The neurosurgical treatment of intracranial vascular malformations, particularly with the use of plastics and polarographic measurements.
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Biomedical subjects
Publications and source records attributed to H Handa.
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This article describes a new nonsuture method for microvascular anastomoses that uses plastic adhesives and soluble tube stents made of polyvinyl alcohol (PVA). Three soluble tubes were studied: one tube with a monolayered wall and two bilayered tubes of different thicknesses. The layers of the bilayered tubes consisted of PVA of different degrees of solubility. As plastic adhesives, ethyl 2-cyanoacrylate, isopropyl 2-cyanoacrylate, isobutyl 2-cyanoacrylate, and methyl 2-cyanoacrylate were employed; methyl 2-cyanoacrylate was by far the least effective. Anastomoses were performed on the common carotid artery of rats, and macroscopic, angiographic, and histologic investigations were carried out at intervals ranging from seven days to six months. The patency rates were 81% for the monolayered tube, and 92% and 98% for the bilayered tubes. The principal advantage of this method is that blood flow can be reestablished through the anastomosed site immediately after release of the hemostatic clamps.
The effects of the administration of a 3-day course of 13-cis retinoic acid in combination with interferon a [RA/IFN] on the leukemia cells was measured in vivo in 43 patients with chronic myelogenous leukemia. The administration of RA/IFN was associated with a significant fall in the white blood cell count of patients with chronic-phase disease and with a fall in the percentage S-phase cells in CML patients regardless of the stage of their leukemia. In two thirds of the patients studied the administration of RA/IFN was also associated with an increase in marrow apoptosis. The cytokine combination also suppressed bcl-2 and myc expression in a minority of patients and such expression appears to be associated with response to a treatment regimen which includes RA/IFN. These studies are the first to directly assess the effects of the combination of RA/IFN on chronic myelogenous leukemia cells in vivo in patients. These effects, if seen in other malignant diseases, could account for the therapeutic benefit which has been associated with the administration of this combination of biological agents to patients with malignant disease.
Saccular cerebral aneurysms are induced in rats treated with ligation of one or both of the common carotid arteries, experimental hypertension, and beta-aminopropionitrile feeding. Combination of ligation of the carotid artery and experimental hypertension is the minimal requirement for inducing aneurysms within a few months. beta-aminopropionitrile makes the arterial wall fragile, increasing the incidence of aneurysmal development. Induced aneurysms are strongly related to haemodynamic stresses. They are located on the large arteries at the base of the brain. Some of them apparently originate from the apex of bifurcation. The macroscopic and microscopic findings are generally in accordance with those of spontaneous lesions in man. The results of electron microscope and histochemical studies indicate the participation of leukocytes and their lysosomal enzymes in the development and growth of aneurysms. Adventitial cells are also suggested to be responsible for the growth of aneurysms.
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During stereotactic surgery, electrical impedance was measured by means of a roving electrode technique with a sine wave current of 10 kc. Impedance showed a characteristic decrease when the electrode was passing through the thalamus and consequently the impedance profile corresponding to the thalamic area exhibited the characteristic shape of a 'frying pan'. By observing the impedance, it is possible to differentiate the thalamic gray matter from the surrounding structures with some accuracy.
The fluorescence histochemical method of Falck et al. was applied to 40 gerbil brains after ligation of a unilateral common carotid artery to investigate alterations of brain dopamine in the acute stage of cerebral ischemia. The distribution of dopaminergic terminals and cell bodies in gerbils is the same as in other mammals. On the ligated side after one hour of ischemia, diffuse green fluorescence of dopaminergic terminals showed only a slight decrease in intensity when compared to the nonligated side. But white matter and bundles of myelinated fibers adjacent to and in the dopamine-rich regions had an intense green fluorescence in contrast to the non-ligated side where they are normally non-fluorescent. This is considered to indicate the extraneuronal leakage and diffusion of dopamine. The intensity of extraneuronal green fluorescence was especially high in glial cells. Occasionally, there was also an unusual green fluorescence in the lumen of small vessels in dopamine-rich regions on the ligated side. Dopaminergic cell bodies in the substantia nigra on the ligated side revealed a conspicuous reduction in the fluorescence intensity in severely affected cases. After 2 or 3 hours of ischemia, there was a marked reduction or disappearance of the diffuse green fluorescence on the ligated side. This may be attributed in part to further diffusion of leaked dopamine.
