Vasodilatation effect of farnesylacetones,active constituents of Sargassum siliquastrum,on the basilar and carotid arteries of rabbits

Two farnesylacetones, 311 and 312, major active constituents of Sargassum siliquastrum collected from the coast of the East Sea in Korea, showed a moderate vasodilatation effect on the basilar arteries of rabbits. Therefore, treatment with farnesylacetones 311 and 312 may selectively accelerate cerebral blood flow through dilatation of the basilar artery.     

Arachidonate dilates basilar artery by lipoxygenase-dependent mechanism and activation of K(+) channels

Dilatation of cerebral arterioles in response to arachidonic acid is dependent on activity of cyclooxygenase. In this study, we examined mechanisms that mediate dilatation of the basilar artery in response to arachidonate. Diameter of the basilar artery (baseline diameter = 216 +/- 7 micrometer) (means +/- SE) was measured using a cranial window in anesthetized rats. Arachidonic acid (10 and 100 microM) produced concentration-dependent vasodilatation that was not inhibited by indomethacin (10 mg/kg iv) or N(G)-nitro-L-arginine (100 microM) but was inhibited markedly by baicalein (10 micrometerM) or nordihydroguaiaretic acid (NDGA; 10 microM), inhibitors of the lipoxygenase pathway. Dilatation of the basilar artery was also inhibited markedly by tetraethylammonium ion (TEA; 1 mM) or iberiotoxin (50 nM), inhibitors of calcium-dependent potassium channels. For example, 10 microM arachidonate dilated the basilar artery by 19 +/- 7 and 1 +/- 1% in the absence and presence of iberiotoxin, respectively. Measurements of membrane potential indicated that arachidonate produced hyperpolarization of the basilar artery that was blocked completely by TEA. Incubation with [(3)H]arachidonic acid followed by reverse-phase and chiral HPLC indicated that the basilar artery produces relatively small quantities of prostanoids but large quantities of 12(S)-hydroxyeicosatetraenoic acid (12-S-HETE), a lipoxygenase product. Moreover, the production of 12-HETE was inhibited by baicalein or NDGA. These findings suggest that dilatation of the basilar artery in response to arachidonate is mediated by a product(s) of the lipoxygenase pathway, with activation of calcium-dependent potassium channels and hyperpolarization of vascular muscle.     

Angiology of the brain of the baboon Papio ursinus, the vervet monkey Cercopithecus pygerithrus, and the bushbaby Galago senegalensis

The investigation was undertaken to compare the blood supply and venous drainage of the brain of the baboon P. ursinus, the vervet monkey C. pygerithrus, and the bushbaby G. senegalensis with that of man, because these animals are extensively used as research models. The blood supply of the three primates was found to be similar in each case. Like man they have a complete circulus arteriosus; but they have a single anterior cerebral artery, whereas man has paired anterior cerebral arteries. The arterial supply to the cerebellum in the primates is similar to that in man, the main difference being a "common inferior cerebellar artery" which bifurcates to form the anterior inferior cerebellar and posterior inferior cerebellar arteries. In man, these arteries arise separately from the basilar artery and vertebral arteries, respectively. The dural venous drainage was also found to be similar in these primates but was far more extensive than in man. The primates have additional sinuses--the more important of these being the "basisphenoid sinus" and the petrosquamous sinus. The former drains the basilar sinus and is itself drained via the vertebral venous plexus and internal jugular vein. The latter drains via the petrosquamous foramen into the retromandibular vein. The petrosquamous sinus has a rostral extension which drains through the foramen ovale and two lateral and medial connecting sinuses which drain the cavernous and basilar sinuses, respectively. These sinuses are not found in man.     

