CEREBRAL THROMBOSIS AND EMBOLISM—A Method of Treatment

Acute cerebral thrombosis and embolism give rise to arterial spasm, edema, and anoxia of the cerebral tissues supplied by the affected artery or arteries. Sympathetic block induced by injecting the stellate ganglion with procaine appears to relieve spasm and results in improved cerebral circulation and clinical improvement in a significant number of cases. Sympathetic block should be combined with the usual supportive measures and not infrequently with anticoagulants. Every effort should be made to institute treatment as soon as possible after the onset of symptoms.     

Cerebral thrombosis and embolism; a method of treatment

Acute cerebral thrombosis and embolism give rise to arterial spasm, edema, and anoxia of the cerebral tissues supplied by the affected artery or arteries. Sympathetic block induced by injecting the stellate ganglion with procaine appears to relieve spasm and results in improved cerebral circulation and clinical improvement in a significant number of cases. Sympathetic block should be combined with the usual supportive measures and not infrequently with anticoagulants. Every effort should be made to institute treatment as soon as possible after the onset of symptoms.     

The role of intimal hyperplasia in arterial spasm.

It has been postulated that even moderate spasm in an artery with intimal hyperplasia can produce organ hypoxia because there is an excessive reduction in the diameter of the lumen. To test this hypothesis we created intimal hyperplasia in one femoral artery in five pigs and then induced arterial spasm by administering ergonovine maleate. Arterial spasm did not produce a greater reduction in the luminal diameter of the femoral artery with intimal hyperplasia than it did in the normal femoral artery. Until further evidence appears this hypothesis must be viewed with caution.     

Intracranial Aneurysms

A reappraisal of case histories of patients with ruptured intracranial aneurysms emphasized the importance of clinically recognizing severe spasm that contraindicates early angiography and large cerebral haematomas that require immediate evacuation. Observation from the day of haemorrhage is important; most recurrent episodes with cerebral signs in the first 10 days were due to spasm; haemorrhage was more common during the following two weeks. In many attacks the signs were not sufficiently distinctive for diagnosis of spasm or haematoma.     

Local cerebral tissue glucose utilization in graded arterial hemorrhagic hypotension, studied by the 14C-2-deoxyglucose method in rats.

The effect of hemorrhagic arterial hypotension on local cerebral glucose metabolism was studied on 33 rats. The mean arterial pressure was set with the aid of a reservoir at 80, 60, 50 and 40 mmHg pressures. Local cerebral glucose utilization was measured with the 14C-2-D-deoxyglucose accumulation autoradiographic technique. Local glucose consumption decreased somewhat in cortical structures when mean arterial pressure was reduced to 60-50 mmHg. Further decrease in mean arterial pressure to 50-40 mmHg caused inhomogeneity of tissue metabolism. Columns and patches of high glucose consumption interchanged with areas of very low glucose consumption in most telencephalic and cerebellar gray matter structures. Brain stem and white matter structures seem to be less sensitive to decreased mean arterial pressure in the range studied. We found a decrease in glucose utilization rather than an increase with decreasing mean arterial pressure down to 60-50 mmHg (in the range of the autoregulation of cerebral circulation). This finding makes it improbable that autoregulation would be connected with elevated anaerobic metabolism of the tissue. Patchy areas and columns of high glucose consumption found at 50-40 mmHg in all probability reflect areas of increased anaerobic metabolism of glucose. Here, circulation was not enough to transport adequate quantity of oxygen to the tissue, but still it transported relative large amount of glucose. Columns and patches of very low glucose consumption should reflect areas, where circulation was inadequate to transport both enough glucose and oxygen.     

Failure of cerebral autoregulation as a cause of brain dysfunction in the elderly.

Cerebral blood flow in relation to change in arterial pressure was measured in 11 elderly patients with postural hypotension. Seven patients with symptoms showed bilateral or unilateral failure of cerebral autoregulation, while the four asymptomatic patients did not. Variations in cerebral autoregulation would explain why some elderly people with minor falls of systemic arterial pressure develop clinical signs of cerebral ischaemia whereas others with greater falls in blood pressure remain asymptomatic. Elderly patients with impaired autoregulation may be at risk of brain damage from minor falls in blood pressure.     

