain may reflect underlying symptomatic coronary artery disease (CAD) even when conventional electrocardiographic stress testing does not indicate ischemia.

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

Hydroxyl radicals' production and ECG parameters during ischemia and reperfusion in rat, guinea pig and rabbit isolated heart.

PubMed

Paulova, Hana; Stracina, Tibor; Jarkovsky, Jiri; Novakova, Marie; Taborska, Eva

2013-06-01

Ischemic and reperfusion injury is a serious condition related to numerous biochemical and electrical abnormalities of the myocardium. It has been repeatedly studied in various animal models. In this study, the production of hydroxyl radicals and electrophysiological parameters were compared in three species. Rat, guinea pig and rabbit isolated hearts were perfused according to Langendorff under strictly identical conditions. The heart rate and arrhythmia were monitored during ischemia and reperfusion periods at defined time intervals; the production of hydroxyl radical was determined by HPLC as 2.5-dihydroxybenzoic acid (2.5-DHBA) formed by salicylic acid hydroxylation. Relationship between arrhythmias and production of 2.5-DHBA was studied. The inter-species differences were observed in timing of arrhythmias onset and their severity, and in the production of 2.5-DHBA in both ischemia and reperfusion. The most considerable changes were observed in rats, where arrhythmias appeared early and with highest severity during ischemia on one side and the regular rhythm was restored early and completely during reperfusion. The corresponding changes in the production of 2.5-DHBA were observed. It can be concluded that rat isolated heart is the most suitable model for evaluation of ischemia/reperfusion injury under given experimental conditions.

Designing a warm-up protocol for elite bob-skeleton athletes.

PubMed

Cook, Christian; Holdcroft, Danny; Drawer, Scott; Kilduff, Liam P

2013-03-01

To investigate how different warm-ups influenced subsequent sled-pull sprint performance in Olympic-level bob-skeleton athletes as part of their preparation for the 2010 Winter Olympics. Three female and 3 male athletes performed 5 different randomized warm-ups of differing intensities, durations, and timing relative to subsequent testing, each 2 days apart, all repeated twice. After warm-ups, testing on a sled-pull sprint over 20 m, 3 repeats 3 min apart, took place. Performance testing showed improvement (P < .001, ES > 1.2) with both increasing intensity of warm-up and closeness of completion to testing, with 20-m sled sprinting being 0.1-0.25 s faster in higher-intensity protocols performed near testing In addition, supplementing the warm-ups by wearing of a light survival coat resulted in further performance improvement (P = .000, ES 1.8). Changing timing and intensity of warm-up and using an ancillary passive heat-retention device improved sprint performance in Olympic-level bob-skeleton athletes. Subsequent adoption of these on the competitive circuit was associated with a seasonal improvement in push times and was ultimately implemented in the 2010 Winter Olympics.

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

Relative roles of differential SST warming, uniform SST warming and land surface warming in determining the Walker circulation changes under global warming

NASA Astrophysics Data System (ADS)

Zhang, Lei; Li, Tim

2017-02-01

Most of CMIP5 models projected a weakened Walker circulation in tropical Pacific, but what causes such change is still an open question. By conducting idealized numerical simulations separating the effects of the spatially uniform sea surface temperature (SST) warming, extra land surface warming and differential SST warming, we demonstrate that the weakening of the Walker circulation is attributed to the western North Pacific (WNP) monsoon and South America land effects. The effect of the uniform SST warming is through so-called "richest-get-richer" mechanism. In response to a uniform surface warming, the WNP monsoon is enhanced by competing moisture with other large-scale convective branches. The strengthened WNP monsoon further induces surface westerlies in the equatorial western-central Pacific, weakening the Walker circulation. The increase of the greenhouse gases leads to a larger land surface warming than ocean surface. As a result, a greater thermal contrast occurs between American Continent and equatorial Pacific. The so-induced zonal pressure gradient anomaly forces low-level westerly anomalies over the equatorial eastern Pacific and weakens the Walker circulation. The differential SST warming also plays a role in driving low-level westerly anomalies over tropical Pacific. But such an effect involves a positive air-sea feedback that amplifies the weakening of both east-west SST gradient and Pacific trade winds.

Delayed warming hiatus over the Tibetan Plateau

NASA Astrophysics Data System (ADS)

An, Wenling; Hou, Shugui; Hu, Yongyun; Wu, Shuangye

2017-03-01

A reduction in the warming rate for the global surface temperature since the late 1990s has attracted much attention and caused a great deal of controversy. During the same time period, however, most previous studies have reported enhanced warming over the Tibetan Plateau (TP). In this study we further examined the temperature trend of the TP and surrounding areas based on the homogenized temperature records for the period 1980-2014, we found that for the TP regions lower than 4000 m the warming rate has started to slow down since the late 1990s, a similar pattern consistent with the whole China and the global temperature trend. However, for the TP regions higher than 4000 m, this reduction in warming rate did not occur until the mid-2000s. This delayed warming hiatus could be related to changes in regional radiative, energy, and land surface processes in recent years.

Neuroprotective effect of p-coumaric acid in rat model of embolic cerebral ischemia

PubMed Central

Guven, Mustafa; Aras, Adem Bozkurt; Akman, Tarik; Sen, Halil Murat; Ozkan, Adile; Salis, Osman; Sehitoglu, Ibrahim; Kalkan, Yildiray; Silan, Coskun; Deniz, Mustafa; Cosar, Murat

2015-01-01

Objective(s): Stroke poses a crucial risk for mortality and morbidity. Our study aimed to investigate the effect of p-coumaric acid on focal cerebral ischemia in rats. Material and Methods: Rats were randomly divided into four groups, namely Group I (control rats), Group II (ischemia rats), Group III (6 hr ischemia + p-coumaric acid rats) and Group IV (24 hr ischemia + p-coumaric acid rats). Cerebral ischemia was induced via intraluminal monofilament occlusion model. In all groups, the brain was removed after the procedure and rats were sacrificed. Malondialdehyde, superoxide dismutase and nuclear respiratory factor-1 were measured in the ischemic hemisphere. The histopathological changes were observed in the right hemisphere within the samples. Functional assessment was performed for neurological deficit scores. Results: Following the treatment, biochemical factors changed significantly. Histopathologically, it was shown that p-coumaric acid decreased the oxidative damage. The neurological deficit scores of p-coumaric acid-treated rats were significantly improved after cerebral ischemia. Conclusion: Our results showed that p-coumaric acid is a neuroprotective agent on account of its strong anti-oxidant and anti-apoptotic features. Moreover, p-coumaric acid decreased the focal ischemia. Extra effort should be made to introduce p-coumaric acid as a promising therapeutic agent to be utilized for treatment of human cerebral ischemia in the future. PMID:26019798

Reactive oxygen species mediate liver injury through parenchymal nuclear factor-kappaB inactivation in prolonged ischemia/reperfusion.

PubMed

Llacuna, Laura; Marí, Montserrat; Lluis, Josep M; García-Ruiz, Carmen; Fernández-Checa, José C; Morales, Albert

2009-05-01

Nuclear factor (NF)-kappaB participates in ischemia/reperfusion (I/R) hepatic signaling, stimulating both protective mechanisms and the generation of inflammatory cytokines. After analyzing NF-kappaB activation during increasing times of ischemia in murine I/R, we observed that the nuclear translocation of p65 paralleled Src and IkappaB tyrosine phosphorylation, which peaked after 60 minutes of ischemia. After extended ischemic periods (90 to 120 minutes) however, nuclear p65 levels were inversely correlated with the progressive induction of oxidative stress. Despite this profile of NF-kappaB activation, inflammatory genes, such as tumor necrosis factor (TNF) and interleukin (IL)-1beta, predominantly induced by Kupffer cells, increased throughout time during ischemia (30 to 120 minutes), whereas protective NF-kappaB-dependent genes, such as manganese superoxide dismutase (Mn-SOD), expressed in parenchymal cells, decreased. Consistent with this behavior, gadolinium chloride pretreatment abolished TNF/IL-1beta up-regulation during ischemia without affecting Mn-SOD levels. Interestingly, specific glutathione (GSH) up-regulation in hepatocytes by S-adenosylmethionine increased Mn-SOD expression and protected against I/R-mediated liver injury despite TNF/IL-1beta induction. Similar protection was achieved by administration of the SOD mimetic MnTBAP. In contrast, indiscriminate hepatic GSH depletion by buthionine-sulfoximine before I/R potentiated oxidative stress and decreased both nuclear p65 and Mn-SOD expression levels, increasing TNF/IL-1beta up-regulation and I/R-induced liver damage. Thus, the divergent role of NF-kappaB activation in selective liver cell populations underlies the dichotomy of NF-kappaB in hepatic I/R injury, illustrating the relevance of specifically maintaining NF-kappaB activation in parenchymal cells.

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

Optical Response of Warm Dense Matter Using Real-Time Electron Dynamics

NASA Astrophysics Data System (ADS)

Baczewski, Andrew; Shulenburger, Luke; Desjarlais, Michael; Magyar, Rudolph

2014-03-01

The extreme temperatures and solid-like densities in warm dense matter present a unique challenge for theory, wherein neither conventional models from condensed matter nor plasma physics capture all of the relevant phenomenology. While Kubo-Greenwood DFT calculations have proven capable of reproducing optical properties of WDM, they require a significant number of virtual orbitals to reach convergence due to their perturbative nature. Real-time TDDFT presents a complementary framework with a number of computationally favorable properties, including reduced cost complexity and better scalability, and has been used to reproduce the optical response of finite and ordered extended systems. We will describe the use of Ehrenfest-TDDFT to evolve coupled electron-nuclear dynamics in WDM systems, and the subsequent evaluation of optical response functions from the real-time electron dynamics. The advantages and disadvantages of this approach will be discussed relative to the current state-of-the-art. Sandia National Laboratories is a multi-program laboratory managed and operated by Sandia Corporation, a wholly owned subsidiary of Lockheed Martin Corporation, for the U.S. Department of Energy's National Security Administration under contract DE-AC04-94AL85000.

The effect of aloe vera on ischemia--Reperfusion injury of sciatic nerve in rats.

PubMed

Guven, Mustafa; Gölge, Umut Hatay; Aslan, Esra; Sehitoglu, Muserref Hilal; Aras, Adem Bozkurt; Akman, Tarik; Cosar, Murat

2016-04-01

Aloe vera is compound which has strong antioxidant and anti-inflammatory effects. We investigated the neuroprotective role of aloe vera treatment in rats with experimental sciatic nerve ischemia/reperfusion injury. Twenty-eight male Wistar Albino rats were divided equally into 4 groups. Groups; Control group (no surgical procedure or medication), sciatic nerve ischemia/reperfusion group, sciatic nerve ischemia/reperfusion+aloe vera group and sciatic nerve ischemia/reperfusion+methylprednisolone group. Ischemia was performed by clamping the infrarenal abdominal aorta. 24 hours after ischemia, all animals were sacrificed. Sciatic nerve tissues were also examined histopathologically and biochemically. Ischemic fiber degeneration significantly decreased in the pre-treated with aloe vera and treated with methylprednisolone groups, especially in the pre-treated with aloe vera group, compared to the sciatic nerve ischemia/reperfusion group (p<0.05). A significant decrease in MDA, an increase in NRF1 level and SOD activity were observed in the groups which obtained from the AV and MP groups when compared to the sciatic nerve ischemia/reperfusion group. When all results were analysed it was seen that the aloe vera group was not statistically different compared to the MP group (p>0.05). Aloe vera is effective neuroprotective against sciatic nerve ischemia/reperfusion injury via antioxidant and anti-inflammatory properties. Also aloe vera was found to be as effective as MP. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Splicing factor NSSR1 reduces neuronal injury after mouse transient global cerebral ischemia.

PubMed

Qi, Yao; Li, Ya; Cui, Shi-Chao; Zhao, Jing-Jing; Liu, Xiao-Yan; Ji, Chun-Xia; Sun, Feng-Yan; Xu, Ping; Chen, Xian-Hua

2015-05-01

This study focuses on the function of NSSR1, a splicing factor, in neuronal injury in the ischemic mouse brain using the transient global cerebral ischemic mouse model and the cultured cells treated with oxygen-glucose deprivation (OGD). The results showed that the cerebral ischemia triggers the expression of NSSR1 in hippocampal astrocytes, predominantly the dephosphorylated NSSR1 proteins, and the Exon3 inclusive NCAM-L1 variant and the Exon4 inclusive CREB variant. While in the hippocampus of astrocyte-specific NSSR1 conditional knockdown (cKD) mice, where cerebral ischemia no longer triggers NSSR1 expression in astrocytes, the expression of Exon3 inclusive NCAM-L1 variant and Exon4 inclusive CREB variant were no longer triggered as well. In addition, the injury of hippocampal neurons was more severe in astrocyte-specific NSSR1 cKD mice compared with in wild-type mice after brain ischemia. Of note, the culture media harvested from the astrocytes with overexpression of NSSR1 or the Exon3 inclusive NCAM-L1 variant, or Exon4 inclusive CREB variant were all able to reduce the neuronal injury induced by OGD. The results provide the evidence demonstrating that: (1) Splicing factor NSSR1 is a new factor involved in reducing ischemic injury. (2) Ischemia induces NSSR1 expression in astrocytes, not in neurons. (3) NSSR1-mediated pathway in astrocytes is required for reducing ischemic neuronal injury. (4) NCAM-L1 and CREB are probably mediators in NSSR1-mediated pathway. In conclusion, our results suggest for the first time that NSSR1 may provide a novel mechanism for reducing neuronal injury after ischemia, probably through regulation on alternative splicing of NCAM-L1 and CREB in astrocytes. © 2014 Wiley Periodicals, Inc.

Accelerated increase in the Arctic tropospheric warming events surpassing stratospheric warming events during winter: Accelerated Increase in Arctic Warming

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

Wang, S. -Y. Simon; Lin, Yen-Heng; Lee, Ming-Ying

In January 2016, a robust reversal of the Arctic Oscillation (AO) took place associated with a rapid tropospheric warming in the Arctic region; this was followed by the occurrence of a classic sudden stratospheric warming in March-April. The succession of these two distinct Arctic warming events provides a stimulating opportunity to examine their characteristics in terms of similarities and differences. Historical cases of these two types of Arctic warming were identified and validated based upon tropical linkages with the Madden-Julian Oscillation and El Niño as well as those documented in previous studies. Our results indicate a recent and accelerated increasemore » in the tropospheric warming type versus a flat trend in stratospheric warming type. Given that tropospheric warming events occur twice as fast than the stratospheric warming type, the noted increase in the former implies further intensification in midlatitude winter weather extremes similar to those experienced in early 2016. Forced simulations with an atmospheric general circulation model suggest that the reduced Arctic sea ice contributes to the observed increase in the tropospheric warming events and associated impact on the anomalously cold Siberia.« less

Attenuation of intestinal ischemia-reperfusion-injury by β-alanine: a potentially glycine-receptor mediated effect.

