gms | German Medical Science

Objective: Early ischemia plays a key role in the pathophysiology of subarachnoid hemorrhage (SAH). One of the possible mechanisms responsible for post-hemorrhagic ischemia are spasms of cerebral microvessels which were demonstrated in patients and recently by us experimentally. Microvasospasms are present as soon as 3 hours after SAH and are detectable for at least 72 hours. Among other things, local depletion of nitric oxide (NO) may be responsible for the formation of microvasospasm. We recently showed that nitric oxide supplied by inhalation (NO – inhalation, iNO) reaches the cerebral circulation and is released preferentially in hypoxic regions thereby improving cerebral perfusion thus reducing brain damage after ischemic stroke and traumatic brain injury. We therefore hypothesized that iNO might be able to replenish a putative NO deficit and thus ameliorate or even reverse microvasospasm after experimental SAH.

Method: SAH was induced in male C57 bl/6 mice by the MCA filament perforation technique under continuous monitoring of ICP and CBF. The cerebral microcirculation was visualized via a left parietal cranial window after i.v. injection of FITC dextran starting 3 hours after SAH. After baseline measurements animals were ventilated with 50 ppm NO. In a second part of the study long-term effects of iNO (24h of iNO, starting 1 hour after SHAH induction) were evaluated; neurological outcome (multi-variate neuroscore), brain water content (wet-dry method), neuronal damage (histomorphometry), and survival were recorded for up to 7 days.

Results: After experimental SAH NO inhalation at 50 ppm significantly reduced occurrence and severity of vasospasms in the cerebral microvasculature. The effect was most pronounced in smaller arterioles (10-25µm). There was no negative effect on MAP. When applied long term, iNO reduced mortality from 30% to 0 over the first 72h. Neurological outcome and neuronal survival was better in iNO treated animals, furthermore the mice had significantly less brain edema formation. No adverse effect on primary homeostasis was observed.

Conclusions: NO inhalation might therefore be a safe and effective strategy to reduce early brain damage after subarachnoid hemorrhage.