Ischemia-reperfusion lung injury in rabbits: mechanisms of injury and protection

1999 ◽  
Vol 276 (1) ◽  
pp. L137-L145 ◽  
Author(s):  
Tsutomu Sakuma ◽  
Keiji Takahashi ◽  
Nobuo Ohya ◽  
Osamu Kajikawa ◽  
Thomas R. Martin ◽  
...  
Keyword(s):  
Lung Injury ◽  
Pulmonary Edema ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Rabbit Model ◽  
Left Lung ◽  
Lung Water ◽  
Lung Inflation ◽  
Ultrastructural Studies

To study the mechanisms responsible for ischemia-reperfusion lung injury, we developed an anesthetized rabbit model in which the effects of lung deflation, lung inflation, alveolar gas composition, hypothermia, and neutrophils on reperfusion pulmonary edema could be studied. Rabbits were anesthetized and ventilated, and the left pulmonary hilum was clamped for either 2 or 4 h. Next, the left lung was reperfused and ventilated with 100% oxygen. As indexes of lung injury, we measured arterial oxygenation, extravascular lung water, and the influx of a vascular protein (131I-labeled albumin) into the extravascular space of the lungs. The principal results were that 1) all rabbits with the deflation of the lung during ischemia for 4 h died of fulminant pulmonary edema within 1 h of reperfusion; 2) inflation of the ischemic lung with either 100% oxygen, air, or 100% nitrogen prevented the reperfusion lung injury; 3) hypothermia at 6–8°C also prevented the reperfusion lung injury; 4) although circulating neutrophils declined during reperfusion lung injury, there was no increase in interleukin-8 levels in the plasma or the pulmonary edema fluid, and, furthermore, neutrophil depletion did not prevent the reperfusion injury; and 5) ultrastructural studies demonstrated injury to both the lung endothelium and the alveolar epithelium after reperfusion in deflated lungs, whereas the inflated lungs had no detectable injury. In summary, ischemia-reperfusion injury to the rabbit lung can be prevented by either hypothermia or lung inflation with either air, oxygen, or nitrogen.

Imatinib Is Protective Against Ischemia-Reperfusion Injury in an Ex Vivo Rabbit Model of Lung Injury

2018 ◽  
Vol 105 (3) ◽  
pp. 950-956 ◽  
Author(s):  
J. Trent Magruder ◽  
Joshua C. Grimm ◽  
Todd C. Crawford ◽  
Laura Johnston ◽  
Lakshmi Santhanam ◽  
...  
Keyword(s):  
Lung Injury ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ex Vivo ◽  
Ischemia Reperfusion ◽  
Rabbit Model

Abstract 138: Remote Ischemic Postconditioning Alleviates Postresuscitation Inflammatory Response and Pulmonary Edema in a Porcine Model of Cardiac Arrest

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Jiefeng Xu ◽  
Sen Ye ◽  
Zilong Li ◽  
Moli Wang ◽  
Zhengquan Wang ◽  
...  
Keyword(s):  
Cardiac Arrest ◽  
Inflammatory Response ◽  
Pulmonary Edema ◽  
Porcine Model ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Limb Ischemia ◽  
Multiple Organ ◽  
Control Group ◽  
Lung Water

Introduction: Systemic ischemia-reperfusion injury produced by CA and resuscitation can result in severe post-cardiac arrest syndrome; which includes systemic inflammatory response and multiple organ dysfunction syndrome such as acute pulmonary edema. We previously demonstrated that remote ischemic post-conditioning (RIpostC) improved post-resuscitation myocardial and cerebral function in a rat model of CA. In this study, we investigated the effects of RIpostC on inflammatory response and pulmonary edema after CPR in a porcine model. Hypothesis: RIpostC would alleviate post-resuscitation inflammatory response and pulmonary edema in a porcine model of CA. Methods: Fourteen male domestic pigs weighing 37 ± 2 kg were utilized. Ventricular fibrillation was electrically induced and untreated for 10 mins. The animals were then randomized to receive RIpostC or control. Coincident with the start of CPR, RIpostC was induced by four cycles of 5 mins of limb ischemia and then 5 mins of reperfusion. Defibrillation was attempted after 5 mins of CPR. The resuscitated animals were monitored for 4 hrs and observed for an additional 68 hrs. Results: Six of the seven animals in each group were successfully resuscitated. After resuscitation, significantly lower levels of tumor necrosis factor-α and interleukin-6 were measured in the animals that received RIpostC when compared with the control group. Post-resuscitation extra-vascular lung water index was lower in the RIpostC group than in the control group; in which the differences were significant at 2,3 and 4 hrs (Table). Conclusion: In a porcine model of CA, RIpostC significantly alleviates post-resuscitation inflammatory response and pulmonary edema.

