Effect of Lipoxin A4 on Myocardial Ischemia Reperfusion Injury Following Cardiac Arrest in a Rabbit Model

Abstract

In the present study, we investigated the effect of lipoxin A4 on myocardial ischemia-reperfusion injury (IRI) following cardiac arrest (CA) in a rabbit model. Lipoxin A4 is a metabolite of arachidonic acid in the eicosanoid, it is called "brake signal" for its anti-inflammatory activity. Some inflammatory factors (IL-1β, IL-6, TNF-α, and IL-10), NF-κB p65, infarct ratios, apoptotic index, cardiac troponin I (cTnI), hemodynamic and myocardial structures were measured or observed in different groups. Lipoxin A4 inhibits the expression of IL-1β, IL-6, and TNF-α, the values of the infarct ratios, apoptotic index, the level of serum cTnI and NF-κB p65. Meanwhile, it improves the expression of IL-10, hemodynamic, myocardial structure, and function. These indicate that lipoxin A4 mitigates postresuscitation myocardial IRI in which anti-inflammation and suppression of NF-κB activation may play an important role.

Lipoxin A4-Induced Heme Oxygenase-1 Protects Cardiomyocytes against Hypoxia/Reoxygenation Injury via p38 MAPK Activation and Nrf2/ARE Complex

“…Recently, growing evidences demonstrated the efficacy of LXA 4 analogs in treatment of animal arthritis [32], asthma [33], acute lung injury [14], and nephritis [34]. Coupled with previous demonstrations of efficacy of LXA 4 and activation of LXA 4 receptor in treatment of myocardial I/R injury [10], [11], our present results represent useful tools for the development of a new drug for treatment of ischemic heart diseases.…”

“…Previous studies attributed the LXA 4 -induced protection on heart I/R injury to the inhibition of neutrophil recruitment and of pro-inflammatory cytokines production [10], [11]. In the present study, we demonstrated for the first time that LXA 4 -induced HO-1 expression participated in the LXA 4 -imparted protection on heart H/R injury.…”

“…Previous studies have shown that activation of ALX by CGEN-855A provided protection against myocardial I/R injury in both murine and rat models (36 and 25% reduction in infarct size, respectively), and the protective effects were accompanied by inhibition of neutrophil recruitment to the injured heart [10]. LXA 4 mitigated rabbit myocardial I/R injury in which LXA 4 -induced anti-inflammation and suppression of NF-κB activation may play an important role [11]. Besides the anti-inflammatory role of LXA 4 , LXA 4 -evoked expression of HO-1 may be also involved in the LXA 4 -imparted protective effects on myocardial I/R injury.…”

Lipoxin A4Preconditioning and Postconditioning Protect Myocardial Ischemia/Reperfusion Injury in Rats

“…Although there have been reports showing that LXA 4 treatment was protective in cerebral I/R injury in rats [12] and myocardial I/R injury in mice [47] and rabbits [48], ours is the first study to report a protective effect of LXA 4 preconditioning and postconditioning on myocardial I/R injury in rats. Further studies are needed to optimize the dose, the timing, and the route of administration of LXA 4 .…”

Protective Effects of Lipoxin A4 in Testis Injury following Testicular Torsion and Detorsion in Rats

“…Our results also suggested that the expression of NF- κ B in damaged testes has been downregulated by the LXA4 pretreatment. Nuclear factor κ B (NF- κ B) is a primary regulator of gene expression for a large number of cytokines and is activated during IRI of testis [26], and LXA4 have been proposed to directly stimulate gene expression of endogenous anti-inflammatory factors by regulating NF- κ B activation [11]. It is suggested that the protective effect of LXA4 in testicular torsion followed IRI was partially due to its anti-inflammatory properties.…”