Blood oxygenation-level dependent cerebrovascular reactivity imaging as strategy to monitor CSF-hemoglobin toxicity

Objectives: Cell-free hemoglobin in the cerebrospinal fluid (CSF-Hb) maybe one of the main drivers of secondary brain injury after aneurysmal subarachnoid hemor-rhage (aSAH). Haptoglobin scavenging of CSF-Hb has been shown to mitigate cere-brovascular disruption. Using digital subtraction angiography (DSA) and blood oxygenation-level dependent cerebrovascular reactivity imaging (BOLD-CVR) the aim was to assess the acute toxic effect of CSF-Hb on cerebral blood flow and autor-egulation, as well as to test the protective effects of haptoglobin. Methods: DSA imaging was performed in eight anesthetized and ventilated sheep (mean weight: 80.4 kg) at baseline, 15, 30, 45 and 60 minutes after infusion of hemoglobin (Hb) or co-infusion with haptoglobin (Hb:Haptoglobin) into the left lateral ventricle. Addi-tionally, 10 ventilated sheep (mean weight: 79.8 kg) underwent BOLD-CVR imag-ing to assess the cerebrovascular reserve capacity. Results: DSA imaging did not show a difference in mean transit time or cerebral blood flow. Whole-brain BOLD-CVR compared to baseline decreased more in the Hb group after 15 minutes (Hb vs Hb:Haptoglobin:-0.03 +/- 0.01 vs-0.01 +/- 0.02) and remained diminished compared to Hb:Haptoglobin group after 30 minutes (Hb vs Hb:Haptoglobin:-0.03 +/- 0.01 vs 0.0 +/- 0.01), 45 minutes (Hb vs Hb:Haptoglobin:-0.03 +/- 0.01 vs 0.01 +/- 0.02) and 60 minutes (Hb vs Hb:Haptoglobin:-0.03 +/- 0.02 vs 0.01 +/- 0.01). Conclusion: It is dem-onstrated that CSF-Hb toxicity leads to rapid cerebrovascular reactivity impairment, which is blunted by haptoglobin co-infusion. BOLD-CVR may there-fore be further evaluated as a monitoring strategy for CSF-Hb toxicity after aSAH.