Related Experiment Videos
[Effects of anti-rhTNF alpha monoclonal antibody on oxygen extraction in endotoxemic rabbits]
1Department of Aerospace Physiology, The Fourth Military Medical University, Xi'an.
Abstract:
The effects of anti-rhTNF alpha monoclonal antibody (McAb) on oxygen extraction in endotoxemia rabbits were observed by decreasing total oxygen delivery (DO2) with progressive hypoxia. The result showed that the DO2-VO2 relationship in anti-rhTNF alpha McAb group, like the control group, could be clearly divided into "independent" and "dependent" segment, while the non-correlated antibody group, like the endotoxemic group, never presented any plateau upon breathing the air. Critical oxygen delivery (DO2C) and pooled oxygen extraction rate (ER) in anti-rhTNF alpha McAb group were respectively 10.18 +/- 3.21 ml/(min.kg) and 0.690, not significantly different from those in the control group (10.18 +/- 1.69 and 0.730). The ER in non-correlated antibody group was 0.408, which was significantly lower than that in anti-rhTNF alpha McAb group (P < 0.05), while the plasma TNF alpha concentration was significantly higher (P < 0.01). It was concluded that the monoclonal antibody of recombinant human tumor necrosis factor could block or even reverse the pathologic process of oxygen extraction deficiency caused by endotoxemia.
Insights
Recombinant human tumor necrosis factor-alpha monoclonal antibody treatment improved oxygen extraction in endotoxemic rabbits. This therapy reversed endotoxemia-induced oxygen deficiency, restoring normal oxygen delivery and utilization.
Area of Science:
- Physiology
- Immunology
- Pharmacology
Context:
- Endotoxemia, a condition caused by bacterial endotoxins, leads to significant physiological derangements, including impaired oxygen metabolism.
- Tumor necrosis factor-alpha (TNF-α) plays a critical role in the inflammatory cascade during endotoxemia, contributing to cellular dysfunction and altered oxygen extraction.
- Understanding the impact of targeted therapies on oxygen delivery and utilization is crucial for managing sepsis and related conditions.
Purpose:
- To investigate the efficacy of an anti-TNF-α monoclonal antibody in mitigating the detrimental effects of endotoxemia on oxygen extraction in a rabbit model.
- To determine if blocking TNF-α can restore the normal relationship between oxygen delivery (DO2) and oxygen consumption (VO2) during progressive hypoxia in endotoxemia.
- To compare the critical oxygen delivery (DO2C) and oxygen extraction rate (ER) in rabbits treated with anti-TNF-α antibody versus control and non-correlated antibody groups.
Summary:
- Treatment with an anti-TNF-α monoclonal antibody in endotoxemic rabbits prevented the development of oxygen extraction deficiency, maintaining a normal DO2-VO2 relationship.
- The anti-TNF-α antibody group exhibited preserved critical oxygen delivery (DO2C) and oxygen extraction rates (ER), comparable to healthy controls.
- In contrast, rabbits receiving a non-correlated antibody showed significantly impaired oxygen extraction and elevated plasma TNF-α levels, highlighting the specific role of TNF-α.
Impact:
- The findings suggest that targeting TNF-α with monoclonal antibodies can effectively counteract the oxygen metabolism abnormalities induced by endotoxemia.
- This therapeutic strategy holds potential for reversing or blocking the pathological processes that lead to oxygen extraction deficiency in sepsis.
- The study provides a basis for exploring anti-TNF-α therapies as a treatment modality to improve tissue oxygenation and outcomes in patients with endotoxemia and sepsis.