PubMed

Brencher, Lisa; Verhaegh, Rabea; Kirsch, Michael

2017-05-01

Acute mesenteric ischemia is often caused by embolization of the mesenteric arterial circulation. Coherent intestinal injury due to ischemia and following reperfusion get visible on macroscopic and histologic level. In previous studies, application of glycine caused an ameliorated intestinal damage after ischemia-reperfusion in rats. Because we speculated that glycine acted here as a signal molecule, we investigated whether the glycine-receptor agonist β-alanine evokes the same beneficial effect in intestinal ischemia-reperfusion. β-alanine (10, 30, and 100 mg/kg) was administered intravenously. Ischemia/reperfusion of the small intestine was initiated by occluding and reopening the superior mesenteric artery in rats. After 90 min of ischemia and 120 min of reperfusion, the intestine was analyzed with regard to macroscopic and histologic tissue damage, the activity of the saccharase, and accumulation of macrophages. In addition, systemic parameters and metabolic ones (e.g., acid-base balance, electrolytes, and blood glucose) were measured at certain points in time. All three dosages of β-alanine did not change systemic parameters but prevent from hyponatremia during the period of reperfusion. Most importantly, application of 100-mg β-alanine clearly diminished intestinal tissue damage, getting visible on macroscopic and histologic level. In addition, I/R-mediated decrease of saccharase activity and accumulation of macrophages in the small intestine were ameliorated. The present study demonstrated that β-alanine was a potent agent to ameliorate I/R-induced injury of the small intestine. Due to its diminishing effect on the accumulation of macrophages, β-alanine is strongly expected to mediate its beneficial effect via glycine receptors. Copyright © 2017 Elsevier Inc. All rights reserved.

Desferrioxamine in warm reperfusion media decreases liver injury aggravated by cold storage

PubMed Central

Arthur, Peter G; Niu, Xian-Wa; Huang, Wen-Hua; DeBoer, Bastiaan; Lai, Ching Tat; Rossi, Enrico; Joseph, John; Jeffrey, Gary P

2013-01-01

AIM: To evaluate whether desferrioxamine decreases ischemia and perfusion injury aggravated by cold storage (CS) in a rat liver perfusion model. METHODS: Isolated rat livers were kept in CS in University of Wisconsin Solution for 20 h at 4 °C, then exposed to 25 min of warm ischemia (WI) at 37 °C followed by 2 h of warm perfusion (WP) at 37 °C with oxygenated (95% oxygen and 5% carbon dioxide) Krebs-Henseleit buffer. Desferrioxamine (DFO), an iron chelator, was added at different stages of storage, ischemia and perfusion: in CS only, in WI only, in WP only, in WI and perfusion, or in all stages. Effluent samples were collected after CS and after WI. Perfusate samples and bile were collected every 30 min (0, 0.5, 1, 1.5 and 2 h) during liver perfusion. Cellular injury was assessed by the determination of lactate dehydrogenase (LDH) and aspartate aminotransferase (AST) in the effluent and perfusate samples. Total iron was analysed in the perfusate samples. After WP, the liver was collected for the determination of liver swelling (wet to dry ratio) and liver morphological examination (hematoxylin and eosin staining). RESULTS: Increased CS time caused increased liver dysfunction during WP. After 2 h of WP, liver injury was indicated by increased release of AST (0.5 h CS: 9.4 ± 2.2 U/g liver vs 20 h CS: 45.9 ± 10.8 U/g liver, P < 0.05) and LDH (0.5 h CS: 59 ± 14 U/g liver vs 20 h CS: 297 ± 71 U/g liver, P < 0.05). There was an associated increase in iron release into the perfusate (0.5 h CS: 0.11 ± 0.03 μmoL/g liver vs 20 h CS: 0.58 ± 0.10 μmoL/g liver, P < 0.05) and reduction in bile flow (0.5 h CS: 194 ± 12 μL/g vs 20 h CS: 71 ± 8 μL/g liver, P < 0.05). When DFO was added during WI and WP following 20 h of CS, release of iron into the perfusate was decreased (DFO absent 0.58 ± 0.10 μmoL/g liver vs DFO present 0.31 ± 0.06 μmoL/g liver, P < 0.05), and liver function substantially improved with decreased release of AST (DFO absent 45.9 ± 10.8 U

Adverse remodeling of the electrophysiological response to ischemia-reperfusion in human heart failure is associated with remodeling of metabolic gene expression.

PubMed

Ng, Fu Siong; Holzem, Katherine M; Koppel, Aaron C; Janks, Deborah; Gordon, Fabiana; Wit, Andrew L; Peters, Nicholas S; Efimov, Igor R

2014-10-01

Ventricular arrhythmias occur more frequently in heart failure during episodes of ischemia-reperfusion although the mechanisms underlying this in humans are unclear. We assessed, in explanted human hearts, the remodeled electrophysiological response to acute ischemia-reperfusion in heart failure and its potential causes, including the remodeling of metabolic gene expression. We optically mapped coronary-perfused left ventricular wedge preparations from 6 human end-stage failing hearts (F) and 6 donor hearts rejected for transplantation (D). Preparations were subjected to 30 minutes of global ischemia, followed by 30 minutes of reperfusion. Failing hearts had exaggerated electrophysiological responses to ischemia-reperfusion, with greater action potential duration shortening (P<0.001 at 8-minute ischemia; P=0.001 at 12-minute ischemia) and greater conduction slowing during ischemia, delayed recovery of electric excitability after reperfusion (F, 4.8±1.8 versus D, 1.0±0 minutes; P<0.05), and incomplete restoration of action potential duration and conduction velocity early after reperfusion. Expression of 46 metabolic genes was probed using custom-designed TaqMan arrays, using extracted RNA from 15 failing and 9 donor hearts. Ten genes important in cardiac metabolism were downregulated in heart failure, with SLC27A4 and KCNJ11 significantly downregulated at a false discovery rate of 0%. We demonstrate, for the first time in human hearts, that the electrophysiological response to ischemia-reperfusion in heart failure is accelerated during ischemia with slower recovery after reperfusion. This can enhance spatial conduction and repolarization gradients across the ischemic border and increase arrhythmia susceptibility. This adverse response was associated with downregulation of expression of cardiac metabolic genes. © 2014 American Heart Association, Inc.

Does Vibration Warm-up Enhance Kinetic and Temporal Sprint Parameters?

PubMed

Cochrane, D J; Cronin, M J; Fink, P W

2015-08-01

The aim of this study was to investigate the efficacy of vibration warm-up to enhance sprint performance. 12 males involved in representative team sports performed 4 warm-up conditions in a randomised order performed at least 24 h apart; VbX warm-up (VbX-WU); Neural activation warm-up (Neu-WU); Dynamic warm-up (Dyn-WU) and Control (No VbX). Participants completed 5 m sprint at 30 s, 2:30 min and 5 min post warm-up where sprint time, kinetics, and temporal components were recorded. There was no significant (p>0.05) main effect or interaction effect between the split sprint times of 1 m, 2.5 m, and 5 m. There was a condition effect where vertical mean force was significantly higher (p<0.05) in Dyn-WU and Control compared to Neu-WU. No other significant (p>0.05) main and interaction effects in sprint kinetic and temporal parameters existed. Overall, all 4 warm-up conditions produced comparable results for sprint performance, and there was no detrimental effect on short-duration sprint performance using VbX-WU. Therefore, VbX could be useful for adding variety to the training warm-up or be included into the main warm-up routine as a supplementary modality. © Georg Thieme Verlag KG Stuttgart · New York.

The importance of warm season warming to western U.S. streamflow changes

USGS Publications Warehouse

Das, T.; Pierce, D.W.; Cayan, D.R.; Vano, J.A.; Lettenmaier, D.P.

2011-01-01

Warm season climate warming will be a key driver of annual streamflow changes in four major river basins of the western U.S., as shown by hydrological model simulations using fixed precipitation and idealized seasonal temperature changes based on climate projections with SRES A2 forcing. Warm season (April-September) warming reduces streamflow throughout the year; streamflow declines both immediately and in the subsequent cool season. Cool season (October-March) warming, by contrast, increases streamflow immediately, partially compensating for streamflow reductions during the subsequent warm season. A uniform warm season warming of 3C drives a wide range of annual flow declines across the basins: 13.3%, 7.2%, 1.8%, and 3.6% in the Colorado, Columbia, Northern and Southern Sierra basins, respectively. The same warming applied during the cool season gives annual declines of only 3.5%, 1.7%, 2.1%, and 3.1%, respectively. Copyright 2011 by the American Geophysical Union.

Terrestrial carbon cycle affected by non-uniform climate warming

NASA Astrophysics Data System (ADS)

Xia, Jianyang; Chen, Jiquan; Piao, Shilong; Ciais, Philippe; Luo, Yiqi; Wan, Shiqiang

2014-03-01

Feedbacks between the terrestrial carbon cycle and climate change could affect many ecosystem functions and services, such as food production, carbon sequestration and climate regulation. The rate of climate warming varies on diurnal and seasonal timescales. A synthesis of global air temperature data reveals a greater rate of warming in winter than in summer in northern mid and high latitudes, and the inverse pattern in some tropical regions. The data also reveal a decline in the diurnal temperature range over 51% of the global land area and an increase over only 13%, because night-time temperatures in most locations have risen faster than daytime temperatures. Analyses of satellite data, model simulations and in situ observations suggest that the impact of seasonal warming varies between regions. For example, spring warming has largely stimulated ecosystem productivity at latitudes between 30° and 90° N, but suppressed productivity in other regions. Contrasting impacts of day- and night-time warming on plant carbon gain and loss are apparent in many regions. We argue that ascertaining the effects of non-uniform climate warming on terrestrial ecosystems is a key challenge in carbon cycle research.

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.

Dictionary-Driven Ischemia Detection From Cardiac Phase-Resolved Myocardial BOLD MRI at Rest.

PubMed

Bevilacqua, Marco; Dharmakumar, Rohan; Tsaftaris, Sotirios A

2016-01-01

Cardiac Phase-resolved Blood-Oxygen-Level Dependent (CP-BOLD) MRI provides a unique opportunity to image an ongoing ischemia at rest. However, it requires post-processing to evaluate the extent of ischemia. To address this, here we propose an unsupervised ischemia detection (UID) method which relies on the inherent spatio-temporal correlation between oxygenation and wall motion to formalize a joint learning and detection problem based on dictionary decomposition. Considering input data of a single subject, it treats ischemia as an anomaly and iteratively learns dictionaries to represent only normal observations (corresponding to myocardial territories remote to ischemia). Anomaly detection is based on a modified version of One-class Support Vector Machines (OCSVM) to regulate directly the margins by incorporating the dictionary-based representation errors. A measure of ischemic extent (IE) is estimated, reflecting the relative portion of the myocardium affected by ischemia. For visualization purposes an ischemia likelihood map is created by estimating posterior probabilities from the OCSVM outputs, thus obtaining how likely the classification is correct. UID is evaluated on synthetic data and in a 2D CP-BOLD data set from a canine experimental model emulating acute coronary syndromes. Comparing early ischemic territories identified with UID against infarct territories (after several hours of ischemia), we find that IE, as measured by UID, is highly correlated (Pearson's r=0.84) with respect to infarct size. When advances in automated registration and segmentation of CP-BOLD images and full coverage 3D acquisitions become available, we hope that this method can enable pixel-level assessment of ischemia with this truly non-invasive imaging technique.

Dictionary-driven Ischemia Detection from Cardiac Phase-Resolved Myocardial BOLD MRI at Rest

PubMed Central

Bevilacqua, Marco; Dharmakumar, Rohan; Tsaftaris, Sotirios A.

2016-01-01

Cardiac Phase-resolved Blood-Oxygen-Level Dependent (CP–BOLD) MRI provides a unique opportunity to image an ongoing ischemia at rest. However, it requires post-processing to evaluate the extent of ischemia. To address this, here we propose an unsupervised ischemia detection (UID) method which relies on the inherent spatio-temporal correlation between oxygenation and wall motion to formalize a joint learning and detection problem based on dictionary decomposition. Considering input data of a single subject, it treats ischemia as an anomaly and iteratively learns dictionaries to represent only normal observations (corresponding to myocardial territories remote to ischemia). Anomaly detection is based on a modified version of One-class Support Vector Machines (OCSVM) to regulate directly the margins by incorporating the dictionary-based representation errors. A measure of ischemic extent (IE) is estimated, reflecting the relative portion of the myocardium affected by ischemia. For visualization purposes an ischemia likelihood map is created by estimating posterior probabilities from the OCSVM outputs, thus obtaining how likely the classification is correct. UID is evaluated on synthetic data and in a 2D CP–BOLD data set from a canine experimental model emulating acute coronary syndromes. Comparing early ischemic territories identified with UID against infarct territories (after several hours of ischemia), we find that IE, as measured by UID, is highly correlated (Pearson’s r = 0.84) w.r.t. infarct size. When advances in automated registration and segmentation of CP–BOLD images and full coverage 3D acquisitions become available, we hope that this method can enable pixel-level assessment of ischemia with this truly non-invasive imaging technique. PMID:26292338

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.

Space-Time Characterization of Laser Plasma Interactions in the Warm Dense Matter Regime

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

Cao, L F; Uschmann, I; Forster, E

2008-04-30

Laser plasma interaction experiments have been performed using a fs Titanium Sapphire laser. Plasmas have been generated from planar PMMA targets using single laser pulses with 3.3 mJ pulse energy, 50 fs pulse duration at 800 nm wavelength. The electron density distributions of the plasmas in different delay times have been characterized by means of Nomarski Interferometry. Experimental data were compared with hydrodynamic simulation. First results to characterize the plasma density and temperature as a function of space and time are obtained. This work aims to generate plasmas in the warm dense matter (WDM) regime at near solid-density in anmore » ultra-fast laser target interaction process. Plasmas under these conditions can serve as targets to develop x-ray Thomson scattering as a plasma diagnostic tool, e.g., using the VUV free-electron laser (FLASH) at DESY Hamburg.« less

Comparison of Two Types of Warm-Up Upon Repeated-Sprint Performance in Experienced Soccer Players.

PubMed

van den Tillaar, Roland; von Heimburg, Erna

2016-08-01

van den Tillaar, R and von Heimburg, E. Comparison of two types of warm-up upon repeated-sprint performance in experienced soccer players. J Strength Cond Res 30(8): 2258-2265, 2016-The aim of the study was to compare the effects of a long warm-up and a short warm-up upon repeated-sprint performance in soccer players. Ten male soccer players (age, 21.9 ± 1.9 years; body mass, 77.7 ± 8.3 kg; body height, 1.85 ± 0.03 m) conducted 2 types of warm-ups with 1 week in between: a long warm-up (20 minutes: LWup) and a short warm-up (10 minutes: SWup). Each warm-up was followed by a repeated-sprint test consisting of 8 × 30 m sprints with a new start every 30th second. The best sprint time, total sprinting time, and % decrease in time together with heart rate, lactate, and rate of perceived exertion (RPE) were measured. No significant differences in performance were found for the repeated-sprint test parameters (total sprint time: 35.99 ± 1.32 seconds [LWup] and 36.12 ± 0.96 seconds [SWup]; best sprint time: 4.32 ± 0.13 seconds [LWup] and 4.30 ± 0.10 seconds [SWup]; and % sprint decrease: 4.16 ± 2.15% [LWup] and 5.02 ± 2.07% [SWup]). No differences in lactate concentration after the warm-up and after the repeated-sprint test were found. However, RPE and heart rate were significantly higher after the long warm-up and the repeated-sprint test compared with the short warm-up. It was concluded that a short warm-up is as effective as a long warm-up for repeated sprints in soccer. Therefore, in regular training, less warm-up time is needed; the extra time could be used for important soccer skill training.

Is chlormethiazole neuroprotective in experimental global cerebral ischemia? A microdialysis and behavioral study.

