Efficacy of sonothrombolysis in a rat model of embolic ischemic stroke.
The key goal in the treatment of acute ischemic stroke is fast vessel recanalization. Thrombolysis with recombinant tissue plasminogen activator (rt-PA) is efficient in humans but mean time for recanalization is within hours. Ultrasound bio-effects has been shown to facilitate rt-PA mediated thrombolysis in peripheral arteries. We used an embolic stroke model in the rat. In all rats we induced an ischemic stroke by a selective occlusion of the middle cerebral artery with whole blood clots. From an entire collective of 54 rats 47 completed the protocol (n = 7 died early). Four different groups (no treatment n = 6; full dose rt-PA treatment only [10 mg/kg per body weight] n = 14, half dose rt-PA treatment plus ultrasound n = 10, and full dose rt-PA treatment plus ultrasound n = 17) were investigated. We found a significant reduction of absolute as well as relative infarct volume in the full dose rt-PA plus ultrasound group (81+/-72 mm(3); P< 0.05) in comparison to untreated rats (253+/-159 mm(3); P < 0.05) as well as in comparison to rats treated with full dose rt-PA only (167+/-91 mm(3); P < 0.05). There were five intracranial bleedings giving a bleeding rate of 9.3%. In summary: ultrasound treatment in addition to rt-PA is more effective than single rt-PA treatment in reducing infarct volume and safe with regard to bleeding.
Daffertshofer
M
M
Department of Neurology, University of Heidelberg, Universitätsklinikum Mannheim, Theodor-Kutzer-Ufer 1-3, 68135 Mannheim, Germany. daffershofer@neuro.ma.uni-heidelberg.de
Huang
Z
Z
Fatar
M
M
Popolo
M
M
Schroeck
H
H
Kuschinsky
W
W
Moskowitz
M A
MA
Hennerici
M G
MG
D000818:Animals; D003131:Combined Modality Therapy; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D020925:Hypoxia-Ischemia, Brain / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D020244:Infarction, Middle Cerebral Artery / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control / Q000628:therapy*; D019106:Postoperative Hemorrhage / Q000517:prevention & control; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D011993:Recombinant Fusion Proteins / Q000494:pharmacology; D015912:Thrombolytic Therapy / Q000379:methods* / Q000639:trends; D010959:Tissue Plasminogen Activator / Q000494:pharmacology; D016896:Treatment Outcome; D014464:Ultrasonic Therapy / Q000379:methods* / Q000639:trends
D011993:Recombinant Fusion Proteins; D010959:Tissue Plasminogen Activator