Tissue plasminogen activator for the treatment of intraventricular hematoma: the dose-effect relationship.
In this study, we investigated the dose-effect relationship and safety of tissue plasminogen activator (tPA) for the treatment of intraventricular hemorrhage/hematoma (IVH) in rats. Adult male Sprague-Dawley rats were injected with autologous blood into the left lateral ventricle to establish IVH. Two hours later, Ringer's saline or 0.25-2 microg of tPA were administered directly to the IVH over 3 h. The regional cerebral blood flow (rCBF) on the surface of the left parietal cortex was measured with laser Doppler flowmetry. Twenty-four hours after the build-up of IVH, the brains were removed for morphometrical and histological studies. A dose of 0.5-2 microg tPA significantly diminished the IVH in a dose-dependent manner (p < 0.001). However, only the dose of 0.5 microg tPA significantly ameliorated the reduction of rCBF 24 h after IVH (p < 0.01). TPA did not improve the ventricular dilatation on the side with IVH. Instead, 1-2 microg of tPA caused additional injuries, including intraventricular leukocytosis and edema of periventricular tissues and choroid plexus on both hemispheres. These results indicate that higher doses of tPA may have detrimental effects on the brain. The dosage rate of 0.5 microg seems beneficial to treat 5 microl of IVH (equals to a dose of 0.1 mg/ml blood) in our model in terms of the satisfactory fibrinolysis and less damage to the brain.
Wang
Yeou-Chih
YC
Department of Neurosurgery, Taichung Veterans General Hospital, Taichung, Taiwan, ROC. ycwang@vghtc.gov.tw
Lin
Chi-Wen
CW
Shen
Chiung-Chyi
CC
Lai
Shu-Chen
SC
Kuo
Jon-Son
JS
D000818:Animals; D001929:Brain Edema / Q000139:chemically induced; D002543:Cerebral Hemorrhage / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D004305:Dose-Response Relationship, Drug; D006406:Hematoma / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D007276:Injections, Intraventricular; D017078:Laser-Doppler Flowmetry; D020547:Lateral Ventricles / Q000187:drug effects / Q000473:pathology; D007964:Leukocytosis / Q000139:chemically induced; D008297:Male; D010296:Parietal Lobe / Q000098:blood supply / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D010959:Tissue Plasminogen Activator / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use
D010959:Tissue Plasminogen Activator