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Surgical handling characteristics of an ethylene vinyl alcohol copolymer compared with N-butyl cyanoacrylate used for embolization of vessels in an arteriovenous malformation resection model in swine

Eric D. Akin, Eddie Perkins, and Ian B. Ross

Object. There have been significant improvements in neurovascular technology and implants over the past decade. One such material, N-butyl cyanoacrylate (NBCA), is now commercially available for cerebral arteriovenous malformation (AVM) embolization in the US. An ethylene vinyl alcohol copolymer preparation, Onyx, which is currently being evaluated, is approved for use outside North America. Although reports indicate that Onyx may be superior to NBCA from an endovascular perspective, little information exists about its surgical handling characteristics. The purpose of this study was to compare the surgical handling characteristics of Onyx-treated vessels with those of NBCA-embolized vessels in an AVM resection model.

Methods. Fourteen pigs (two groups of seven) were anesthetized. A femoral artery was cannulated, followed by selective catheterization of the ascending pharyngeal arteries. Nidal rete mirabile (RM) embolizations were performed using either 6% Onyx or 20% NBCA. After angiographically confirmed obliteration of flow in the right RM, microsurgical resection of this structure was performed. Surgical handling characteristics of the embolized RM were rated on a scale of 1 to 5 and blood loss was recorded. Different surgeons performed the embolizations and resections. The surgeon who performed resections was blinded to the embolization agent used, and the data analysis was also performed in a blinded fashion. The surgical handling scores were superior (p < 0.05) in the Onyx-treated group. Although there was also less blood loss in this group, the difference was not significant. Subjectively, the surgeon who performed the resections believed that Onyx was softer and handled better than NBCA.

Conclusions. Onyx, which may offer endovascular advantages, also seems to provide benefits for the surgeon.

In Journal of Neurosurgery Volume 98: Issue 2 (Feb 2003)

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Evaluation of the microvasculature and cerebral ischemia after experimental subarachnoid hemorrhage in dogs

Eddie Perkins, Hitoshi Kimura, Andrew D. Parent, and John H. Zhang

Object. Whether cerebral vasospasm occurs only in surface vessels or also in parenchymal arterioles is debatable. The present study was undertaken to evaluate comprehensively the microvasculature of the brainstem after experimental subarachnoid hemorrhage (SAH).

Methods. Nine mongrel dogs of either sex, each weighing between 18 and 24 kg, underwent double blood injections spaced 48 hours apart; the injections were infused into the cisterna magna immediately after angiography of the basilar arteries (BAs). Three additional dogs assigned to a control group received no blood injections. The dogs were killed on Day 7. Axial sections obtained from the midpontine region of both control dogs and animals subjected to SAH were evaluated with respect to the morphological characteristics of vessels and neurons, and for ultrastructural changes.

Severe vasospasm occurred in the BAs of all dogs subjected to SAH. Nevertheless, in these animals, the luminal areas and vessel perimeter in parenchymal arterioles, but not in parenchymal venules, were observed to have increased when compared with those of control dogs (p < 0.01, t-test). No corrugation of the internal elastic lamina was observed and smooth-muscle and endothelial cells remained normal at the ultrastructural level in the dogs with SAH.

Conclusions. In this model, vasospasm of the BAs did not extend into the region of the pons to affect the intraparenchymal arterioles. Dilation of the parenchymal arterioles might serve as compensation for reduced blood flow. Thus, no neuronal ischemia or infarction resulted in the pontine region of the brain.

In Journal of Neurosurgery Volume 97: Issue 4 (Oct 2002)

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Contribution of Src tyrosine kinase to cerebral vasospasm after subarachnoid hemorrhage

Gen Kusaka, Hitoshi Kimura, Ikuyo Kusaka, Eddie Perkins, Anil Nanda, and John H. Zhang

Object. Mitogen-activated protein kinase (MAPK) has been implicated in cerebral vasospasm after subarachnoid hemorrhage (SAH). This study was conducted to investigate whether Src tyrosine kinase, an upstream regulator of MAPK, is involved in cerebral vasospasm.

Methods. An established canine double-hemorrhage model was used. Twenty-four dogs were divided into four groups: control, vehicle-treated, Src inhibitor PP2—treated, and Src inhibitor damnacanthal—treated groups. Vehicle (dimethyl sulfoxide), PP2, or damnacanthal was injected daily into the cisterna magna of 18 dogs at 3 to 6 days after induction of SAH. Angiography was performed on Day 0 (the day on which the first blood injection was administered to induce SAH) and on Day 7. Western blot analysis of Src and MAPK activation in basilar arteries (BAs) collected on Day 7 post-SAH was performed.

