Additive effects of nicorandil on coronary blood flow during continuous administration of nitroglycerin.

OBJECTIVES: We examined whether patients with ischemic heart disease (IHD) should be treated with nicorandil, an adenosine triphosphate-sensitive potassium channel opener, in addition to the regular use of nitrates. BACKGROUND: It has been reported that nicorandil possibly has additive effects on nitroglycerin (NTG) treatment for angina, but the mechanism is not clear. METHODS: We directly measured anterograde coronary blood flow (CBF) with a Doppler guide wire to examine the effects of intravenous administration of NTG (0.3 mg) and nicorandil (6 mg) during continuous administration of NTG at a sufficient dose (25 microg/min) in subjects with normal and stenotic coronary arteries. RESULTS: Additional systemic administration of NTG decreased anterograde CBF (normal -19.7%; stenotic -21.2%). In contrast, nicorandil increased anterograde CBF in both normal (54.6%) and stenotic (89.6%) coronary arteries, without the coronary steal phenomenon. There was a tendency toward nicorandil-dilated diameters in the patients with stenotic arteries (p = 0.06). There were no effects of additional administration on pulmonary artery wedge pressure. There was no difference in changes in heart rate and mean aortic blood pressure between NTG and nicorandil therapy. CONCLUSIONS: These results suggest that in patients treated with nitrates, additional administration of nicorandil is more useful, in terms of increasing CBF, than additional administration of nitrates. Adjunctive use of nicorandil with nitrates may provide the further benefit of myocardial protection and may improve the prognosis of patients with IHD.

Innervation of the cerebral veins as compared with the cerebral arteries: a histochemical and electron microscopic study.

The distribution of nerve fibers in the cerebral veins was studied by catecholamine fluorescence simultaneously with acetylcholinesterase (AChE) histochemistry. A comparison of nerve fibers in the cerebral arteries was made. The ultrastructure of terminal boutons in the veins fixed with potassium permanganate was also studied. In the adventitia of the cerebral artery, green fluorescent aminergic fibers and brownish AChE-reactive (probably cholinergic) fibers were observed. In contrast, the cerebral venous system showed no AChE-positive fibers. Catecholamine fluorescent varicose fibers were detected in the dural sinus, the internal cerebral vein, and the superficial vein of Labbé. The highest density of aminergic fibers was found in the dural sinus and the second highest in the internal cerebral vein. Most of the terminal boutons in the adventitia of the cerebral veins were found adjacent to a muscle-like cell and showed only cored vesicles under electron microscopy. Results of our study suggest that the cerebral venous system has a neurogenic innervation, mainly from aminergic fibers, which is different from the neurogenic supply to the cerebral arterial system.

Immunohistochemical demonstration of vasopressin nerve fibers in the cerebral artery.

Vasopressin-immunoreactive nerve fibers were demonstrated in the cerebral pial arteries by peroxidase immunohistochemistry. In the large pial artery (proximal part of the middle cerebral artery), they ran longitudinally to the long axis of the vessel. They ran in a spiral pattern in the distal part of the middle cerebral artery. Even in small arteries, vasopressin nerve fibers were found arranged in a longitudinal fashion. The present morphological data suggest that vasopressin nerve fibers in the cerebral artery may play a role in cerebral circulation.

A light and electron microscopic immunohistochemical study of vasoactive intestinal polypeptide- and substance P-containing nerve fibers along the cerebral blood vessels: comparison with aminergic and cholinergic nerve fibers.

Vasoactive intestinal polypeptide (VIP)- and substance P-containing nerve fibers were observed in the cerebral blood vessels using an immunohistochemical technique. VIP-containing nerve fibers distributed in a spiral pattern, similar to that of muscle cells. Under electron microscopic observation, VIP-immunoreactive terminals lay close to a muscle cell in the inner layer of the adventitia. In contrast, substance P-containing nerve fibers showed a meshwork pattern in the outer layer of the adventitia. Using both acetylcholinesterase (AChE) staining and VIP immunohistochemistry, AChE-positive and VIP-immunoreactive nerve fibers revealed almost the same distribution in the same specimen. The present data suggest that VIP-containing nerve fibers may play a role in the smooth muscle control of the blood vessels, whereas substance P-containing nerve fibers may not take part in muscle control.

Comparative anatomy of the distribution of catecholamines within the inferior olivary complex from teleosts to primates.

The distribution of catecholamine (CA) in the inferior olivary complex (IO) of various vertebrate (from fish to monkey) was investigated by means of the histofluorescence technique. In addition, using rats, a further attempt was made to elucidate the origins of CA in the IO. The IO of the lower vertebrates (from fish to birds) was in general poorly innervated by the CA neuron system. IO in the lower mammals, such as insectivora and bats, contained only a few CA nerve terminals, while that in the higher mammals such as rat, guinea pig, rabbit, cat, and monkey revealed quite a number. In these animals, species-species patterns of CA nerve terminals were found. In the rat, the highest concentration was observed in the dorsal lamella of the principal nucleus and in guinea pig ventral lamella. In the rabbit and cat, maximum CA nerve terminals were detected in the dorsal accessory nucleus, while in the monkey, they were detected in the medial accessory nucleus. The retrograde tracer technique of horseradish peroxidase (HRP) suggested that the main source of the abundant CA terminals in IO of the rat might be A1, A2, and A3 noradrenaline neurons, though not locus coeruleus and not dopaminergic ones.

Monocular movement of contralateral eye following cortical stimulation in the coronal sulcus of cat.

Monocular movements of the contralateral eye were demonstrated following the stimulation of the internal kneelike portion of the cortex in the coronal sulcus of the cat. The stimulation of this cortical area in the coronal sulcus yielded rapid medial or slightly oblique ventromedial movement of the contralateral eye. While ablation of the same cortical area produced contralateral eye shift toward the dorsolateral side and the shifted eye became uncontrollable. The results suggested that the control mechanism of eye movement involves unilateral innervation system to the contralateral side as seen in the extremities.

The distribution of adrenergic receptors in cerebral blood vessels: an autoradiographic study.

The first morphological evidence of the existence of adrenergic receptors (alpha 1, alpha 2 and beta) within the vascular walls of the central nervous system were presented using the in vitro receptor autoradiographic technique. In the rat pial arteries all three types of adrenergic receptors were demonstrated, whereas the human pial arteries failed to show significant autoradiographic grains of alpha 1 type of adrenergic receptors indicating a considerable inter-species difference in the distribution of adrenergic receptors. alpha 2 and beta receptors in human pial arteries were found not only in the arterial smooth muscle layers but also in the endothelial layers. This suggests a possibility that circulating sympathomimetic agents play some role in controlling the tone or permeability of vascular walls within the central nervous system. A distinct distribution of alpha 1 receptors in cortical layer IV where the vascular plexus was richest may suggest a relation of alpha 1 receptors and blood flow of brain parenchyma.

Unilateral spatial neglect due to a haemorrhagic contusion in the right frontal lobe.

We report two cases of unilateral spatial neglect associated with an isolated right frontal lobe lesion. Case 1 was a 59-year-old, right-handed man, who developed a left hemiplegia, disorientation, and frontal lobe neglect associated with a haemorrhagic contusion following a head injury. Case 2 was a 55-year-old, right-handed man, who also developed disorientation and frontal lobe neglect secondary to a haemorrhagic contusion following a head injury. 99mTc HM-PAO SPECT revealed an isolated reduction in the regional cerebral blood flow (CBF) around the haematoma in the frontal lobe; blood flow to remaining parts of the brain was normal. Damage to the right frontal lobes of these patients was confirmed as being the cause of the unilateral spatial neglect in accordance with the results of CBF studies.

Is unilateral spatial neglect a single phenomenon? A comparative study between exploratory-motor and visual-counting tests.

The aim of this study is to report the preliminary findings of a traditional battery of tests and our original battery capable of assessing the presence of components and extent of lesions in patients with unilateral spatial neglect. Thirty patients who had unilateral spatial neglect with a stroke in the right hemisphere were assessed for unilateral spatial neglect on exploratory-motor (E-M) tasks, visual-counting (V-C) tasks, and traditional neglect batteries at least 4 weeks after the onset. Other neuropsychological tests and computed tomography were also performed to investigate the relationship with neglect. A factor analysis showed that our tasks loaded significantly on three factors. E-M neglect was found in 16 patients, and V-C neglect in 22 patients with unilateral spatial neglect. There were high correlations between E-M neglect and motor paralysis, word fluency, backward digit span and motor impersistence. There were high correlations between V-C neglect and visual-field defect, line bisection, line cancellation and figure copying. Lesions in the frontal lobe, caudate, insula, and anterior portion of the paraventricular white matter were commonly associated with E-M neglect. Lesions in the occipital lobe were also associated with V-C neglect. We suggest that unilateral neglect is not a single phenomenon, but rather involves several different components. We propose that E-M and V-C tasks are useful methods for evaluating the extent of lesions in patients with unilateral spatial neglect.

Regeneration of norepinephrine-containing fibers in occipital cortex of adult cats.

Regeneration of norepinephrine (NE)-containing nerve fibers in occipital cortex of adult cats was studied using morphological and biochemical methods. Initially, degeneration of cortical NE fibers was induced by direct infusion of 6-hydroxydopamine (6-OHDA) for a week. Cortical reinnervation by NE fibers continuously proceeded throughout 52 weeks, the longest survival period studied, after stopping 6-OHDA infusion. The rate of the reinnervation was slower in mature cortex than that obtained earlier in immature cortex. The present results indicate that the regenerative ability of the central NE neurons is universal, not limited to the immature brain. It is implied that the central NE neurons are equipped with a transmitter-specific repair mechanism throughout life.

Tuberous sclerosis with an atypical radiological skull change: case report.

The authors describe a case of tuberous sclerosis with atypical radiological skull change in a 8-year-old Japanese child. A plain roentgenogram showed thinning and convolution of the left occipital bone, and a cortical tuber adjacent to the thinned bone was shown by computed tomography. This kind of skull change may suggest the existence of a cortical tuber in patients with tuberous sclerosis, although this finding has not been reported previously. The mechanism of this skull change is discussed.

Chronic encapsulated intracerebral hematoma during infancy: case report.

Chronic encapsulated intracerebral hematoma is a rare condition. Only four cases have been reported. The cause of this condition is unclear. A case of chronic encapsulated intracerebral hematoma in an 1-year-old infant is reported, and the characteristic findings and their causes are discussed with a literature survey.

Effect of atrial natriuretic peptide on ischemic brain edema: changes in brain water and electrolytes.

The effects of intraventricularly administered atrial natriuretic peptide (ANP) on the brain water, sodium, and potassium contents in ischemic brain edema were investigated. By use of a three-vessel occlusion model, ischemic brain edema was produced in the rat brain by 15 minutes of global ischemia followed by recirculation. Water content was measured by means of a drying/weighing method; sodium and potassium contents were measured by means of flame photometry. The effects of intraventricular administration of ANP were evaluated by a comparison between the groups given 2 and 5 micrograms of atriopeptin II (treated) and those given 0.9% NaCl (sham-treated). The treated groups showed significant decreases in brain water (P less than 0.02) and sodium (P less than 0.01) contents at 15 and 30 minutes after recirculation, whereas the brain potassium contents remained unaltered. Before ischemia and immediately after 15 minutes of ischemia, intraventricularly administered ANP did not significantly change the brain water, sodium, or potassium contents. There was no significant difference in the effect on the amount of brain water and sodium between the two doses (2 and 5 micrograms). These effects of ANP were thought not to be mediated by primary changes in serum osmolality and sodium and potassium concentrations, because intraventricular administration of ANP did not change them significantly. The present results reveal that, in ischemic brain edema, ANP may act directly on the central nervous system to inhibit brain water and sodium accumulation.

Autologous transplantation of the cervical sympathetic ganglion into the parkinsonian brain: case report.

The authors have reported a clinical trial of an autologous cervical sympathetic ganglion transplanted into the brain of a parkinsonian patient. A 45-year-old woman presented with bradykinesia and a gait disturbance for 8 years under L-dopa treatment. The patient underwent stereotactic transplantation of the right stellate ganglion into the right putamen. She showed marked amelioration of bradykinesia and gait disturbance 1 month after the operation, and she was able to conduct her activities of daily living without requiring L-dopa administration. The patient continued to improve gradually until 3 months after the operation. Two years after surgery, the patient functions independently as a housewife. The right hand tremor, however, became slightly worse after the operation, but it was transient. The patient developed a permanent right-sided Horner's syndrome after resection of the cervical sympathetic ganglion. Taken together with our previous data obtained from animal experiments, this case suggests that the autologous cervical sympathetic ganglion can be donor tissue for neural transplantation in Parkinson's disease.

Hemorrhagic infarction after vasospasm due to ruptured cerebral aneurysm.

Hemorrhagic infarction after vasospasm is a rare condition in patients with aneurysmal subarachnoid hemorrhage (SAH). Induced hypertensive therapy is used for patients with vasospasm, but this treatment has a risk of inducing hemorrhagic infarction. A total of 221 patients whose first computed tomographic (CT) scans were examined within 2 weeks after SAH were investigated for this study. There was symptomatic vasospasm in 99 (45%), cerebral infarction in 37 (17%), and hemorrhagic infarction in 13 (6%). Hemorrhagic infarction usually occurred 20 to 30 days after aneurysmal rupture; this period corresponds with the remission stage of the vasospasm. On CT scans, the hemorrhagic infarction was revealed as a leaky hemorrhage in a low density area in 11 cases, and a massive hemorrhage with mass effect was seen in 2 cases. These findings suggest that hemorrhagic infarction after vasospasm may sometimes be fatal. Cerebral blood flow autoregulation in patients with vasospasm was normal or of a hypertensive type during the remission stage of vasospasm, when hemorrhagic infarction usually appeared. This finding shows that induced hypertension therapy is ineffective during this stage; it should be stopped by this stage because it is ineffective and also may aggravate hemorrhagic infarction.

A possible involvement of central atrial natriuretic peptide in cerebral cortical microcirculation.

The possible involvement of atrial natriuretic peptide (ANP) in cerebral cortical microcirculation was investigated in rats by means of laser-Doppler flowmetry and immunohistochemistry. In the laser-Doppler study, local cerebral blood flow (LCBF) changes after the administration of 10(-6) to 10(-8) mol/LANP solution or vehicle (saline solution) as an intracortical injection for 5 minutes were continuously monitored throughout the 30 minutes of the study and were expressed as percentages of preinjection values represented as 0%. The administration of 10(-6) to 10(-8) mol/LANP caused a significant decrease in LCBF; the onset of LCBF responses occurred within a few minutes after the start of the injection and the decrease in LCBF reached the maximum level within 7 to 10 minutes after the completion of the administration, after which LCBF gradually recovered. In the immunohistochemical study, no specific ANP immunoreactivity was found associated with the intraparenchymal blood vessels; however, ANP-immunoreactive neurons were observed primarily in the hypothalamus and septum, in which high concentrations of ANP-containing neurons have been identified. The data from the laser-Doppler study suggest that central ANP may produce a vasoconstriction of the intraparenchymal blood vessels, regardless of whether through direct action on these vessels or through the mediation by some system in the central nervous system. Because there is no evidence for ANP-containing nerves around these vessels, the role of central ANP in the cerebral circulation must await identification of the source of perivascular ANP.