PubMed

Thaminy, S; Reymann, J M; Heresbach, N; Allain, H; Lechat, P; Bentué-Ferrer, D

1997-04-01

Chlormethiazole, an anticonvulsive agent, has been shown to have a possible neuroprotective effect against cerebral ischemia. In addition, chlormethiazole inhibits methamphetamine-induced release of dopamine, protecting against this neurotransmitter's neurotoxicity. The aim of this work was to ascertain whether, in experimental cerebral ischemia, chlormethiazole administration attenuated the ischemia-induced rise of the extracellular concentration of aminergic neurotransmitters and whether it reduces ischemia-induced deficits in memory and learning. Histology for assessment of ischemic damage was a so included. The four-vessel occlusion rat model was used to induce global cerebral ischemia. Aminergic neurotransmitters and their metabolites in the striatal extracellular fluid obtained by microdialysis were assayed by high-performance liquid chromatography-electrochemical detection. The drug was administered either IP (50 mg/kg-1) or directly through the dialysis probe (30 microM) 80 min before ischemia. For the behavioral test and histology, the drug was given IP (100 mg/kg-1) 1 h postischemia. The results obtained did not demonstrate any statistically significant evidence that chlormethiazole has an effect on the ischemia-induced rise in extracellular dopamine and serotonin levels. There was also no variation in metabolite levels. Behavioral measures (learning, recall) were not changed appreciably by the treatment. We observed no significant cell protection in the hippocampus (CA1, CA1), striatum, and entorhinal cortex in animals treated with chlormethiazole. We conclude that, under our experimental conditions, chlormethiazole has little or no effect on the neurochemical, neurobehavioral, and histological consequences of global cerebral ischemia.

Reparative neurogenesis after cerebral ischemia: Clinical application prospects

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

Khodanovich, M. Yu., E-mail: khodanovich@mail.tsu.ru

At the present time two main approaches are in the focus of neurobiological studies of brain recovery after a stroke. One of them is concerned with the infusion of stem cells in damaged brain. The second approach is directed at the stimulation of endogenous reparative processes, in particular, adult neurogenesis. This review considers alterations of adult neurogenesis caused by cerebral ischemia and possible pathways of its regulation. Multiple studies on animal models have shown that adult neurogenesis is mostly increased by cerebral ischemia. In spite of increasing proliferation and moving neural progenitors to infarct zone, most newborn neurons die beforemore » reaching maturity. Besides, an increase of neurogenesis in pathological conditions is mainly due to recruitment of new stem cells, but not due to an additional precursor-cells division that results in an overall decline of the regeneration capacity. Thus, the endogenous reparative mechanisms are not sufficient, and the search for new targets to promote proliferation, survival, and maturation of new neurons after a stroke is needed. Neurotransmitter systems and anti-inflammatory drugs are considered as potential regulators of post-ischemic neurogenesis growth factors.« less

Design and performance of combined infrared canopy and belowground warming in the B4WarmED (Boreal Forest Warming at an Ecotone in Danger) experiment.

PubMed

Rich, Roy L; Stefanski, Artur; Montgomery, Rebecca A; Hobbie, Sarah E; Kimball, Bruce A; Reich, Peter B

2015-06-01

Conducting manipulative climate change experiments in complex vegetation is challenging, given considerable temporal and spatial heterogeneity. One specific challenge involves warming of both plants and soils to depth. We describe the design and performance of an open-air warming experiment called Boreal Forest Warming at an Ecotone in Danger (B4WarmED) that addresses the potential for projected climate warming to alter tree function, species composition, and ecosystem processes at the boreal-temperate ecotone. The experiment includes two forested sites in northern Minnesota, USA, with plots in both open (recently clear-cut) and closed canopy habitats, where seedlings of 11 tree species were planted into native ground vegetation. Treatments include three target levels of plant canopy and soil warming (ambient, +1.7°C, +3.4°C). Warming was achieved by independent feedback control of voltage input to aboveground infrared heaters and belowground buried resistance heating cables in each of 72-7.0 m(2) plots. The treatments emulated patterns of observed diurnal, seasonal, and annual temperatures but with superimposed warming. For the 2009 to 2011 field seasons, we achieved temperature elevations near our targets with growing season overall mean differences (∆Tbelow ) of +1.84°C and +3.66°C at 10 cm soil depth and (∆T(above) ) of +1.82°C and +3.45°C for the plant canopies. We also achieved measured soil warming to at least 1 m depth. Aboveground treatment stability and control were better during nighttime than daytime and in closed vs. open canopy sites in part due to calmer conditions. Heating efficacy in open canopy areas was reduced with increasing canopy complexity and size. Results of this study suggest the warming approach is scalable: it should work well in small-statured vegetation such as grasslands, desert, agricultural crops, and tree saplings (<5 m tall). © 2015 John Wiley & Sons Ltd.

Monitoring somatosensory evoked potentials in spinal cord ischemia-reperfusion injury

PubMed Central

Ji, Yiming; Meng, Bin; Yuan, Chenxi; Yang, Huilin; Zou, Jun

2013-01-01

It remains unclear whether spinal cord ischemia-reperfusion injury caused by ischemia and other non-mechanical factors can be monitored by somatosensory evoked potentials. Therefore, we monitored spinal cord ischemia-reperfusion injury in rabbits using somatosensory evoked potential detection technology. The results showed that the somatosensory evoked potential latency was significantly prolonged and the amplitude significantly reduced until it disappeared during the period of spinal cord ischemia. After reperfusion for 30–180 minutes, the amplitude and latency began to gradually recover; at 360 minutes of reperfusion, the latency showed no significant difference compared with the pre-ischemic value, while the somatosensory evoked potential amplitude in-creased, and severe hindlimb motor dysfunctions were detected. Experimental findings suggest that changes in somatosensory evoked potential latency can reflect the degree of spinal cord ischemic injury, while the amplitude variations are indicators of the late spinal cord reperfusion injury, which provide evidence for the assessment of limb motor function and avoid iatrogenic spinal cord injury. PMID:25206629

Regulator of calcineurin 1 (Rcan1) has a protective role in brain ischemia/reperfusion injury

PubMed Central

2012-01-01

Background An increase in intracellular calcium concentration [Ca2+]i is one of the first events to take place after brain ischemia. A key [Ca2+]i-regulated signaling molecule is the phosphatase calcineurin (CN), which plays important roles in the modulation of inflammatory cascades. Here, we have analyzed the role of endogenous regulator of CN 1 (Rcan1) in response to experimental ischemic stroke induced by middle cerebral artery occlusion. Methods Animals were subjected to focal cerebral ischemia with reperfusion. To assess the role of Rcan1 after stroke, we measured infarct volume after 48 h of reperfusion in Rcan1 knockout (KO) and wild-type (WT) mice. In vitro studies were performed in astrocyte-enriched cortical primary cultures subjected to 3% oxygen (hypoxia) and glucose deprivation (HGD). Adenoviral vectors were used to analyze the effect of overexpression of Rcan1-4 protein. Protein expression was examined by immunohistochemistry and immunoblotting and expression of mRNA by quantitative real-time Reverse-Transcription Polymerase Chain Reaction (real time qRT-PCR). Results Brain ischemia/reperfusion (I/R) injury in vivo increased mRNA and protein expression of the calcium-inducible Rcan1 isoform (Rcan1-4). I/R-inducible expression of Rcan1 protein occurred mainly in astroglial cells, and in an in vitro model of ischemia, HGD treatment of primary murine astrocyte cultures induced Rcan1-4 mRNA and protein expression. Exogenous Rcan1-4 overexpression inhibited production of the inflammatory marker cyclo-oxygenase 2. Mice lacking Rcan1 had higher expression of inflammation associated genes, resulting in larger infarct volumes. Conclusions Our results support a protective role for Rcan1 during the inflammatory response to stroke, and underline the importance of the glial compartment in the inflammatory reaction that takes place after ischemia. Improved understanding of non-neuronal mechanisms in ischemic injury promises novel approaches to the treatment of

[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.

[Antioxidant effects of antihypoxic drugs in cerebral ischemia].

PubMed

Plotnikov, M B; Kobzeva, E A; Plotnikova, T M

1992-05-01

Cerebral ischemia in rats (both carotid arteries occlusion) during 30 min, 3 hours and recirculation (1 hour) after ischemia (30 min) stimulated diene conjugates and fluorescent products accumulation in brain tissue. Intraperitoneal injection of sodium hydroxybutyrate (100 mg/kg), bemitil (50 mg/kg), ethomersol (50 mg/kg) reduced brain lipid peroxidation and did not yield in this respect to emoxypin (5 mg/kg). In contrast to emoxypin, sodium hydroxybutyrate, bemitil and ethomersol had no antiradical activity.

Magnetic Resonance Imaging Allows the Evaluation of Tissue Damage and Regeneration in a Mouse Model of Critical Limb Ischemia.

PubMed

Zaccagnini, Germana; Palmisano, Anna; Canu, Tamara; Maimone, Biagina; Lo Russo, Francesco M; Ambrogi, Federico; Gaetano, Carlo; De Cobelli, Francesco; Del Maschio, Alessandro; Esposito, Antonio; Martelli, Fabio

2015-01-01

Magnetic resonance imaging (MRI) provides non-invasive, repetitive measures in the same individual, allowing the study of a physio-pathological event over time. In this study, we tested the performance of 7 Tesla multi-parametric MRI to monitor the dynamic changes of mouse skeletal muscle injury and regeneration upon acute ischemia induced by femoral artery dissection. T2-mapping (T2 relaxation time), diffusion-tensor imaging (Fractional Anisotropy) and perfusion by Dynamic Contrast-Enhanced MRI (K-trans) were measured and imaging results were correlated with histological morphometric analysis in both Gastrocnemius and Tibialis anterior muscles. We found that tissue damage positively correlated with T2-relaxation time, while myofiber regeneration and capillary density positively correlated with Fractional Anisotropy. Interestingly, K-trans positively correlated with capillary density. Accordingly, repeated MRI measurements between day 1 and day 28 after surgery in ischemic muscles showed that: 1) T2-relaxation time rapidly increased upon ischemia and then gradually declined, returning almost to basal level in the last phases of the regeneration process; 2) Fractional Anisotropy dropped upon ischemic damage induction and then recovered along with muscle regeneration and neoangiogenesis; 3) K-trans reached a minimum upon ischemia, then progressively recovered. Overall, Gastrocnemius and Tibialis anterior muscles displayed similar patterns of MRI parameters dynamic, with more marked responses and less variability in Tibialis anterior. We conclude that MRI provides quantitative information about both tissue damage after ischemia and the subsequent vascular and muscle regeneration, accounting for the differences between subjects and, within the same individual, between different muscles.

The impact of global warming on Mount Everest.

PubMed

Moore, G W K; Semple, John L

2009-01-01

Global warming impacts a wide range of human activities and ecosystems. One unanticipated consequence of the warming is an increase in barometric pressure throughout the troposphere. Mount Everest's extreme height and resulting low barometric pressure places humans near its summit in an extreme state of hypoxia. Here we quantify the degree with which this warming is increasing the barometric pressure near Everest's summit and argue that it is of such a magnitude as to make the mountain, over time, easier to climb.

[Warming up with endotrainer prior to laparoscopic cholecystectomy].

PubMed

Troncoso-Bacelis, Alicia; Soto-Amaro, Jaime; Ramírez-Velázquez, Carlos

Laparoscopic cholecystectomy is a safe and effective treatment and remains the gold standard in patients with benign disease. However it presents difficulties such as: the limited movement range of the instruments, the loss of depth perception, haptic feedback and the fulcrum effect. Previous training can optimize surgical performance in patients to master basic skills. Assess the effectiveness of surgeons warming up with an endotrainer before performing laparoscopic cholecystectomy. Single-blind controlled clinical trial with 16 surgeons who performed 2 laparoscopic cholecystectomies, the first according to standard practice and the second with warm-up comprising 5 MISTELS system exercises. Patient and surgeon demographics were recorded, in addition to findings and complications during and after surgery for each procedured. We found a decrease in surgical time of 76.88 (±18.87) minutes in the group that did not warm up to prior to surgery compared with 72.81 (±35.5) minutes in the group with warm-up (p=0.0196). In addition, increased bleeding occurred in the procedures performed with warm-up 31.25 (±30.85) ml compared with the group that had no warm-up 23.94 (±15.9) (p=0.0146). Performing warm up on a MISTELS system endotrainer before performing laparoscopic cholecystectomy reduces the operating time of surgery for all surgeons. Surgery bleeding increases in operations performed by surgeons with less experience in laparoscopic surgery. Copyright © 2016 Academia Mexicana de Cirugía A.C. Publicado por Masson Doyma México S.A. All rights reserved.

Alda-1, an ALDH2 activator, protects against hepatic ischemia/reperfusion injury in rats via inhibition of oxidative stress.

PubMed

Zhang, Tao; Zhao, Qiang; Ye, Fang; Huang, Chan-Yan; Chen, Wan-Mei; Huang, Wen-Qi

2018-04-13

Previous studies have proved that activation of aldehyde dehydrogenase two (ALDH2) can attenuate oxidative stress through clearance of cytotoxic aldehydes, and can protect against cardiac, cerebral, and lung ischemia/reperfusion (I/R) injuries. In this study, we investigated the effects of the ALDH2 activator Alda-1 on hepatic I/R injury. Partial warm ischemia was performed in the left and middle hepatic lobes of Sprague-Dawley rats for 1 h, followed by 6 h of reperfusion. Rats received either Alda-1 or vehicle by intravenous injection 30 min before ischemia. Blood and tissue samples of the rats were collected after 6-h reperfusion. Histological injury, proinflammatory cytokines, reactive oxygen species (ROS), cellular apoptosis, ALDH2 expression and activity, 4-hydroxy-trans-2-nonenal (4-HNE) and malondialdehyde (MDA) were measured. BRL-3A hepatocytes were subjected to hypoxia/reoxygenation (H/R). Cell viability, ROS, and mitochondrial membrane potential were determined. Pretreatment with Alda-1 significantly alleviated I/R-induced elevations of alanine aminotransferase and aspartate amino transferase, and significantly blunted the pathological injury of the liver. Moreover, Alda-1 significantly inhibited ROS and proinflammatory cytokines production, 4-HNE and MDA accumulation, and apoptosis. Increased ALDH2 activity was found after Alda-1 administration. No significant changes in ALDH2 expression were observed after I/R. ROS was also higher in H/R cells than in control cells, which was aggravated upon treatment with 4-HNE, and reduced by Alda-1 treatment. Cell viability and mitochondrial membrane potential were inhibited in H/R cells, which was attenuated upon Alda-1 treatment. Activation of ALDH2 by Alda-1 attenuates hepatic I/R injury via clearance of cytotoxic aldehydes.

Simulation of future global warming scenarios in rice paddies with an open-field warming facility

PubMed Central

2011-01-01

To simulate expected future global warming, hexagonal arrays of infrared heaters have previously been used to warm open-field canopies of upland crops such as wheat. Through the use of concrete-anchored posts, improved software, overhead wires, extensive grounding, and monitoring with a thermal camera, the technology was safely and reliably extended to paddy rice fields. The system maintained canopy temperature increases within 0.5°C of daytime and nighttime set-point differences of 1.3 and 2.7°C 67% of the time. PMID:22145582

Photothrombosis-induced Focal Ischemia as a Model of Spinal Cord Injury in Mice

PubMed Central

Zhang, Nannan; Ding, Shinghua

2015-01-01

Spinal cord injury (SCI) is a devastating clinical condition causing permanent changes in sensorimotor and autonomic functions of the spinal cord (SC) below the site of injury. The secondary ischemia that develops following the initial mechanical insult is a serious complication of the SCI and severely impairs the function and viability of surviving neuronal and non-neuronal cells in the SC. In addition, ischemia is also responsible for the growth of lesion during chronic phase of injury and interferes with the cellular repair and healing processes. Thus there is a need to develop a spinal cord ischemia model for studying the mechanisms of ischemia-induced pathology. Focal ischemia induced by photothrombosis (PT) is a minimally invasive and very well established procedure used to investigate the pathology of ischemia-induced cell death in the brain. Here, we describe the use of PT to induce an ischemic lesion in the spinal cord of mice. Following retro-orbital sinus injection of Rose Bengal, the posterior spinal vein and other capillaries on the dorsal surface of SC were irradiated with a green light resulting in the formation of a thrombus and thus ischemia in the affected region. Results from histology and immunochemistry studies show that PT-induced ischemia caused spinal cord infarction, loss of neurons and reactive gliosis. Using this technique a highly reproducible and relatively easy model of SCI in mice can be achieved that would serve the purpose of scientific investigations into the mechanisms of ischemia induced cell death as well as the efficacy of neuroprotective drugs. This model will also allow exploration of the pathological changes that occur following SCI in live mice like axonal degeneration and regeneration, neuronal and astrocytic Ca2+ signaling using two-photon microscopy. PMID:26274772

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

Ischemia causes muscle fatigue

NASA Technical Reports Server (NTRS)

Murthy, G.; Hargens, A. R.; Lehman, S.; Rempel, D. M.