scholarly journals Gut Lymph Purification in Rats With Acute Lung Injury Caused By Gut Ischemia Reperfusion Injury

2021 ◽  
Author(s):  
Can Jin ◽  
Shucheng Zhang ◽  
Linlin Wu ◽  
Bohan Li ◽  
Meimei Shi ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Reperfusion Injury ◽  
Lung Tissue ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Mononuclear Phagocyte ◽  
Alveolar Epithelial Cells ◽  
Expression Level ◽  
Tissue Samples

Abstract Rationale: It is unclear whether removing the danger-associated molecular patterns (DAMPs) of gut lymph (GL) in the rats of gut ischemia-reperfusion injury (GIRI) model may reduce the distant organ lung injury.Objective: To determine whether oXiris gut lymph purification (GLP) may remove the DAMPs of GL in the rats’ model of acute lung injury (ALI) caused by GIRI.Methods: The experimental rats were divided into four groups: Sham group, GIRI group, GIRI + gut lymph drainage (GLD) group, and GIRI + GLP group. After successful modeling, the lung tissue samples of rats in each group were taken for hematoxylin-eosin (HE) staining and detection of expression levels of apoptotic indexes. The level of DAMPs was detected in blood and lymph. We observed its microstructure of type II alveolar epithelial cells (AECⅡ), and detected the expression level of apoptosis indexes.Measurements and Main Results: GIRI-induced destruction of alveolar structure, thickened alveolar walls, inflammatory cell infiltration emerged in the GIRI group, HMGB-1 and IL-6 levels significantly increased, and HSP70 and IL-10 levels reduced in lymph and serum. Compared with GIRI group, the lung tissue damage in GIRI + GLP group significantly improved, the expression level of HMGB-1 and IL-6 in the lymph and serum reduced, and HSP70 and IL-10 increased. The organelle structure of AECII in GIRI + GLP group was significantly improved compared with the GIRI group. Conclusions: oXiris GLP blocks the key link between DAMPs and mononuclear phagocyte system to inhibit inflammation and cell apoptosis, thereby reducing ALI induced by GIRI.

scholarly journals TLR4 as receptor for HMGB1-mediated acute lung injury after liver ischemia/reperfusion injury

2013 ◽  
Vol 93 (7) ◽  
pp. 792-800 ◽  
Author(s):  
Zhongwei Yang ◽  
Yuxiao Deng ◽  
Diansan Su ◽  
Jie Tian ◽  
Yuan Gao ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Liver Ischemia

Src protein tyrosine kinase family and acute inflammatory responses

2006 ◽  
Vol 291 (2) ◽  
pp. L129-L141 ◽  
Author(s):  
Daisuke Okutani ◽  
Monika Lodyga ◽  
Bing Han ◽  
Mingyao Liu
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Tyrosine Kinase ◽  
Reperfusion Injury ◽  
Protein Tyrosine Kinase ◽  
Inflammatory Responses ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Critical Role ◽  
Protein Tyrosine

Acute inflammatory responses are one of the major underlying mechanisms for tissue damage of multiple diseases, such as ischemia-reperfusion injury, sepsis, and acute lung injury. By use of cellular and molecular approaches and transgenic animals, Src protein tyrosine kinase (PTK) family members have been identified to be essential for the recruitment and activation of monocytes, macrophages, neutrophils, and other immune cells. Src PTKs also play a critical role in the regulation of vascular permeability and inflammatory responses in tissue cells. Importantly, animal studies have demonstrated that small chemical inhibitors for Src PTKs attenuate tissue injury and improve survival from a variety of pathological conditions related to acute inflammatory responses. Further investigation may lead to the clinical application of these inhibitors as drugs for ischemia-reperfusion injury (such as stroke and myocardial infarction), sepsis, acute lung injury, and multiple organ dysfunction syndrome.

