Reversal of delayed vasospasm by an inhibitor of the synthesis of 20-HETE

2005 ◽  
Vol 289 (5) ◽  
pp. H2203-H2211 ◽  
Author(s):  
Kazuhiko Takeuchi ◽  
Marija Renic ◽  
Quinn C. Bohman ◽  
David R. Harder ◽  
Noriyuki Miyata ◽  
...  
Keyword(s):  
Blood Flow ◽  
Cerebral Vasospasm ◽  
Time Course ◽  
Cerebral Arteries ◽  
Cerebral Vasculature ◽  
Doppler Flowmetry ◽  
Delayed Cerebral Vasospasm ◽  
A Value ◽  
Intracisternal Injection ◽  
Basilar Arteries

This study characterized the time course of changes in cerebral blood flow (CBF) and vascular diameter in a dual-hemorrhage model of subarachnoid hemorrhage (SAH) in rats and examined whether acute blockade of the synthesis of 20-hydroxyeicosatetraenoic acid (20-HETE) with N-(3-chloro-4-morpholin-4-yl)phenyl- N′-hydroxyimido formamide (TS-011) can reverse delayed vasospasm in this model. Rats received an intracisternal injection of blood (0.4 ml) on day 0 and a second injection 2 days later. CBF was sequentially measured using laser-Doppler flowmetry, and the diameters of the cerebral arteries were determined after filling the cerebral vasculature with a casting compound. CBF fell to 67% of control after the first intracisternal injection of blood but returned to a value near control 24 h later. CBF again fell to 63% of control after a second intracisternal injection of blood and remained 30% below control for 5 days. The fall in CBF after the second intracisternal injection of blood was associated with a sustained 30% reduction in the diameters of the middle cerebral, posterior communicating, and basilar arteries. Acute blockade of the synthesis of 20-HETE with TS-011 (0.1 mg/kg iv), 5 days after the second SAH, increased the diameters of the cerebral arteries, and CBF returned to control. These results indicate that the rats develop delayed vasospasm after induction of the dual-hemorrhage model of SAH and that blockade of the synthesis of 20-HETE fully reverses cerebral vasospasm in this model. They also implicate 20-HETE in the development and maintenance of delayed cerebral vasospasm.

scholarly journals The Phosphodiesterase 3 Inhibitor Cilostazol Dilates Large Cerebral Arteries in Humans without Affecting Regional Cerebral Blood Flow

2004 ◽  
Vol 24 (12) ◽  
pp. 1352-1358 ◽  
Author(s):  
Steffen Birk ◽  
Christina Kruuse ◽  
Kenneth A. Petersen ◽  
Olga Jonassen ◽  
Peer Tfelt-Hansen ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Cerebral Vasospasm ◽  
Regional Cerebral Blood Flow ◽  
Cerebral Arteries ◽  
Superficial Temporal Artery ◽  
Mean Flow ◽  
Regional Cerebral Blood ◽  
Delayed Cerebral Vasospasm

Cilostazol, an inhibitor of phosphodiesterase (PDE) type 3, is used clinically in peripheral artery disease. PDE3 inhibitors may be clinically useful in the treatment of delayed cerebral vasospasm after subarachnoid hemorrhage. The authors present the first results on the effect of cilostazol on cerebral hemodynamics in normal participants. In this double-blind, randomized, crossover study, 200 mg cilostazol or placebo was administered orally to 12 healthy participants. Cerebral blood flow was measured using 133Xe inhalation and single photon emission computerized tomography. Mean flow velocity in the middle cerebral arteries (VMCA) was measured with transcranial Doppler, and the superficial temporal and radial arteries diameters were measured with ultrasonography. During the 4-hour observation period, there was no effect on systolic blood pressure ( P = 0.28), but diastolic blood pressure decreased slightly compared with placebo ( P = 0.04). VMCA decreased 21.5 ± 5.7% after cilostazol and 5.5 ± 12.2% after placebo ( P = 0.02, vs. placebo), without any change in global or regional cerebral blood flow. The superficial temporal artery diameter increased 17.6 ± 12.3% ( P < 0.001 vs. baseline) and radial artery diameter increased 12.6 ± 8.6% ( P < 0.001 vs. baseline). Adverse events, especially headache, were common. The findings suggest that cilostazol is an interesting candidate for future clinical trials of delayed cerebral vasospasm.