Activation of the Arachidonate 5-Lipoxygenase Pathway in the Canine Basilar Artery After Experimental Subarachnoidal Hemorrhage

Severe cerebral vasospasm as confirmed by angiography was induced in dogs by injection of autologous blood into the cisterna magna, and the resultant leukotriene formation in the isolated basilar artery was examined. When stimulated with calcium ionophore (A 23187), the arteries of the treated animals produced a significant amount of leukotrienes B4 (85 +/- 12 pmol/mg protein, n = 3) and C4 (72 +/- 14 pmol/mg), in addition to 5(S)-hydroxy-6,8,11,14-eicosatetraenoic acid. Structural elucidations of these metabolites were performed by radioimmunoassays or gas chromatography-mass spectrometry, following purification with HPLC. The artery of the untreated dog produced none of these compounds from either exogenous or endogenous arachidonic acid, under stimulation with the calcium ionophore. However, the homogenates from both animals converted exogenous leukotriene A4 to leukotrienes B4 and C4. These observations suggest that the normal basilar artery contains no detectable amount of 5-lipoxygenase, and that a prominent activation of this enzyme occurred (2.1 nmol 5-HETE/5 min/mg of protein) after subarachnoidal hemorrhage. The observation that fatty acid hydroperoxides stimulated the 5-lipoxygenase activity indicates a possible role of lipid peroxides in the development of vasospasm.     

Role of Cl- current in endothelin-1-induced contraction in rabbit basilar artery

Cl- efflux induces depolarization and contraction of smooth muscle cells. This study was undertaken to explore the role of Cl- channels in endothelin-1 (ET-1)-induced contraction in rabbit basilar artery. Male New Zealand White rabbits (n = 26), weighing 1.8-2.5 kg, were euthanized by an overdose of pentobarbital. The basilar arteries were removed for isometric tension recording. ET-1 produced a concentration-dependent contraction of the rabbit basilar artery in the normal Cl- Krebs-Henseleit bicarbonate buffer (123 mM Cl-). The ET-1-induced contraction was reduced by the following manipulations: 1) inhibition of Na+-K+-2Cl- cotransporter with bumetanide (3 x 10(-5) and 10(-4) M), 2) bicarbonate-free solution to disable Cl-/HCO exchanger, and 3) preincubation of rings with the Cl- channel blockers niflumic acid, 5-nitro-2-(3-phenylpropylamino)benzoic acid, and indanyloxyacetic acid 94. The ET-1-induced contraction was enhanced by substitution of extracellular Cl- (10 mM) with methanesulfonic acid (113 mM). Cl- channels are involved in ET-1-induced contraction in the rabbit basilar artery.     

20-Hydroxyeicosatetraenoic acid is a potent dilator of mouse basilar artery: role of cyclooxygenase

20-Hydroxyeicosatetraenoic acid (20-HETE), an arachidonic acid (AA) metabolite synthesized by cytochrome P-450 omega-oxidases, is reported to produce vasoconstriction in the cerebral circulation. However, we find that like 14,15-epoxyeicosatrienoic acid (14,15-EET), 20-HETE produces dilation of mouse basilar artery preconstricted with U-46619 in vitro. Indomethacin inhibited the vasodilation produced by 20-HETE but not by 14,15-EET, suggesting a cyclooxygenase (COX)-dependent mechanism. Metabolic studies indicated several mechanisms that may play a role in this process. Mouse brain endothelial cells (MBEC) converted 20-HETE to 20-OH-PGE(2), which was as potent as PGE(2) in dilating the basilar artery. 20-HETE also stimulated AA release and PGE(2) and 6-keto-PGF(1alpha) production in MBEC. Furthermore, the basilar artery converted 20-HETE to 20-COOH-AA, which also produced COX-dependent dilation of the basilar artery. 20-COOH-AA increased AA release and PGE(2) and 6-keto-PGF(1alpha) production by the MBEC, but to a lesser extent than 20-HETE. Whereas the conversion of 20-HETE to 20-OH-PGE(2) and production of endogenous prostaglandins probably are primarily responsible for vasodilation, the production of 20-COOH-AA also may contribute to this process.     