scholarly journals Autophagy Decreases Alveolar Epithelial Cell Injury by Suppressing the NF-κB Signaling Pathway and Regulating the Release of Inflammatory Mediators

2018 ◽  
Author(s):  
Tao Fan ◽  
Shuo Yang ◽  
Zhixin Huang ◽  
Wei Wang ◽  
Shize Pan ◽  
...  
Keyword(s):  
Epithelial Cell ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Alveolar Epithelial Cell ◽  
Ischemia Reperfusion ◽  
Left Lung ◽  
Alveolar Epithelial ◽  
Group Blocking

AbstractTo research the impact of autophagy on alveolar epithelial cell inflammation and its possible mechanism in early stages of hypoxia, we established a cell hypoxia-reoxygenation model and orthotopic left lung ischemia-reperfusion model. Rat alveolar epithelial cells stably expressing GFP-LC3 were treated with an autophagy inhibitor (3-methyladenine, 3-MA) or autophagy promoter (rapamycin), followed by hypoxia-reoxygenation treatment at 2, 4 and 6h in vitro. In vivo, twenty-four male Sprague-Dawley rats were randomly divided into four groups (model group: no blocking of hilum in the left lung; control group: blocking of hilum in the left lung for 1h with DMSO lavage; 3-MA group: blocking of hilum in the left lung for 1h with 100ml/kg of 3-MA (5μmol/L) solution lavage; rapamycin group: blocking of hilum in the left lung for 1h with 100ml/kg of rapamycin (250nmol/L) solution lavage) to establish an orthotopic left lung ischemia model. This study demonstrated that rapamycin significantly suppressed the NF-κB signaling pathway, restrained the expression of pro-inflammatory factors. A contrary result was confirmed by 3-MA pretreatment. These findings indicate that autophagy reduces ischemia-reperfusion injury by repressing inflammatory signaling pathways in the early stage of hypoxia in vitro and in vivo. This could be a new protective method for lung ischemia-reperfusion injury.

scholarly journals Η επίδραση του είδους της ισχαιμικής επανάρδευσης σε συνδυασμό με την πίεση των αεραγωγών στην προκαλούμενη απο τον αναπνευστήρα πνευμονική βλάβη

2014 ◽  
Author(s):  
Μαρίνα Μπαλανίκα
Keyword(s):  
Tumor Necrosis Factor ◽  
Lung Injury ◽  
Reperfusion Injury ◽  
Tumor Necrosis ◽  
Ischemia Reperfusion Injury ◽  
Ex Vivo ◽  
Ischemia Reperfusion ◽  
Ventilator Induced Lung Injury ◽  
Necrosis Factor

