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(Stroke. 2008;39:3073.)
© 2008 American Heart Association, Inc.

Original Contributions

Safety Profile of Transcranial Near-Infrared Laser Therapy Administered in Combination With Thrombolytic Therapy to Embolized Rabbits

Paul A. Lapchak, PhD; Moon-Ku Han, MD; Karmen F. Salgado, BSc; Jackson Streeter, MD Justin A. Zivin, MD, PhD

From the Department of Neuroscience (P.A.L., J.A.Z.), University of California San Diego, La Jolla, Calif; the Veterans Administration San Diego Healthcare System (P.A.L., M.-K.H., K.F.S., J.A.Z.), Stroke Research, San Diego, Calif; the Veterans Medical Research Foundation (P.A.L., J.A.Z.), San Diego, Calif; and Photothera Inc (J.S.), Carlsbad, Calif.

Correspondence to Paul A. Lapchak, PhD, University of California San Diego, Department of Neuroscience, MTF 316, 9500 Gilman Drive, La Jolla, CA 92093-0624. E-mail plapchak{at}ucsd.edu

Background and Purpose— Transcranial near-infrared laser therapy (TLT) is currently under investigation in a pivotal clinical trial that excludes thrombolytic therapy. To determine if combining tissue plasminogen activator (tPA; Alteplase) and TLT is safe, this study assessed the safety profile of TLT administered alone and in combination with Alteplase. The purpose for this study is to determine if the combination of TLT and thrombolysis should be investigated further in a human clinical trial.

Methods— We determined whether postembolization treatment with TLT in the absence or presence of tPA would affect measures of hemorrhage or survival after large clot embolism-induced strokes in New Zealand white rabbits.

Results— TLT did not significantly alter hemorrhage incidence after embolization, but there was a trend for a modest reduction of hemorrhage volume (by 65%) in the TLT-treated group compared with controls. Intravenous administration of tPA, using an optimized dosing regimen, significantly increased hemorrhage incidence by 160%. The tPA-induced increase in hemorrhage incidence was not significantly affected by TLT, although there was a 30% decrease in hemorrhage incidence in combination-treated rabbits. There was no effect of TLT on hemorrhage volume measured in tPA-treated rabbits and no effect of any treatment on 24-hour survival rate.

Conclusion— In the embolism model, TLT administration did not affect the tPA-induced increase in hemorrhage incidence. TLT may be administered safely either alone or in combination with tPA because neither treatment affected hemorrhage incidence or volume. Our results support the study of TLT in combination with Alteplase in patients with stroke.

Key Words: intracerebral hemorrhage • ischemic stroke • neuroprotection • tissue plasminogen activator • transcranial laser therapy