gms | German Medical Science

Objective: CSDs have been detected in patients within days after SAH, often accompanied by inverse vasomotor responses (spreading ischemia, Dreier et al., 2013). While no CSDs were detectable in animal models at 3-78h after SAH (Oka et al., 2017), there is strong evidence for a very early occurrence of CSDs within the first hours after SAH (Hartings et al., 2017; Shimizu et al., 2018). We elicited CSDs up to 6 h after SAH and characterized their haemodynamic responses.

Methods: For preliminary analysis, in 15 male Wistar rats (4 excluded, 11 used for analysis; 6 SAH, 5 sham), SAH was induced by cisterna magna injection of autologous blood (0.5ml, 60s), and ICP, MAP, EEG and CBF (laser speckle analysis) were recorded up to 6h after SAH under isoflurane-fentanyl. CSDs were elicited at 30min and every hour after SAH by short topical application of KCl. CBF changes were calculated as % change from baseline before blood injection, and CSD responses were analyzed for initial hypoperfusion and peak hyperemia as % change of CBF from pre-CSD values. Data in the figure are presented as median (25/75percentile, min and max), tested for significance by 2way ANOVA and Sidak’s multiple comparison with p<0.05 as significance level.

Results: After blood injection, CBF dramatically decreased to 8 (+/-3)% followed by a continuous recovery until 3–6h. Despite fast removal of KCl, small clusters of CSDs were not always avoidable, with no difference in the mean total numbers of CSDs per animal (SAH: 11.5, sham: 11). CBF responses were analyzed only on first CSD of a cluster. Under sham conditions, 56 (+/-21)% of the CSDs showed an initial hypoperfusion and all CSDs induced a strong hyperemia, whereas after SAH, in 92 (+/-11)% an initial hypoperfusion and in 90 (+/-9)% a mild hyperemia was detected. There was a tendency towards a stronger initial hypoperfusion in SAH compared to sham at each time point (p<0.05 at 3h, [Figure 1 left [Fig. 1]]). Hyperemia was significantly larger in sham compared with SAH at all time points >30min [Figure 1 right [Fig. 1]].

Conclusion: Our data demonstrate that CSDs elicited in the early phase after SAH show less hyperemia and a tendency towards stronger initial hypoperfusion, starting from already reduced resting CBF values after SAH. It can be speculated that these vasomotor responses also occur with spontaneous CSDs and may contribute to tissue damage already at these early time points.