scholarly journals Lung Protection Strategies during Cardiopulmonary Bypass Affect the Composition of Blood Electrolytes and Metabolites—A Randomized Controlled Trial

2018 ◽  
Vol 7 (11) ◽  
pp. 462 ◽  
Author(s):  
Katrine Buggeskov ◽  
Raluca Maltesen ◽  
Bodil Rasmussen ◽  
Munsoor Hanifa ◽  
Morten Lund ◽  
...  

Cardiac surgery with cardiopulmonary bypass (CPB) causes an acute lung ischemia-reperfusion injury, which can develop to pulmonary dysfunction postoperatively. This sub-study of the Pulmonary Protection Trial aimed to elucidate changes in arterial blood gas analyses, inflammatory protein interleukin-6, and metabolites of 90 chronic obstructive pulmonary disease patients following two lung protective regimens of pulmonary artery perfusion with either hypothermic histidine-tryptophan-ketoglutarate (HTK) solution or normothermic oxygenated blood during CPB, compared to the standard CPB with no pulmonary perfusion. Blood was collected at six time points before, during, and up to 20 h post-CPB. Blood gas analysis, enzyme-linked immunosorbent assay, and nuclear magnetic resonance spectroscopy were used, and multivariate and univariate statistical analyses were performed. All patients had decreased gas exchange, augmented inflammation, and metabolite alteration during and after CPB. While no difference was observed between patients receiving oxygenated blood and standard CPB, patients receiving HTK solution had an excess of metabolites involved in energy production and detoxification of reactive oxygen species. Also, patients receiving HTK suffered a transient isotonic hyponatremia that resolved within 20 h post-CPB. Additional studies are needed to further elucidate how to diminish lung ischemia-reperfusion injury during CPB, and thereby, reduce the risk of developing severe postoperative pulmonary dysfunction.

2019 ◽  
Vol 2019 ◽  
pp. 1-17 ◽  
Author(s):  
Limei Zhang ◽  
Hanyu Liu ◽  
Lili Jia ◽  
Jingshu Lyu ◽  
Ying Sun ◽  
...  

Background. The neuronal injury and cognitive dysfunction after liver transplantation have severe effects on the prognosis and life quality of patients. Accumulating evidence suggests that both exosomes and pyroptosis could participate in hepatic ischemia-reperfusion injury (HIRI) and play key roles in neuronal death. However, the link between exosomes and neuronal pyroptosis in HIRI awaits further investigation. Methods. After establishing the HIRI rat models, we primarily studied the role of pyroptosis in hippocampal and cortical neuron injury through detecting NOD-like receptor protein 3 (NLRP3), pro-caspase-1, cleaved-caspase-1, apoptosis-associated speck-like protein containing CARD (ASC), gasdermin D (GSDMD), interleukin-1beta (IL-1β), and interleukin-18 (IL-18) expressions with western blotting, immunohistochemical staining, and enzyme-linked immunosorbent assay (ELISA). Then, we intravenously injected normal male rats with exosomes isolated from the sera of HIRI-challenged rats and pretreated rats with MCC950, a specific inhibitor of NLRP3, and carried out the same assay. We also detected the levels of reactive oxygen species (ROS), superoxide dismutase (SOD), and malondialdehyde (MDA) in the hippocampal and cortical tissues. Results. The results indicated that NLRP3 inflammasome and caspase-1-dependent pyroptosis were activated in the hippocampus and cortex of HIRI rats. Furthermore, serum-derived exosomes from HIRI-challenged rats not only had the ability to cross the blood-brain barrier (BBB) but also had the similar effects on neuronal pyroptosis. Moreover, ROS and MDA productions were induced in the HIRI and exosome-challenged groups. In addition, to some degree, MCC950 could alleviate HIRI-mediated hippocampal and cortical neuronal pyroptosis. Conclusion. This study experimentally demonstrated that circulating exosomes play a critical role in HIRI-mediated hippocampal and cortical injury through regulating neuronal pyroptosis.


Blood ◽  
1994 ◽  
Vol 84 (7) ◽  
pp. 2322-2328 ◽  
Author(s):  
D Mihelcic ◽  
B Schleiffenbaum ◽  
TF Tedder ◽  
SR Sharar ◽  
JM Harlan ◽  
...  