Participation of Lipoxygenase Products from Arachidonic Acid in the Pathogenesis of Cerebral Vasospasm

To examine the possible involvement of lipoxygenase products from arachidonic acid in the pathogenesis of delayed vasospasm after subarachnoid hemorrhage (SAH), we measured the contents of hydroxyeicosatetraenoic acids (HETEs) in the subarachnoid clot, the cerebrospinal fluid, and the basilar artery, using the canine "two-hemorrhage" model. Lipoxygenase activity in the subarachnoid clot and the basilar artery was measured, ex vivo, using samples obtained 7 days after SAH. For a quantitative analysis of HETEs, each sample was homogenized with either ice-cold saline or methanol. The lipid extract was then submitted to reverse-phase HPLC. The identity of each HETE was further confirmed using straight-phase HPLC and gas chromatography-mass spectrometry. When the basilar artery was homogenized with ice-cold saline, a significant increase in the 5-HETE content was observed on SAH day 8. However, when the artery was homogenized with methanol, HETEs were not detected. In the case of incubation in the presence of arachidonic acid and calcium ionophore A23187, the 5-lipoxygenase activity was remarkably increased in the basilar artery exposed to SAH, compared to that of normal dogs. The subarachnoid clot contained a significant amount of 12-HETE (average 1.8 nmol/g wet weight) from day 2 to day 8. The administration of 1,2-bis(nicotinamido)propane significantly ameliorated vasospasm in the two-hemorrhage model, simultaneously inhibiting the 5-lipoxygenase activity of the basilar artery. Our observations show that the activities of 12- and 5-lipoxygenases are significantly increased after SAH in the subarachnoid clot and the basilar artery, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)     

Acetylsalicylic acid provides cerebrovascular protection from oxidant damage in salt-loaded stroke-prone rats

Inflammatory processes may play a pivotal role in the pathogenesis of cerebrovascular injury in salt-loaded stroke-prone spontaneously hypertensive rats (SHRSP). Recent reports revealed that acetylsalicylic acid (aspirin) has anti-oxidative properties and elicits nitric oxide release by a direct activation of the endothelial NO synthase. The present study was designed to determine whether low-dose aspirin might prevent cerebrovascular injury in salt-loaded SHRSP by protecting oxidative damage. Nine-week-old SHRSP were fed a 0.4% NaCl or a 4% NaCl diet with or without treatment by naproxen (20 mg/kg/day), salicylic acid (5 mg/kg/day), or aspirin (5 mg/kg/day) for 5 weeks. Blood pressure, blood brain barrier impairment, mortality, and the parameters of cerebrovascular inflammation and damage were compared among them. High salt intake in SHRSP significantly increased blood brain barrier impairment and early mortality, which were suppressed by treatment with aspirin independent of changes in blood pressure. Salt loading significantly increased superoxide production in basilar arteries of SHRSP, which were significantly suppressed by treatment with aspirin. Salt loading also significantly decreased NOS activity in the basilar arteries of SHRSP, which were significantly improved by treatment with aspirin. At 5 weeks after salt loading, macrophage accumulation and matrix metalloproteinase-9 activity at the stroke-negative area in cerebral cortex of SHRSP were significantly reduced by treatment with aspirin. These results suggest that low-dose aspirin may exert protective effects against cerebrovascular inflammation and damage by salt loading through down-regulation of superoxide production and induction of nitric oxide synthesis.     

Superoxide levels and function of cerebral blood vessels after inhibition of CuZn-SOD