2001-01-01

The purpose of this investigation was to determine whether ischemia, which reduces oxygenation in the extensor carpi radialis (ECR) muscle, causes a reduction in muscle force production. In eight subjects, muscle oxygenation (TO2) of the right ECR was measured noninvasively and continuously using near infrared spectroscopy (NIRS) while muscle twitch force was elicited by transcutaneous electrical stimulation (1 Hz, 0.1 ms). Baseline measurements of blood volume, muscle oxygenation and twitch force were recorded continuously, then a tourniquet on the upper arm was inflated to one of five different pressure levels: 20, 40, 60 mm Hg (randomized order) and diastolic (69 +/- 9.8 mm Hg) and systolic (106 +/- 12.8 mm Hg) blood pressures. Each pressure level was maintained for 3-5 min, and was followed by a recovery period sufficient to allow measurements to return to baseline. For each respective tourniquet pressure level, mean TO2 decreased from resting baseline (100% TO2) to 99 +/- 1.2% (SEM), 96 +/- 1.9%, 93 +/- 2.8%, 90 +/- 2.5%, and 86 +/- 2.7%, and mean twitch force decreased from resting baseline (100% force) to 99 +/- 0.7% (SEM), 96 +/- 2.7%, 93 +/- 3.1%, 88 +/- 3.2%, and 86 +/- 2.6%. Muscle oxygenation and twitch force at 60 mm Hg tourniquet compression and above were significantly lower (P < 0.05) than baseline value. Reduced twitch force was correlated in a dose-dependent manner with reduced muscle oxygenation (r = 0.78, P < 0.001). Although the correlation does not prove causation, the results indicate that ischemia leading to a 7% or greater reduction in muscle oxygenation causes decreased muscle force production in the forearm extensor muscle. Thus, ischemia associated with a modest decline in TO2 causes muscle fatigue.

Ischemia/reperfusion-induced injury of forebrain mitochondria and protection by ascorbate.

PubMed

Sciamanna, M A; Lee, C P

1993-09-01

Complete, reversible forebrain ischemia was induced with a seven-vessel occlusion rat model. Previous studies of ischemic (M. A. Sciamanna, J. Zinkel, A. Y. Fabi, and C. P. Lee, 1992, Biochim. Biophys. Acta 1134, 223-232) rat brain mitochondria (RBM) showed that ischemia of 30 min caused an approximately 60% decrease in State 3 respiratory rates with both succinate and NAD-linked substrates and also in energy-linked Ca2+ transport. No significant change was seen in the State 4 rates. The inhibition of respiration could be prevented by EGTA or ruthenium red. In this paper it is shown that reperfusion (5 h) following ischemia (30 min) further impaired RBM respiratory activities (succinate and NAD-linked substrates). The presence of EGTA or ruthenium red in the assay medium did not protect against ischemia/reperfusion-induced injury. The effects of ascorbate, an oxygen radical scavenger, were studied. RBM isolated from ascorbate-treated animals (0.8 mg ascorbate/kg body weight) after ischemia (30 min) alone showed only a slight increase in State 3 (approximately 25%) and a decrease in State 4 (approximately 20%) activities with succinate, when compared to untreated 30-min ischemic animals, whereas, with glutamate+malate little or no effect was seen. The respiratory activities of RBM from ascorbate-treated, ischemic/reperfused (30 min/5 h) rats were restored to approximately 65% of controls levels. Ascorbate protection was dose-dependent with maximum protection at 0.8 mg ascorbate/kg body weight of rat. The k of succinate oxidase-supported Ca2+ uptake also returned to 62% of control values. Protection by ascorbate was most effective when administered prior to the onset of ischemia and provided partial protection when administered after the onset of reperfusion. These results suggest that ischemia-induced injury is primarily mediated by disruption of cellular Ca2+ homeostasis, and reperfusion-induced injury by peroxidative events.

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

Reconciling controversies about the ‘global warming hiatus’

NASA Astrophysics Data System (ADS)

Medhaug, Iselin; Stolpe, Martin B.; Fischer, Erich M.; Knutti, Reto

2017-05-01

Between about 1998 and 2012, a time that coincided with political negotiations for preventing climate change, the surface of Earth seemed hardly to warm. This phenomenon, often termed the ‘global warming hiatus’, caused doubt in the public mind about how well anthropogenic climate change and natural variability are understood. Here we show that apparently contradictory conclusions stem from different definitions of ‘hiatus’ and from different datasets. A combination of changes in forcing, uptake of heat by the oceans, natural variability and incomplete observational coverage reconciles models and data. Combined with stronger recent warming trends in newer datasets, we are now more confident than ever that human influence is dominant in long-term warming.

Interleukin-13 protects mouse intestine from ischemia and reperfusion injury through regulation of innate and adaptive immunity.

PubMed

Farmer, Douglas G; Ke, Bibo; Shen, Xiu-Da; Kaldas, Fady M; Gao, Feng; Watson, Melissa J; Busuttil, Ronald W; Kupiec-Weglinski, Jerzy W

2011-04-15

Ischemia-reperfusion (I/R) injury is a major factor leading to intestinal dysfunction or graft loss after intestinal surgery or transplantation. This study investigated the cytoprotective effects and putative mechanisms of interleukin (IL)-13 after intestinal I/R injury in the mouse. Mouse warm intestinal I/R injury induced by clamping the superior mesenteric artery for 100 min with tissue analysis at 4 and 24 hr after reperfusion. Treated animals received intravenous recombinant murine IL-13 (rIL-13) and anti-IL-13 antibody, whereas controls received saline. rIL-13 administration markedly prolonged animal survival (100% vs. 50% in saline controls) and resulted in near normal histopathological architecture. rIL-13 treatment also significantly decreased myeloperoxidase activity. Mice conditioned with rIL-13 had a markedly depressed Toll-like receptor-4 expression and increased the expression of Stat6, antioxidant hemeoxygenase-1, and antiapoptotic A20, Bcl-2/Bcl-xl, compared with that of controls. Unlike in controls, the expression of mRNA coding for IL-2/interferon-γ, and interferon-γ-inducible protein (IP)-10/monocyte chemotactic protein-1 remained depressed, whereas that of IL-13/IL-4 reciprocally increased in the mice treated with rIL-13. Administration of anti-IL13 antibody alone or in combination with rIL-13 resulted in outcomes similar to that seen in controls. This study demonstrates for the first time that IL-13 plays a protective role in intestinal warm I/R injury and a critical role in the regulation of Stat6 and Toll-like receptor-4 signaling. The administration of IL-13 exerts cytoprotective effects in this model by regulating innate and adaptive immunity while the removal of IL-13 using antibody therapy abrogates this effect.

Seagrass ecophysiological performance under ocean warming and acidification.

PubMed

Repolho, Tiago; Duarte, Bernardo; Dionísio, Gisela; Paula, José Ricardo; Lopes, Ana R; Rosa, Inês C; Grilo, Tiago F; Caçador, Isabel; Calado, Ricardo; Rosa, Rui

2017-02-01

Seagrasses play an essential ecological role within coastal habitats and their worldwide population decline has been linked to different types of anthropogenic forces. We investigated, for the first time, the combined effects of future ocean warming and acidification on fundamental biological processes of Zostera noltii, including shoot density, leaf coloration, photophysiology (electron transport rate, ETR; maximum PSII quantum yield, F v /F m ) and photosynthetic pigments. Shoot density was severely affected under warming conditions, with a concomitant increase in the frequency of brownish colored leaves (seagrass die-off). Warming was responsible for a significant decrease in ETR and F v /F m (particularly under control pH conditions), while promoting the highest ETR variability (among experimental treatments). Warming also elicited a significant increase in pheophytin and carotenoid levels, alongside an increase in carotenoid/chlorophyll ratio and De-Epoxidation State (DES). Acidification significantly affected photosynthetic pigments content (antheraxanthin, β-carotene, violaxanthin and zeaxanthin), with a significant decrease being recorded under the warming scenario. No significant interaction between ocean acidification and warming was observed. Our findings suggest that future ocean warming will be a foremost determinant stressor influencing Z. noltii survival and physiological performance. Additionally, acidification conditions to occur in the future will be unable to counteract deleterious effects posed by ocean warming.

Seagrass ecophysiological performance under ocean warming and acidification

PubMed Central

Repolho, Tiago; Duarte, Bernardo; Dionísio, Gisela; Paula, José Ricardo; Lopes, Ana R.; Rosa, Inês C.; Grilo, Tiago F.; Caçador, Isabel; Calado, Ricardo; Rosa, Rui

2017-01-01

Seagrasses play an essential ecological role within coastal habitats and their worldwide population decline has been linked to different types of anthropogenic forces. We investigated, for the first time, the combined effects of future ocean warming and acidification on fundamental biological processes of Zostera noltii, including shoot density, leaf coloration, photophysiology (electron transport rate, ETR; maximum PSII quantum yield, Fv/Fm) and photosynthetic pigments. Shoot density was severely affected under warming conditions, with a concomitant increase in the frequency of brownish colored leaves (seagrass die-off). Warming was responsible for a significant decrease in ETR and Fv/Fm (particularly under control pH conditions), while promoting the highest ETR variability (among experimental treatments). Warming also elicited a significant increase in pheophytin and carotenoid levels, alongside an increase in carotenoid/chlorophyll ratio and De-Epoxidation State (DES). Acidification significantly affected photosynthetic pigments content (antheraxanthin, β-carotene, violaxanthin and zeaxanthin), with a significant decrease being recorded under the warming scenario. No significant interaction between ocean acidification and warming was observed. Our findings suggest that future ocean warming will be a foremost determinant stressor influencing Z. noltii survival and physiological performance. Additionally, acidification conditions to occur in the future will be unable to counteract deleterious effects posed by ocean warming. PMID:28145531

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.

Animal models of ischemia-reperfusion-induced intestinal injury: progress and promise for translational research

PubMed Central

Gonzalez, Liara M.; Moeser, Adam J.

2014-01-01

Research in the field of ischemia-reperfusion injury continues to be plagued by the inability to translate research findings to clinically useful therapies. This may in part relate to the complexity of disease processes that result in intestinal ischemia but may also result from inappropriate research model selection. Research animal models have been integral to the study of ischemia-reperfusion-induced intestinal injury. However, the clinical conditions that compromise intestinal blood flow in clinical patients ranges widely from primary intestinal disease to processes secondary to distant organ failure and generalized systemic disease. Thus models that closely resemble human pathology in clinical conditions as disparate as volvulus, shock, and necrotizing enterocolitis are likely to give the greatest opportunity to understand mechanisms of ischemia that may ultimately translate to patient care. Furthermore, conditions that result in varying levels of ischemia may be further complicated by the reperfusion of blood to tissues that, in some cases, further exacerbates injury. This review assesses animal models of ischemia-reperfusion injury as well as the knowledge that has been derived from each to aid selection of appropriate research models. In addition, a discussion of the future of intestinal ischemia-reperfusion research is provided to place some context on the areas likely to provide the greatest benefit from continued research of ischemia-reperfusion injury. PMID:25414098

Protective Effect of Platelet Rich Plasma on Experimental Ischemia/Reperfusion Injury in Rat Ovary.

PubMed

Bakacak, Murat; Bostanci, Mehmet Suhha; İnanc, Fatma; Yaylali, Asli; Serin, Salih; Attar, Rukset; Yildirim, Gazi; Yildirim, Ozge Kizilkale

2016-01-01

Ovarian torsion is a common cause of local ischemic damage, reduced follicular activity and infertility. Platelet-rich plasma (PRP) contains growth factors with demonstrated cytoprotective properties; so we evaluated PRP efficacy in a rat ischemia/reperfusion (I/R) model. Sixty adult female Sprague-Dawley albino rats were randomly assigned to 6 groups of 8 animals each: Sham, Ischemia, I/R, Sham + PRP, I + PRP and I/R + PRP; and the remaining 12 used to prepare PRP. Ischemia groups were subjected to bilateral adnexal torsion for 3 h, while I/R and I/R + PRP groups received subsequent detorsion for 3 h. Intraperitoneal PRP was administered 30 min prior to ischemia (Ischemia + PRP) or reperfusion (I/R + PRP). Total oxidant status (TOS), oxidative stress index (OSI) and total ovarian histopathological scores were higher in Ischemia and I/R groups than in the Sham group (p < 0.05). PRP decreased mean TOS, OSI and histopathological scores in I + PRP and I/R + PRP groups compared to the corresponding Ischemia and I/R groups (p < 0.001). There was a strong correlation between total histopathological score and OSI (r = 0.877, p < 0.001). Peritoneal vascular endothelial growth factor was significantly higher in PRP-treated groups than corresponding untreated groups (p < 0.05). PRP is effective for the prevention of ischemia and reperfusion damage in rat ovary. © 2015 S. Karger AG, Basel.

Impact of thermal time shift on wheat phenology and yield under warming climate in the Huang-Huai-Hai Plain, China

NASA Astrophysics Data System (ADS)

Xiao, Dengpan; Qi, Yongqing; Li, Zhiqiang; Wang, Rende; Moiwo, Juana P.; Liu, Fengshan

2017-03-01

Given climate change can potentially influence crop phenology and subsequent yield, an investigation of relevant adaptation measures could increase the understanding and mitigation of these responses in the future. In this study, field observations at 10 stations in the Huang-Huai-Hai Plain of China (HHHP) are used in combination with the Agricultural Production Systems Simulator (APSIM)-Wheat model to determine the effect of thermal time shift on the phenology and potential yield of wheat from 1981-2009. Warming climate speeds up winter wheat development and thereby decreases the duration of the wheat growth period. However, APSIM-Wheat model simulation suggests prolongation of the period from flowering to maturity (Gr) of winter wheat by 0.2-0.8 d•10yr-1 as the number of days by which maturity advances, which is less than that by which flowering advances. Based on computed thermal time of the two critical growth phases of wheat, total thermal time from floral initiation to flowering (TT_floral_initiation) increasesd in seven out of the 10 investigated stations. Alternatively, total thermal time from the start of grainfilling to maturity (TT_start_ grain_fill) increased in all investigated stations, except Laiyang. It is thus concluded that thermal time shift during the past three decades (1981-2009) prolongs Gr by 0.2-3.0 d•10yr-1 in the study area. This suggests that an increase in thermal time (TT) of the wheat growth period is critical for mitigating the effect of growth period reduction due to warming climatic condition. Furthermore, climate change reduces potential yield of winter wheat in 80% of the stations by 2.3-58.8 kg•yr-1. However, thermal time shift (TTS) increases potential yield of winter wheat in most of the stations by 3.0-51.0 kg•yr-1. It is concluded that wheat cultivars with longer growth periods and higher thermal requirements could mitigate the negative effects of warming climate on crop production in the study area.

Predator contributions to belowground responses to warming

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

Maran, A. M.; Pelini, S. L.