scholarly journals Amylin: Localization, Effects on Cerebral Arteries and on Local Cerebral Blood Flow in the Cat

2001 ◽  
Vol 1 ◽  
pp. 168-180 ◽  
Author(s):  
Lars Edvinsson ◽  
Peter J. Goadsby ◽  
Rolf Uddman
Keyword(s):  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Blood Vessels ◽  
Cerebral Arteries ◽  
In Vivo Studies ◽  
Cerebral Blood Vessels ◽  
Local Cerebral Blood Flow ◽  
Doppler Flowmetry

Amylin and adrenomedullin are two peptides structurally related to calcitonin gene-related peptide (CGRP). We studied the occurrence of amylin in trigeminal ganglia and cerebral blood vessels of the cat with immunocytochemistry and evaluated the role of amylin and adrenomedullin in the cerebral circulation by in vitro and in vivo pharmacology. Immunocytochemistry revealed that numerous nerve cell bodies in the trigeminal ganglion contained CGRP immunoreactivity (-ir); some of these also expressed amylin-ir but none adrenomedullin-ir. There were numerous nerve fibres surrounding cerebral blood vessels that contained CGRP-ir. Occasional fibres contained amylin-ir while we observed no adrenomedullin-ir in the vessel walls. With RT-PCR and Real-Time�PCR we revealed the presence of mRNA for calcitonin receptor-like receptor (CLRL) and receptor-activity-modifying proteins (RAMPs) in cat cerebral arteries. In vitro studies revealed that amylin, adrenomedullin, and CGRP relaxed ring segments of the cat middle cerebral artery. CGRP and amylin caused concentration-dependent relaxations at low concentrations of PGF2a-precontracted segment (with or without endothelium) whereas only at high concentration did adrenomedullin cause relaxation. CGRP8-37 blocked the CGRP and amylin induced relaxations in a parallel fashion. In vivo studies of amylin, adrenomedullin, and CGRP showed a brisk reproducible increase in local cerebral blood flow as examined using laser Doppler flowmetry applied to the cerebral cortex of the a-chloralose�anesthetized cat. The responses to amylin and CGRP were blocked by CGRP8-37. The studies suggest that there is a functional sub-set of amylin-containing trigeminal neurons which probably act via CGRP receptors.

scholarly journals Blood flow to bone marrow during development of anemia or polycythemia in the rat

Blood ◽  
1992 ◽  
Vol 79 (3) ◽  
pp. 594-601 ◽  
Author(s):  
PO Iversen ◽  
G Nicolaysen ◽  
HB Benestad
Keyword(s):  
Bone Marrow ◽  
Blood Flow ◽  
Hemolytic Anemia ◽  
Time Course ◽  
Relative Increase ◽  
Detectable Effect ◽  
A Value ◽  
Microsphere Method ◽  
Radioactive Microsphere Method ◽  
Increased Blood Flow

Abstract We applied the radioactive microsphere method to follow the magnitude and time course (0 to 96 hours) of blood flow changes during development and recovery from anemia in awake rats. Blood flow was also monitored during a 96-hour period after polycythemia was induced (erythropoietin administered subcutaneously [SC]). The possible influence of innervation was also examined. After a blood loss of approximately 50% (hypovolemia), blood flow to the femoral marrow tripled within 12 hours and remained elevated for the entire 96-hour period. The relative increase in blood flow to the femoral bone was even greater. Similar findings were obtained in rats with phenylhydrazine (PHZ) hemolytic anemia (normovolemia). Denervation had no detectable effect on the increased blood flow to either marrow or bone. The augmented blood flow during hemolytic anemia was accompanied by a doubling of the oxygen consumption rate by the marrow, while the glucose uptake was not detectably altered. Erythropoietin supplements (3 x 1,000 IU/kg, SC, 6-hour intervals) increased blood flow to the marrow by approximately 25% after 48 hours, and at 72 hours the blood flow had reached a value twice that obtained under control conditions. These results indicate that blood flow to bone marrow is highly variable and hormonally and/or locally regulated. This may have practical consequences for marrow transplantation technology and for administration of drug therapy to patients with insufficient bone marrow hematopoiesis.