The goal of this study was to examine the role of endogenous copper/zinc (CuZn)-superoxide dismutase (SOD) on superoxide levels and on responses of cerebral blood vessels to stimuli that are mediated by nitric oxide (acetylcholine) and cyclooxygenase-dependent mechanisms (bradykinin and arachidonic acid). Levels of superoxide in the rabbit basilar artery were measured using lucigenin-enhanced chemiluminescence (5 microM lucigenin). Diethyldithiocarbamate (DDC; 10 mM), an inhibitor of CuZn-SOD, increased superoxide levels by approximately 2.4-fold (P < 0.05) from a baseline value of 1.0 +/- 0.2 relative light units x min(-1) x mm(-2) (means +/- SE). The diameter of cerebral arterioles (baseline diameter, 99 +/- 3 microm) was also measured using a closed cranial window in anesthetized rabbits. Topical application of DDC attenuated responses to acetylcholine, bradykinin, and arachidonate, but not nitroprusside. For example, 10 microM arachidonic acid dilated cerebral arterioles by 40 +/- 5 and 2 +/- 2 microm under control conditions and after DDC, respectively (P < 0.05). These inhibitory effects of DDC were reversed by the superoxide scavenger 4,5-dihydroxy-1,3-benzenedisulfonic acid (10 mM). Arachidonate increased superoxide levels in the basilar artery moderately under normal conditions and this increase was greatly augmented in the presence of DDC. These findings suggest that endogenous CuZn-SOD limits superoxide levels under basal conditions and has a marked influence on increases in superoxide in vessels exposed to arachidonic acid. The results also suggest that nitric oxide- and cyclooxygenase-mediated responses in the cerebral microcirculation are dependent on normal activity of CuZn-SOD.     

Effects of interrupted and uninterrupted occlusion of the basilar artery on cerebral blood flow, and on neurological and histological outcome in rats with subarachnoid hemorrhage.

Most neurosurgeons consider temporary vessel occlusion for aneurysmal clipping an effective technique that facilitates dissection between the aneurysm and the parent vessel. It is generally believed that repeated short periods of cerebral ischemia are safer for the brain than a single long episode. The aim of this study was to identify whether interrupted and uninterrupted vessel occlusion differs with regard to changes in brain tissue and cerebral hemodynamics after subarachnoid hemorrhage (SAH). Fifty Spraque Dawley rats (300-350 g) were placed under general anaesthesia and ventilated. The basilar artery was exposed through a transclival approach. Baseline local cerebral blood flow (LCBF) values was measured, and then the basilar artery was punctured, causing subarachnoid hemorrhage (SAH). Group I (n = 24) was subjected to 60 min of interrupted basilar artery occlusion, defined as 5 min of reperfusion after every 10 min of occlusion, group II (n = 26) 60 min of uninterrupted artery occlusion. Three days after completion of the experiment, each rat was neurologically evaluated and decapitated. Coronal brain slices were obtained and stained to assess infarct volume. Immediately after SAH, LCBF fell by 58% in group I, and by 52% in group II. In group I, each ischemic insult brought a similar reduction in LCBF, and after each release of the occlusion there was a rapid rise in flow. In group II, the LCBF values dropped initially and remained at low levels until the end of the study. The 2,3,5 triphenyltetrazolium chloride stained sections showed similar volumes of brainstem infarction in both groups (38.3 +/- 9.2 mm3 vs. 34.3 +/- 8.7 mm3, respectively; p > 0.05). The results suggest that there is no neuroprotective advantage to either interrupted or uninterrupted temporary blockage of blood flow during neurovascular procedures after SAH in the basilar artery region.     

Hemoglobin, NO, and 20-HETE interactions in mediating cerebral vasoconstriction following SAH

