A review of hemoglobin and the pathogenesis of cerebral vasospasm.

Macdonald, R. Loch; Weir, Bryce

doi:10.1161/01.str.22.8.971

Cited by 545 publications

(341 citation statements)

References 191 publications

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“…Since the heparinized blood (containing 100 U ml À1 heparin) can be assumed to be almost completely devoid of the activity of thrombin and other heparin-sensitive proteinases, the heparin-sensitive proteinases could not account for all mechanisms for the induction of hyper-responsiveness. Known spasmogens such as platelet products (Yanamoto et al, 1992;Tosaka et al, 2001) and free radicals (Macdonald and Weir, 1991) could be other factors contributing to induction of the upregulation of PAR 1 and hyper-contractile responsiveness. Such factors, however, remain to be identified.…”

Section: Discussionmentioning

confidence: 99%

“…The increased production of spasmogens (Macdonald and Weir, 1991;Tosaka et al, 2001) and/or increased vascular responsiveness (Harder et al, 1987;Todo et al, 1998;Sato et al, 2000) is considered to contribute to the development of vasospasm. A clinical study demonstrated that the incidence of post-haemorrhagic vasospasm correlates with the amount of peri-arterial blood clotting (Fisher et al, 1980).…”

Section: Introductionmentioning

confidence: 99%

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Up‐regulation of proteinase‐activated receptor 1 and increased contractile responses to thrombin after subarachnoid haemorrhage

Maeda

Hirano

Kai

et al. 2007

British J Pharmacology

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Background and purpose: The mechanism for the development of post-haemorrhagic cerebral vasospasm after subarachnoid haemorrhage (SAH) still remains unknown. Experimental approach: We investigated the role of thrombin and its receptor PAR 1 in the development of hyper-contractility of the basilar artery in a rabbit double haemorrhage model, which received two injections of autologous blood into the cisterna magna. Key results: In the basilar artery isolated from the control rabbits, thrombin, only at 10 units ml À1 , induced a transient endothelium-dependent relaxation and a slight smooth muscle contraction. In SAH, the contractile response to thrombin was markedly enhanced, while the endothelium-dependent relaxant effect of thrombin remained unchanged. The enhancement of the contractile responses was also observed in the absence of endothelium and thrombin induced an enhanced contraction at concentrations higher than 0.3 units ml À1 . The contractile response to PAR 1 -activating peptide was also enhanced after SAH. However, the contractile responses to high K þ and endothelin-1, and the myofilament Ca 2 þ -sensitivity remained unchanged after SAH. An immunoblot analysis suggested the up-regulation of PAR 1 in the smooth muscle of the basilar artery. The heparinization of blood before injection prevented the enhancement of the contractile responses to thrombin and PAR 1 -activating peptide. Conclusions and implications:The present study demonstrated, for the first time, that the contractile response of the basilar artery to thrombin was markedly enhanced after SAH. Mechanistically, our findings suggested that the activation of thrombin following hemorrhage up-regulated the expression of PAR 1 , thereby inducing the hyper-responsiveness to thrombin.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Up‐regulation of proteinase‐activated receptor 1 and increased contractile responses to thrombin after subarachnoid haemorrhage

Maeda

Hirano

Kai

et al. 2007

British J Pharmacology

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“…That is, delayed vasospasm is maximal at about a week after SAH at a time when CSF levels of Hb are low. Nevertheless, if Hb concentrations were very high in the clot immediately adjacent to blood vessels, and are substantially different than what is detected in the CSF, Hb could contribute to delayed vasospasm in brain after SAH (Janjua and Mayer, 2003;Macdonald and Weir, 1991).…”

Section: Two Classes Of Compounds That Could Cause Vasospasmmentioning

confidence: 97%

BilirubinOxidation Products (BOXes) and Their Role in Cerebral Vasospasm after Subarachnoid Hemorrhage

