Intestinal Preconditioning Ameliorates Ischemia-Reperfusion Induced Acute Lung Injury in Rats: An Experimental Study (original) (raw)
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Journal of Surgical Research, 2008
Background. A pivotal role of phospholipase A 2 (PLA 2) and platelet-activating factor-acetylhydrolase (PAF-AcH) as enzymes involved in lung inflammation has recently been suggested. The objective of this study was to elucidate the role and the time dependence of PLA 2 and PAF-AcH fluctuations in the lung relative to the evolution of intestinal ischemiareperfusion (IIR). Materials and methods. Rats were randomly allocated to five groups of IIR induced by occlusion of the superior mesenteric artery for 45 min followed by 1 min, 2, 4, and 8 h of reperfusion (expGroups) and five corresponding sham groups (sGroups). Bronchoalveolar lavage fluid was obtained from the right lung and its biochemical (protein, PLA 2 , PAF-AcH) and cytological characteristics were determined. Plasma malonyldialdehyde was measured as a marker of lipid peroxidation. The 4 and 8 h reperfusion expGroups had significantly (P < 0.05) elevated alveolar-arterial O 2 gradient values compared with the corresponding controls. Total protein, PLA 2 and PAF-AcH levels significantly (P < 0.05) increased in expGroups compared with the corresponding shams after 4 h of reperfusion. Total bronchoalveolar lavage fluid cells and plasma malonyldialdehyde were significantly (P < 0.05) elevated in expGroups compared with the sGroups after 2 h of reperfusion. Conclusions. PLA 2 could act synergistically or parallel with the reactive oxygen species produced during IIR, resulting in the induction or even in the exacerbation of the inflammatory reaction in acute respiratory distress syndrome. PAF-AcH could play an antiinflammatory role by reducing the concentration of PAF.
Transplantation Proceedings, 2014
The aim of this study was evaluate the beta blocker atenolol (AT) and ischemic preconditioning (IPC) strategies for tissue protection against systemic effects of intestinal ischemia (I) and reperfusion (R) injury. Forty-two rats were pretreated with AT (1.5 mg $ kg À1 ), 0.9% saline solution (SS; 0.1 mL), or IPC and then subjected to prolonged occlusion of the superior mesenteric artery for 60 minutes leading to I followed or not by 120 minutes of R, according to the group. For IPC, 5 minutes of I prior to 10 minutes of R were established. After this process of I or I-R, the right lung of each animal was adequately prepared for staining with hematoxylin and eosin and subsequent histologic analysis for quantification of inflammatory infiltrate was done. The left lung was frozen and prepared for assessment of oxidative stress by the quantification of thiobarbituric acid-reactivity substances (TBARS). Histologic analysis showed an important inflammatory infiltrate in the I-R þ SS (I-R þ SS ¼ 4.5), which was significantly (P < .05) reduced by IPC (I-R þ IPC ¼ 3.0) or AT (I-R þ AT ¼ 3.0). Likewise, the TBARS levels were decreased by both strategies (I-R þ SS ¼ 0.63; I-R þ IPC ¼ 0.23; I-R þ AT ¼ 0.38; P < .05). Our results showed that AT and IPC attenuate pulmonary lesions caused by intestinal I and R process.
Annals of Surgical Treatment and Research, 2019
To research the effects of iloprost (IL) and hyperbaric oxygen (HBO) combination treatment on lung injury and on tumor necrosis factor alpha (TNF-α), myeloperoxidase (MPO), malondialdehyde (MDA), and soluble intercellular adhesion molecule-1 (sICAM-1) levels after tissue or organ ischemia-reperfusion, and on ischemia-reperfusion induced lung neutrophil sequestration. Methods: Forty white New Zealand rabbits were assigned randomly into 5 groups: HBO, IL, HBO+IL, control, and sham groups. TNF-α values were checked before ischemia, in the 1st hour of ischemia and in the 1st and 4th hours of reperfusion, also at the end of reperfusion period, plasma and tissue MPO values, MDA values, and sICAM-1 levels were detected. After sacrifice, the degree of lung injury was determined by histopathological examination. Results: Compared to the control group all therapy groups showed a drastically meaningful reduction in TNF-α increase in 1, 2, and 4 hours. Plasma and lung MDA, MPO, and sICAM-1 levels were significantly lower in IL, HBO, HBO+IL, and sham groups compared with the control group. IL and/or HBO suppressed MDA and MPO increase in the lung tissue and in plasma. Additionally, histopathological score was significantly lower in HBO, IL, HBO+IL, and sham groups than that of the control group. Conclusion: Both HBO and IL therapy have a beneficial effect by causing a meaningful reduction in TNF-α production, MPO, MDA, sICAM-1 levels and pulmonary neutrophil sequestration; which play a role, especially, in ischemia reperfusion induced lung damage.