Recent studies have indicated that 20-hydroxyeicosatetraenoic acid (20-HETE) contributes to the fall in cerebral blood flow (CBF) after subarachnoid hemorrhage (SAH), but the factors that stimulate the production of 20-HETE are unknown. This study examines the role of vasoactive factors released by clotting blood vs. the scavenging of nitric oxide (NO) by hemoglobin (Hb) in the fall in CBF after SAH. Intracisternal (icv) injection of blood produced a greater and more prolonged (120 vs. 30 min) decrease in CBF than that produced by a 4% solution of Hb. Pretreating rats with N(omega)-nitro-l-arginine methyl ester (l-NAME; 10 mg/kg iv) to block the synthesis of NO had no effect on the fall in CBF produced by an icv injection of blood. l-NAME enhanced rather than attenuated the fall in CBF produced by an icv injection of Hb. Blockade of the synthesis of 20-HETE with TS-011 (0.1 mg/kg iv) prevented the sustained fall in CBF produced by an icv injection of blood and the transient vasoconstrictor response to Hb. Hb (0.1%) reduced the diameter of the basilar artery (BA) of rats in vitro by 10 +/- 2%. This response was reversed by TS-011 (100 nM). Pretreatment of vessels with l-NAME (300 muM) reduced the diameter of BA and blocked the subsequent vasoconstrictor response to the addition of Hb to the bath. TS-011 returned the diameter of vessels exposed to l-NAME and Hb to that of control. These results suggest that the fall in CBF after SAH is largely due to the release of vasoactive factors by clotting blood rather than the scavenging of NO by Hb and that 20-HETE contributes the vasoconstrictor response of cerebral vessels to both Hb and blood.     

阻断猫基底动脉引起的延髓缺血和呼吸血压效应的研究

目的 :通过结扎基底动脉主干不同节段观察脑干缺血范围和神经元形态学变化以及呼吸活动和动脉血压的变化 ,为进一步探讨脑干缺血影响呼吸和循环等功能活动的机制和防治措施提供依据。方法 :以猫为实验对象 ,结扎基底动脉主干不同节段 ,分析脑干缺血区血管密度和神经元形态学变化 ,以膈肌肌电和股动脉血压为指标 ,观察呼吸活动和血压的变化。结果 :结扎基底动脉可引起延髓血管密度减小 ,引起延髓缺血。结扎基底动脉不同节段引起的缺血范围有明显重叠 ,缺血区主要位于闩平面吻端的延髓。缺血区神经元胞体肿胀 ,尼氏染色着色变浅 ,尼氏体减少。动物的吸气时程 (TI)和呼气时程 (TE)缩短 ,呼吸频率 (RF)增快 ,平均动脉血压 (MBP)下降 ,均P <0 .0 5,呼吸幅度 (A)无明显变化。结论 :基底动脉不同节段对延髓的血液供应有明显重叠 ,延髓缺血可引起呼吸和血压改变 ,延髓缺血性神经元损伤是引起呼吸、血压改变的结构基础     

Amplification of sumatriptan-induced contraction in rabbit saphenous vein but not in basilar artery

The modulation of serotonin (5-HT(1B/1D)) receptor-induced vascular contractility by histamine and U-46619 was compared in the rabbit basilar artery and saphenous vein. In the saphenous vein, histamine (5 x 10(-7) M) significantly increased the potency (from pEC(50) of 6.0 to 6.8) and efficacy (from 52.3% to 88.2%) of sumatriptan. Likewise, U-46619 (5 x 10(-9) M) also increased the potency (from pEC(50) of 5.9 to 6.6) and efficacy (from 51.8% to 92.1%) of sumatriptan in the saphenous vein. In contrast, equieffective concentrations of histamine (10(-7) M) and U-46619 (3 x 10(-9) M) failed to amplify contraction to sumatriptan in the basilar artery. Contraction to sumatriptan was inhibited by nitrendipine (10(-7) M) in the basilar artery but not in the saphenous vein, suggesting that different contractile signaling mechanisms are operating in these tissues. Furthermore, U-46619- and thrombin-induced contractility in the basilar artery were also not amplified by histamine, suggesting that lack of amplification of contraction in the basilar artery was not restricted to sumatriptan but was rather a characteristic of this cerebral vessel. These data suggest that in the in vivo plasma milieu sumatriptan will more markedly contract the peripheral saphenous vein than the basilar artery, a cerebral blood vessel.     