scholarly journals Comparison of the Inhibitory Effects of Antithrombin III, α2-Macroglobulin, and Thrombin in Human Basilar Arteries: Relevance to Cerebral Vasospasm

1987 ◽  
Vol 7 (1) ◽  
pp. 68-73 ◽  
Author(s):  
Richard P. White
Keyword(s):  
Cerebral Vasospasm ◽  
Antithrombin Iii ◽  
Cerebral Arteries ◽  
Inhibitory Effect ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Vasorelaxant Effect ◽  
Basal Tone ◽  
At Iii ◽  
Basilar Arteries

Isolated human basilar arteries were used in this study to evaluate the inhibitory effect of antithrombin III (AT III), thrombin, and α2-macroglobulin (α2-M) on contractions elicited by K+, serotonin (5-HT), prostaglandin (PG) D2, PGF2α, and plasmin. α2-M (0.5–1.0 mg/ml) failed to affect the contractions produced by contractile agonists significantly but did notably reduce the basal tone of the arteries. Thrombin (1 and 10 U/ml) reduced basal tone and significantly inhibited the contractions elicited by K+, PGF2α, and plasmin. The relaxant effect of thrombin was abolished by procedures that destroy endothelium and by exposing the artery to thrombin for prolonged periods (tachyphylaxis). AT III (1–6 U/ml) reduced basal tone and significantly inhibited, in a concentration-dependent manner, the contractile responses to K+, 5-HT, PGD2, PGF2α, and plasmin. In sharp contrast to thrombin, AT III did not induce tachyphylaxis nor was its vasorelaxant effect significantly reduced by destruction of the endothelium. The results show AT III to be a potent and nonspecific inhibitor of human cerebral arteries and support the hypothesis that AT III may contribute to the delay of cerebral vasospasm seen in patients who experience aneurysmal hemorrhage.

DELAYED CEREBRAL VASOSPASM SECONDARY TO BACTERIAL MENINGITIS AFTER LUMBOSACRAL SPINAL SURGERY

Neurosurgery ◽  
2007 ◽  
Vol 60 (1) ◽  
pp. E206-E207 ◽  
Author(s):  
Kaisorn Chaichana ◽  
Lee H. Riley ◽  
Rafael J. Tamargo
Keyword(s):  
Case Report ◽  
Cerebral Vasospasm ◽  
Spinal Surgery ◽  
Time Course ◽  
Doppler Sonography ◽  
Clinical Presentation ◽  
Transcranial Doppler Sonography ◽  
Catheter Angiography ◽  
Delayed Cerebral Vasospasm ◽  
Appropriate Therapy

Abstract OBJECTIVE Delayed cerebral vasospasm is an under-recognized complication of meningitis. This case report is important because it is the first to definitively associate vasospasm with meningitis using catheter angiography. Furthermore, it is the first to correlate the time course of delayed cerebral vasospasm with meningitis. CLINICAL PRESENTATION We present a patient who developed a partial expressive aphasia 9 days after developing meningitis, consistent with cerebral vasospasm, after lumbosacral spinal surgery. INTERVENTION Vasospasm was confirmed by angiography and transcranial Doppler sonography, and symptoms responded to hypervolemia, hypertension, and hemodilution therapy. CONCLUSION If a patient develops neurological symptoms consistent with a timeline of delayed cerebral vasospasm in the setting of meningitis, angiographic evaluation and appropriate therapy should be pursued.

scholarly journals Relative Cerebral Ischemia in SHR Due to Hypotensive Hemorrhage: Cerebral Function, Blood Flow and Extracellular Levels of Lactate and Purine Catabolites

1989 ◽  
Vol 9 (3) ◽  
pp. 364-372 ◽  
Author(s):  
Jon O. Skarphedinsson ◽  
Mats Sandberg ◽  
Henrik Hagberg ◽  
Stefan Carlsson ◽  
Peter Thorén
Keyword(s):  
Heart Rate ◽  
Blood Flow ◽  
Cerebral Ischemia ◽  
Cerebral Arteries ◽  
Control Level ◽  
Partial Recovery ◽  
Metabolic Disturbances ◽  
Marked Rise ◽  
Doppler Flowmetry ◽  
Arterial Blood