表面肌电信号的下肢痉挛信号的特征分析与识别

脑卒中患者康复治疗中会引起下肢肌肉痉挛,这种现象给患者的康复训练过程带来极大的危害,因此能够在训练过程中识别痉挛并及时中断训练具有重要的实际意义。本研究通对下肢表面肌电信号的采集,采用基于形状的模版匹配法来识别痉挛信号,并以皮尔逊相关系数来分析表征下肢痉挛信号的相关性大小。分析结果表明,通过仿真验证了模版匹配法在个人痉挛信号识别中的准确性,显示了在泛用痉挛信号识别中的可行性。     

Comparison of two methods of altering blood pressures for assessing neonatal cerebral blood flow autoregulation

The cerebral blood flow of newborn lambs at reduced and elevated arterial blood pressures, induced by intravenous infusion of sodium nitroprusside and phenylephrine hydrochloride as well as blood withdrawal and reinfusion, were compared. Both blood withdrawal and sodium nitroprusside infusion reduced mean arterial pressure from 83 to 60 mmHg (1 mmHg = 133 Pa). Reinfusion of blood increased arterial pressure to 94 mmHg. Phenylephrine hydrochloride infusion increased arterial pressure to 102 mmHg. The cerebral blood flows at corresponding arterial pressures were similar (coefficient of correlation = 0.88, P less than 0.01). Cerebral blood flow before and after infusion of phenylephrine hydrochloride and sodium nitroprusside into the brain via the carotid artery did not change. The results indicate that blood-borne phenylephrine hydrochloride and sodium nitroprusside, in concentrations that would alter arterial blood pressure significantly from its resting level, do not change cerebral blood flow directly.     

Microsurgical Treatment of Hemifacial Spasm

Five cases of idiopathic hemifacial spasm have been successfully treated by operative manipulation of arterial branches compressing the VIIth nerve in the posterior fossa. Terminology, clinical presentation, pathology and therapeutic approaches to hemifacial spasm are discussed. Hearing loss due to operatively induced vascular impairment of the inner ear, a complication in our first case, should be avoidable.Our experience indicates that hemifacial spasm reflects mild chronic compression of the facial nerve. The proposed mechanism is transaxonal excitation between afferent and efferent fibers.     

Relaxant effects on iloprost in canine cerebral artery.

Iloprost caused relaxation of rings of canine cerebral arteries precontracted with prostaglandin F2 alpha or the thromboxane A2 analogue U46619, but it was without effect on arteries precontracted with potassium chloride. Pretreatment with iloprost did not significantly affect the concentration-response curve to any agent. Contractile responses to oxyhemoglobin were completed relaxed by iloprost. In arteries from animals with moderate cerebrovascular spasm, the response to prostaglandin F2 alpha was also reduced by iloprost. The observation that iloprost relaxes the response to oxyhemoglobin to prostaglandin F2 alpha in spastic arteries may be of interest in the management of cerebral vasospasm.     

Cerebral arteries can generate 5- and 15-hydroxyeicosatetraenoic acid from arachidonic acid

Products of the lipoxygenase pathway have been implicated in the development of the cerebrovascular spasm that arises after subarachnoid hemorrhage. In particular the hydroperoxyeicosatetranenoic acids (HPETEs), which are unstable and break down rapidly to the corresponding 5-hydroxy acids (HETEs), are vasoconstrictor agents that mimic some aspects of cerebrovascular spasm. It is not, however, well established whether segments of cerebral artery can manufacture these products. We have studied the lipoxygenase product profile of cerebral arteries stimulated with arachidonic acid. Rings of bovine cerebral arteries were incubated in Krebs solution containing arachidonic acid. The lipoxygenase products were studied using high performance liquid chromatography. The largest peaks had the retention times of 5- and 15-HETEs, and the identity of these peaks was confirmed using specific radioimmunoassays. Stimulation with arachidonic acid resulted in a time- and dose-dependent increase in the formation of both HETEs, with 15-HETE being most abundant. The release of both HETEs was markedly reduced in the presence of AA-861, an inhibitor of lipoxygenase, but not with the cyclooxygenase inhibitor indomethacin. These data are thus consistent with our previous suggestion that the contractile activity of arachidonic acid in cerebral arteries arises, at least in part, from HPETE formation and with a possible role for these compounds in cerebral vasospasm.     

LARYNGOSPASM FROM THE ANESTHESIOLOGIST'S VIEWPOINT

Laryngeal spasm is a problem constantly confronting the anesthetist. It can be serious and may produce fatal cerebral or cardiac complications. Etiologic agents include primary vagal hypertonicity, anoxemia, and painful stimulation of whatever source.Laryngeal spasm must be differentiated from simple obstruction by the tongue or foreign bodies, epiglottic impaction, laryngeal edema, tracheal spasm and collapse, and bronchial spasm.Proper checking of the patient before anesthesia and adequate premedication with atropine or scopolamine are preventive measures of great value. Once spasm has developed the etiologic agent should be removed if possible. Other measures include intravenous administration of atropine or curare, tracheal intubation, and tracheotomy.     