Aalpha,beta-methylene ATP enhances P2Y4 contraction of rabbit basilar artery

Interactions between different selective P2 receptor agonists have been used as tools to identify different P2 receptor subtypes. In the present study, we examined the P2 receptor subtypes and the mechanisms of potentiation of UTP contraction (P2Y contraction) by alpha,beta-methylene ATP [(2-carboxypiperazin-4-yl)propyl-1-phosphanoic acid (CPP), a P2X agonist] using isometric tension in the denuded rabbit basilar artery. We made the following observations: 1). a predominant P2X receptor contraction was observed in the rabbit ear artery by the rank order of CPP > 2-methylthioATP > ATP > UTP; 2). functional P2Y receptors were observed in the rabbit basilar artery by the rank order of UTP > ATP = CPP = 2-methylthioATP; 3). CPP potentiated UTP-, ATP-, and ATPgammaS-induced contractions, possibly by activation of P2Y4 receptors because ATPgammaS does not activate P2Y6 receptors; and 4). ectonucleotidase did not play a predominant role in the potentiative effect of CPP because Evans blue, Ca(2+)-free medium, or divalent cation Ni(2+) did not affect the effect of CPP. Evans blue potentiated the contraction by UTP but not by ATP or ATPgammaS. We conclude that CPP enhanced P2Y4-mediated contraction in the rabbit basilar artery, and the influence by ectonucleotidases on CPP-potentiation remains unclear.     

Modeling the active process of the cochlea: phase relations, amplification, and spontaneous oscillation.

The high sensitivity and sharp frequency selectivity of acoustical signal transduction in the cochlea suggest that an active process pumps energy into the basilar membrane's oscillations. This function is generally attributed to outer hair cells, but its exact mechanism remains uncertain. Several classical models of amplification represent the load upon the basilar membrane as a single mass. Such models encounter a fundamental difficulty, however: the phase difference between basilar-membrane movement and the force generated by outer hair cells inhibits, rather than amplifies, the modeled basilar-membrane oscillations. For this reason, modelers must introduce artificially either negative impedance or an appropriate phase shift, neither of which is justified by physical analysis of the system. We consider here a physical model based upon the recent demonstration that the basilar membrane and reticular lamina can move independently, albeit with elastic coupling through outer hair cells. The mechanical model comprises two resonant masses, representing the basilar membrane and the reticular lamina, coupled through an intermediate spring, the outer hair cells. The spring's set point changes in response to displacement of the reticular lamina, which causes deflection of the hair bundles, variation of outer hair cell length and, hence, force production. Depending upon the frequency of the acoustical input, the basilar membrane and reticular lamina can oscillate either in phase or in counterphase. In the latter instance, the force produced by hair cells leads basilar-membrane oscillation, energy is pumped into basilar-membrane movement, and an external input can be strongly amplified. The model is also capable of producing spontaneous oscillation. In agreement with experimental observations, the model describes mechanical relaxation of the basilar membrane after electrical stimulation causes outer hair cells to change their length.     

The ultrastructural basis of the permeability of arterial endothelium to horseradish peroxidase

The thoracic aorta and basilar artery, in which the incidence of atherosclerosis is known to be different, were examined to elucidate the correlation between the structure of the intercellular cleft junction between adjacent endothelial cells and its permeability to HRP. Tannic acid or HRP in the vessel lumen passed through the intercellular clefts of the thoracic aorta into the subendothelial space, whereas in the basilar artery they were unable to penetrate beyond the tight junction of the intercellular clefts. Freeze-fracture replicas revealed that the tight junctions of the thoracic aorta consisted of one to two junctional strands in most areas of the cleaved planes, with discontinuities in some places, whereas those of the basilar artery consisted of a continuous belt-like meshwork of six anastomosing junctional strands on average. These observations confirm that the structure of endothelial junctions in arteries has a close correlation with the permeability of the intercellular clefts to HRP.     