Abstract The leukocyte adhesion molecule L-selectin mediates neutrophil adhesive interactions with endothelial cells and is in part responsible for neutrophil rolling. We examined the role of L-selectin in ischemia- reperfusion injury of rabbit ears using a monoclonal antibody (MoAb) directed to a functional epitope of L-selectin. Arterial blood flow to the rabbit ear was occluded for six hours with ambient temperature at 23 degrees C to 24 degrees C. Rabbits were treated at reperfusion with saline (n = 8), the L-selectin function-blocking LAM1–3 MoAb (2 mg/kg), or the nonfunction-blocking LAM1–14 MoAb (2 mg/kg). Tissue injury was determined by measuring edema and necrosis. Edema in the LAM1–3 MoAb- treated group (peak = 25 +/- 4 mL) was significantly less (P < .05) than in saline-treated (peak = 40 +/- 8 mL) and LAM1–14 MoAb-treated (peak = 41 +/- 6 mL) groups. Tissue necrosis at 7 days was not observed in the LAM1–3 MoAb-treated group, whereas significant necrosis (P < .05) was seen in the saline- (8% +/- 3% necrosis) and LAM1–14 MoAb- treated (7% +/- 3% necrosis) group. We conclude that blocking L- selectin ameliorates necrosis and edema after ischemia and reperfusion in the rabbit ear, presumably by blocking neutrophil rolling.


2020 ◽  
Vol 21 (15) ◽  
pp. 5336
Author(s):  
Irina A. Mandel ◽  
Yuri K. Podoksenov ◽  
Irina V. Suhodolo ◽  
Darya A. An ◽  
Sergey L. Mikheev ◽  
...  

The aim of the experiment was to evaluate the effect of preconditioning based on changes in inspiratory oxygen fraction on endothelial function in the model of ischemia-reperfusion injury of the myocardium in the condition of cardiopulmonary bypass. The prospective randomized study included 32 rabbits divided into four groups: hypoxic preconditioning, hyperoxic preconditioning, hypoxic-hyperoxic preconditioning, and control group. All animals were anesthetized and mechanically ventilated. We provided preconditioning, then started cardiopulmonary bypass, followed by induced acute myocardial infarction (ischemia 45 min, reperfusion 120 min). We investigated endothelin-1, nitric oxide metabolites, asymmetric dimethylarginine during cardiopulmonary bypass: before ischemia, after ischemia, and after reperfusion. We performed light microscopy of myocardium, kidney, lungs, and gut mucosa. The endothelin-1 level was much higher in the control group than in all preconditioning groups after ischemia. The endothelin-1 even further increased after reperfusion. The total concentration of nitric oxide metabolites was significantly higher after all types of preconditioning compared with the control group. The light microscopy of the myocardium and other organs revealed a diminished damage extent in the hypoxic-hyperoxic preconditioning group as compared to the control group. Hypoxic-hyperoxic preconditioning helps to maintain the balance of nitric oxide metabolites, reduces endothelin-1 hyperproduction, and enforces organ protection.


2021 ◽  
Vol 14 ◽  
Author(s):  
Yanxia Fei ◽  
Jiali Shao ◽  
Ge Huang ◽  
Lijuan Wang ◽  
Shuangfa Zou ◽  
...  

Background and Objective: Hepatic ischemia-reperfusion injury (HIRI) results in serious complications after liver resection and transplantation. Edaravone (ED) has a protective effect on IRI. This study was designed to evaluate whether ED could protect the liver of rats from HIRI injury and explored its exosomal miRNA-related mechanism. Methods: The sham group, hepatic ischemia/reperfusion (IR group), and hepatic ischemia/reperfusion + edaravone (ED group) models were established. We determined the protective effect of ED by measuring alanine aminotransferase (ALT), aspartate aminotransferase (AST), malondialdehyde (MDA), superoxide dismutase (SOD); enzyme-linked immunosorbent assay for tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β); hematoxylin-eosin staining and immunohistochemistry for histopathological changes. Exosomal miRNAs were subjected to second-generation sequencing to identify their differential expression. The results were analyzed using bioinformatics methods and validated using real-time quantitative polymerase chain reaction (RT-qPCR). Results: HIRI rats showed higher levels of ALT, AST, oxidative stress, and inflammatory markers; ED attenuated these effects. The sequencing results showed 6 upregulated and 13 downregulated miRNAs in the IR vs. sham groups, 10 upregulated and 10 downregulated miRNAs in the ED vs. IR groups. PC-3p-190-42101 was screened as an overlapping differentially expressed miRNA, and RT-qPCR validation showed that its expression in HIRI rats was significantly decreased; ED prevented this downregulation. Moreover, the expression of PC-3P-190-42101 was significantly correlated with the level of inflammatory factors. Conclusion: These findings indicate that ED can regulate the level of inflammatory factors by affecting the expression of miRNA PC-3p-190-42101 in plasma exosomes to protect the liver from IRI.


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