Hemodynamic changes were examined with an ultrasonic Doppler flowmeter and with a sound-spectrograph in 5 patients with internal carotid giant aneurysms or with recurrent laryngeal cancer undergoing gradual carotid occlusion. The ultrasonic Doppler technique was useful for preoperative assessment of intracranial cross-filling and as a practical guide for the graded reduction of blood flow in the carotid artery. The degree of flow increase in the contralateral carotid artery when the ipsilateral carotid artery was totally occluded was greater in postoperative gradual occlusion than in intraoperative rapid occlusion. In one patient with bilateral internal carotid artery giant aneurysms, whose left internal carotid artery had already been ligated at its origin, gradual occlusion of the right internal carotid artery was performed after the bilateral superficial temporal artery-middle cerebral artery (STA-MCA) anastomoses. Flow in the donor artery of the right STA-MCA anastomosis developed with increasing occlusion of the right internal carotid artery.
The elastic properties of the basilar artery were studied in control and treated dogs in which 3 ml of blood was injected intracisternally. Vascular specimens were resected transclivally as cylindrical segments and their external diameters were measured in vitro in the pressure range from 0 mm Hg to 250 mm Hg in the active condition of smooth muscle in Krebs-Ringer solution and in the passive condition in saline solution. The development of cerebral vasospasm was confirmed comparing the diameter difference between these two conditions. The experimental data indicated that vasospasm was most prominent on the 7th day after the treatment of blood injection. In the passive condition no significant dimensional change (i.e. radius and wall thickness) was observed between the control and the treated arteries at various pressure levels. These results imply that the luminal narrowing under vasospasm is not attributable to an irreversible organic change in the wall but to the constriction of vascular smooth muscle. The treated arteries are more distensible and have lower elastic moduli than the control arteries, possibly due to a change in the content of their connective tissues. These changes of the passive elastic properties of arterial walls after blood injection might be one of the factors affecting the development of cerebral vasospasm.
Two experiments were done with a prototype mini-NMR imager to evaluate the potential application of nuclear magnetic resonance (NMR) imaging in neuropathology. Cryo-injury-induced brain edema in brain slices from 22 adult male rats was imaged for observing the chronological sequences. Blood-brain barrier permeability changes were evaluated in 12 other brain slice images. EDTA-2Na-Mn solution was intravenously injected as an indicator of blood-brain barrier permeability. Contrast enhancement was achieved by changing the NMR imaging parameters. High resolution imaging permitted visualization of the corpus callosum, the thickness of which was only 0.2-0.4 mm. The extent of edema in gray matter was clearly shown with a striking contrast; no consistent findings were seen with slight differences in water content between edema and the surrounding normal cortex. As a result, the chronological sequences of brain edema were clearly observed. Mn-EDTA leaking from the circulating blood through the damaged capillary wall had a "paradoxical enhancement" effect on the NMR images; this effect might be suitable for evaluating blood-brain barrier permeability changes in NMR images.
We studied the mechanical properties of canine basilar arteries subjected to experimental subarachnoid hemorrhage (SAH). Smooth muscle contractility was determined from pressure-diameter curves obtained after subjecting the basilar arteries to three different conditions: Krebs-Ringer solution (KRS), Krebs-Ringer solution containing serotonin (5HT), and saline solution. Pressure-diameter curves obtained in KRS and 5HT are biphasic and have sharp flexions that yield flexion points. The pressure level at the flexion point increases as vasospasm increases. Strong constriction is retained up to that pressure above which the constriction is released abruptly. These data suggest that increasing the intraluminal pressure dilates the spastic artery nonlinearly and that induced hypertension could relieve the cerebral ischemia caused by vasospasm if blood pressure were maintained above the flexion point. The contractile response of spastic arterial wall to serotonin remains unchanged after SAH although the spastic constriction increases progressively and becomes maximal seven days after SAH. The lesser the arterial wall stiffness, the more efficiently it constricts. This means that the diminution of arterial stiffness observed after SAH might be one of the factors promoting the development of vasospasm.