Clark

Sharp

2006

J Cereb Blood Flow Metab

113

110

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Many factors have been postulated to cause delayed subarachnoid hemorrhage (SAH)-induced vasospasm, including hemoglobin, nitric oxide, endothelin, and free radicals. We propose that free radicals (because of the high levels that are produced in the blood clots surrounding blood vessels after SAH) act on bilirubin, biliverdin, and possibly heme to produce BOXes (Bilirubin OXidized Products). Bilirubin oxidation products act on vascular smooth muscle cells to produce chronic vasoconstriction and vasospasm combined with a vasculopathy because of smooth muscle cell injury. This review summarizes recent evidence that BOXes play a role in SAH-induced vasospasm. The data supporting a role for BOXes includes (1) identification of molecules in cerebrospinal fluid (CSF) of patients with vasospasm after SAH that have structures consistent with BOXes; (2) BOXes are vasoactive in vitro and mimic the biochemical actions of CSF of patients with vasospasm; (3) BOXes are vasoactive in vivo, constricting rat cerebral vessels; and (4) there is a correlation between clinical occurrence of vasospasm and BOXes concentration in our preliminary study of patients with SAH. Since oxidation of bilirubin, biliverdin, and perhaps heme is proposed to produce BOXes that contribute to vasospasm, either blocking bilirubin formation, inactivating bilirubin or BOXes, or removing all of the blood clot before vasospasm are potential treatment targets.

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“…16) Cerebral vasospasm is associated with decreased local synthesis of nitric oxide (NO) caused by disturbed endothelial NO synthetase activity due to endothelial cell damage. Local concentrations of NO are also reduced due to the high binding affinity with oxyhemoglobin (oxyHb) derived from the subarachnoid clot around the brain surface and major blood vessels.…”

Section: Introductionmentioning

confidence: 99%

“…Local concentrations of NO are also reduced due to the high binding affinity with oxyhemoglobin (oxyHb) derived from the subarachnoid clot around the brain surface and major blood vessels. 16,17) NO is involved in the regulation of the cerebral circulation, and is accepted as the most effective relaxing agent for the cerebral arterial network, and participates in the maintenance of resting cerebrovascular tone. 7,8) Depletion of NO is thought to be important in the pathogenesis of cerebral vasospasm.…”

Section: Introductionmentioning

confidence: 99%

In Vitro Effects of New Generation Fungal Derived Nitric Oxide Donors on Rabbit Basilar Artery

Islam

Ohkuma

Kimura

et al. 2003

Neurol. Med. Chir.(Tokyo)

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The fungal derived nitric oxide donors, (E)-ethyl-2-[(E)-hydroxyimino]-5-nitro-3-hexenamide (FK409) and N-[(E)-4-ethyl-3-[(Z)-hydroxyimino]-5-nitro-3-hexen-1-yl]-3-pyridinecarboxamide (FR144420), were evaluated for the treatment and prevention of cerebral vasospasm induced by subarachnoid hemorrhage (SAH) by an in vitro study using rabbit basilar artery. The tension-relaxation of a 3 mm-long artery segment was carried out in a micro-tissue organ bath with a real-time recorder to record the tension-relaxation curve. Steady contraction of the specimens was induced by KCl (n ＝ 12) and oxyhemoglobin (oxyHb) (n ＝ 12). Sodium nitroprusside was used for comparison. Each of the agents was added in ascending concentration. Relaxation caused by FK409 and FR144420 was significantly greater (p º 0.05) than that by sodium nitroprusside. Relaxation effects of FK409 and FR144420 on the KCl-induced steady contraction were better than those on the oxyHb-induced contraction. FK409 and FR144420 have potential uses for the treatment and prevention of SAH-induced cerebral vasospasm.

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A review of hemoglobin and the pathogenesis of cerebral vasospasm.

Cited by 545 publications

References 191 publications

Up‐regulation of proteinase‐activated receptor 1 and increased contractile responses to thrombin after subarachnoid haemorrhage

Up‐regulation of proteinase‐activated receptor 1 and increased contractile responses to thrombin after subarachnoid haemorrhage

BilirubinOxidation Products (BOXes) and Their Role in Cerebral Vasospasm after Subarachnoid Hemorrhage

In Vitro Effects of New Generation Fungal Derived Nitric Oxide Donors on Rabbit Basilar Artery

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