Resuscitation, 2010
Aim of the study: Acute lung injury (ALI) develops in various clinical situations and is associated with high morbidity and mortality and therapeutic hypothermia (HT) has been studied to attenuate the ALI. However, the optimal method of rewarming has not been determined. We determined the effect of speed of rewarming and the administration of anti-inflammatory or anti-oxidant agents on ALI in an intestinal ischemia and reperfusion (I/R) model treated with HT. Materials and methods: A Sprague-Dawley rat model of intestine ischemia and reperfusion was used. Two parallel animal experiments were conducted. In the survival study, rats (n = 5 per group) underwent normothermic intestinal ischemia (60 min, 36-38 • C) and then randomized into 7 groups with reperfusion: normothermia (NT), HT without rewarming (30-32 • C, HT), 2 h HT + rewarming for 1 h (RW1), 2 h HT + rewarming for 2 h (RW2), RW1 + N-acetyl cysteine (RW-NAC), RW1 + ethylpyruvate (RW-EP), and RW1 + dexamethasone (RW + Dexa). In the second experiment, we investigated the histological and biochemical effects on the lung 4 h after reperfusion (n = 8 per group). Results: The survival rate was lowest after NT. The HT, RW2, and RW-Dexa groups survived longer than the RW1, RW-NAC, and RW-EP groups. ALI scores were lower in the HT, RW2, and RW-Dexa groups than RW1. Lung malondialdehyde content was also lower in these groups. Interleukin (IL)-6 was significantly higher in the RW1 group. Inducible NO synthase gene expression in lung was lower in the HT, RW2, and RW-Dexa than RW1, and serum NO was lower in the RW2 and RW-Dexa than RW1. Conclusion: Gradual rewarming and administration of dexamethasone improved survival and attenuated ALI after intestinal I/R injury treated with HT in rats.
European Journal of Cardio-Thoracic Surgery, 2013
OBJECTIVES: Lung ischaemia/reperfusion (IR) induces a systemic inflammatory response that causes damage to remote organs. The liver is particularly sensitive to circulating inflammatory mediators that occur after IR of remote organs. Recently, remote ischaemic preconditioning has been proposed as a surgical tool to protect several organs from IR. The present study was designed to investigate a possible protective effect of lung ischaemic preconditioning (IP) against the liver inflammatory response to lung IR.
Gut Ischemia/Reperfusion Induced Acute Lung Injury is an Alveolar Macrophage Dependent Event
The Journal of Trauma: Injury, Infection, and Critical Care, 2008
Background: Although the role of the lung alveolar macrophage (AM) as a mediator of acute lung injury (ALI) after lung ischemia/reperfusion (I/R) has been suggested by animal experiments, it has not been determined whether AMs mediate ALI after intestinal I/R. The objective of this study was to determine the effect of AM elimination on ALI after intestinal I/R in rats. Methods: Male Wistar rats (n ؍ 90) were randomly divided into three groups: the clodronate-liposomes (CLOD-LIP) group received intratracheal treatment with CLOD-LIP; the liposomes (LIP) group received intratracheal treatment with LIP; and the nontreated (UN-TREAT) group received no treatment. Twenty-four hours later each group was randomly divided into three subgroups: the intestinal I/R subgroup was subjected to 45-minute intestinal ischemia and 2-hour reperfusion; the laparotomy (LAP) subgroup was subjected to LAP and sham procedures; the control (CTR) subgroup received no treatment. At the end of reperfusion, ALI was quantitated in all the animals by the Evans blue dye (EBD) method. Results: ALI values are expressed as EBD lung leakage (g EBD/g dry lung weight). EBD lung leakage values in the CLOD-LIP group were 32.59 ؎ 12.74 for I/R, 27.74 ؎ 7.99 for LAP, and 33.52 ؎ 10.17 for CTR. In the LIP group, lung leakage values were 58.02 ؎ 18.04 for I/R, 31.90 ؎ 8.72 for LAP, and 27.17 ؎ 11.48 for CTR. In the UNTREAT group, lung leakage values were 55.60 ؎ 10.96 for I/R, 35.99 ؎ 6.89 for LAP, and 30.83 ؎ 8.41 for CTR. Within each group, LAP values did not differ from CTR values. However, in the LIP and UNTREAT groups, values for both the LAP and CTR subgroups were lower than values for the I/R subgroup (p < 0.001). The CLOD-LIP I/R subgroup value was less (p < 0.001) than the I/R subgroup values in the LIP and UNTREAT groups. These results indicated that I/R provokes ALI that can be prevented by CLOD-LIP treatment, and further suggested that AMs are essential for ALI occurrence induced by intestinal I/R in rats.