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In helically-cut strips of dog basilar and mesenteric arteries, the isometric tension developed by application of ghost-free hemolysate from dog erythrocytes was recorded. The hemolysate contracted basilar arteries in a concentration-dependent fashion, the response being attenuated by treatment with either aspirin or polyphloretin phosphate, a prostaglandin antagonist. Mesenteric arteries were contracted only slightly by high concentrations of hemolysate. When the mesenteric arteries had partially been contracted with prostaglandin F2 alpha or norepinephrine, the hemolysate induced relaxations, which were abolished by aspirin in approximately half the preparations used. Studies on rat stomach strips exposed to superfusate of dog cerebral arteries showed a release of prostaglandin-like substance by the hemolysate application. It may be concluded that the hemolysate contracts basilar arteries and relaxes mesenteric arteries, mainly through prostaglandins synthesized in and released from the vascular wall. Such a mechanism may be involved in the pathogenesis of cerebral vasospasm following a subarachnoid hemorrhage.
Though unilateral blood distribution of the vertebral artery has not been studied in humans, it is significant when considering the ischemic events especially embolic occlusion in vertebrobasilar system. To clarify the blood distribution, Krypton-81m was continuously infused into the vertebral arteries of 10 patients. Radioactivity was recorded by a rotating gamma camera. The perfusion images, reconstructed by computer in the transaxial plane, were classified according to whether the distribution was equal, or predominantly unilateral. Overlapping of blood supply from each vertebral artery was studied. In addition, the perfusion from one of the vertebral arteries revealed four distribution patterns with respect to laterality. A) ipsilateral; B) contralateral; C) bilateral; D) mosaic. Images obtained following perfusion of the vertebral artery show less uniformity compared to that of the internal carotid artery, suggesting a complicated vascular supply of the vertebral basilar territory. This complex distribution can be classified by the use of continuous infusion of Krypton-81m.
The nature of alpha adrenergic receptors in human cerebral arteries was characterized and alteration of these receptors after subarachnoid hemorrhage (SAH) was examined using a radioligand binding assay. The specific 3H-prazosin binding to human cerebral arteries was saturable and of high affinity (KD = 4.1 nM) with a Bmax of 92 fmol/mg protein. Specific 3H-yohimbine binding to these tissues was also saturable and of high affinity (KD = 23 nM) with a Bmax 250 fmol/mg protein. IC50 values of adrenergic agents for 3H-prazosin binding were as follows: prazosin, 1.2 X 10(-10) M; phentolamine, 1.3 x 10(-6) M; yohimbine, 1.2 x 10(-5); norepinephrine, 4.9 x 10(-4) M; epinephrine greater than 1 x 10(-3) M. IC50 values of adrenergic agents for 3H-yohimbine binding were as follows: phentolamine, 1.7 x 10(-7) M; yohimbine, 4.2 x 10(-7) M; prazosin, 1.9 x 10(-5) M; epinephrine, 4.4 x 10(-5) M; norepinephrine, 7.9 x 10(-4) M. KD and Bmax of 3H-prazosin and 3H-yohimbine binding after SAH were compared with findings in the non-SAH group. KD and Bmax of 3H-prazosin binding of SAH group were 6 +/- 3 nM and 90 +/- 10 fmol/mg protein, respectively (N = 3). KD and Bmax of 3H-yohimbine binding of SAH group were 42 +/- 6 nM and 460 +/- 30 fmol/mg protein, respectively (N = 5). On the other hand, KD and Bmax of 3H-prazosin binding in the non-SAH group were 4 +/- 1 nM and 90 +/- 20 fmol/mg protein, respectively (N = 5), KD and Bmax of 3H-yohimbine binding of non-SAH group were 20 +/- 5 nM and 260 +/- 30 fmol/mg protein, respectively (N = 6).(ABSTRACT TRUNCATED AT 250 WORDS)
The nature of beta adrenergic receptors in human cerebral arteries was characterized and alteration of these receptors after subarachnoid hemorrhage was examined using a radioligand binding assay. The specific 3H-dihydroalprenolol, a beta adrenergic antagonist, binding to human cerebral arteries was saturable and of high affinity (KD = 12.3 nM) with a Bmax of 790 fmol/mg protein. Ki values and Hill coefficients of adrenergic agents for 3H-dihydroalprenolol were as follows; propranolol, 4.1 X 10(-8)M, 1.01; isoproterenol, 1.7 X 10(-6)M, 0.80; epinephrine, 8.3 X 10(-6)M, 0.48; norepinephrine, 2.3 X 10(-5)M, 0.45; metoprolol, 6.8 X 10(-8)M and 7.9 X 10(-6)M, 0.62; butoxamine, 2.2 X 10(-8)M and 2.1 X 10(-6)M, 0.43. The analysis of inhibition of specific 3H-dihydroalprenolol binding by these adrenergic agents suggests that human cerebral arteries contain a high density of beta adrenergic receptors and that the receptors are classified into two types, namely beta 1 and beta 2 adrenergic receptors. The calculated beta 1/beta 2 ratio from Hofstee plots was approximately 4/6. KD and Bmax of 3H-dihydroalprenolol binding to the cerebral arteries after subarachnoid hemorrhage were compared with those of control group. KD and Bmax of 3H-dihydroalprenolol binding of subarachnoid hemorrhage group were 13.9 nM and 1140 fmol/mg protein, respectively. The calculated beta 1/beta 2 ratio was approximately 6/4. These data suggest that the density of total beta adrenergic receptors increased without any significant change in the affinity after subarachnoid hemorrhage and that the increase of beta 1 adrenergic receptors was dominant.
Various concentrations of acetylcholine (ACh) produced dose dependent relaxations of isolated, helical preparations of human cerebral arteries and these responses were blocked by atropine. The median effective concentration (EC50) of ACh was 6.1 +/- 0.2 X 10(-6)M. ACh produced dual responses in isolated dog cerebral arteries. ACh in low concentrations produced relaxation, and contraction occurred when the concentration was raised to 1 X 10(-5)M. The EC50 of ACh which produced relaxation, in dog cerebral arteries was 7.2 +/- 0.2 X 10(-7)M. Muscarinic cholinergic receptors in these arteries were analyzed directly using 3H-QNB as the ligand. The specific 3H-QNB binding to the arteries was saturable and of KD = 1.5 nM and Bmax = 93 fmol/mg protein in human cerebral arteries and KD = 0.59 nM, Bmax = 340 fmol/mg protein in dog cerebral arteries. Specific binding of 3H-QNB was displaced by muscarinic cholinergic agents. Ki values and Hill coefficients were as follows: QNB, 1.0 X 10(-9)M, 0.89; atropine, 1.1 X 10(-8)M, 0.95; ACh, 0.8 X 10(-8)M and 2.1 X 10(-6)M, 0.54; carbachol, 1.2 X 10(-7)M and 4.3 X 10(-5)M, 0.33 in human cerebral arteries and QNB, 0.55 X 10(-9)M, 0.85; atropine 0.9 X 10(-9)M, 1.00; ACh, 0.9 X 10(-9)M and 1.1 X 10(-6)M, 0.43; carbachol 6.3 X 10(-8)M and 1.1 X 10(-5)M, 0.36 in dog cerebral arteries. Endogenous choline acetyltransferase (ChAT) activity was 1.6 +/- 0.4 nmol/mg protein/hr in human cerebral arteries and 3.7 +/- 0.1 nmol/mg protein/hr in dog cerebral arteries.(ABSTRACT TRUNCATED AT 250 WORDS)
To obtain information about the early changes of experimentally induced cerebral aneurysms in rats, the luminal surface of branching areas of their cerebral arteries was examined with a scanning electron microscope. At the branching sites of major cerebral arteries in the control animals, the intima just distal to the apex markedly protruded into the lumen forming a linear bank-like intimal pad. Along and distal to this pad, there was a shallow long groove (juxta-apical groove). Such grooves were much deeper and wider in experimental animals than those in the control rats. By studying various stages of early aneurysmal changes, cerebral aneurysms were proven to develop from such grooves. In deep juxta-apical grooves and small aneurysms, round regenerated endothelial cells with a large number of microvilli were diffusely present. Degenerated cells with balloons and craters were observed intermingled with such regenerated cells. Interendothelial gaps were also seen. The present study showed the complex structure of the apex of arterial bifurcation in rats, including bank-like intimal pads. Such complex structures of the branching sites were considered to be responsible for the initiation of cerebral aneurysms due to endothelial injury possibly caused by turbulent flow there.