Activation of Rho-associated kinase during augmented contraction of the basilar artery to serotonin after subarachnoid hemorrhage

Delayed cerebral vasospasm after subarachnoid hemorrhage (SAH) may be due, in part, to altered regulation of arterial smooth muscle contraction. Contraction of cerebral arteries to serotonin is augmented after experimental SAH. We hypothesized that activation of Rho-associated kinase (Rho kinase) contributes to augmented contraction of cerebral arteries to serotonin after SAH. Autologous arterial blood (SAH) or artificial cerebrospinal fluid (control) was injected into the cisterna magna of anesthetized rabbits. At 2 days after injection, the basilar artery was excised and isometric contraction of arterial rings was recorded. Maximum contraction of the basilar artery to serotonin was augmented about fourfold in SAH compared with control rabbits (P < 0.01). Contraction to histamine was similar in the two groups. Fasudil hydrochloride (3 mumol/l), an inhibitor of Rho kinase, markedly attenuated serotonin-induced contraction. Fasudil had little effect on contractions induced by histamine or phorbol 12,13-dibutyrate. In addition, phosphorylation of myosin phosphatase, a major target of Rho kinase in regulation of smooth muscle contraction, in the basilar artery was examined by Western blotting. In basilar arteries of SAH, but not control, rabbits, serotonin increased phosphorylation of myosin phosphatase about twofold at Thr(853) of the myosin-targeting subunit. These results suggest that enhanced activation of Rho kinase contributes to augmented contraction of the basilar artery to serotonin after SAH.     

Effect of endothelin-1 receptor antagonist BQ-123 on basilar artery diameter after subarachnoid hemorrhage (SAH) in rats.

Aim of the study was to quantify cerebral vasospasm in rats after subarachnoid hemorrhage (SAH) by morphometric examination of basilar artery and to evaluate the influence of endothelin receptor blocker BQ-123 on basilar artery constriction. The rat cisterna magna (CM) was cannulated and after 7 days SAH was developed by administration of 100 microl autologic, non-heparinized blood to the CM. The sham subarachnoid hemorrhage was developed by intracisternal administration of 100 microl of artificial cerebrospinal fluid. Endothelin receptor blocker BQ-123 was injected into the CM in a dose of 40 nmol diluted in 50 microl of cerebrospinal fluid 20 min. before SAH, and 24h and 48 h after SAH. After perfusion fixation the brains were removed from the skull and histological preparations of basilar artery were done. The internal diameter and wall thickness of basilar arteries was measured by interactive morphometric method. The most severe vasospasm was found in rats after SAH. The presence of numerous infiltrations composed of neutrophils and macrophages correlated with advanced vasospasm (index of constriction 5 times lower than in normal), suggesting the role of other factors participating in the late phase of vasospasms after SAH. Administration of BQ-123 in the late phase after SAH caused the dilatation of basilar artery. Following the administration of BQ-123 in the late phase (48 h after SAH) the basilar artery dilated, its wall became thinner, and the number of leukocyte infiltrations in the subarachnoid space decreased compared to the values after SAH alone.     

Time course of production of hydroxyl free radical after subarachnoid hemorrhage in dogs

Vasospasm after subarachnoid hemorrhage (SAH) is associated with lipid peroxidation. However, lipid peroxides increase in a delayed fashion after SAH and may be a byproduct of but not a cause of vasospasm. This study correlated vasospasm with hydroxyl free radical and lipid peroxide levels. 24 dogs had baseline cerebral angiography and induction of SAH by 2 injections of blood into the cisterna magna at baseline and 2 days later. Angiography was repeated 4, 7, 10, 14 or 21 days after the first injection (n = 4 per group) and a microdialysis catheter was inserted into the premedullary cistern. Control dogs (n = 4) underwent angiography and microdialysis but not SAH. Salicylic acid, 100 mg/kg, was administered intravenously, and microdialysis fluid was collected and analyzed by high pressure liquid chromatography for 2,3- and 2,5-dihydroxybenzoic acids (DHBA). Malondialdehyde was measured in subarachnoid clot removed from the prepontine cistern and in the basilar artery itself at the time of euthanasia. Significant vasospasm developed 4 to 14 days after SAH. Malondialdehyde levels were significantly elevated in the basilar artery and subarachnoid clot 4 days after SAH (p < 0.0001, ANOVA) but not at other times. 2,5-DHBA levels were significantly greater than control at 4 to 14 days and they peaked at 4 days (p < 0.05, ANOVA). 2,3-DHBA was significantly increased at 4 days after SAH (p < 0.05, ANOVA). There were significant correlations between basilar artery malondialdehyde levels and vasospasm and cerebrospinal fluid 2,5-DHBA levels and vasospasm. These results suggest the presence of hydroxyl free radical after SAH and demonstrate a correlation between such production, as measured by trapping with salicylate, and the early phase of vasospasm. The correlation with vasospasm implicates free radicals and lipid peroxidation in this phase of vasospasm.     