Pressure-induced myogenic tone and role of 20-HETE in mediating autoregulation of cerebral blood flow

While myogenic force in response to a changing arterial pressure has been described early in the 20th century, it was not until 1984 that the effect of a sequential increase in intraluminal pressure on cannulated cerebral arterial preparations was found to result in pressure-dependent membrane depolarization associated with spike generation and reduction in lumen diameter. Despite a great deal of effort by different laboratories and investigators, the identification of the existence of a mediator of the pressure-induced myogenic constriction in arterial muscle remained a challenge. It was the original finding by our laboratory that demonstrated the capacity of cerebral arterial muscle cells to express the cytochrome P-450 4A enzyme that catalyzes the formation of the potent vasoconstrictor 20-hydroxyeicosatetraenoic acid (20-HETE) from arachidonic acid, the production of which in cerebral arterial muscle cells increases with the elevation in intravascular pressure. 20-HETE activates protein kinase C and causes the inhibition of Ca(2+)-activated K(+) channels, depolarizes arterial muscle cell membrane, and activates L-type Ca(2+) channel to increase intracellular Ca(2+) levels and evoke vasoconstriction. The inhibition of 20-HETE formation attenuates pressure-induced arterial myogenic constriction in vitro and blunts the autoregulation of cerebral blood flow in vivo. We suggest that the formation and action of cytochrome P-450-derived 20-HETE in cerebral arterial muscle could play a critically important role in the control of cerebral arterial tone and the autoregulation of cerebral blood flow under physiological conditions.     

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.     

Middle cerebral artery blood velocity during intense static exercise is dominated by a Valsalva maneuver.

Lifting of a heavy weight may lead to "blackout" and occasionally also to cerebral hemorrhage, indicating pronounced consequences for the blood flow through the brain. We hypothesized that especially strenuous respiratory straining (a Valsalva-like maneuver) associated with intense static exercise would lead to a precipitous rise in mean arterial and central venous pressures and, in turn, influence the middle cerebral artery blood velocity (MCA V(mean)) as a noninvasive indicator of changes in cerebral blood flow. In 10 healthy subjects, MCA V(mean) was evaluated in response to maximal static two-legged exercise performed either with a concomitantly performed Valsalva maneuver or with continued ventilation and also during a Valsalva maneuver without associated exercise (n = 6). During static two-legged exercise, the largest rise for mean arterial pressure and MCA V(mean) was established at the onset of exercise performed with a Valsalva-like maneuver (by 42 +/- 5 mmHg and 31 +/- 3% vs. 22 +/- 6 mmHg and 25 +/- 6% with continued ventilation; P < 0.05). Profound reductions in MCA V(mean) were observed both after exercise with continued ventilation (-29 +/- 4% together with a reduction in the arterial CO(2) tension by -5 +/- 1 Torr) and during the maintained Valsalva maneuver (-21 +/- 3% together with an elevation in central venous pressure to 40 +/- 7 mmHg). Responses to performance of the Valsalva maneuver with and without exercise were similar, reflecting the deterministic importance of the Valsalva maneuver for the central and cerebral hemodynamic response to intense static exercise. Continued ventilation during intense static exercise may limit the initial rise in arterial pressure and may in turn reduce the risk of hemorrhage. On the other hand, blackout during and after intense static exercise may reflect a reduction in cerebral blood flow due to expiratory straining and/or hyperventilation.     

Angiographic diagnosis of hemorrhagic myocardial infarct

Hemorrhagic myocardial infarction (HMI) has certain angiographic features that make it possible to diagnose it during the patient's life. HMI angiographic criteria are hypervascularization of an infarction zone in the late arterial phase, an intense contrast of an infarction zone in the parenchymal phase, extravasation of a contrast medium in an infarction zone in the venous phase of coronarography lasting for a long time, and slow discharge of a contrast medium from the distal vascular channel of an infarction zone. HMI characteristic features require thorough phase-by-phase angiographic investigation of the coronary arteries in all MI patients, especially in young ones and those after intracoronary thrombolytic therapy. The detected morphological spasm of microcirculatory vessels and veins disturbing the blood outflow from an infarction zone, noticeable hemorrhages in its interstice prove to be the morphological substantiation of HMI angiographic signs.     

