Anat Cell Biol.  2018 Jun;51(2):128-135. 10.5115/acb.2018.51.2.128.

The relationship between low survival and acute increase of tumor necrosis factor α expression in the lung in a rat model of asphyxial cardiac arrest

• Park Y
• Tae HJ
• Cho JH
• Kim IS
• Ohk TG
• Park CW
• Moon JB
• Shin MC
• Lee TK
• Lee JC
• Park JH
• Ahn JH
• Kang SH
• Won MH
• Cho JH

• KMID: 2421177
• DOI: http://doi.org/10.5115/acb.2018.51.2.128

Abstract

Cardiac arrest (CA) is sudden loss of heart function and abrupt stop in effective blood flow to the body. The patients who initially achieve return of spontaneous circulation (RoSC) after CA have low survival rate. It has been known that multiorgan dysfunctions after RoSC are associated with high morbidity and mortality. Most previous studies have focused on the heart and brain in RoSC after CA. Therefore, the aim of this research was to perform serological, physiological, and histopathology study in the lung and to determine whether or how pulmonary dysfunction is associated with low survival rate after CA. Experimental animals were divided into sham-operated group (n=14 at each point in time), which was not subjected to CA operation, and CA-operated group (n=14 at each point in time), which was subjected to CA. The rats in each group were sacrificed at 6 hours, 12 hours, 24 hours, and 2 days, respectively, after RoSC. Then, pathological changes of the lungs were analyzed by hematoxylin and eosin staining, Western blot and immunohistochemistry for tumor necrosis factor α (TNF-α). The survival rate after CA was decreased with time past. We found that histopathological score and TNF-α immunoreactivity were significantly increased in the lung after CA. These results indicate that inflammation triggered by ischemia-reperfusion damage after CA leads to pulmonary injury/dysfunctions and contributes to low survival rate. In addition, the finding of increase in TNF-α via inflammation in the lung after CA would be able to utilize therapeutic or diagnostic measures in the future.

Keyword

Asphyxial cardiac arrest; Post-cardiac arrest syndrome; Lung; Tumor necrosis factor α

MeSH Terms

Animals
Blotting, Western
Brain
Eosine Yellowish-(YS)
Heart
Heart Arrest*
Hematoxylin
Humans
Immunohistochemistry
Inflammation
Lung*
Models, Animal*
Mortality
Rats*
Survival Rate
Tumor Necrosis Factor-alpha*
Eosine Yellowish-(YS)
Hematoxylin
Tumor Necrosis Factor-alpha

Figure

• 

  Fig. 1 H&E staining of the lung of the sham (A) and cardiac arrest (CA) operation (B–E) groups. In the CA operated lungs, histopathology is markedly increased at 12-hour post-CA (P<0.05). The histopathological change is more increased at 1- and 2-day post-CA, showing the thickness of alveolar septa and infiltration of a number of inflammatory cells and that alveoli are filled with pigment-laden macrophages and red blood cells. Scale bar=100 µm. (F) Lung lesion score of the sham and CA operation groups (n=7 per group; *P<0.05, significantly different from the sham group). The bars indicated the mean±standard error of mean.

• 

  Fig. 2 Western blot analysis of tumor necrosis factor α (TNF-α) in the lung of the sham and cardiac arrest (CA) operated groups. TNF-α protein level is highest 1 day after CA. Relative optical density (ROD) as the mean percentage values of the immunoblot band is represented (n=7 per group; *P<0.05, significantly different from the sham group). The bars indicate the mean±standard error of mean.

• 

  Fig. 3 Immunohistochemistry of tumor necrosis factor α (TNF-α) in the lung of the sham (A) and cardiac arrest (CA) operated (B–E) groups. TNF-α immunoreactivity is shown in the bronchial epithelium from 6-hour post-CA, which is gradually increased with time. TNF-α immunoreactive cells (arrows) are found in the parenchyma from 12-hour post-CA. Scale bar=100 µm. (F) Relative optical density (ROD) of TNF-α immunoreactive structures in the sham and CA operation groups (n=7 per group; *P<0.05, significantly different from the sham group). The bars indicate the mean±standard error of mean.

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