Artikel
Therapeutic effect of inhaled NO on secondary brain damage after subarachnoid hemorrhage in mice
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Autoren
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Sergej Feiler
- Neurochirurgische Klinik, Klinikum der Universität München-Großhadern, Ludwig-Maximilians-Universität, München, Deutschland; Institut für Chirurgische Forschung, Klinikum der Universität München-Großhadern, Ludwig-Maximilians-Universität, München, Deutschland
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S. Thal
- Klinik für Anästhesiologie und Intensivmedizin Johannes Gutenberg-Universität Mainz, Deutschland
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B. Friedrich
- Institut für Chirurgische Forschung, Klinikum der Universität München-Großhadern, Ludwig-Maximilians-Universität, München, Deutschland; Royal College of Surgeons in Ireland, Dublin, Irland
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Nikolaus Plesnila
- Royal College of Surgeons in Ireland, Dublin, Irland
| Veröffentlicht: | 16. September 2010 |
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Gliederung
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Objective: Delayed and possibly also early vasospasm are risk factors for high mortality and poor neurological outcome after subarachnoid hemorrhage (SAH). Among others, cerebral vasospasm may be caused by the release of oxy-hemoglobin from the subarachnoid clot and subsequent scavenging of the endogenous endothelial vasodilator nitric oxide (NO). So far, therapeutic approaches to replenish the post-hemorrhagic lack of NO were not successful due to systemic side effects of the applied NO donors, most importantly, systemic hypotension which worsens cerebral ischemia. Recently, we showed that inhaled NO (NOi) is transported via the blood stream to the brain where it is released in areas of reduced perfusion thus redistributing blood flow to areas in need without systemic side effects. Therefore, the aim of the current study was to investigate the therapeutic potential of NOi after SAH.
Methods: SAH was induced by intraluminal filament perforation model in male C57/Bl6 mice. Anesthesia (midazolam, medetomidine, fentanyl) was applied by intra-peritoneal injection. Cerebral blood flow and intracranial pressure were continuously monitored intra-operatively. After SAH anesthesia was terminated and mice were transferred to cages containing 30% O2, 70% N2 with or without 50 ppm NO. Brain water content and intracranial pressure were determined 24 hours after SAH, neurological deficits were assessed over a period of 7 days using a multi modal outcome score; mortality was recorded over 7 days.
Results: NOi significantly reduced brain edema formation 24 h after SAH (76.7±0.7% vs. 78.2±0.6% in controls; p<0.001) and lowered the mortality during the first week after SAH from 30% in control mice (3/10) to 0% (6/6). There was no significant difference in neurological outcome among surviving animals.
Conclusions: These results support the hypotheses that nitric oxide is involved in secondary brain damage after SAH and that NO inhalation may be a promising strategy for the treatment of SAH.
