BACKGROUND AND PURPOSE: In a model of mechanical focal ischemia, we investigated the involvement of thrombolysis products (TLP) in recombinant tissue plasminogen activator (rtPA)-induced intracerebral complications and the effects on infarct volume and postischemic endothelial function. METHODS: Hemorrhage incidence and severity were evaluated by histomorphometric analysis in male spontaneously hypertensive rats (SHR) subjected to 60-minute intraluminal middle cerebral artery (MCA) occlusion and receiving intravenously 5 hours later either saline, rtPA (3, 10, or 30 mg/kg), or rtPA (10 mg/kg) associated with TLP (rtPA+TLP). In addition, MCA reactivity was assessed in rtPA- or rtPA+TLP-treated SHR versus control Wistar-Kyoto rats or SHR. RESULTS: No hemorrhage was observed visually in SHR receiving saline. In contrast, rtPA administration induced hemorrhagic complications in infarcted areas in a dose-independent manner. Administration of rtPA+TLP solution, containing a high concentration of plasmin, did not affect hemorrhage incidence but significantly increased hemorrhage severity (8.8+/-2.3 petechiae versus 3.0+/-1.0 petechiae in rtPA group; P<0.001). This increased severity was associated with a significant increase of both infarct volume (182+/-10 versus 144+/-15 mm3 in rtPA group; P<0.01) and postischemic impairment of MCA endothelium-dependent relaxation (9+/-0.5% versus 13+/-1% in rtPA group; P<0.05). CONCLUSIONS: Treatment with rtPA led to intracerebral hemorrhages, in contrast to saline-treated animals, and the presence of TLP increased the severity of these hemorrhages, in parallel with increased infarct volume and worsened endothelial function.
BACKGROUND AND PURPOSE: In a model of mechanical focal ischemia, we investigated the involvement of thrombolysis products (TLP) in recombinant tissue plasminogen activator (rtPA)-induced intracerebral complications and the effects on infarct volume and postischemic endothelial function. METHODS:Hemorrhage incidence and severity were evaluated by histomorphometric analysis in male spontaneously hypertensiverats (SHR) subjected to 60-minute intraluminal middle cerebral artery (MCA) occlusion and receiving intravenously 5 hours later either saline, rtPA (3, 10, or 30 mg/kg), or rtPA (10 mg/kg) associated with TLP (rtPA+TLP). In addition, MCA reactivity was assessed in rtPA- or rtPA+TLP-treated SHR versus control Wistar-Kyoto rats or SHR. RESULTS: No hemorrhage was observed visually in SHR receiving saline. In contrast, rtPA administration induced hemorrhagic complications in infarcted areas in a dose-independent manner. Administration of rtPA+TLP solution, containing a high concentration of plasmin, did not affect hemorrhage incidence but significantly increased hemorrhage severity (8.8+/-2.3 petechiae versus 3.0+/-1.0 petechiae in rtPA group; P<0.001). This increased severity was associated with a significant increase of both infarct volume (182+/-10 versus 144+/-15 mm3 in rtPA group; P<0.01) and postischemic impairment of MCA endothelium-dependent relaxation (9+/-0.5% versus 13+/-1% in rtPA group; P<0.05). CONCLUSIONS: Treatment with rtPA led to intracerebral hemorrhages, in contrast to saline-treated animals, and the presence of TLP increased the severity of these hemorrhages, in parallel with increased infarct volume and worsened endothelial function.
Authors: George W J Harston; Brad A Sutherland; James Kennedy; Alastair M Buchan Journal: J Cereb Blood Flow Metab Date: 2010-08-25 Impact factor: 6.200
Authors: Glen C Jickling; Xinhua Zhan; Bradley P Ander; Renée J Turner; Boryana Stamova; Huichun Xu; Yingfang Tian; Dazhi Liu; Ryan R Davis; Paul A Lapchak; Frank R Sharp Journal: BMC Genomics Date: 2010-04-21 Impact factor: 3.969
Authors: Joseph C LaManna; Valery Novokhatny; Philip Scuderi; Stephen R Petteway; Vikram Arora; R Christian Crumrine; Victor J Marder; G McLeod Taylor; Constantinos P Tsipis Journal: Exp Transl Stroke Med Date: 2012-05-16