Η ισχαιμική βλάβη επανάρδευσης των πνευμόνων (LUNG ISCHEMIA REPERFUSION INJURY-LIRI) παραμένει η κυριότερη αιτία της οξείας απόρριψης των πνευμονικών μοσχευμάτων ενώ το μηχανικό stress που προκαλεί η εφαρμογή μηχανικού αερισμού αντιπροσωπεύει ένα επιπρόσθετο σημαντικό πλήγμα με καθοριστικό ρόλο στην τελική έκβαση μιας ιδιαίτερα πολύπλοκης διαδικασίας. Σκοπός της μελέτης μας ήταν να διερευνηθεί η συνδυασμένη επίδραση της μετά από ισχαιμία βλάβης επανάρδευσης και της προκαλούμενης από τον μηχανικό αερισμό πνευμονικής βλάβης (VENTILATOR INDUCED LUNG INJURY-VILI) σε πνεύμονα κουνελιού. Μελετήθηκαν 60 ex vivo παρασκευάσματα καρδιάς - πνευμόνων που τυχαιο-ποιήθηκαν σε τρία ζεύγη υπο-ομάδων (6 υπο-ομάδες συνολικά των 10 ζώων) με βάση τις συνθήκες επανάρδευσης (Υπεροξική→PO2>300 mmHg, Υποξική→ PO2=40-45 mmHg, Νορμοξική επανάρδευση→PaO2=120-170 mmHg). Όσον αφορά στην κατανομή στις κατηγορίες μηχανικού αερισμού ελεγχόμενης πίεσης, τα παρασκευάσματα κάθε ζεύγους χωρίστηκαν σε δύο υπο-ομάδες και συγκεκριμένα υπο-ομάδα χαμηλών πιέσεων (Pmax 15 cm H20) και υπο-ομάδα υψηλών πιέσεων (Pmax 25 cm H20). Δείκτες της προκαλούμενης πνευμονικής βλάβης αποτέλεσαν η αύξηση του βάρους του παρασκευάσματος καθώς και η αύξηση του συντελεστή υπερδιήθησης (Kfc). Η μέτρηση των κυτταροκινών στο βρογχοκυψελιδικό έκπλυμα (BALF) στο τέλος του πρωτοκόλλου, συνέβαλλε στην ολοκληρωμένη διερεύνηση της ενδεχόμενης βλάβης.Κύριο εύρημα της μελέτης μας αποτελεί η μεγαλύτερη αύξηση βάρους που παρουσίασαν τα πειραματόζωα που αερίστηκαν με μηχανικό αερισμό υψηλών πιέσεων (Pmax 25 cm H20) σε σχέση με τις αντίστοιχες υπο-ομάδες που αερίστηκαν με μηχανικό αερισμό χαμηλών πιέσεων (Pmax 15 cm H20) (p<0,05). Ανάλογη αύξηση παρουσίασε ο συντελεστής υπερδιήθησης (Kfc) στις υπο-ομάδες μηχανικού αερισμού υψηλών πιέσεων (p<0.05), ενώ οι μεταβολές του (dKfc) ήταν στατιστικά σημαντικότερες στην υπο-ομάδα εκείνη όπου ο αερισμός υψηλών πιέσεων συνδυάστηκε με υπεροξικές συνθήκες επανάρδευσης (p<0,05 συγκριτικά με τις υπο-ομάδες υποξικής και νορμοξικής επανάρδευσης σε συνδυασμό με μηχανικό αερισμό υψηλών πιέσεων, p<0,001 συγκριτικά με τις υπο-ομάδες υπεροξικής, υποξικής και νορμοξικής επανάρδευσης σε συνδυασμό με μηχανικό αερισμό χαμηλών πιέσεων). Τα επίπεδα του παράγοντα νέκρωσης του όγκου (Tumor Necrosis Factor – TNF-a) και τα αντίστοιχα επίπεδα της μαλονυλ- διαλδεϋδης (MDA) στο βρογχοκυψελιδικό έκπλυμα (BALF) δεν παρουσίασαν στατιστικά σημαντικές διαφορές αν και οι τιμές του TNF-a ήταν υψηλότερες στις ομάδες που αερίστηκαν με μηχανικό αερισμό υψηλών πιέσεων.Συμπερασματικά, από τη μελέτη μας προκύπτει ότι η βαρύτητα της πνευμο-νικής βλάβης (δημιουργία πνευμονικού οιδήματος) καθορίζεται κυρίως από τα χαρακτηριστικά του μηχανικού αερισμού (μηχανικός αερισμός με υψηλές τελοεισπνευστικές πιέσεις και υψηλούς τελοεισπνευστικούς όγκους). Παρ’ όλα αυτά, διαπιστώθηκε ότι ο συνδυασμός μη προστατευτικού μηχανικού αερισμού υψηλών πιέσεων με συγκεκριμένες συνθήκες μερικής πίεσης οξυγόνου στο υγρό της επανάρδευ¬σης και ειδικότερα με υπεροξική επανάρδευση, συμβάλλει στη διαμόρφωση της βαρύτητας της προκαλούμενης πνευμονικής βλάβης.

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