Cerebral blood flow (CBF, by laser Doppler flowmetry) and extracellular cortical concentrations (by microdialysis) of adenosine, inosine, xanthine, hypoxanthine, and lactate were measured together with somatosensory evoked potentials (SEP) in chloralose-anaesthetized spontaneously hypertensive rats (SHR) during relative cerebral ischemia induced by hypotensive hemorrhage. Reduction of mean arterial blood pressure (MABP) to 40–50 mm Hg, which decreased SEP to about 50% of prebleeding control level, decreased CBF only to about 75% of control due to cerebrovascular “autoregulation.” A secondary, marked rise in cerebrovascular resistance (CVR) occurred after about 15 min in parallel with a striking increase in heart rate (after initial bradycardia). This late rise in heart rate is probably elicited by relative ischemia in medullary centers. The increase in CVR might indicate increased sympathetic nerve activity to the circle of Willis and large cerebral arteries. Cortical lactate increased initially but started to decline after about 30 min, and after 2 h it was not significantly higher than control. Cortical adenosine, inosine, hypoxanthine, and xanthine increased slowly and were significantly elevated after 50 min of hemorrhage. After 80 min, adenosine and inosine had returned to initial levels, while hypoxanthine and xanthine were further elevated. Despite the apparent partial recovery of metabolic disturbances during late hemorrhage, and with a blood flow maintained at 75% of resting control, SEP did not improve. It is suggested that the depression of SEP is not primarily caused by circulatory-metabolic derangements, but instead by activation of specific inhibitory systems.

scholarly journals Concentrations of estradiol, progesterone and testosterone in sefrum and cerebrospinal fluid of patients with aneurysmal subarachnoid hemorrhage correlate weakly with transcranial Doppler flow velocities

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Jan Martin ◽  
Eva Plank ◽  
Bernhard Ulm ◽  
Jens Gempt ◽  
Maria Wostrack ◽  
...  
Keyword(s):  
Blood Flow ◽  
Cerebrospinal Fluid ◽  
Cerebral Blood Flow ◽  
Subarachnoid Hemorrhage ◽  
Cerebral Vasospasm ◽  
Transcranial Doppler ◽  
Aneurysmal Subarachnoid Hemorrhage ◽  
Cerebral Arteries ◽  
Blood Flow Velocities ◽  
Flow Velocities

Abstract Background The implication of the steroids estradiol, progesterone and testosterone in cerebral vasospasm after aneurysmal subarachnoid hemorrhage (aSAH) has not been comprehensively assessed. In rodents, studies suggested beneficial effects of steroids on cerebral vasospasm after experimental SAH. Studies in humans are warranted, however, a general dilemma of human studies on neuroactive substances is that the brain is not directly accessible and that concentrations in the periphery may not adequately parallel concentrations in the central compartments. In the present study, concentrations of estradiol, progesterone and testosterone in serum and cerebrospinal fluid (CSF) of patients with aSAH were determined. Blood flow velocities in cerebral arteries were measured by transcranial Doppler sonography (TCD). The aim of this study was to evaluate the correlations between the cerebral blood flow velocities and levels of estradiol, progesterone and testosterone in CSF and serum. Results Samples of serum and CSF of 42 patients with aSAH were collected concomitantly daily or every other day via the arterial line and the external ventricular drainage for two weeks after the hemorrhage. Blood flow velocities in the cerebral arteries were determined by TCD. Total estradiol, progesterone and testosterone concentrations were measured by electro-chemiluminescence immunoassay. The strength of correlation was assessed by Spearman’s rank correlation coefficient. The correlation analysis revealed very weak correlations between cerebral blood flow velocities and concentrations of estradiol, progesterone and testosterone levels in both compartments with correlation coefficients below 0.2. Conclusions In humans with aSAH, merely very weak correlations between flow velocities in cerebral arteries and concentrations of estradiol, progesterone and testosterone in serum and CSF were demonstrated. These results suggest a limited influence of the respective steroids on cerebral vascular tone although vasodilatory effects were described in rodent studies. Thus, the implication of steroids in processes of neurological deterioration warrants further clarification.