Identifying the factors that control soil CO 2 emissions will improve our ability to predict the magnitude of climate change–soil ecosystem feedbacks. Despite the integral role of invertebrates in belowground systems, they are excluded from climate change models. Soil invertebrates have consumptive and nonconsumptive effects on microbes, whose respiration accounts for nearly half of soil CO 2 emissions. By altering the behavior and abundance of invertebrates that interact with microbes, invertebrate predators may have indirect effects on soil respiration. We examined the effects of a generalist arthropod predator on belowground respiration under different warming scenarios. Based on research suggesting invertebratesmore » may mediate soil CO 2 emission responses to warming, we predicted that predator presence would result in increased emissions by negatively affecting these invertebrates. We altered the presence of wolf spiders ( Pardosa spp.) in mesocosms containing a forest floor community. To simulate warming, we placed mesocosms of each treatment in ten open-top warming chambers ranging from 1.5° to 5.5°C above ambient at Harvard Forest, Massachusetts, USA. As expected, CO 2 emissions increased under warming and we found an interactive effect of predator presence and warming, although the effect was not consistent through time. The interaction between predator presence and warming was the inverse of our predictions: Mesocosms with predators had lower respiration at higher levels of warming than those without predators. Carbon dioxide emissions were not significantly associated with microbial biomass. Here, we did not find evidence of consumptive effects of predators on the invertebrate community, suggesting that predator presence mediates response of microbial respiration to warming through nonconsumptive means. In our system, we found a significant interaction between warming and predator presence that warrants further research into mechanism and

Predator contributions to belowground responses to warming

DOE PAGES

Maran, A. M.; Pelini, S. L.

2016-09-26

Identifying the factors that control soil CO 2 emissions will improve our ability to predict the magnitude of climate change–soil ecosystem feedbacks. Despite the integral role of invertebrates in belowground systems, they are excluded from climate change models. Soil invertebrates have consumptive and nonconsumptive effects on microbes, whose respiration accounts for nearly half of soil CO 2 emissions. By altering the behavior and abundance of invertebrates that interact with microbes, invertebrate predators may have indirect effects on soil respiration. We examined the effects of a generalist arthropod predator on belowground respiration under different warming scenarios. Based on research suggesting invertebratesmore » may mediate soil CO 2 emission responses to warming, we predicted that predator presence would result in increased emissions by negatively affecting these invertebrates. We altered the presence of wolf spiders ( Pardosa spp.) in mesocosms containing a forest floor community. To simulate warming, we placed mesocosms of each treatment in ten open-top warming chambers ranging from 1.5° to 5.5°C above ambient at Harvard Forest, Massachusetts, USA. As expected, CO 2 emissions increased under warming and we found an interactive effect of predator presence and warming, although the effect was not consistent through time. The interaction between predator presence and warming was the inverse of our predictions: Mesocosms with predators had lower respiration at higher levels of warming than those without predators. Carbon dioxide emissions were not significantly associated with microbial biomass. Here, we did not find evidence of consumptive effects of predators on the invertebrate community, suggesting that predator presence mediates response of microbial respiration to warming through nonconsumptive means. In our system, we found a significant interaction between warming and predator presence that warrants further research into mechanism and

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

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.

Improving Ischemia Reperfusion Injury in Vascularized Composite Tissue Allotransplantation Via Histone Deacetylase Modulation

DTIC Science & Technology

2017-10-01

of the author(s) and should not be construed as an official Department of the Army position, policy or decision unless so designated by other...average 1 hour per response, including the time for reviewing instructions, searching existing data sources, gathering and maintaining the data needed...IRI) in scenarios relevant to limb transplantation using mouse models for experimentation. Limitations in tolerated ischemia times limits the scope

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

Inhibition of CD26/DPP IV attenuates ischemia/reperfusion injury in orthotopic mouse lung transplants: the pivotal role of vasoactive intestinal peptide.

PubMed

Jungraithmayr, Wolfgang; De Meester, Ingrid; Matheeussen, Veerle; Inci, Ilhan; Augustyns, Koen; Scharpé, Simon; Weder, Walter; Korom, Stephan

2010-04-01

The T cell activation Ag CD26/dipeptidylpeptidase IV (DPP IV) combines co-stimulatory and enzymatic properties. Catalytically, it functions as an exopeptidase, modulating biological activity of key chemokines and peptides. Here we investigated the effect of organ-specific inhibition of DPP IV catalytic activity on ischemia/reperfusion injury after extended ischemia in the mouse model of orthotopic single lung transplantation. C57BL/6 mice were syngeneically, transplanted, grafts were perfused and stored in Perfadex with (treated) or without (control) a DPP IV enzymatic activity inhibitor (AB192). Transplantation was performed after 18h cold ischemia time; following 2-h reperfusion, grafts were analyzed for oxygenation, thiobarbituric acid-reactive substances, histomorphology, and immunohistochemistry was performed for leukocyte Ag 6, myeloperoxidase, hemoxygenase 1, vasoactive intestinal protein (VIP), and real-time PCR for VIP. Treatment with the DPP IV inhibitor AB192 resulted in significant improvement of gas exchange, less lipid oxidation, preservation of parenchymal ultrastructure, reduced neutrophil infiltration, reduced myeloperoxidase expression, increased hemoxygenase 1 expression, pronounced expression of VIP in alveolar macrophages and increased mRNA expression of VIP. Inhibition of intragraft DPP IV catalytic activity with AB192 strikingly ameliorates ischemia/reperfusion injury after extended ischemia. Furthermore, preservation of endogenous intragraft VIP levels correlate with maintaining lung function and structural integrity. Copyright (c) 2009 Elsevier Inc. All rights reserved.

Research on trend of warm-humid climate in Central Asia

NASA Astrophysics Data System (ADS)

Gong, Zhi; Peng, Dailiang; Wen, Jingyi; Cai, Zhanqing; Wang, Tiantian; Hu, Yuekai; Ma, Yaxin; Xu, Junfeng

2017-07-01

Central Asia is a typical arid area, which is sensitive and vulnerable part of climate changes, at the same time, Central Asia is the Silk Road Economic Belt of the core district, the warm-humid climate change will affect the production and economic development of neighboring countries. The average annual precipitation, average anneal temperature and evapotranspiration are the important indexes to weigh the climate change. In this paper, the annual precipitation, annual average temperature and evapotranspiration data of every pixel point in Central Asia are analyzed by using long-time series remote sensing data to analyze the trend of warm and humid conditions. Finally, using the model to analyzed the distribution of warm-dry trend, the warm-wet trend, the cold-dry trend and the cold-wet trend in Central Asia and Xinjiang area. The results showed that most of the regions of Central Asia were warm-humid and warm-dry trends, but only a small number of regions showed warm-dry and cold-dry trends. It is of great significance to study the climatic change discipline and guarantee the ecological safety and improve the ability to cope with climate change in the region. It also provide scientific basis for the formulation of regional climate change program. The first section in your paper

[The relationship between ischemic preconditioning-induced infarction size limitation and duration of test myocardial ischemia].

PubMed

Blokhin, I O; Galagudza, M M; Vlasov, T D; Nifontov, E M; Petrishchev, N N

2008-07-01

Traditionally infarction size reduction by ischemic preconditioning is estimated in duration of test ischemia. This approach limits the understanding of real antiischemic efficacy of ischemic preconditioning. Present study was performed in the in vivo rat model of regional myocardial ischemia-reperfusion and showed that protective effect afforded by ischemic preconditioning progressively decreased with prolongation of test ischemia. There were no statistically significant differences in infarction size between control and preconditioned animals when the duration of test ischemia was increased up to 1 hour. Preconditioning ensured maximal infarction-limiting effect in duration of test ischemia varying from 20 to 40 minutes.

Eutrophication and Warming Boost Cyanobacterial Biomass and Microcystins.

PubMed

Lürling, Miquel; van Oosterhout, Frank; Faassen, Elisabeth

2017-02-11

Eutrophication and warming are key drivers of cyanobacterial blooms, but their combined effects on microcystin (MC) concentrations are less studied. We tested the hypothesis that warming promotes cyanobacterial abundance in a natural plankton community and that eutrophication enhances cyanobacterial biomass and MC concentrations. We incubated natural seston from a eutrophic pond under normal, high, and extreme temperatures (i.e., 20, 25, and 30 °C) with and without additional nutrients added (eutrophication) mimicking a pulse as could be expected from projected summer storms under climate change. Eutrophication increased algal- and cyanobacterial biomass by 26 and 8 times, respectively, and led to 24 times higher MC concentrations. This effect was augmented with higher temperatures leading to 45 times higher MC concentrations at 25 °C, with 11 times more cyanobacterial chlorophyll- a and 25 times more eukaryote algal chlorophyll- a . At 30 °C, MC concentrations were 42 times higher, with cyanobacterial chlorophyll- a being 17 times and eukaryote algal chlorophyll- a being 24 times higher. In contrast, warming alone did not yield more cyanobacteria or MCs, because the in situ community had already depleted the available nutrient pool. MC per potential MC producing cell declined at higher temperatures under nutrient enrichments, which was confirmed by a controlled experiment with two laboratory strains of Microcystis aeruginosa. Nevertheless, MC concentrations were much higher at the increased temperature and nutrient treatment than under warming alone due to strongly promoted biomass, lifting N-imitation and promotion of potential MC producers like Microcystis . This study exemplifies the vulnerability of eutrophic urban waters to predicted future summer climate change effects that might aggravate cyanobacterial nuisance.

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.

In Potential Stroke Patients on Warfarin, the International Normalized Ratio Predicts Ischemia.

PubMed

Cao, Cathy; Martinelli, Ashley; Spoelhof, Brian; Llinas, Rafael H; Marsh, Elisabeth B

2017-01-01

Stroke can occur in patients on warfarin despite anticoagulation. Patients with a low international normalized ratio (INR) should theoretically be at greater risk for ischemia than those who are therapeutic. Therefore, INR may be able to indicate whether new neurological deficits are more likely strokes or stroke mimics in patients on warfarin. This study evaluates the association and predictive value of INR in determining the likelihood of ischemia. Patients were identified using the acute stroke registry at a Primary Stroke Center from January 2013 through December 2014. All adult patients undergoing evaluation for acute stroke with prior documented use of warfarin and an INR level at presentation were included. Data were collected regarding patient demographics, medical comorbidities, stroke severity, reason for anticoagulation, and laboratory studies including INR. Student t tests and χ2 analysis were used to evaluate factors associated with increased likelihood of ischemia (stroke or transient ischemic attack) versus mimic. Significant results were entered into a multivariable regression analysis. Sensitivity and specificity analyses were conducted to determine the predictive value of INR for ischemic risk. 116 patients were included; 46 were diagnosed with ischemia, 70 were diagnosed as mimics. 75% of patients were on warfarin for atrial fibrillation versus 25% for venous thrombosis. A statistically significant difference in mean INR for patients with ischemia (n = 46) versus mimics (n = 70) was observed (1.7 vs. 2.8; p < 0.001). In multivariable analysis, both sub-therapeutic INR (p < 0.001) and atrial fibrillation (p = 0.014) were predictors of ischemia. In patients with an INR ≥2, the predictive value of having a non-ischemic etiology was 79%. No patient with an INR of ≥3.6 was found to have ischemia. Sub-therapeutic INR and atrial fibrillation are strongly associated with ischemia in patients on warfarin presenting with acute neurologic symptoms

Global brain ischemia and reperfusion.

PubMed

White, B C; Grossman, L I; O'Neil, B J; DeGracia, D J; Neumar, R W; Rafols, J A; Krause, G S

1996-05-01

Brain damage accompanying cardiac arrest and resuscitation is frequent and devastating. Neurons in the hippocampus CA1 and CA4 zones and cortical layers III and V are selectively vulnerable to death after injury by ischemia and reperfusion. Ultrastructural evidence indicates that most of the structural damage is associated with reperfusion, during which the vulnerable neurons develop disaggregation of polyribosomes, peroxidative damage to unsaturated fatty acids in the plasma membrane, and prominent alterations in the structure of the Golgi apparatus that is responsible for membrane assembly. Reperfusion is also associated with vulnerable neurons with prominent production of messenger RNAs for stress proteins and for the proteins of the activator protein-1 complex, but these vulnerable neurons fail to efficiently translate these messages into the proteins. The inhibition of protein synthesis during reperfusion involves alteration of translation initiation factors, specifically serine phosphorylation of the alpha-subunit of eukaryotic initiation factor-2 (elF-2 alpha). Growth factors--in particular, insulin--have the potential to reverse phosphorylation of elF-2 alpha, promote effective translation of the mRNA transcripts generated in response to ischemia and reperfusion, enhance neuronal defenses against radicals, and stimulate lipid synthesis and membrane repair. There is now substantial evidence that the insulin-class growth factors have neuron-sparing effects against damage by radicals and ischemia and reperfusion. This new knowledge may provide a fundamental basis for a rational approach to "cerebral resuscitation" that will allow substantial amelioration of the often dismal neurologic outcome now associated with resuscitation from cardiac arrest.

Southern Ocean warming due to human influence

NASA Astrophysics Data System (ADS)

Fyfe, John C.

2006-10-01

I show that the latest series of climate models reproduce the observed mid-depth Southern Ocean warming since the 1950s if they include time-varying changes in anthropogenic greenhouse gases, sulphate aerosols and volcanic aerosols in the Earth's atmosphere. The remarkable agreement between observations and state-of-the art climate models suggests significant human influence on Southern Ocean temperatures. I also show that climate models that do not include volcanic aerosols produce mid-depth Southern Ocean warming that is nearly double that produced by climate models that do include volcanic aerosols. This implies that the full effect of human-induced warming of the Southern Ocean may yet to be realized.

40 CFR Table A-1 to Subpart A of... - Global Warming Potentials

Code of Federal Regulations, 2013 CFR

2013-07-01

... 40 Protection of Environment 22 2013-07-01 2013-07-01 false Global Warming Potentials A Table A-1... A-1 to Subpart A of Part 98—Global Warming Potentials Global Warming Potentials [100-Year Time Horizon] Name CAS No. Chemical formula Global warming potential(100 yr.) Carbon dioxide 124-38-9 CO2 1...

40 CFR Table A-1 to Subpart A of... - Global Warming Potentials

Code of Federal Regulations, 2014 CFR

2014-07-01

... 40 Protection of Environment 21 2014-07-01 2014-07-01 false Global Warming Potentials A Table A-1... A-1 to Subpart A of Part 98—Global Warming Potentials Global Warming Potentials [100-Year Time Horizon] Name CAS No. Chemical formula Global warming potential(100 yr.) Carbon dioxide 124-38-9 CO2 1...

Global warming without global mean precipitation increase?

PubMed Central

Salzmann, Marc

2016-01-01

Global climate models simulate a robust increase of global mean precipitation of about 1.5 to 2% per kelvin surface warming in response to greenhouse gas (GHG) forcing. Here, it is shown that the sensitivity to aerosol cooling is robust as well, albeit roughly twice as large. This larger sensitivity is consistent with energy budget arguments. At the same time, it is still considerably lower than the 6.5 to 7% K−1 decrease of the water vapor concentration with cooling from anthropogenic aerosol because the water vapor radiative feedback lowers the hydrological sensitivity to anthropogenic forcings. When GHG and aerosol forcings are combined, the climate models with a realistic 20th century warming indicate that the global mean precipitation increase due to GHG warming has, until recently, been completely masked by aerosol drying. This explains the apparent lack of sensitivity of the global mean precipitation to the net global warming recently found in observations. As the importance of GHG warming increases in the future, a clear signal will emerge. PMID:27386558

Global warming without global mean precipitation increase?

PubMed

Salzmann, Marc

2016-06-01

Global climate models simulate a robust increase of global mean precipitation of about 1.5 to 2% per kelvin surface warming in response to greenhouse gas (GHG) forcing. Here, it is shown that the sensitivity to aerosol cooling is robust as well, albeit roughly twice as large. This larger sensitivity is consistent with energy budget arguments. At the same time, it is still considerably lower than the 6.5 to 7% K(-1) decrease of the water vapor concentration with cooling from anthropogenic aerosol because the water vapor radiative feedback lowers the hydrological sensitivity to anthropogenic forcings. When GHG and aerosol forcings are combined, the climate models with a realistic 20th century warming indicate that the global mean precipitation increase due to GHG warming has, until recently, been completely masked by aerosol drying. This explains the apparent lack of sensitivity of the global mean precipitation to the net global warming recently found in observations. As the importance of GHG warming increases in the future, a clear signal will emerge.

