Nitrite infusions to prevent delayed cerebral vasospasm in a primate model of subarachnoid hemorrhage - PubMed (original) (raw)
Nitrite infusions to prevent delayed cerebral vasospasm in a primate model of subarachnoid hemorrhage
Ryszard M Pluta et al. JAMA. 2005.
Abstract
Context: Delayed cerebral vasospasm causes permanent neurological deficits or death in at least 15% of patients following otherwise successful treatment for ruptured intracranial aneurysm. Decreased bioavailability of nitric oxide has been associated with the development of cerebral vasospasm.
Objective: To determine whether infusions of nitrite will prevent delayed cerebral vasospasm.
Design, setting, and subjects: A total of 14 anesthetized cynomolgus monkeys had an autologous blood clot placed around the right middle cerebral artery. Cerebral arteriography was performed before clot placement and on days 7 and 14 to assess vasospasm. The study was conducted from August 2003 to February 2004.
Interventions: A 90-mg sodium nitrite intravenous solution infused over 24 hours plus a 45-mg sodium nitrite bolus daily (n = 3); a 180-mg sodium nitrite intravenous solution infused over 24 hours (n = 3); or a control saline solution infusion (n = 8). Each was infused continuously for 14 days.
Main outcome measures: Nitrite, S-nitrosothiol, and methemoglobin levels in blood and cerebrospinal fluid and degree of arteriographic vasospasm.
Results: In control monkeys, mean (SD) cerebrospinal fluid nitrite levels decreased from 3.1 (1.5) micromol/L to 0.4 (0.1) micromol/L at day 7 and to 0.4 (0.4) micromol/L at day 14 (P = .03). All 8 control monkeys developed significant vasospasm of the right middle cerebral artery, which was complicated by stroke and death in 1 animal. Sodium nitrite infusions increased the nitrite and methemoglobin levels (<2.1% of total hemoglobin) in the blood and cerebrospinal fluid without evoking systemic hypotension. Nitrite infusion prevented development of vasospasm (no animals developed significant vasospasm; mean [SD] reduction in right middle cerebral artery area on day 7 after subarachnoid hemorrhage of 8% [9%] in nitrite-treated monkeys vs 47% [5%] in saline-treated controls; P<.001). There was a negative correlation between the concentration of nitrite in cerebrospinal fluid and the degree of cerebral vasospasm (P<.001). Pharmacological effects of nitrite infusion were also associated with the formation of S-nitrosothiol in cerebrospinal fluid. There was no clinical or pathological evidence of nitrite toxicity.
Conclusion: Subacute sodium nitrite infusions prevented delayed cerebral vasospasm in a primate model of subarachnoid hemorrhage.
Comment in
- Methodological standards in human vs animal clinical trials.
Heard K, Bebarta VS, Lowenstein SR. Heard K, et al. JAMA. 2005 Jul 6;294(1):40; author reply 40-1. doi: 10.1001/jama.294.1.40-a. JAMA. 2005. PMID: 15998885 No abstract available.
Similar articles
- Reversal of cerebral vasospasm via intravenous sodium nitrite after subarachnoid hemorrhage in primates.
Fathi AR, Pluta RM, Bakhtian KD, Qi M, Lonser RR. Fathi AR, et al. J Neurosurg. 2011 Dec;115(6):1213-20. doi: 10.3171/2011.7.JNS11390. Epub 2011 Sep 2. J Neurosurg. 2011. PMID: 21888479 Free PMC article. - Increased cerebral blood flow but no reversal or prevention of vasospasm in response to L-arginine infusion after subarachnoid hemorrhage.
Pluta RM, Afshar JK, Thompson BG, Boock RJ, Harvey-White J, Oldfield EH. Pluta RM, et al. J Neurosurg. 2000 Jan;92(1):121-6. doi: 10.3171/jns.2000.92.1.0121. J Neurosurg. 2000. PMID: 10616090 - Delayed cerebral vasospasm and nitric oxide: review, new hypothesis, and proposed treatment.
Pluta RM. Pluta RM. Pharmacol Ther. 2005 Jan;105(1):23-56. doi: 10.1016/j.pharmthera.2004.10.002. Pharmacol Ther. 2005. PMID: 15626454 Review. - Sodium nitrite as a therapeutic agent for central nervous system diseases.
Pluta RM, Oldfield EH. Pluta RM, et al. Surg Neurol. 2006 Jul;66(1):5-7; discussion 8-10. doi: 10.1016/j.surneu.2005.10.017. Surg Neurol. 2006. PMID: 16793425 Review. No abstract available.
Cited by
- Nitrite as regulator of hypoxic signaling in mammalian physiology.
van Faassen EE, Bahrami S, Feelisch M, Hogg N, Kelm M, Kim-Shapiro DB, Kozlov AV, Li H, Lundberg JO, Mason R, Nohl H, Rassaf T, Samouilov A, Slama-Schwok A, Shiva S, Vanin AF, Weitzberg E, Zweier J, Gladwin MT. van Faassen EE, et al. Med Res Rev. 2009 Sep;29(5):683-741. doi: 10.1002/med.20151. Med Res Rev. 2009. PMID: 19219851 Free PMC article. Review. - Nitrite reductase activity of myoglobin regulates respiration and cellular viability in myocardial ischemia-reperfusion injury.
Hendgen-Cotta UB, Merx MW, Shiva S, Schmitz J, Becher S, Klare JP, Steinhoff HJ, Goedecke A, Schrader J, Gladwin MT, Kelm M, Rassaf T. Hendgen-Cotta UB, et al. Proc Natl Acad Sci U S A. 2008 Jul 22;105(29):10256-61. doi: 10.1073/pnas.0801336105. Epub 2008 Jul 16. Proc Natl Acad Sci U S A. 2008. PMID: 18632562 Free PMC article. - Dysfunction of nitric oxide synthases as a cause and therapeutic target in delayed cerebral vasospasm after SAH.
Pluta RM. Pluta RM. Acta Neurochir Suppl. 2008;104:139-47. doi: 10.1007/978-3-211-75718-5_28. Acta Neurochir Suppl. 2008. PMID: 18456999 Free PMC article. Review. - Sodium nitrite promotes regional blood flow in patients with sickle cell disease: a phase I/II study.
Mack AK, McGowan Ii VR, Tremonti CK, Ackah D, Barnett C, Machado RF, Gladwin MT, Kato GJ. Mack AK, et al. Br J Haematol. 2008 Sep;142(6):971-8. doi: 10.1111/j.1365-2141.2008.07259.x. Epub 2008 Jul 11. Br J Haematol. 2008. PMID: 18671702 Free PMC article. Clinical Trial. - Preserving vessel function during ischemic disease: new possibilities of inorganic nitrite therapy.
Kevil CG, Patel RP. Kevil CG, et al. Expert Rev Cardiovasc Ther. 2008 Oct;6(9):1175-9. doi: 10.1586/14779072.6.9.1175. Expert Rev Cardiovasc Ther. 2008. PMID: 18939904 Free PMC article. No abstract available.
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources