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  • By Author: Kassell, Neal F. x
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Hiroo Johshita, Neal F. Kassell, Tomio Sasaki and Hisayuki Ogawa

✓ To evaluate microcirculatory disturbance and cerebral edema associated with subarachnoid hemorrhage (SAH), both stereological morphometry on the intraparenchymal capillary network and microgravimetry were performed on a rabbit SAH model. Autologous arterial blood (5 ml) was injected into the cisterna magna, and the animals were sacrificed at intervals of 6 hours, 1 day, 2 days, or 6 days after SAH. Capillaries in the piriform cortex, parasagittal cortex, and ventral brain stem of the midline-hemisectioned brain were injected with Evans blue dye 1 minute before sacrifice, and were planimetrically evaluated under a fluorescence microscope connected to an image analysis system. Stereological and morphological parameters including the volume density, surface density, numerical density, minimum intercapillary distance, and the diameter of Evans blue-perfused capillaries were also computed.

In the piriform cortex and ventral brain stem, the volume and surface densities were significantly reduced and the minimum intercapillary distance was significantly increased 1 to 2 days after SAH. In the parasagittal cortex far from the cisternal clot, changes in the parameters were minimal. Cerebral blood volume (CBV) in the normal condition and edema formation associated with SAH were studied by the microgravimetric technique. The mean CBV in the parasagittal cortex, piriform cortex, and brain stem was 6.9%, 6.8%, and 5.6%, respectively. Following SAH, specific gravity in the piriform cortex and the ventral brain stem of the other side of the hemisectioned brain was significantly decreased at 1 to 2 days, showing a change parallel to that of the stereological parameters. The results obtained from the morphometric technique indicated the occurrence of impaired capillary perfusion and reduced capillary blood volume following SAH, while microgravimetry suggested the formation of brain edema during this period. These changes in the intraparenchymal vessels may play an important role in the pathophysiology of SAH.

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Dennis G. Vollmer, Kazuhiro Hongo, Neal F. Kassell, Hisayuki Ogawa, Tetsuya Tsukahara and R. Michael Lehman

✓ The ability of antithrombin III, an endogenous plasma glycoprotein, to reverse the arterial narrowing in a rabbit model of cerebral vasospasm was evaluated. The vasodilator activity of antithrombin III on rabbit arteries was first assessed in vitro using a myograph-arterial ring preparation. Antithrombin III (10 IU/ml) induced a 55.4% ± 2.66% (mean ± standard error of the mean) relaxation in basilar artery precontracted with serotonin (5-HT) in five specimens as compared with a 9.8% ± 1.6% relaxation of common carotid artery in six specimens. For in vivo analysis, 21 New Zealand White male rabbits were separated into three groups: Group 1 served as normal controls; Group 2 received a subarachnoid blood injection (SAH) and were sacrificed on Day 3 thereafter; and Group 3 animals were subjected to SAH, then received a 2-hour intracisternal infusion of antithrombin III (100 IU) in saline prior to sacrifice on Day 3. Basilar artery caliber was determined using a morphometric method to analyze perfusion-fixed arterial segments. Control basilar artery diameter in Group 1 was 0.64 ± 0.02 mm. In Group 2 a 27% reduction in arterial caliber to 0.47 ± 0.03 mm was observed by Day 3 post SAH (p < 0.0001). Group 3 animals had a mean basilar artery diameter of 0.68 ± 0.02 mm. This was significantly larger than the untreated SAH rabbits in Group 2 (p < 0.0001), but not different from control artery diameters in Group 1. The findings demonstrate that antithrombin III in saline has a significant ability to reverse delayed narrowing of the rabbit basilar artery after SAH.

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Tadayoshi Nakagomi, Kazuhiro Hongo, Neal F. Kassell, Tomio Sasaki, R. Michael Lehman, Hisayuki Ogawa, Dennis G. Vollmer and James C. Torner

✓ Endothelium-dependent relaxation was induced by acetylcholine (ACh), adenosine triphosphate (ATP), and thrombin in isolated cerebral and extracerebral arteries obtained from rabbits and dogs. Using an isometric tension-recording method, the authors then examined the difference in the extent of relaxation between the cerebral and extracerebral arteries. In rabbits, the dose-response curve of the basilar artery for ACh was significantly different (p < 0.05) from curves of the femoral and common carotid arteries. The IC50 value (the concentration inducing a one-half inhibition of the initial contractile tone) for the basilar artery in ACh-induced relaxation was significantly higher (p < 0.05) than for the common carotid artery, although the mean maximum relaxation of the basilar artery to ACh was not significantly different from that seen in extracerebral arteries. The relaxing effect of ACh in dogs was much less in the middle cerebral and basilar arteries than in the common carotid, vertebral, and femoral arteries. On the other hand, both ATP (in rabbits and dogs) and thrombin (in dogs) induced significantly more (p < 0.05) relaxation in the cerebral arteries than in the extracerebral arteries.

Endothelium-dependent relaxation induced by ACh or ATP has been demonstrated in a wide range of arteries from a variety of animals. The present results suggest that ATP has a more important role than ACh in the regulation of the vascular tone of the major cerebral arteries in these two species.

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Kazuhiro Hongo, Neal F. Kassell, Tadayoshi Nakagomi, Tomio Sasaki, Tetsuya Tsukahara, Hisayuki Ogawa, Dennis G. Vollmer and R. Michael Lehman

✓ Vascular contractions in response to KCl and serotonin (5-hydroxytryptamine, 5-HT) in rabbit basilar artery were studied in vitro using an isometric tension-measurement technique. Hemoglobin ( 10−5 M) markedly augmented contractions induced by 5-HT (10−9 to 10−6 M) and slightly augmented those induced by KCl (20 to 80 mM) in arteries with intact endothelium. On the other hand, the augmentation induced by hemoglobin was almost abolished in arteries that were chemically denuded of endothelial cells by pretreatment with saponin. Since hemoglobin is known to be a selective inhibitor of endothelium-derived relaxing factor (EDRF), it is possible that the augmentation of contraction by hemoglobin in endothelium-intact arteries was mediated via an inhibition of spontaneously released EDRF. The effect of subarachnoid hemorrhage (SAH) on spontaneously released EDRF was investigated by injecting 5 ml of blood into the cisterna magna and sacrificing the rabbits 2 days later. Arteries after SAH showed a significant reduction in hemoglobin-induced augmentation compared to that seen in control arteries with intact endothelium. This result suggests that spontaneously released EDRF is significantly reduced after SAH. It is concluded that EDRF is released spontaneously in the rabbit basilar artery and that inhibition of its release might be involved in pathogenesis of cerebral vasospasm.