This document discusses cerebral vasospasm that can occur after subarachnoid hemorrhage (SAH) in 30-60% of patients. It presents a study investigating sodium nitrite (NaNO2) as a potential new therapeutic option for treating and reversing vasospasm through nitric oxide replacement. The study administered NaNO2 via continuous intravenous infusion to cynomolgus macaques and found it was effective and safe at reversing established vasospasm without changes in vital signs. Further investigation is still needed to evaluate the treatment in patients.

2. Object
• SAH-vasospasm
– 30~60%
– between days 3 and 12 post-SAH
– 30%: suffer major neurological deficits
• the lack of effective treatment paradigms
– need new therapeutic options

3. Object
• NO (nitric oxide) replacement Tx
– directly contribute to vasospasm
– classic NO donors
• sodium nitroprusside, nitroglycerin
• adverse effects
– drop in blood pressure
– drug tolerance
– rebound phenomenon
– new NO donor: NaNO2(sodium nitrite)
• can effectively prevent SAH-induced vasospasm
• not known if it can reverse vasospasm

4. Methods
• Animal population
– Fourteen cynomolgus macaques (3-
12kg)
• SAH clot placement
– the proximal 14mm of the right MCA, distal
ICA, proximal ACA
– autologous blood (Lt femoral a.)
– 5cc clot was placed around the exposed arteries

5. Methods
• Sodium Nitrite
– obtained from the NIH Pharmacy
– treatment dose
• the maximum tolerated dose in a healthy human
volunteer phase I safety and toxicity study
• 300mcg/kg/hr
• Experimental design

6. Results

8. Results

11. Discussion
• Currently available methods
– balloon angioplasty
– direct intraarterial administration of
papaverine, nicardipine to the affected arteries
– hemodynamic therapy
• transient and/or ineffective
– complications
• thromboembolism, vessel rupture, arterial
dissection, bleeding
• intrease in ICP

12. Discussion
• the therapeutic effect lasts the duration of the
infusion and approximately 4 hrs after
cessation of the infusion
• continuous infusion over 8 hrs
– can be sustained if the infusion is not
discontunued
• contunuous NaNO2 infusion during spasm
– could provide continued therapeutic effect
• no change
– HR, BP, RR

13. Discussion
• Limitation
– animal model
– cardiac
dysfunction, hydrocephalus, increased ICP
which can occur in Pts with SAH
– combination of other pharmaceutical agents
(CCB)
• require further investigation

14. Conclusions
• Intravenous infusion of NaNO2
– safe, effective for reversing established
cerebral vasospasm after SAH in a primate
model
– this treatment strategy may be useful