Cardioprotective effect of δ-opioid receptor agonist vs mild therapeutic hypothermia in a rat model of cardiac arrest with extracorporeal life support

Rungatscher, Alessio; Linardi, Daniele; Giacomazzi, Alice; Tessari, Maddalena; Menon, Tiziano; Mazzucco, Alessandro; Faggian, Giuseppe

doi:10.1016/j.resuscitation.2012.06.016

Cited by 18 publications

(10 citation statements)

References 28 publications

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“…The present study has generated fundamental information on the role of oxygenator of ECC in activating inflammatory signalling pathways on leukocytes. By the use of a previously reported and validated rat model of ECC [ 11 , 12 ], we have demonstrated for the first time that oxygenator has a pivotal role in triggering leukocyte activation and subsequent inflammatory response.…”

Section: Discussionmentioning

confidence: 99%

“…The left femoral artery was cannulated with a heparinized 24-gauge Teflon catheter to monitor systemic arterial pressure and to collect arterial blood for gas analysis. Central cannulation was performed as previously described [ 11 , 12 ]. In brief, after complete sternotomy, a venous cannula (a modified 4-hole 16-gauge Angiocath catheter) was advanced into the right atrium using a right transsuperior vena cava approach, allowing excellent drainage.…”

Section: Methodsmentioning

confidence: 99%

“…Full heparinization (500 IU/kg) was assured after surgical preparation and immediately before ECC initiation to reduce overall blood loss. ECC was set up as previously described [ 11 , 12 ]. The setup consisted of a venous reservoir, a roller pump, a hollow fiber oxygenator (Sorin, Mirandola, Italy), and a vacuum regulator with an applied pressure of −30 mm H 2 O to facilitate venous drainage, all connected by 1.6-mm internal diameter plastic tubing.…”

Section: Methodsmentioning

confidence: 99%

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Oxygenator Is the Main Responsible for Leukocyte Activation in Experimental Model of Extracorporeal Circulation: A Cautionary Tale

Rungatscher

Tessari

Stranieri

et al. 2015

Mediators of Inflammation

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In order to assess mechanisms underlying inflammatory activation during extracorporeal circulation (ECC), several small animal models of ECC have been proposed recently. The majority of them are based on home-made, nonstandardized, and hardly reproducible oxygenators. The present study has generated fundamental information on the role of oxygenator of ECC in activating inflammatory signaling pathways on leukocytes, leading to systemic inflammatory response, and organ dysfunction. The present results suggest that experimental animal models of ECC used in translational research on inflammatory response should be based on standardized, reproducible oxygenators with clinical characteristics.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Oxygenator Is the Main Responsible for Leukocyte Activation in Experimental Model of Extracorporeal Circulation: A Cautionary Tale

Rungatscher

Tessari

Stranieri

et al. 2015

Mediators of Inflammation

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“…The tidal volume was 6 ml/kg, and the respiratory rate was 50–60 breaths/min with an air–oxygen mixture (inspired oxygen fraction = 0.5) (Rungatscher et al, 2015). The left femoral artery was cannulated with a heparinized 24-gauge Teflon catheter to monitor the systemic arterial pressure, and central cannulation was performed, as previously described (Rungatscher et al, 2013). Briefly, after complete sternotomy, a venous cannula (a modified 4-hole 16-gauge Angiocath catheter) was introduced into the right atrium with proper drainage.…”

Section: Methodsmentioning

confidence: 99%

Cardioprotective Effects of Sphingosine-1-Phosphate Receptor Immunomodulator FTY720 in a Clinically Relevant Model of Cardioplegic Arrest and Cardiopulmonary Bypass