Anti-inflammatory effects of Chinese medicinal herbs on cerebral ischemia.

PubMed

Su, Shan-Yu; Hsieh, Ching-Liang

2011-07-09

Recent studies have demonstrated the importance of anti-inflammation, including cellular immunity, inflammatory mediators, reactive oxygen species, nitric oxide and several transcriptional factors, in the treatment of cerebral ischemia. This article reviews the roles of Chinese medicinal herbs as well as their ingredients in the inflammatory cascade induced by cerebral ischemia. Chinese medicinal herbs exert neuroprotective effects on cerebral ischemia. The effects include inhibiting the activation of microglia, decreasing levels of adhesion molecules such as intracellular adhesion molecule-1, attenuating expression of pro-inflammatory cytokines such as interleukin-1β and tumor necrosis factor-α, reducing inducible nitric oxide synthase and reactive oxygen species, and regulating transcription factors such as nuclear factor-κB.

Warming experiments underpredict plant phenological responses to climate change

USGS Publications Warehouse

Wolkovich, Elizabeth M.; Cook, Benjamin I.; Allen, Jenica M.; Crimmins, Theresa M.; Betancourt, Julio L.; Travers, Steven E.; Pau, Stephanie; Regetz, James; Davies, T. Jonathan; Kraft, Nathan J.B.; Ault, Toby R.; Bolmgren, Kjell; Mazer, Susan J.; McCabe, Gregory J.; McGill, Brian J.; Parmesan, Camille; Salamin, Nicolas; Schwartz, Mark D.; Cleland, Elsa E.

2012-01-01

Warming experiments are increasingly relied on to estimate plant responses to global climate change. For experiments to provide meaningful predictions of future responses, they should reflect the empirical record of responses to temperature variability and recent warming, including advances in the timing of flowering and leafing. We compared phenology (the timing of recurring life history events) in observational studies and warming experiments spanning four continents and 1,634 plant species using a common measure of temperature sensitivity (change in days per degree Celsius). We show that warming experiments underpredict advances in the timing of flowering and leafing by 8.5-fold and 4.0-fold, respectively, compared with long-term observations. For species that were common to both study types, the experimental results did not match the observational data in sign or magnitude. The observational data also showed that species that flower earliest in the spring have the highest temperature sensitivities, but this trend was not reflected in the experimental data. These significant mismatches seem to be unrelated to the study length or to the degree of manipulated warming in experiments. The discrepancy between experiments and observations, however, could arise from complex interactions among multiple drivers in the observational data, or it could arise from remediable artefacts in the experiments that result in lower irradiance and drier soils, thus dampening the phenological responses to manipulated warming. Our results introduce uncertainty into ecosystem models that are informed solely by experiments and suggest that responses to climate change that are predicted using such models should be re-evaluated.

Warming Experiments Underpredict Plant Phenological Responses to Climate Change

NASA Technical Reports Server (NTRS)

Wolkovich, E. M.; Cook, B. I.; Allen, J. M.; Crimmins, T. M.; Betancourt, J. L.; Travers, S. E.; Pau, S.; Regetz, J.; Davies, T. J.; Kraft, N. J. B.;

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.

Protective effect of extract of Cordyceps sinensis in middle cerebral artery occlusion-induced focal cerebral ischemia in rats

PubMed Central

2010-01-01

Background Ischemic hypoxic brain injury often causes irreversible brain damage. The lack of effective and widely applicable pharmacological treatments for ischemic stroke patients may explain a growing interest in traditional medicines. From the point of view of "self-medication" or "preventive medicine," Cordyceps sinensis was used in the prevention of cerebral ischemia in this paper. Methods The right middle cerebral artery occlusion model was used in the study. The effects of Cordyceps sinensis (Caterpillar fungus) extract on mortality rate, neurobehavior, grip strength, lactate dehydrogenase, glutathione content, Lipid Peroxidation, glutathione peroxidase activity, glutathione reductase activity, catalase activity, Na+K+ATPase activity and glutathione S transferase activity in a rat model were studied respectively. Results Cordyceps sinensis extract significantly improved the outcome in rats after cerebral ischemia and reperfusion in terms of neurobehavioral function. At the same time, supplementation of Cordyceps sinensis extract significantly boosted the defense mechanism against cerebral ischemia by increasing antioxidants activity related to lesion pathogenesis. Restoration of the antioxidant homeostasis in the brain after reperfusion may have helped the brain recover from ischemic injury. Conclusions These experimental results suggest that complement Cordyceps sinensis extract is protective after cerebral ischemia in specific way. The administration of Cordyceps sinensis extract significantly reduced focal cerebral ischemic/reperfusion injury. The defense mechanism against cerebral ischemia was by increasing antioxidants activity related to lesion pathogenesis. PMID:20955613

Protective effect of extract of Cordyceps sinensis in middle cerebral artery occlusion-induced focal cerebral ischemia in rats.

PubMed

Liu, Zhenquan; Li, Pengtao; Zhao, Dan; Tang, Huiling; Guo, Jianyou

2010-10-19

Ischemic hypoxic brain injury often causes irreversible brain damage. The lack of effective and widely applicable pharmacological treatments for ischemic stroke patients may explain a growing interest in traditional medicines. From the point of view of "self-medication" or "preventive medicine," Cordyceps sinensis was used in the prevention of cerebral ischemia in this paper. The right middle cerebral artery occlusion model was used in the study. The effects of Cordyceps sinensis (Caterpillar fungus) extract on mortality rate, neurobehavior, grip strength, lactate dehydrogenase, glutathione content, Lipid Peroxidation, glutathione peroxidase activity, glutathione reductase activity, catalase activity, Na+K+ATPase activity and glutathione S transferase activity in a rat model were studied respectively. Cordyceps sinensis extract significantly improved the outcome in rats after cerebral ischemia and reperfusion in terms of neurobehavioral function. At the same time, supplementation of Cordyceps sinensis extract significantly boosted the defense mechanism against cerebral ischemia by increasing antioxidants activity related to lesion pathogenesis. Restoration of the antioxidant homeostasis in the brain after reperfusion may have helped the brain recover from ischemic injury. These experimental results suggest that complement Cordyceps sinensis extract is protective after cerebral ischemia in specific way. The administration of Cordyceps sinensis extract significantly reduced focal cerebral ischemic/reperfusion injury. The defense mechanism against cerebral ischemia was by increasing antioxidants activity related to lesion pathogenesis.

Asymmetric effects of daytime and night-time warming on Northern Hemisphere vegetation.

PubMed

Peng, Shushi; Piao, Shilong; Ciais, Philippe; Myneni, Ranga B; Chen, Anping; Chevallier, Frédéric; Dolman, Albertus J; Janssens, Ivan A; Peñuelas, Josep; Zhang, Gengxin; Vicca, Sara; Wan, Shiqiang; Wang, Shiping; Zeng, Hui

2013-09-05

Temperature data over the past five decades show faster warming of the global land surface during the night than during the day. This asymmetric warming is expected to affect carbon assimilation and consumption in plants, because photosynthesis in most plants occurs during daytime and is more sensitive to the maximum daily temperature, Tmax, whereas plant respiration occurs throughout the day and is therefore influenced by both Tmax and the minimum daily temperature, Tmin. Most studies of the response of terrestrial ecosystems to climate warming, however, ignore this asymmetric forcing effect on vegetation growth and carbon dioxide (CO2) fluxes. Here we analyse the interannual covariations of the satellite-derived normalized difference vegetation index (NDVI, an indicator of vegetation greenness) with Tmax and Tmin over the Northern Hemisphere. After removing the correlation between Tmax and Tmin, we find that the partial correlation between Tmax and NDVI is positive in most wet and cool ecosystems over boreal regions, but negative in dry temperate regions. In contrast, the partial correlation between Tmin and NDVI is negative in boreal regions, and exhibits a more complex behaviour in dry temperate regions. We detect similar patterns in terrestrial net CO2 exchange maps obtained from a global atmospheric inversion model. Additional analysis of the long-term atmospheric CO2 concentration record of the station Point Barrow in Alaska suggests that the peak-to-peak amplitude of CO2 increased by 23 ± 11% for a +1 °C anomaly in Tmax from May to September over lands north of 51° N, but decreased by 28 ± 14% for a +1 °C anomaly in Tmin. These lines of evidence suggest that asymmetric diurnal warming, a process that is currently not taken into account in many global carbon cycle models, leads to a divergent response of Northern Hemisphere vegetation growth and carbon sequestration to rising temperatures.

Root and Shoot Phenology May Respond Differently to Warming

NASA Astrophysics Data System (ADS)

Radville, L.; Eissenstat, D. M.; Post, E.

2015-12-01

Climate change is increasing temperatures and extending the growing season for many organisms. Shifts in phenology have been widely reported in response to global warming and have strong effects on ecosystem processes and greenhouse gas emissions. It is well understood that warming generally advances aboveground plant phenology, but the influence of temperature on root phenology is unclear. Most terrestrial biosphere models assume that root and shoot growth occur at the same time and are influenced by warming in the same way, but recent studies suggest that this may not be the case. Testing this assumption is particularly important in the Arctic where over 70% of plant biomass can be belowground and warming is happening faster than in other ecosystems. In 2013 and 2014 we examined the timing of root growth in the Arctic in plots that had been warmed or unwarmed for 10 years. We found that peak root growth occurred about one month before leaf growth, suggesting that spring root phenology is not controlled by carbon produced during spring photosynthesis. If root phenology is not controlled by photosynthate early in the season, earlier spring leaf growth may not cause earlier spring root growth. In support of this, we found that warming advanced spring leaf cover but did not significantly affect root phenology. Root growth was not significantly correlated with soil temperature and did not appear to be limited by near-freezing temperatures above the permafrost. These results suggest that although shoots are influenced by temperature, roots in this system may be more influenced by photosynthesis and carbon storage. Aboveground phenology, one of the most widely measured aspects of climate change, may not represent whole-plant phenology and may be a poor indicator of the timing of whole-plant carbon fluxes. Additionally, climate model assumptions that roots and shoots grow at the same time may need to be revised.

Ischemia-reperfusion of human skeletal muscle during aortoiliac surgery: effects of acetylcarnitine.

PubMed

Adembri, C; Domenici, L L; Formigli, L; Brunelleschi, S; Ferrari, E; Novelli, G P

1994-10-01

Our previous study on human skeletal muscle undergoing ischemia and reperfusion has revealed that granulocytes, which infiltrate the muscle tissue in large numbers, play an important role in mediating fibre injuries by producing superoxide anion (O2-) which is responsible for membrane lipid peroxidation. In the current study, five patients undergoing aortic reconstructive surgery were given acetyl-carnitine (2 mg/kg i.v. plus 1 mg/kg/min for 30 min) prior to the induction of ischemia. Muscle biopsies and blood samples were examined: a) after anaesthesia; b) at the end of ischemia; and c) 30 min after reperfusion, with the aim of elucidating whether acetylcarnitine could prevent the infiltration and/or the activation of granulocytes and eventually skeletal muscle injuries. During ischemia and reperfusion complement activation recruited numerous granulocytes into the muscle tissue, but, contrary to the untreated samples, the ability for O2(-)-generation of these cells remained at low levels and was comparable to that of ischemia even when molecular O2 was reintroduced to the tissue. Accordingly, the morphological changes of the postischemic muscle fibers were substantially reduced when compared to the untreated samples; in fact, the mitochondrial swelling was only moderate and the intramitochondrial dense bodies were small and scarce. The current findings support a positive role of acetyl-carnitine in ameliorating the ischemia-reperfusion (I-R)-induced damage of human skeletal muscle.

Activation of Chymotrypsin-Like Activity of the Proteasome during Ischemia Induces Myocardial Dysfunction and Death.

PubMed

Sanchez, Gina; Berrios, Daniela; Olmedo, Ivonne; Pezoa, Javier; Riquelme, Jaime A; Montecinos, Luis; Pedrozo, Zully; Donoso, Paulina

2016-01-01

Inhibitors of the ubiquitin-proteasome system improve hemodynamic parameters and decrease the infarct size after ischemia reperfusion. The molecular basis of this protection is not fully understood since most available data report inhibition of the 26 proteasome after ischemia reperfusion. The decrease in cellular ATP levels during ischemia leads to the dissociation of the 26S proteasome into the 19S regulatory complex and the 20S catalytic core, which results in protein degradation independently of ubiquitination. There is scarce information on the activity of the 20S proteasome during cardiac ischemia. Accordingly, the aim of this work was to determine the effects of 30 minutes of ischemia, or 30 min of ischemia followed by 60 minutes of reperfusion on the three main peptidase activities of the 20S proteasome in Langendorff perfused rat hearts. We found that 30 min of ischemia produced a significant increase in the chymotrypsin-like activity of the proteasome, without changes in its caspase-like or trypsin-like activities. In contrast, all three activities were decreased upon reperfusion. Ixazomib, perfused before ischemia at a concentration that reduced the chymotrypsin-like activity to 50% of the control values, without affecting the other proteasomal activities, improved the hemodynamic parameters upon reperfusion and decreased the infarct size. Ixazomib also prevented the 50% reduction in RyR2 content observed after ischemia. The protection was lost, however, when simultaneous inhibition of chymotrypsin-like and caspase-like activities of the proteasome was achieved at higher concentration of ixazomib. Our results suggest that selective inhibition of chymotrypsin-like activity of the proteasome during ischemia preserves key proteins for cardiomyocyte function and exerts a positive impact on cardiac performance after reperfusion.

Could cirrus clouds have warmed early Mars?

NASA Astrophysics Data System (ADS)

Ramirez, Ramses M.; Kasting, James F.

2017-01-01

The presence of the ancient valley networks on Mars indicates that the climate at 3.8 Ga was warm enough to allow substantial liquid water to flow on the martian surface for extended periods of time. However, the mechanism for producing this warming continues to be debated. One hypothesis is that Mars could have been kept warm by global cirrus cloud decks in a CO2sbnd H2O atmosphere containing at least 0.25 bar of CO2 (Urata and Toon, 2013). Initial warming from some other process, e.g., impacts, would be required to make this model work. Those results were generated using the CAM 3-D global climate model. Here, we use a single-column radioactive-convective climate model to further investigate the cirrus cloud warming hypothesis. Our calculations indicate that cirrus cloud decks could have produced global mean surface temperatures above freezing, but only if cirrus cloud cover approaches ∼75 - 100% and if other cloud properties (e.g., height, optical depth, particle size) are chosen favorably. However, at more realistic cirrus cloud fractions, or if cloud parameters are not optimal, cirrus clouds do not provide the necessary warming, suggesting that other greenhouse mechanisms are needed.

