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Effect of hemorrhagic shock duration on the activity of nuclear Ca2+/Mg(2+)-dependent DNA-endonucleases in canine
V L Kozhura1, N V Nosova, I S Novoderzhkina
1Institute for General Reanimatology, Russian Academy of Medical Sciences, Moscow.
Insights
Hemorrhagic shock in dogs significantly increases nuclear DNA-endonuclease activity, particularly after 2 hours. This enzyme activity correlates with neuronal nuclear damage during prolonged shock.
Area of Science:
- Biochemistry
- Cell Biology
- Pathophysiology
Background:
- Hemorrhagic shock can lead to cellular damage.
- Nuclear enzymes play a role in cellular processes.
- The impact of shock on nuclear DNA-endonuclease activity is not fully understood.
Purpose of the Study:
- To investigate the correlation between the duration of arterial hypotension during hemorrhagic shock and nuclear Ca2+/Mg(2+)-dependent DNA-endonuclease activity in dogs.
- To examine the structural changes in neuron nuclei during hemorrhagic shock.
Main Methods:
- Induction of hemorrhagic shock in dogs.
- Measurement of nuclear Ca2+/Mg(2+)-dependent DNA-endonuclease activity at various time points.
- Electron-microscopic analysis of neuron nuclei structure.
Main Results:
- A direct correlation was found between the duration of hypotension and increased DNA-endonuclease activity.
- Significant increases in enzyme activity were observed after 2 hours of hypotension, rising further with prolonged shock.
- Electron microscopy revealed reduced chromatin and clarified nuclear matrices in neurons after 2-4 hours of shock.
Conclusions:
- Increased nuclear endonuclease activity is a significant factor in neuronal nuclear damage during prolonged hemorrhagic shock.
- Endonuclease-mediated DNA degradation may contribute to the destructive processes observed in cortical neurons.
Abstract:
A direct correlation between the duration of arterial hypotension (40 mmHg) and the activity value of nuclear Ca2+/Mg(2+)-dependent DNA-endonucleases was revealed in dogs exposed to hemorrhagic shock. Thus, an increase in the activity of endonucleases was significant after 2 h of arterial hypotension. During that period there activity amounted to 4149 +/- 295 units/mg of protein instead of 2839 +/- 231 units/mg protein in the control (P < 0.01). With the prolonged hemorrhagic shock, the activity of DNA-endonucleases continued to increase. By 4 h of hemorrhagic shock it reached 5021 +/- 443 units/mg protein and by 6 h, 8661 +/- 338 units/mg protein which was three times the control values (P < 0.01). An electron-microscopic study of the structure of neuron nuclei karioplasm showed that by 2-4 h of hemorrhagic shock some neurons showed reduced chromatin content, and the nuclear matrix had clarified with the formation of electron-translucent empty zones. We think that the sharp increase in the nuclear endonuclease activity and the subsequent endonucleolysis can be regarded as a pathogenetic factor in the destructive processes taking place in the nuclei of cortex neurons during prolonged periods of hemorrhagic shock.