et al. 2019

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Objective: FTY720, an immunomodulator derived from sphingosine-1-phosphate, has recently demonstrated its immunomodulatory, anti-inflammatory, anti-oxidant, anti-apoptotic and anti-inflammatory properties. Furthermore, FTY720 might be a key pharmacological target for preconditioning. In this preclinical model, we have investigated the effects of FTY720 on myocardium during reperfusion in an experimental model of cardioplegic arrest (CPA) and cardiopulmonary bypass. Methods: 30 Sprague–Dawley rats (300–350 g) were randomized into two groups: Group-A, treated with FTY720 1 mg/kg via intravenous cannulation, and Group-B, as control. After 15 min of treatment, rats underwent CPA for 30 min followed by initiation of extracorporeal life support for 2 h. Support weaning was done, and blood and myocardial tissues were collected for analysis. Hemodynamic parameters, inflammatory mediators, nitro-oxidative stress, neutrophil infiltration, immunoblotting analysis, and immunohistochemical staining were analyzed and compared between groups. Results: FTY720 treatment activated the Akt/Erk1/2 signaling pathways, reduced the level of inflammatory mediators, activated antiapoptotic proteins, and inhibited proapoptotic proteins, leading to reduced nitro-oxidative stress and cardiomyocyte apoptosis. Moreover, significant preservation of high-energy phosphates were observed in the FTY720-treated group. This resulted in improved recovery of left ventricular systolic and diastolic functions. Conclusion: The cardioprotective mechanism in CPA is associated with activation of prosurvival cell signaling pathways that prevents myocardial damage. FTY720 preserves high-energy phosphates attenuates myocardial inflammation and oxidative stress, and improves cardiac function.

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“…Of the three classic opioid receptor groups, µ , δ, and κ, (D-Ala2, D-Leu5)-enkephalin (DADLE) is a small molecule δ receptor agonist that was developed and synthesized by Sigma-Aldrich (St. Louis, MO, USA). DADLE has been observed to specifically activate the δ receptor and studies have demonstrated that treatment with DADLE can have a protective effect on I/R injury in heart and brain tissue ( 9 , 10 ). In addition, DADLE has protective effects in I/R injury models of other organs, including the lung, liver and kidney ( 11 – 13 ).…”

Section: Introductionmentioning

confidence: 99%

Protection of rat intestinal epithelial cells from ischemia/reperfusion injury by (D-Ala2, D-Leu5)-enkephalin through inhibition of the MKK7-JNK signaling pathway

Wang

Tang

et al. 2015

Molecular Medicine Reports

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Previous studies have demonstrated that (D-Ala2, D-Leu5)-enkephalin (DADLE) protects rats from hepatic ischemia/reperfusion (I/R) injury. In the present study, DADLE was also observed to alleviate IR-induced intestinal epithelial cell injury in rats by inhibiting mitogen-activated protein kinase kinase 7 (MKK7)-c-Jun N-terminal kinase (JNK) pathway signaling. To investigate the protective effect of DADLE on hypoxia/reoxygenation injury in rat intestinal epithelial cells, rat intestinal epithelial cells were treated with different concentrations of DADLE, following which the cell survival rate was determined using a tetrazolium (MTT) colorimetric assay, and apoptosis was determined using flow cytometry. To confirm whether the protective effect of DADLE was due to its effect on MKK7-JNK signaling, the phosphorylation levels of MKK7 and JNK were analyzed using western blot analysis following treatment with different concentrations of DADLE. The results demonstrated that, following treatment with DADLE, the survival rate of the rat intestinal cells subjected to I/R-induced injury increased significantly and the apoptotic rate decreased in a concentration-dependent manner. In addition, the levels of phosphorylated MKK7 and JNK decreased in a concentration-dependent manner following treatment with DADLE. Silencing the gene expression of MKK7 using small interfering RNA prior to DADLE treatment resulted in a reduction in the protective effects of DADLE on the rat intestinal epithelial cells subjected to I/R injury. Collectively, the results of the present study demonstrated that the protective effects of DADLE in I/R injury in rat intestinal cells occurred through inhibition of the MKK7-JNK pathway.

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Cardioprotective effect of δ-opioid receptor agonist vs mild therapeutic hypothermia in a rat model of cardiac arrest with extracorporeal life support

Cited by 18 publications

References 28 publications

Oxygenator Is the Main Responsible for Leukocyte Activation in Experimental Model of Extracorporeal Circulation: A Cautionary Tale

Oxygenator Is the Main Responsible for Leukocyte Activation in Experimental Model of Extracorporeal Circulation: A Cautionary Tale

Cardioprotective Effects of Sphingosine-1-Phosphate Receptor Immunomodulator FTY720 in a Clinically Relevant Model of Cardioplegic Arrest and Cardiopulmonary Bypass

Protection of rat intestinal epithelial cells from ischemia/reperfusion injury by (D-Ala2, D-Leu5)-enkephalin through inhibition of the MKK7-JNK signaling pathway

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