Hydrogen Sulfide Preconditioning Protects Rat Liver against Ischemia/Reperfusion Injury by Activating Akt-GSK-3β Signaling and Inhibiting Mitochondrial Permeability Transition

PubMed Central

Zhang, Hao; Xu, Fengying; Zou, Zui; Liu, Meng; Wang, Quanxing; Miao, Mingyong; Shi, Xueyin

2013-01-01

Hydrogen sulfide (H2S) is the third most common endogenously produced gaseous signaling molecule, but its impact on hepatic ischemia/reperfusion (I/R) injury, especially on mitochondrial function, remains unclear. In this study, rats were randomized into Sham, I/R, ischemia preconditioning (IPC) or sodium hydrosulfide (NaHS, an H2S donor) preconditioning groups. To establish a model of segmental (70%) warm hepatic ischemia, the hepatic artery, left portal vein and median liver lobes were occluded for 60 min and then unclamped to allow reperfusion. Preconditioning with 12.5, 25 or 50 μmol/kg NaHS prior to the I/R insult significantly increased serum H2S levels, and, similar to IPC, NaHS preconditioning decreased alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels in the plasma and prevented hepatocytes from undergoing I/R-induced necrosis. Moreover, a sub-toxic dose of NaHS (25 μmol/kg) did not disrupt the systemic hemodynamics but dramatically inhibited mitochondrial permeability transition pore (MPTP) opening and thus prevented mitochondrial-related cell death and apoptosis. Mechanistic studies revealed that NaHS preconditioning markedly increased the expression of phosphorylated protein kinase B (p-Akt), phosphorylated glycogen synthase kinase-3 beta (p-GSK-3β) and B-cell lymphoma-2 (Bcl-2) and decreased the release of mitochondrial cytochrome c and cleaved caspase-3/9 levels. Therefore, NaHS administration prior to hepatic I/R ameliorates mitochondrial and hepatocellular damage through the inhibition of MPTP opening and the activation of Akt-GSK-3β signaling. Furthermore, this study provides experimental evidence for the clinical use of H2S to reduce liver damage after perioperative I/R injury. PMID:24058562

Desert hedgehog promotes ischemia-induced angiogenesis by ensuring peripheral nerve survival.

PubMed

Renault, Marie-Ange; Chapouly, Candice; Yao, Qinyu; Larrieu-Lahargue, Frédéric; Vandierdonck, Soizic; Reynaud, Annabel; Petit, Myriam; Jaspard-Vinassa, Béatrice; Belloc, Isabelle; Traiffort, Elisabeth; Ruat, Martial; Duplàa, Cécile; Couffinhal, Thierry; Desgranges, Claude; Gadeau, Alain-Pierre

2013-03-01

Blood vessel growth and patterning have been shown to be regulated by nerve-derived signals. Desert hedgehog (Dhh), one of the Hedgehog family members, is expressed by Schwann cells of peripheral nerves. The purpose of this study was to investigate the contribution of Dhh to angiogenesis in the setting of ischemia. We induced hindlimb ischemia in wild-type and Dhh(-/-) mice. First, we found that limb perfusion is significantly impaired in the absence of Dhh. This effect is associated with a significant decrease in capillary and artery density in Dhh(-/-). By using mice in which the Hedgehog signaling pathway effector Smoothened was specifically invalidated in endothelial cells, we demonstrated that Dhh does not promote angiogenesis by a direct activation of endothelial cells. On the contrary, we found that Dhh promotes peripheral nerve survival in the ischemic muscle and, by doing so, maintains the pool of nerve-derived proangiogenic factors. Consistently, we found that denervation of the leg, immediately after the onset of ischemia, severely impairs ischemia-induced angiogenesis and decreases expression of vascular endothelial growth factor A, angiopoietin 1, and neurotrophin 3 in the ischemic muscle. This study demonstrates the crucial roles of nerves and factors regulating nerve physiology in the setting of ischemia-induced angiogenesis.

Soil warming, carbon–nitrogen interactions, and forest carbon budgets

PubMed Central

Melillo, Jerry M.; Butler, Sarah; Johnson, Jennifer; Mohan, Jacqueline; Steudler, Paul; Lux, Heidi; Burrows, Elizabeth; Bowles, Francis; Smith, Rose; Scott, Lindsay; Vario, Chelsea; Hill, Troy; Burton, Andrew; Zhou, Yu-Mei; Tang, Jim

2011-01-01

Soil warming has the potential to alter both soil and plant processes that affect carbon storage in forest ecosystems. We have quantified these effects in a large, long-term (7-y) soil-warming study in a deciduous forest in New England. Soil warming has resulted in carbon losses from the soil and stimulated carbon gains in the woody tissue of trees. The warming-enhanced decay of soil organic matter also released enough additional inorganic nitrogen into the soil solution to support the observed increases in plant carbon storage. Although soil warming has resulted in a cumulative net loss of carbon from a New England forest relative to a control area over the 7-y study, the annual net losses generally decreased over time as plant carbon storage increased. In the seventh year, warming-induced soil carbon losses were almost totally compensated for by plant carbon gains in response to warming. We attribute the plant gains primarily to warming-induced increases in nitrogen availability. This study underscores the importance of incorporating carbon–nitrogen interactions in atmosphere–ocean–land earth system models to accurately simulate land feedbacks to the climate system. PMID:21606374

Exploring the pattern of blood donor beliefs in first-time, novice, and experienced donors: differentiating reluctant altruism, pure altruism, impure altruism, and warm glow.

PubMed

Ferguson, Eamonn; Atsma, Femke; de Kort, Wim; Veldhuizen, Ingrid

2012-02-01

Using constructs from the Theory of Planned Behavior and theories of altruism, this article explores how multiple motivations and beliefs for blood donation are clustered and change across the donor career. In so doing important distinctions, for blood donation, between impure altruism, pure altruism, and warm glow are explored. Measures of intentions, cognitive and affective attitudes, role merger, pure altruism, trust, self-efficacy, subjective and moral norms, and habit formation were assessed in a sample of 12,580 whole blood donors. Analyses showed that a distinction between first-time, novice (one to four donations), and experienced donors (five or more donations) is justified. Principal components analysis and confirmatory factor analytic Multiple-Indicator Multiple-Causal models were used to compare models across these groups. A cognition-behavior (CB) factor, including intentions, was common to all groups. First-time and novice donors were marked by a newly identified motivational factor: "reluctant altruism" (i.e., the motivation to donate because of a lack of trust in others). First-time donors exhibited an impure altruism factor whereas for experienced donors warm glow and pure altruism factors were observed. For first-time donors impure altruism and reluctant altruism were both associated with the CB factor in females and impure altruism only in males. For both sexes reluctant altruism was associated of the CB factor in novice donors and warm glow and pure altruism for experienced donors. New avenues for intervention are suggested by the emergence of reluctant altruism for novice donors and warm glow for experienced donors. The importance of distinguishing aspects of altruism is highlighted. © 2012 American Association of Blood Banks.

Late calcium EDTA rescues hippocampal CA1 neurons from global ischemia-induced death.

PubMed

Calderone, Agata; Jover, Teresa; Mashiko, Toshihiro; Noh, Kyung-min; Tanaka, Hidenobu; Bennett, Michael V L; Zukin, R Suzanne

2004-11-03

Transient global ischemia induces a delayed rise in intracellular Zn2+, which may be mediated via glutamate receptor 2 (GluR2)-lacking AMPA receptors (AMPARs), and selective, delayed death of hippocampal CA1 neurons. The molecular mechanisms underlying Zn2+ toxicity in vivo are not well delineated. Here we show the striking finding that intraventricular injection of the high-affinity Zn2+ chelator calcium EDTA (CaEDTA) at 30 min before ischemia (early CaEDTA) or at 48-60 hr (late CaEDTA), but not 3-6 hr, after ischemia, afforded robust protection of CA1 neurons in approximately 50% (late CaEDTA) to 75% (early CaEDTA) of animals. We also show that Zn2+ acts via temporally distinct mechanisms to promote neuronal death. Early CaEDTA attenuated ischemia-induced GluR2 mRNA and protein downregulation (and, by inference, formation of Zn2+-permeable AMPARs), the delayed rise in Zn2+, and neuronal death. These findings suggest that Zn2+ acts at step(s) upstream from GluR2 gene downregulation and implicate Zn2+ in transcriptional regulation and/or GluR2 mRNA stability. Early CaEDTA also blocked mitochondrial release of cytochrome c and Smac/DIABLO (second mitochondria-derived activator of caspases/direct inhibitor of apoptosis protein-binding protein with low pI), caspase-3 activity (but not procaspase-3 cleavage), p75NTR induction, and DNA fragmentation. These findings indicate that CaEDTA preserves the functional integrity of the mitochondrial outer membrane and arrests the caspase death cascade. Late injection of CaEDTA at a time when GluR2 is downregulated and caspase is activated inhibited the delayed rise in Zn2+, p75NTR induction, DNA fragmentation, and cell death. The finding of neuroprotection by late CaEDTA administration has striking implications for intervention in the delayed neuronal death associated with global ischemia.

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.

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

Combined metabolic and transcriptional profiling identifies pentose phosphate pathway activation by HSP27 phosphorylation during cerebral ischemia.

PubMed

Imahori, Taichiro; Hosoda, Kohkichi; Nakai, Tomoaki; Yamamoto, Yusuke; Irino, Yasuhiro; Shinohara, Masakazu; Sato, Naoko; Sasayama, Takashi; Tanaka, Kazuhiro; Nagashima, Hiroaki; Kohta, Masaaki; Kohmura, Eiji

2017-05-04

The metabolic pathophysiology underlying ischemic stroke remains poorly understood. To gain insight into these mechanisms, we performed a comparative metabolic and transcriptional analysis of the effects of cerebral ischemia on the metabolism of the cerebral cortex using middle cerebral artery occlusion (MCAO) rat model. Metabolic profiling by gas-chromatography/mass-spectrometry analysis showed clear separation between the ischemia and control group. The decreases of fructose 6-phosphate and ribulose 5-phosphate suggested enhancement of the pentose phosphate pathway (PPP) during cerebral ischemia (120-min MCAO) without reperfusion. Transcriptional profiling by microarray hybridization indicated that the Toll-like receptor and mitogen-activated protein kinase (MAPK) signaling pathways were upregulated during cerebral ischemia without reperfusion. In relation to the PPP, upregulation of heat shock protein 27 (HSP27) was observed in the MAPK signaling pathway and was confirmed through real-time polymerase chain reaction. Immunoblotting showed a slight increase in HSP27 protein expression and a marked increase in HSP27 phosphorylation at serine 85 after 60-min and 120-min MCAO without reperfusion. Corresponding upregulation of glucose 6-phosphate dehydrogenase (G6PD) activity and an increase in the NADPH/NAD + ratio were also observed after 120-min MCAO. Furthermore, intracerebroventricular injection of ataxia telangiectasia mutated (ATM) kinase inhibitor (KU-55933) significantly reduced HSP27 phosphorylation and G6PD upregulation after MCAO, but that of protein kinase D inhibitor (CID755673) did not affect HSP27 phosphorylation. Consequently, G6PD activation via ischemia-induced HSP27 phosphorylation by ATM kinase may be part of an endogenous antioxidant defense neuroprotection mechanism during the earliest stages of ischemia. These findings have important therapeutic implications for the treatment of stroke. Copyright © 2017 IBRO. Published by Elsevier Ltd. All

Teaching Global Warming

NASA Astrophysics Data System (ADS)

Hobson, Art

2004-05-01

Every citizen's education should include socially relevant science courses because, as the American Association for the Advancement of Science puts it, "Without a scientifically literate population, the outlook for a better world is not promising." I have developed a conceptual liberal-arts physics course that covers the major principles of classical physics, emphasizes modern/contemporary physics, and includes societal topics such as global warming, ozone depletion, transportation, exponential growth, scientific methodology, risk assessment, nuclear weapons, nuclear power, and the energy future. The societal topics, occupying only about 15% of the class time, appear to be the main cause of the surprising popularity of this course among non-scientists. I will outline some ideas for incorporating global warming into such a course or into any other introductory physics course. For further details, see my textbook Physics: Concepts and Connections (Prentice Hall, 3rd edition 2003).

Warm-up Practices in Elite Boxing Athletes: Impact on Power Output.

PubMed

Cunniffe, Brian; Ellison, Mark; Loosemore, Mike; Cardinale, Marco

2017-01-01

Cunniffe, B, Ellison, M, Loosemore, M, and Cardinale, M. Warm-up practices in elite boxing athletes: Iimpact on power output. J Strength Cond Res 31(1): 95-105, 2017-This study evaluated the performance impact of routine warm-up strategies in elite Olympic amateur boxing athletes and physiological implications of the time gap (GAP) between warm-up and boxing activity. Six male boxers were assessed while performing standardized prefight warm-up routines. Core and skin temperature measurements (Tcore and Tskin), heart rate, and upper- and lower-body power output (PO) were assessed before and after warm-up, during a 25-minutes GAP and after 3 × 2 minutes rounds of sparring. Reflected temperature (Tc) was also determined using high-resolution thermal images at fixed time-points to explore avenues for heat loss. Despite individual differences in warm-up duration (range 7.4-18.5 minutes), increases in Tcore and Tskin occurred (p ≤ 0.05). Corresponding increases (4.8%; p ≤ 0.05) in countermovement jump (CMJ) height and upward-rightward shifts in upper-body force-velocity and power-velocity curves were observed. Athletes remained inactive during the 25-minutes GAP with a gradual and significant increase in Tc occurring by the end of GAP suggesting the likelihood of heat loss. Decreases in CMJ height and upper-body PO were observed after 15 minutes and 25 minutes GAP (p ≤ 0.05). By the end of GAP period, all performance variables had returned to pre-warm-up values. Results suggest routine warm-ups undertaken by elite boxers have acute effects on power-generating capacity. Gradual decreases in performance variables are evident with inactivity and seem related to alterations in body temperature. Considering the constraints of major competitions and time spent in air conditioned holding areas before fights, practitioners should be aware of the potential of nullifying the warm-up effects.

Local warming: daily temperature change influences belief in global warming.

PubMed

Li, Ye; Johnson, Eric J; Zaval, Lisa

2011-04-01

Although people are quite aware of global warming, their beliefs about it may be malleable; specifically, their beliefs may be constructed in response to questions about global warming. Beliefs may reflect irrelevant but salient information, such as the current day's temperature. This replacement of a more complex, less easily accessed judgment with a simple, more accessible one is known as attribute substitution. In three studies, we asked residents of the United States and Australia to report their opinions about global warming and whether the temperature on the day of the study was warmer or cooler than usual. Respondents who thought that day was warmer than usual believed more in and had greater concern about global warming than did respondents who thought that day was colder than usual. They also donated more money to a global-warming charity if they thought that day seemed warmer than usual. We used instrumental variable regression to rule out some alternative explanations.