Regional cerebral blood flow in cats with cross-linked hemoglobin transfusion during focal cerebral ischemia

The beneficial effect of hemodilution on cerebral blood flow (CBF) during focal cerebral ischemia is mitigated by reduced arterial oxygen content (CaO2). In anesthetized cats subjected to permanent middle cerebral artery occlusion, the time course of regional CBF was evaluated after isovolemic exchange transfusion with either albumin or a tetrameric hemoglobin-based oxygen carrier. The transfusion started 30 min after arterial occlusion. We tested the hypothesis that bulk oxygen transport (CBF x CaO2) to ischemic tissue is increased by hemoglobin transfusion at a hematocrit of 18% compared with albumin-transfused cats at a hematocrit of 18% or control cats at a hematocrit of 30% and equivalent arterial pressure. In the nonischemic hemisphere, CBF increased selectively after albumin transfusion, and oxygen transport was similar among groups. In the ischemic cortex, albumin transfusion increased CBF, but oxygen transport was not increased above that of the control group. Hemoglobin transfusion increased both CBF and oxygen transport in the ischemic cortex above values in the control group, but the increase was delayed until 4 h of ischemia. Consequently, acute injury volume measured at 6 h of ischemia was not significantly attenuated. In contrast to the cortex, CBF in the ischemic caudate nucleus was not substantially increased by either albumin or hemoglobin transfusion. Therefore, in a large animal model of permanent focal ischemia in which transfusion starts 30 min after ischemia, tetrameric cross-linked hemoglobin transfusion can augment oxygen transport to the ischemic cortex, but the increase can be delayed and not necessarily provide protection. Moreover, an end-artery region such as the caudate nucleus is less likely to benefit from hemodilution.     

HYPOTHERMIA IN CEREBRAL RESUSCITATION

A correlative review of experimental and clinical brain injury was undertaken for the purpose of assessing the therapeutic value of the delayed application of hypothermia in the management of cerebral injury. For any post-injury treatment to be possible, it must be assumed that there is a progressive intrinsic adverse response of the brain to injury for some hours after the actual injury.The value of any therapeutic effort in treating the injured brain remains to be proven, although there is considerable theoretical and indirect clinical evidence to suggest that hypothermia may be a potent tool. Study should be directed toward a clinically applicable technique which would provide means of distinguishing between reversible and irreversible interruption of cerebral function.     

Elevated Aminopeptidase P Attenuates Cerebral Arterial Responses to Bradykinin in Fawn-Hooded Hypertensive Rats

Cerebral arterial myogenic and autoregulatory responses are impaired in Fawn Hooded hypertensive (FHH) rats. Cerebral autoregulatory responses are restored in the congenic rat strain in which a segment of chromosome 1 from the Brown Norway (BN) rat was transferred into the FHH genetic background (FHH.1BN). The impact of this region on cerebral arterial dilator responses remains unknown. Aminopeptidase is a gene that was transferred into the FHH genetic background to generate the FHH.1BN rats and is responsible for degradation of the vasodilator bradykinin. Thus, we hypothesized that FHH rats will have increased aminopeptidase P levels with impaired cerebral arterial responses to bradykinin compared to BN and FHH.1BN rats. We demonstrated higher cerebral arterial expression of aminopeptidase P in FHH compared to BN rats. Accordingly, we demonstrated markedly impaired cerebral arterial dilation to bradykinin in FHH compared to BN rats. Interestingly, aminopeptidase P expression was lower in FHH.1BN compared to FHH rats. Decreased aminopeptidase P levels in FHH.1BN rats were associated with increased cerebral arterial bradykinin-induced dilator responses. Aminopeptidase P inhibition by apstatin improved cerebral arterial bradykinin dilator responses in FHH rats to a level similar to FHH.1BN rats. Unlike bradykinin, cerebral arterial responses to acetylcholine were similar between FHH and FHH.1BN groups. These findings indicate decreased bradykinin bioavailability contributes to impaired cerebral arterial dilation in FHH rats. Overall, these data indicate an important role of aminopeptidase P in the impaired cerebral arterial function in FHH rat.     

Neuroprotective effect of hexasulfobutylated C60 on rats subjected to focal cerebral ischemia

The effects of hexasulfobutylated C60 (FC4S), a free radical remover, on the total volume infarct size elicited by the damaging effects of focal cerebral ischemia were studied on Long-Evans rats in vivo. FC4S was administered intravenously either 15 min before middle cerebral artery (MCA) occlusion (pretreatment groups) or it was injected when the common carotid arteries clips were removed (treatment groups). FC4S did not alter the pH, blood gases, heart rate, or mean arterial blood pressure in either pretreatment or treatment groups of the rats. However, after administration of FC4S at dosages of 10 and 100 microg/kg, the total volume of infarction was significantly reduced in both pretreatment and treatment groups. In addition, after FC4S administration, the nitric oxide (NO) content in plasma was increased and the lactate dehydrogenase (LDH) levels was decreased. It is concluded that FC4S may be used as a neuroprotective agent on focal cerebral ischemia. The beneficial effects may be partly related to its antioxidant property and to the upregulation of NO production of the compound.