Severe vasospasm was observed in the BAs of vehicle-treated dogs. Mild vasospasm was observed in all dogs treated with Src inhibitors. Phosphorylated Src and MAPK were increased after SAH and activation of these kinases in the BAs was abolished by PP2 and damnacanthal.

Conclusions. The tyrosine kinase Src is an important upstream regulator of MAPK, and inhibition of Src might offer a new therapy in the management of cerebral vasospasm.

In Journal of Neurosurgery Volume 99: Issue 2 (Aug 2003)

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Posttreatment with adenovirus-mediated gene transfer of calcitonin gene—related peptide to reverse cerebral vasospasm in dogs

Motoyoshi Satoh, Eddie Perkins, Hitoshi Kimura, Jiping Tang, Yi Chun, Donald D. Heistad, and John H. Zhang

Object. Gene transfer to cerebral vessels is a promising new therapeutic approach for cerebral vasospasm after subarachnoid hemorrhage (SAH). This study was undertaken to explore whether a delayed treatment with adenovirus encoding the prepro-calcitonin gene—related peptide (CGRP), 2 days after initial blood injection, reduces cerebral vasospasm in a double-hemorrhage model of severe vasospasm in dogs.

Methods. In 20 dogs, arterial blood was injected into the cisterna magna on Days 0 and 2. Thirty minutes after the second blood injection, the animals received either adenovirus encoding the prepro-CGRP gene (AdCMVCGRP—treated group, eight dogs) or adenovirus encoding the β-galactosidase gene (AdCMVβgal—treated group, six dogs) under the cytomegalovirus (CMV) promoter. One group of dogs did not receive treatment and served as controls (control SAH group, six dogs). Angiography was performed on Days 0 and 7 to assess cerebral vasospasm. On Day 7 following angiography, the animals were killed and their brains were stained with X-gal to detect the distribution of gene expression. Cerebrospinal fluid (CSF) was also tested for CGRP immunoreactivity.

Severe vasospasm was observed in control SAH dogs on Day 7, and the mean basilar artery (BA) diameter was 53.4 ± 5.5% of the value measured on Day 0. Treatment with AdCMVβgal did not alter vasospasm (the BA diameter was 55 ± 3.9% of that measured on Day 0). The leptomeninges and adventitia of the BAs of dogs treated using AdCMVβgal demonstrated positive staining with X-gal. High levels of CGRP were measured in CSF from dogs that received AdCMVCGRP. In the group treated with AdCMVCGRP, vasospasm was significantly reduced (the BA diameter was 78.2 ± 5.3% of that measured on Day 0, p < 0.05 compared with the control SAH group and the AdCMVβgal group).

Conclusions. In a model of severe vasospasm in dogs, gene transfer of CGRP after injection of blood attenuated cerebral vasospasm after SAH.

In Journal of Neurosurgery Volume 97: Issue 1 (Jul 2002)

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Anatomical study of the thoracolumbar radiculomedullary arteries, including the Adamkiewicz artery and supporting radiculomedullary arteries

Jorge E. Alvernia, Emile Simon, Krishnakant Khandelwal, Cara D. Ramos, Eddie Perkins, Patrick Kim, Patrick Mertens, Raffaella Messina, Gustavo Luzardo, and Orlando Diaz

OBJECTIVE

The aim of this paper was to identify and characterize all the segmental radiculomedullary arteries (RMAs) that supply the thoracic and lumbar spinal cord.

METHODS

All RMAs from T4 to L5 were studied systematically in 25 cadaveric specimens. The RMA with the greatest diameter in each specimen was termed the artery of Adamkiewicz (AKA). Other supporting RMAs were also identified and characterized.

RESULTS

A total of 27 AKAs were found in 25 specimens. Twenty-two AKAs (81%) originated from a left thoracic or a left lumbar radicular branch, and 5 (19%) arose from the right. Two specimens (8%) had two AKAs each: one specimen with two AKAs on the left side and the other specimen with one AKA on each side. Eight cadaveric specimens (32%) had 10 additional RMAs; among those, a single additional RMA was found in 6 specimens (75%), and 2 additional RMAs were found in each of the remaining 2 specimens (25%). Of those specimens with a single additional RMA, the supporting RMA was ipsilateral to the AKA in 5 specimens (83%) and contralateral in only 1 specimen (17%). The specimens containing 2 additional RMAs were all (100%) ipsilateral to their respective AKAs.

CONCLUSIONS

The segmental RMAs supplying the thoracic and lumbar spinal cord can be unilateral, bilateral, or multiple. Multiple AKAs or additional RMAs supplying a single anterior spinal artery are common and should be considered when dealing with the spinal cord at the thoracolumbar level.

In Journal of Neurosurgery: Spine Volume 38: Issue 2 (Feb 2023)