颈性眩晕中医证型与经颅超声脑动脉血流检测结果的相关性分析

摘要 目的：分析颈性眩晕中医证型与经颅超声脑动脉血流检测结果的相关性。方法：选取2021年5月-2023年5月收治颈性眩晕患者作为研究对象,根据不同中医证型分为痰湿中阻组、肝阳上亢组、肝肾阴虚组和气血亏虚组,每组各纳入20例;并另选取健康体检患者30例作为对照组,均给予多普勒超声检查。分析不同中医证型者与对照组者多普勒超声检查特征与脑动脉血流变化[左右椎动脉、基底动脉及大脑中动脉收缩期峰值血流速度（VS）、平均血流速度(Vm)、舒张期峰值血流速度(Vd)及搏动指数(PI)]。结果：痰湿中阻组、肝肾阴虚组和气血亏虚组左右椎动脉、基底动脉及大脑中动脉VS均低于对照组（P＜0.05）;肝阳上亢组左右椎动脉、基底动脉及大脑中动脉VS均高于对照组（P＜0.05）;不同中医证型组间VS比较,肝阳上亢组＞痰湿中阻组＞肝肾阴虚组＞气血亏虚组;痰湿中阻组左右椎动脉、基底动脉均高于对照组（P＜0.05）,大脑中动脉Vm均低于对照组（P＜0.05）;肝阳上亢组左右椎动脉、基底动脉及大脑中动脉Vm均高于对照组（P＜0.05）;肝肾阴虚组左右椎动脉、基底动脉及大脑中动脉Vm均低于对照组（P＜0.05）;气血亏虚组大脑中动脉Vm均低于对照组（P＜0.05）,左右椎动脉、基底动脉Vm和对照组无显著性差异（P>0.05）;不同中医证型组间Vm比较,肝阳上亢组＞痰湿中阻组＞气血亏虚组＞肝肾阴虚组;痰湿中阻组左右椎动脉、基底动脉Vd均低于对照组（P＜0.05）,大脑中动脉Vd均高于对照组（P＜0.05）;肝阳上亢组左右椎动脉、基底动脉及大脑中动脉Vd均低于对照组（P＜0.05）;肝肾阴虚组左右椎动脉及大脑中动脉Vd均低于对照组（P＜0.05）,基底动脉Vd和对照组无差异（P＞0.05）;气血亏虚组左右椎动脉Vd均低于对照组（P＜0.05）,基底动脉Vd和对照组无差异（P＞0.05）,大脑中动脉Vd均高于对照组（P＜0.05）;不同中医证型组间Vd比较,气血亏虚组＞痰湿中阻组＞肝肾阴虚组＞肝阳上亢组;痰湿中阻组和气血亏虚组左右椎动脉、基底动脉及大脑中动脉PI均低于对照组（P＜0.05）;肝阳上亢组和肝肾阴虚组左右椎动脉、基底动脉及大脑中动脉PI均高于对照组（P＜0.05）;不同中医证型组间PI比较,肝阳上亢组＞肝肾阴虚组＞痰湿中阻组＞气血亏虚组。结论：不同中医证型的眩晕患者会出现不同程度脑动脉血流动力学异常,且不同组间存在差异,通过经颅多普勒超声检查,可以对眩晕中医证型提供参考价值。