Pineoblastoma with an unusually long survival. Case report.

The authors report a case of pineoblastoma with a 9-year follow-up period after stereotaxic biopsy, a shunting procedure, and radiotherapy. Light and electron microscopic studies of biopsy and autopsy specimens revealed no cell differentiation of the pineoblastoma. The possible factors predisposing to long survival are discussed in comparison with the course in patients with medulloblastoma.

Bilateral morning glory syndrome associated with sphenoid encephalocele. Case report.

Morning glory syndrome is a congenital anomaly of the optic disc in which the disc is enlarged and excavated, with white glial tissue in the center. A case is presented of morning glory syndrome associated with sphenoid encephalocele, median cleft lip, and agenesis of the corpus callosum. A 22-day-old boy was referred to the Wakayama Medical College Hospital for management of dyspnea due to a soft-tissue mass in the oral cavity. Magnetic resonance imaging revealed a mass extending through a bone defect in the sphenoid region and into the oral cavity. Surgical repair was attempted through a bifrontal craniotomy. A bone defect was identified in the sphenoid plate, through which the arachnoid membrane was connected to the oral cavity. Both optic nerves were elongated and adhered to the encephalocele. The wall of the meningocele was compressed digitally through the oral cavity and sutured to the dura mater of the bone defect. The operative findings suggest that a basal encephalocele protruding from a bone defect in the sphenoid plate may disturb the normal development of the optic nerve.

The association of intracranial aneurysms and arteriovenous malformation of the brain. Case report.

A case of intracranial multiple aneurysms associated with an arteriovenous malformation (AVM) is described. Three aneurysms were found arising from an enlarged anterior cerebral artery feeding an AVM. In spite of the fact that two of these aneurysms received no surgical treatment, they disappeared almost completely several months after excision of the AVM. Seventy-three previously reported cases of cerebral aneurysms associated with AVM's are reviewed, and the effect of hemodynamic stresses on the development of these aneurysms is summarized.

A role of the central catecholamine neuron in cerebral circulation.

The effect of the central catecholaminergic neurons on the cerebral microcirculation was investigated by means of a unilateral intracerebral injection of 6-hydroxydopamine (6-OHDA) which produced the degeneration of catecholamine (CA) nerve terminals. Subsequent observation with CA histofluorescence revealed an absence of CA fibers in the vicinity of the 6-OHDA injection site. A significant increase in regional cerebral blood flow (rCBF), measured by the hydrogen clearance method, was demonstrated in the CA-depleted cortex under normocapnia as compared with rCBF in the control cortex (CA-depleted cortex 47.0 +/- 2.8 ml/100 gm/min; control cortex 38.5 +/- 3.5 ml/100 gm/min; p less than 0.005). The increased rCBF in the cortex treated with 6-OHDA was suppressed by the iontophoretic replacement of noradrenaline (NA) to the CA-depleted cortex. An iontophoretic replacement of 10(-5) M dopamine (DA) mildly suppressed the increased rCBF in the 6-OHDA-treated cortex. The CO2 reactivity in the CA-depleted cortex was significantly lower than that of the control cortex (CA-depleted cortex 2.13% +/- 0.6%/mm Hg; control cortex 3.53% +/- 0.70%/mm Hg). No change was noticeable in the cerebral glucose metabolism in the CA-depleted cortex in an investigation based on tritiated (3H)-deoxyglucose uptake. It is suggested that the 6-OHDA-induced change in cerebral blood flow (CBF) is not secondary to alterations in cerebral metabolic rate, and that the central NA neuron system innervating intraparenchymal blood vessels regulates CBF through a direct vasoconstrictive effect on the cerebral blood vessels. The central DA neuron system may modulate the cerebral circulation as a mild vasoconstrictor.