Journal of Surgical Research, 2011
Background. Intestinal ischemia-reperfusion is a common medical event associated with both clinical and experimental distant organ injury. In particular, the lung tissue appears to be susceptible to injury resulting from systemic inflammatory mediator activation. Drotrecogin a (activated) or recombinant human activated protein C has antithrombotic, antiinflammatory, and profibrinolytic properties. We hypothesized that APC infusion would decrease lung inflammation and ameliorate lung injury resulting from intestinal ischemia-reperfusion (IIR). A rat model of intestinal ischemia-reperfusion was used to test this hypothesis, and several parameters of lung injury were measured in lung samples. Material and Methods. Forty Wistar albino rats were divided into four groups: a sham-operated group (Sham), an ischemic control group (IIR), an APCinfusion group (IIR'APC), and a normal saline-infusion group (IIR'NS) (n [ 10, each). A marker for lipid peroxidation, malondialdehyde (MDA), free radical scavenger glutathione peroxidase (GSH-Px), an index of polymorphonuclear neutrophils, myeloperoxidase (MPO) activity, and lung polymorphonuclear leukocytes (PMNL) were investigated in the lung tissue samples. Results. MDA and MPO levels, and lung PMNL sequestration were decreased, but GSH-Px levels were increased in APC treated group versus IIR group. MDA levels were decreased and GSH-Px levels were increased in NS treated group versus IIR group. MPO levels and lung PMNL counts were similar across the IIR and IIR'NS groups. Conclusions. This study documents that APC attenuates acute lung injury in intestinal ischemiareperfusion. NS infusion had also some favorable effects regarding MDA and MPO.
Acta Anaesthesiologica Scandinavica, 2006
Sepsis and septic shock are are among the major causes of mortality in intensive care units. The lung and kidney are the organs most affected by sepsis. Evidence exists that lipid peroxidation and apoptosis may be responsible for the high mortality due to sepsis. Ischemic preconditioning (IP) is a method for the protection of tissues and organs against ischemia/reperfusion injury by reducing reactive oxygen species levels, lipid peroxidation and apoptosis. In the present study, the effects of IP were investigated in cecal ligation and puncture (CLP)-induced sepsis in rats. The three groups of animals used in the present controlled study were the sham-operated group (sham, n=7), which only underwent a laparotomy; the sepsis group (sepsis, n=7), which underwent cecal ligation and perforation; and the IP + sepsis group (IP+sepsis, n=7), which underwent CLP immediately prior to the application of three cycles of IP to the hind limb. The study was terminated at 6 h after the induction of CLP. Blood, kidney and lung tissue samples were collected for the determination of serum creatinine, blood urea nitrogen (BUN), neutrophil gelatinase-associated lipocalin (NGAL) and lung tissue malondialdehyde (MDA) levels, as well as histological examination. The serum creatinine, plasma NGAL and lung tissue MDA levels in the sepsis group were significantly increased compared with those in the sham and the IP+sepsis groups (P<0.05). Alveolar macrophage counts, histological kidney and lung injury scores, kidney (caspase 3) and lung tissue immuonreactivity (M30) scores in the sepsis group were also significantly increased compared with those in the sham and IP+sepsis groups (P<0.05). The alveolar macrophage count in the IP+sepsis group was increased compared with that in the sham group (P<0.05). In conclusion, IP inhibits lipid peroxidation and attenuates histological injury and apoptosis in the lung and kidney during sepsis.
Transplantation Proceedings, 2013
The intestine is highly sensitive to ischemia-reperfusion injury (IRI), a phenomenon occurring in different intestinal diseases. Several strategies to mitigate IRI are in experimental stages; unfortunately, no consensus has been reached about the most appropriate one. We report a protocol to study ischemic preconditioning (IPC) evaluation in mice and to combine IPC and tacrolimus (TAC) pretreatment in a warm ischemia model. Mice were divided into treated (IPC, TAC, and IPC þ TAC) and untreated groups before intestinal ischemia. IPC, TAC, and IPC þ TAC groups were able to decrease postreperfusion nitrites levels (P < .05). IPC-containing groups had a major beneficial effect by preserving the integrity of the intestinal histology (P < .05) and improving animal survival (P < .002) compared with TAC alone or the untreated group. The IPC þ TAC group was the only one that showed significant improvement in lung histological analysis (P < .05). The TAC and IPC þ TAC groups down-regulated intestinal expression of interleukin (II)-6 and IL1b more than 10-fold compared with the control group. Although IPC and TAC alone reduced intestinal IRI, the used of a combined therapy produced the most significant results in all the local and distant evaluated parameters.