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Lipid peroxidation as a cause of cerebral vasospasm
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Free radical reactions from clot lysis, like lipid peroxidation, contribute to chronic vasospasm after subarachnoid hemorrhage (SAH). This study shows increased vasocontractile capacity and substances linked to vasospasm in SAH patients.
Area of Science:
- Biomedical Research
- Vascular Biology
- Neuroscience
Background:
- Subarachnoid hemorrhage (SAH) is often complicated by cerebral vasospasm.
- The exact mechanisms underlying chronic vasospasm in SAH remain incompletely understood.
- Free radical reactions are implicated in various pathological processes.
Purpose of the Study:
- To investigate the role of free radical reactions, specifically lipid peroxidation, in the development of vasospasm following SAH.
- To examine the vasocontractile activities of various substances in vitro and in vivo.
- To correlate biochemical markers with clinical vasospasm in SAH patients.
Main Methods:
- In vitro assessment of vasocontractile activities of oxyhemoglobin, methemoglobin, lipid peroxides, and hydrogen peroxide on canine basilar arteries.
- Incubation of canine arterial blood to monitor changes in vasocontractile capacity and TBA-reactive substances over time.
- Clinical study of SAH patients measuring TBA-reactive substances in cerebrospinal fluid (CSF).
- In vivo study in dogs involving cisternal injection of 15-hydroxyeicosatetraenoic acid (15-HPAA) and subsequent histological analysis of basilar arteries.
Main Results:
- In vitro, all tested substances exhibited dose-dependent vasocontractile effects.
- Incubated arterial blood showed parallel increases in vasocontractile capacity and TBA-reactive substances.
- SAH patients with angiographically confirmed vasospasm had elevated TBA-reactive substances in CSF.
- Cisternal injection of 15-HPAA induced initial and prolonged basilar artery contraction.
- Histological examination revealed endothelial cell destruction and media damage consistent with vasospasm.
Conclusions:
- Lipid peroxidation, a marker of free radical reactions initiated by clot lysis, plays a significant role in the pathogenesis of chronic vasospasm in SAH.
- These findings provide a mechanistic link between blood degradation products and vascular dysfunction after SAH.
- The study highlights potential therapeutic targets for preventing or treating vasospasm in SAH.
Abstract:
In the present study, the vasocontractile activities of purified oxyhemoglobin, methemoglobin, peroxides of linoleic and arachidonic acid, and hydrogen peroxide were examined in vitro, using the canine basilar artery. It was shown that all of them possess a vasocontractile capacity in a dose-dependent fashion. Fresh canine arterial blood was incubated at 37 degree C for 2 weeks, and the daily change of its vasocontractile capacity and the amount of TBA-reactive substance was studied. This study revealed a gradual and parallel increase in both of them. In a clinical study with 32 SAH patients, the amount of TBA-reactive substance in the CSF was more elevated when angiographically confirmed vasospasm was present. The angiographical and histological responses of the basilar artery to the cisternal injection of 15-HPAA were studied in dogs. The cisternal injection of 15-HPAA (0.2 and 2.0 mg dissolved in bovine serum) caused a mild initial contraction of the basilar artery that lasted about 7 hours. On the third day, a stronger contraction occurred, persisting thereafter until sacrifice. Electronmicroscopy of those arterial samples revealed the disappearance of myofibrils, pyknotic changes of nuclei, and the appearance of vacuoles as well as electron-dense granules in the tunica media. The prolonged arterial contraction was always associated with remarkable destruction of the endothelial cells. These changes were essentially the same as those in experimental and clinical vasospasm. These data strongly indicate that free radical reactions initiated by clot lysis, represented by lipid peroxidation, plays an important role in the genesis of chronic vasospasm in subarachnoid hemorrhage.