[The nitric oxide metabolism in the hypoxic, ischemic and reperfused human skeletal muscle cell: clinical and therapeutical observations].

Abstract

BACKGROUND:

The biochemical and metabolic role played by nitric oxide (NO) in course of oxidative stress due to cell hypoxia, ischemia and reperfusion has a determinant relevance in the mitochondrial adaptive changes which antagonize the irreversible morpho-functional damage. In particular conditions, such as in prolonged ischemia and/or exogenous NO supplementation, this element is present in the radical form (NOO*) concurring to peroxidative cell injury. Aim of this study was to investigate these opposite NO aspects in hypoxic, ischemic and reperfused human skeletal muscle tissue.

METHODS:

Skeletal muscle samples were taken during elective knee orthopedic surgery in 10 consecutive patients. The biopsies were obtained before, after 5+/-1 min and 58+/-2 min from tourniquet application and then after 18+/-3 min following muscle reperfusion. The samples, immediately frozen in liquid nitrogen, were assayed for endocellular free NO following the gas-amperometric method described by Palmerini C.

RESULTS:

When compared with normoxic tissues, a significant decrease in free NO content was observed in hypoxic samples. After about 60 min of prolonged ischemia the NO levels show an evident increase, while the tissue reperfusion leads to a progressive restoration of physiological content in the cellular free nitric oxide.

CONCLUSIONS:

The obtained data in hypoxic muscle cell seem to underline the pivotal role played by NO in adapting the cytochrome c oxidase oxidative activity to lower O2 bio-availability. On the other hand the prolonged ischemia leads to a consistent NOO* generation triggered by oxyradical generation and Ca2+ intracellular over load. Even if the tissue reoxygenation restores the normal NO levels it is arguable that the pre-treatment of ischemic cell with antioxidants, Ca-antagonist and Dexamethasone supplementation could represent a crucial and specific therapeutic approach to critically ill patient.

• Authors: G G Corbucci, C Palmerini, R Palombari, B Lettieri, E Grella, C Velluti, C Chelo
• Journal: Minerva anestesiologica (Minerva Anestesiol) Vol. 67 Issue 5 Pg. 387-92 (May 2001) ISSN: 0375-9393 [Print] Italy
• Vernacular Title: L'ossido nitrico nella cellula muscolare umana ischemica e riperfusa: connessioni cliniche e terapeutiche.
• PMID: 11382828 (Publication Type: English Abstract, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Nitric Oxide

Topics

• Adult
• Cell Hypoxia
• Female
• Humans
• In Vitro Techniques
• Ischemia (metabolism)
• Male
• Muscle, Skeletal (blood supply, cytology, metabolism)
• Nitric Oxide (metabolism)
• Regional Blood Flow
• Reperfusion