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Endovascular Ultraviolet Laser-Facilitated Reversal of Vasospasm Induced by Subarachnoid Hemorrhage in Canines

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Subarachnoid Hemorrhage

Part of the book series: Acta Neurochirurgica Supplement ((NEUROCHIRURGICA,volume 127))

Summary

Background: Because treatments for cerebral arterial spasm—a delayed consequence of subarachnoid hemorrhage (SAH)—are clinically inconsistent, we describe here a new method for reversal of arterial spasm, possibly extensible to nitric oxide (NO)-sensitive microvasculature.

Methods: We subjected dogs to the intracisternal double-hemorrhage model of SAH (autologous blood injection on days 1 and 3) and began endovascular treatment of the spasmed basilar artery (BA) on Day 4. A conical-tip fused silica optical fiber was introduced via a microcatheter (inserted femorally) into the proximal vicinity of the spasmed BA. After local saline flushing of blood, an ultraviolet (UV) pulsed laser beam (355 nm Nd:YAG) was focused into the optical fiber and converted into a concentric ring beam, which facilitated endovascular irradiation for 30 s at intensities of 12–20 W/cm2. BA diameters were measured angiographically using a semiautomated routine over the entire BA length as well as the proximal, medial, and distal segments.

Results: On Day 4 the BAs had constricted by 21 ± 11%. After UV laser irradiation on Day 4, the constricted BAs dilated to 93 ± 15% of their normal diameters within minutes, and the dilation (91 ± 12%) persisted on Day 5. Most BA segments recovered to their respective baselines after UV irradiation, even when the UV beam was located considerably proximal to the BA origin. At days 4 and 5, the percent BA dilation normalized to Day 4 pre-treatment decreased linearly (by scatter plot, p < 0.02) over a range of about 60 mm from the UV irradiation site.

Conclusions: We conjecture that the vasodilator nitric oxide, produced at high local concentration from its vascular storage forms (chiefly nitrites) by UV laser-induced photoscission, stimulates a wave of arterial dilation, possibly by longitudinal propagation of transnitrosation reactions in the arterial wall, which reverses cerebral vasospasm semi-locally and thus avoids the deleterious effects of systemic treatment.

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Abbreviations

BA:

Basilar artery

eNOS:

Endothelial nitric oxide synthase

Nd:YAG:

Neodymium yttrium aluminum garnet

NO:

Nitric oxide

SAH:

Subarachnoid hemorrhage

UV:

Ultraviolet

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Acknowledgments

The optical fiber/microcatheter system was provided by OpusGen LLC of Doral, FL, under the name Opus-14 which, upon testing in rats and dogs (described above), led to a Phase I clinical trial on ischemic stroke in Italy in 2010, but OpusGen LLC ceased operations in 2013 when stentrievers became the accepted intervention. We thank Dr. Martin Feelisch for helpful comments regarding the propagating wave mechanism of dilation and Dr. Kunjan Dave for assistance with EndNote. Dr. Watson thanks Dr. John Zhang for suggesting that a canine model be used in what evolved into the present study.

Funding: Initial work on UV laser vasodilation was supported by grant R01 NS23244 (to Dr. Watson) from the National Institute of Neurological Diseases and Stroke. Subsequently, the same agency funded a collaboration via translational grant R21 NS48297 (to Dr. Watson) with VasCon LLC of Doral, FL, to develop the endovascular UV laser delivery system (then known as the Opus-14). To conduct the canine study, Dr. Hurst received research funds from VasCon LLC’s successor OpusGen LLC of Doral, FL, and the University of Pennsylvania SRA. Since March 2013, further commercialization has been the responsibility of Photothrombotics, Inc., Miami Beach, FL.

Conflict of Interest: US patent 6,593,944B1 entitled “Dethrombosis by Vasodilation” was awarded to Dr. Watson in 2003 and provided the conceptual backing for the dog study described herein; in 2013 the patent was assigned to Photothrombotics, Inc.

Drs. Sadasivan and Hurst report no conflicts.

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Authors and Affiliations

  1. Departments of Neurology and Biomedical Engineering, University of Miami Miller School of Medicine, Miami, FL, USA

    Brant D. Watson

  2. Department of Neurological Surgery, Stony Brook University Medical Center, Stony Brook, NY, USA

    Chander Sadasivan

  3. Department of Radiology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA

    Robert W. Hurst

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  1. Brant D. Watson
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  2. Chander Sadasivan
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  3. Robert W. Hurst
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Correspondence to Brant D. Watson .

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Editors and Affiliations

  1. Department of Anethesiology, Loma Linda University Medical Center, Loma Linda, CA, USA

    Robert D. Martin

  2. Department of Neurosurgery, Loma Linda University Medical Center, Loma Linda, CA, USA

    Warren Boling

  3. Department of Neurosurgery, First Affiliated Hospital of Soochow University, Suzhou, China

    Gang Chen

  4. Department of Anesthesiology and Physiology, Loma Linda University Medical Center, Loma Linda, CA, USA

    John H. Zhang

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Watson, B.D., Sadasivan, C., Hurst, R.W. (2020). Endovascular Ultraviolet Laser-Facilitated Reversal of Vasospasm Induced by Subarachnoid Hemorrhage in Canines. In: Martin, R., Boling, W., Chen, G., Zhang, J. (eds) Subarachnoid Hemorrhage. Acta Neurochirurgica Supplement, vol 127. Springer, Cham. https://doi.org/10.1007/978-3-030-04615-6_19

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