Activation of Chymotrypsin-Like Activity of the Proteasome during Ischemia Induces Myocardial Dysfunction and Death

PubMed Central

Sanchez, Gina; Berrios, Daniela; Olmedo, Ivonne; Pezoa, Javier; Riquelme, Jaime A.; Montecinos, Luis; Pedrozo, Zully; Donoso, Paulina

2016-01-01

Inhibitors of the ubiquitin-proteasome system improve hemodynamic parameters and decrease the infarct size after ischemia reperfusion. The molecular basis of this protection is not fully understood since most available data report inhibition of the 26 proteasome after ischemia reperfusion. The decrease in cellular ATP levels during ischemia leads to the dissociation of the 26S proteasome into the 19S regulatory complex and the 20S catalytic core, which results in protein degradation independently of ubiquitination. There is scarce information on the activity of the 20S proteasome during cardiac ischemia. Accordingly, the aim of this work was to determine the effects of 30 minutes of ischemia, or 30 min of ischemia followed by 60 minutes of reperfusion on the three main peptidase activities of the 20S proteasome in Langendorff perfused rat hearts. We found that 30 min of ischemia produced a significant increase in the chymotrypsin-like activity of the proteasome, without changes in its caspase-like or trypsin-like activities. In contrast, all three activities were decreased upon reperfusion. Ixazomib, perfused before ischemia at a concentration that reduced the chymotrypsin-like activity to 50% of the control values, without affecting the other proteasomal activities, improved the hemodynamic parameters upon reperfusion and decreased the infarct size. Ixazomib also prevented the 50% reduction in RyR2 content observed after ischemia. The protection was lost, however, when simultaneous inhibition of chymotrypsin-like and caspase-like activities of the proteasome was achieved at higher concentration of ixazomib. Our results suggest that selective inhibition of chymotrypsin-like activity of the proteasome during ischemia preserves key proteins for cardiomyocyte function and exerts a positive impact on cardiac performance after reperfusion. PMID:27529620

Detection of exercise-induced myocardial ischemia from symptomatology experienced during testing in men and women

PubMed Central

D’Antono, Bianca; Dupuis, Gilles; Fortin, Christophe; Arsenault, André; Burelle, Denis

2006-01-01

BACKGROUND AND OBJECTIVES To examine the capacity of angina and related symptoms experienced during exercise-stress testing to detect the presence of ischemia, controlling for other clinical factors. METHOD The authors undertook a prospective study of 482 women and 425 men (mean age 58 years) undergoing exercise stress testing with myocardial perfusion imaging. One hundred forty-six women and 127 men reported chest pain, and of these, 25% of women and 66% of men had myocardial perfusion imaging evidence of ischemia during testing. The present article focuses on patients with chest pain during testing. MAIN OUTCOME MEASURES Outcome measures included chest pain localization, extension, intensity and quality, as well as the presence of various nonpain-related symptoms. Backward logistical regression analyses were performed separately on men and women who had experienced chest pain during testing. RESULTS Men who described their chest pain as ‘heavy’ were 4.6 times more likely to experience ischemia during testing (P=0.039) compared with other men, but this pain descriptor only slightly improved accuracy of prediction beyond that provided by control variables. In women, several symptoms added to the sensitivity of the prediction, such as a numb feeling in the face or neck region (OR 4.5; P=0.048), a numb feeling in the chest area (OR 14.6; P=0.003), muscle tension (OR 5.2; P=0.013), and chest pain that was described as hot or burning (OR 4.3; P=0.014). CONCLUSIONS A more refined evaluation of symptoms experienced during testing was particularly helpful in improving detection of ischemia in women, but not in men. Attention to these symptoms may favour timely diagnosis of myocardial perfusion defects in women. PMID:16639477

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 Cardiovascular Risk in the Prediction and Timing of Cardiac Events After Exercise Echocardiogram Testing Without Ischemia.

PubMed

Velasco Del Castillo, Sonia; Antón Ladislao, Ane; Gómez Sánchez, Verónica; Onaindia Gandarias, José Juan; Cacicedo Fernández de Bobadilla, Ángela; Rodríguez Sánchez, Ibon; Laraudogoitia Zaldumbide, Eva

2017-09-01

There have been no analyses of the influence of cardiovascular risk as a predictor of events in patients with exercise echocardiography (EE) without ischemia. Our objective was to determine the predictors of cardiac events, paying special attention to cardiovascular risk. This study included 1640 patients with EE without ischemia. Of these, there were 1206 with no previously known coronary artery disease (CAD), whose risk of a fatal cardiovascular disease event was estimated according to the European SCORE (Systematic COronary Risk Evaluation) risk assessment system, and 434 with known CAD. The primary endpoint was cardiac event-free survival (EFS) (cardiac death, nonfatal acute coronary syndrome, and coronary revascularization). After a median follow-up of 35 [23-54] months, no differences were found in cardiac EFS between patients with a SCORE ≥ 10 or diabetes and patients with previous CAD (89.8% vs 87.1%). In the first year, cardiac EFS was high in all groups (99.4% if SCORE < 5; 100% if 5-9; 98% if ≥ 10 or diabetes and 97% in patients with CAD). In the third year, cardiac EFS was similar in the group with SCORE ≥ 10 or diabetes (94.5%) and patients with CAD (91.1%, P = NS). In these patients, the annualized event rate was 2.8% and 2.55%, respectively, and was significantly higher than in groups with SCORE < 5 (0.6%) and SCORE 5-9 (0.12%). The most frequent events were non-ST-segment elevation acute coronary syndrome and late revascularization. Predictors of cardiac events were previous CAD, SCORE ≥ 10 or diabetes mellitus, creatinine clearance, left ventricular ejection fraction, and chest pain during EE. Initial outcome after an EE without ischemia is favorable but is subsequently modulated by cardiovascular risk. Copyright © 2016 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.

Substance P induces cardioprotection in ischemia-reperfusion via activation of AKT.

PubMed

Jubair, Shaiban; Li, Jianping; Dehlin, Heather M; Manteufel, Edward J; Goldspink, Paul H; Levick, Scott P; Janicki, Joseph S

2015-08-15

Accumulating evidence indicates that substance P is cardioprotective following ischemia-reperfusion primarily due to its potent coronary vasodilator actions. However, an anti-apoptotic effect of substance P has been observed in tenocytes following ischemia, which involved activation of the AKT pathway. This suggests the possibility that substance P also provides cardioprotection via direct actions to activate AKT in myocardial cells. The purpose of this study was to test the hypothesis that substance P attenuates ischemia-related cell death via direct effects on myocardial cells by activating cell survival pathways. Seven-week-old male Sprague-Dawley rats, anesthetized with intraperitoneal pentobarbital sodium (100 mg/kg), were used. The ability of substance P to prevent cellular damage was assessed following ischemia-reperfusion in an isolated heart preparation and in short-term hypoxia without reperfusion using a left ventricular tissue slice culture preparation. In addition, the NK-1 receptor and AKT involvement was assessed using the NK-1 receptor antagonist L732138 and the AKT inhibitor LY294002. The results indicate that substance P reduced the ischemia-related release of lactate dehydrogenase in both preparations and the degree of apoptosis and necrosis in the hypoxic left ventricular slices, indicating its ability to attenuate cell damage; and induced AKT phosphorylation, with both the AKT inhibitor and NK-1 receptor antagonist preventing the increased phosphorylation of AKT and the ability of substance P to attenuate hypoxic cellular damage. It is concluded that substance P reduces ischemia/hypoxia-induced myocardial cell death by acting directly on cardiac cells to initiate cell survival pathways via the NK-1 receptor and AKT. Copyright © 2015 the American Physiological Society.

Substance P induces cardioprotection in ischemia-reperfusion via activation of AKT

PubMed Central

Jubair, Shaiban; Li, Jianping; Dehlin, Heather M.; Manteufel, Edward J.; Goldspink, Paul H.; Levick, Scott P.

2015-01-01

Accumulating evidence indicates that substance P is cardioprotective following ischemia-reperfusion primarily due to its potent coronary vasodilator actions. However, an anti-apoptotic effect of substance P has been observed in tenocytes following ischemia, which involved activation of the AKT pathway. This suggests the possibility that substance P also provides cardioprotection via direct actions to activate AKT in myocardial cells. The purpose of this study was to test the hypothesis that substance P attenuates ischemia-related cell death via direct effects on myocardial cells by activating cell survival pathways. Seven-week-old male Sprague-Dawley rats, anesthetized with intraperitoneal pentobarbital sodium (100 mg/kg), were used. The ability of substance P to prevent cellular damage was assessed following ischemia-reperfusion in an isolated heart preparation and in short-term hypoxia without reperfusion using a left ventricular tissue slice culture preparation. In addition, the NK-1 receptor and AKT involvement was assessed using the NK-1 receptor antagonist L732138 and the AKT inhibitor LY294002. The results indicate that substance P reduced the ischemia-related release of lactate dehydrogenase in both preparations and the degree of apoptosis and necrosis in the hypoxic left ventricular slices, indicating its ability to attenuate cell damage; and induced AKT phosphorylation, with both the AKT inhibitor and NK-1 receptor antagonist preventing the increased phosphorylation of AKT and the ability of substance P to attenuate hypoxic cellular damage. It is concluded that substance P reduces ischemia/hypoxia-induced myocardial cell death by acting directly on cardiac cells to initiate cell survival pathways via the NK-1 receptor and AKT. PMID:26071541

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

Effects of vinpocetine and ozagrel on behavioral recovery of rats after global brain ischemia.

PubMed

Jincai, Wang; Tingfang, Dong; Yongheng, Zhang; Zhongmin, Lu; Kaihua, Zhai; Xiaohong, Liu

2014-04-01

Brain ischemia leads to severe disruption of the nervous system and recovery is often prolonged. Rehabilitative post-ischemia pharmacological treatment may therefore be important for behavioral recovery, especially for cognition and motor behavior. The present study investigated the effects of combined vinpocetine and ozagrel administration on the behavioral recovery of rats from global brain ischemia. The results suggest that the combined treatment leads to significantly better improvement compared to single drug administration. We conclude that the combined use of vinpocetine and ozagrel may provide beneficial effects to patients suffering from brain ischemia. Copyright © 2013 Elsevier Ltd. All rights reserved.

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.

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

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

Energy Drinks and Myocardial Ischemia: A Review of Case Reports.

PubMed

Lippi, Giuseppe; Cervellin, Gianfranco; Sanchis-Gomar, Fabian

2016-07-01

The use and abuse of energy drinks (EDs) is constantly increasing worldwide. We performed a systematic search in Medline, Scopus and Web of Science to identify evidence about the potential link between these beverages and myocardial ischemia. Overall, 8 case reports could be detected, all of which described a realistic association between large intake of EDs and episodes of myocardial ischemia. Interestingly, no additional triggers of myocardial ischemia other than energy drinks could be identified in the vast majority of cases. Some plausible explanations can be brought in support of this association. Most of the biological effects of EDs are seemingly mediated by a positive inotropic effect on cardiac function, which entails increase in heart rate, cardiac output and contractility, stroke volume and arterial blood pressure. Additional biological abnormalities reported after EDs intake include increased platelet aggregation, endothelial dysfunction, hyperglycemia as well as an increase in total cholesterol, triglycerides and low-density lipoprotein cholesterol. Although a causal relationship between large consumption of EDs and myocardial ischemia cannot be definitely established so far, concerns about the cardiovascular risk of excessive consumption of these beverages are seemingly justified.

Blood vessel control of macrophage maturation promotes arteriogenesis in ischemia.

PubMed

Krishnasamy, Kashyap; Limbourg, Anne; Kapanadze, Tamar; Gamrekelashvili, Jaba; Beger, Christian; Häger, Christine; Lozanovski, Vladimir J; Falk, Christine S; Napp, L Christian; Bauersachs, Johann; Mack, Matthias; Haller, Hermann; Weber, Christian; Adams, Ralf H; Limbourg, Florian P

2017-10-16

Ischemia causes an inflammatory response that is intended to restore perfusion and homeostasis yet often aggravates damage. Here we show, using conditional genetic deletion strategies together with adoptive cell transfer experiments in a mouse model of hind limb ischemia, that blood vessels control macrophage differentiation and maturation from recruited monocytes via Notch signaling, which in turn promotes arteriogenesis and tissue repair. Macrophage maturation is controlled by Notch ligand Dll1 expressed in vascular endothelial cells of arteries and requires macrophage canonical Notch signaling via Rbpj, which simultaneously suppresses an inflammatory macrophage fate. Conversely, conditional mutant mice lacking Dll1 or Rbpj show proliferation and transient accumulation of inflammatory macrophages, which antagonizes arteriogenesis and tissue repair. Furthermore, the effects of Notch are sufficient to generate mature macrophages from monocytes ex vivo that display a stable anti-inflammatory phenotype when challenged with pro-inflammatory stimuli. Thus, angiocrine Notch signaling fosters macrophage maturation during ischemia.Molecular mechanisms of macrophage-mediated regulation of artery growth in response to ischemia are poorly understood. Here the authors show that vascular endothelium controls macrophage maturation and differentiation via Notch signaling, which in turn promotes arteriogenesis and ischemic tissue recovery.

Evaluation of Aged Garlic Extract Neuroprotective Effect in a Focal Model of Cerebral Ischemia

NASA Astrophysics Data System (ADS)

Aguilera, Penélope; Maldonado, Perla D.; Ortiz-Plata, Alma; Barrera, Diana; Chánez-Cárdenas, María Elena

2008-02-01

The oxidant species generated in cerebral ischemia have been implicated as important mediators of neuronal injury through damage to lipids, DNA, and proteins. Since ischemia as well as reperfusion insults generate oxidative stress, the administration of antioxidants may limit oxidative damage and ameliorate disease progression. The present work shows the transitory neuroprotective effect of the aged garlic extract (AGE) administration (a proposed antioxidant compound) in a middle cerebral artery occlusion (MCAO) model in rats and established its therapeutic window. To determine the optimal time of administration, animal received AGE (1.2 mL/kg) intraperitoneally 30 min before onset of reperfusion (-0.5 R), at the beginning of reperfusion (0R), or 1 h after onset of reperfusion (1R). Additional doses were administrated after 1, 2, or 3 h after onset of reperfusion. To establish the therapeutic window of AGE, the infarct area was determined for each treatment after different times of reperfusion. Results show that the administration of AGE at the onset of reperfusion reduced the infarct area by 70% (evaluated after 2 h reperfusion). The therapeutic window of AGE was determined. Repeated doses did not extend the temporal window of protection. A significant reduction in the nitrotyrosine level was observed in the brain tissue subjected to MCAO after AGE treatment at the onset of reperfusion. Data in the present work show that AGE exerts a transitory neuroprotective effect in response to ischemia/reperfusion-induced neuronal injury.

Consumed Ischemia of Lower Limbs in the Newborn: A Case Report

PubMed Central

Hamid, Jiber; Rita, Hajji; Youssef, Zrihni; Abdellatif, Bouarhroum

2013-01-01

The limb ischemia is a rare phenomenon in the newborn. It is most often a postnatal ischemia secondary to arterial or venous catheterization, to neonatal infection. Maternal diabetes is most often implicated. The diagnosis implies an urgent situation which may result in extremity gangrene and ultimate loss of limb. PMID:24251263

miR-21 contributes to xenon-conferred amelioration of renal ischemia-reperfusion injury in mice.

PubMed

Jia, Ping; Teng, Jie; Zou, Jianzhou; Fang, Yi; Zhang, Xiaoyan; Bosnjak, Zeljko J; Liang, Mingyu; Ding, Xiaoqiang

2013-09-01

MicroRNAs participate in the regulation of numerous physiological and disease processes. The in vivo role of microRNAs in anesthetics-conferred organoprotection is unknown. Mice were exposed for 2 h to either 70% xenon, or 70% nitrogen, 24 h before the induction of renal ischemia-reperfusion injury. The role of microRNA, miR-21, in renal protection conferred by the delayed xenon preconditioning was examined using in vivo knockdown of miR-21 and analysis of miR-21 target pathways. Xenon preconditioning provided morphologic and functional protection against renal ischemia-reperfusion injury (n = 6), characterized by attenuation of renal tubular damage, apoptosis, and oxidative stress. Xenon preconditioning significantly increased the expression of miR-21 in the mouse kidney. A locked nucleic acid-modified anti-miR-21, given before xenon preconditioning, knocked down miR-21 effectively, and exacerbated subsequent renal ischemia-reperfusion injury. Mice treated with anti-miR-21 and ischemia-reperfusion injury showed significantly higher serum creatinine than antiscrambled oligonucleotides-treated mice, 24 h after ischemia-reperfusion (1.37 ± 0.28 vs. 0.81 ± 0.14 mg/dl; n = 5; P < 0.05). Knockdown of miR-21 induced significant up-regulation of programmed cell death protein 4 and phosphatase and tensin homolog deleted on chromosome 10, two proapoptotic target effectors of miR-21, and resulted in significant down-regulation of phosphorylated protein kinase B and increased tubular cell apoptosis. In addition, xenon preconditioning up-regulated hypoxia-inducible factor-1α and its downstream effector vascular endothelial growth factor in a time-dependent manner. Knockdown of miR-21 resulted in a significant decrease of hypoxia-inducible factor-1α. These results indicate that miR-21 contributes to the renoprotective effect of xenon preconditioning.