Investigation of image-guided sonothrombolysis in a porcine acute ischemic stroke model

Author(s):  
William T. Shi ◽  
Thomas R. Porter ◽  
Francois Vignon ◽  
Jeffry E. Powers ◽  
Shunji Gao ◽  
...  
2021 ◽  
pp. 0271678X2110249
Author(s):  
Giorgio FM Cattaneo ◽  
Andrea M Herrmann ◽  
Sebastian A Eiden ◽  
Manuela Wieser ◽  
Elias Kellner ◽  
...  

Selective therapeutic hypothermia (TH) showed promising preclinical results as a neuroprotective strategy in acute ischemic stroke. We aimed to assess safety and feasibility of an intracarotid cooling catheter conceived for fast and selective brain cooling during endovascular thrombectomy in an ovine stroke model. Transient middle cerebral artery occlusion (MCAO, 3 h) was performed in 20 sheep. In the hypothermia group (n = 10), selective TH was initiated 20 minutes before recanalization, and was maintained for another 3 h. In the normothermia control group (n = 10), a standard 8 French catheter was used instead. Primary endpoints were intranasal cooling performance (feasibility) plus vessel patency assessed by digital subtraction angiography and carotid artery wall integrity (histopathology, both safety). Secondary endpoints were neurological outcome and infarct volumes. Computed tomography perfusion demonstrated MCA territory hypoperfusion during MCAO in both groups. Intranasal temperature decreased by 1.1 °C/3.1 °C after 10/60 minutes in the TH group and 0.3 °C/0.4 °C in the normothermia group (p < 0.001). Carotid artery and branching vessel patency as well as carotid wall integrity was indifferent between groups. Infarct volumes (p = 0.74) and neurological outcome (p = 0.82) were similar in both groups. Selective TH was feasible and safe. However, a larger number of subjects might be required to demonstrate efficacy.


2015 ◽  
Vol 8 (4) ◽  
pp. 418-422 ◽  
Author(s):  
Thomas K Mattingly ◽  
Lynn M Denning ◽  
Karen L Siroen ◽  
Barb Lehrbass ◽  
Pablo Lopez-Ojeda ◽  
...  

BackgroundTotal body hypothermia is an established neuroprotectant in global cerebral ischemia. The role of hypothermia in acute ischemic stroke remains uncertain. Selective application of hypothermia to a region of focal ischemia may provide similar protection with more rapid cooling and elimination of systemic side effects. We studied the effect of selective endovascular cooling in a focal stroke model in adult domestic swine.MethodsAfter craniotomy under general anesthesia, a proximal middle cerebral artery branch was occluded for 3 h, followed by 3 h of reperfusion. In half of the animals, selective hypothermia was induced during reperfusion using a dual lumen balloon occlusion catheter placed in the ipsilateral common carotid artery. Following reperfusion, the animals were sacrificed. Brain MRI and histology were evaluated by experts who were blinded to the intervention.Results25 animals were available for analysis. Using selective hypothermia, hemicranial temperature was successfully cooled to a mean of 26.5°C. Average time from start of perfusion to attainment of moderate hypothermia (<30°C) was 25 min. Mean MRI stroke volumes were significantly reduced by selective cooling (0.050±0.059 control, 0.005±0.011 hypothermia (ratio stroke:hemisphere volume) (p=0.046). Stroke pathology volumes were reduced by 42% compared with controls (p=0.256).ConclusionsSelective moderate hypothermia was rapidly induced using endovascular techniques in a clinically realistic swine stroke model. A significant reduction in stroke volume on MRI was observed. Endovascular selective hypothermia can provide neuroprotection within time frames relevant to acute ischemic stroke treatment.


Stroke ◽  
2017 ◽  
Vol 48 (suppl_1) ◽  
Author(s):  
Sheng Wen Yeh ◽  
Yinghua Jiang ◽  
Tzulin Yeh ◽  
Wendy Chern

Background and rationale: DC007 is a synthetic small molecule with multiple pharmacological activities. It has been shown to have thrombolytic, anti-platelet and free radical scavenging activities in vitro. To explore its potential in treating acute ischemic stroke, we evaluated its safety and efficacy using a thromboembolic stroke model in rattus and in Cynomolgus macaque. Methods: Effects of DC007 (10mg/kg) were compared to intravenous tPA (10mg/kg in rat; 0.9mg/kg in monkey) using a model of focal embolic cerebral ischemia in rats and monkeys. Pre-formed blood clots were introduced into middle cerebral artery through catheter cannulated into internal carotid artery of the animals. Animals (12 rats per group; 4 monkeys per group) were randomized to receive intravenous infusion of saline, tPA or DC007 at 3 hours after embolization was confirmed. Results: DC007 reduced brain infarction and hemispheric swelling in the stroke rats more significantly than saline or tPA did, when treatments were given at 3 hours after stroke onset. At 24 hours after stroke, infraction volumes were 49.36%, 31.98%, and 40.66% for saline, DC007 and tPA group, respectively; while brain swelling rates were 17.67%, 13.20% and 22.58% for saline, DC007 and tPA group, respectively. In the thromboembolic stroke model in monkey, DC007 also showed a stronger beneficial effect on vessel patency (DC007: 46.3±10.3% vs. tPA: 22.2±12.8% in the 8 hours time period after stroke), brain infarction (DC007: 3361±354 mm 3 vs. tPA: 9072±2096 mm 3 measured by MRI at 24 hours after stroke) and neurobehavioral score measured at 72 hours after stroke (DC007: 46.3±10.3 vs. tPA: 60±9.8, where score 0 indicated normal, while score 77 indicated death). Conclusions: DC007 appears to be a more potent thrombolytic compound with superior safety profile than IV rt-PA when given at 3 hours after the stroke onset in rats and monkeys. Further investigation is warranted for its potential in the treatment of AIS clinically.


Stroke ◽  
2007 ◽  
Vol 38 (6) ◽  
pp. 1820-1825 ◽  
Author(s):  
Karen C. Johnston ◽  
Douglas P. Wagner ◽  
Xin-Qun Wang ◽  
George C. Newman ◽  
Vincent Thijs ◽  
...  

Author(s):  
Ling Deng ◽  
Yi Guo ◽  
Jingdong Liu ◽  
Xuan Wang ◽  
Sha Chen ◽  
...  

Sign in / Sign up

Export Citation Format

Share Document