Cerebral vasospasm: contractile activity of hemoglobin in isolated canine basilar arteries

1980 ◽  
Vol 53 (6) ◽  
pp. 787-793 ◽  
Author(s):  
Takeo Tanishima
Keyword(s):  
Cerebral Vasospasm ◽  
Basilar Artery ◽  
Contractile Activity ◽  
Cerebral Arteries ◽  
Adenosine Monophosphate ◽  
Active Species ◽  
Exchange Chromatography ◽  
Basilar Arteries ◽  
Chronic Cerebral Vasospasm

✓ Recent studies suggest the possible role of the red blood cell (RBC) in causing chronic cerebral vasospasm. However, the basic action of hemoglobin (Hb), the major component of the RBC, on cerebral arteries remains unknown. The present study was undertaken to analyze the contractile effects of human Hb (purified by ion-exchange chromatography) on canine arteries in vitro. The contractile activity of lysed RBC was shown to be derived from Hb. Hemoglobin in oxygenated form (oxyHb) caused a maximum contraction equal to about 70% of that induced by serotonin in the basilar artery. Ferrous Hb's (oxyHb and carboxyHb) produced much greater contraction than ferric Hb's (methemoglobin and cyanmethemoglobin), suggesting that superoxide radicals, an active species of oxygen, may be related to the contractile activity of Hb. Neither methysergide, phentolamine, mepyramine, nor aspirin inhibited the vasoconstrictive activity of oxyHb. This finding indicates that the activation of serotonergic, alpha-adrenergic, or histaminergic H1 receptors, or prostaglandin synthesis may not be involved in the mechanism of action of oxyHb. The constituents of Hb caused little or no contraction as compared with Hb as a whole. The basilar artery was more highly sensitive to Hb than arteries from other anatomical locations. Cyclic adenosine monophosphate caused a very slight decrease in the Hb-induced contraction. It is concluded that oxyHb can contract cerebral arteries in vitro. These results, coupled with recent reports on the participation of the RBC in producing chronic vasospasm, strongly suggest that oxyHb released from RBC's plays an important role in the pathogenesis of chronic cerebral vasospasm.

Novel vasodilatory effect of intracisternal injection of magnesium sulfate solution on spastic cerebral arteries in the canine two-hemorrhage model of subarachnoid hemorrhage

2009 ◽  
Vol 110 (1) ◽  
pp. 73-78 ◽  
Author(s):  
Kentaro Mori ◽  
Masahiro Miyazaki ◽  
Yasukazu Hara ◽  
Yasuhisa Aiko ◽  
Takuji Yamamoto ◽  
...  
Keyword(s):  
Subarachnoid Hemorrhage ◽  
Cerebral Vasospasm ◽  
Cerebral Arteries ◽  
Sulfate Solution ◽  
Canine Model ◽  
Superior Cerebellar Artery ◽  
Vasodilatory Effect ◽  
Vertebrobasilar Artery ◽  
Intracisternal Injection ◽  
Before And After

Object The extracellular Mg++ has a vasodilatory effect on the cerebral artery. The present study investigated the effect of intracisternal injection of MgSO4 solution on cerebral vasospasm in a canine model of subarachnoid hemorrhage (SAH). Methods Subarachnoid hemorrhage was induced in 10 beagles using the two-hemorrhage model. Angiography of the vertebrobasilar artery was performed on Day 1 (baseline values before SAH) and on Day 7 (during cerebral vasospasm after induced SAH) before and after intracisternal injection of 0.5 ml/kg of 15 mmol/L MgSO4 solution into the cerebellomedullary cistern. Results The cerebrospinal fluid Mg++ concentration was significantly increased to 3.15 ± 1.14 mEq/L after intracisternal injection from the preinjection value (1.45 ± 0.09 mEq/L; p < 0.01). The diameters of the basilar artery, vertebral artery, and superior cerebellar artery on Day 7 were significantly decreased to 58.0 ± 10.9%, 71.0 ± 10.1%, and 60.9 ± 13.8%, respectively, of their baseline diameters on Day 1 (p < 0.01). After intracisternal injection of MgSO4, these diameters significantly increased to 73.8 ± 14.3%, 83.0 ± 14.8%, and 74.1 ± 13.5%, respectively (p < 0.01). Conclusions Intracisternal injection of MgSO4 solution causes significant dilation of spastic cerebral arteries in the canine two-hemorrhage model of SAH.

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