Selective intra-carotid blood cooling in acute ischemic stroke: A safety and feasibility study in an ovine stroke model

Abstract

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.

Comparison of Large Animal Models for Acute Ischemic Stroke: Which Model to Use?

“…Similarly, responses to currently employed clinical interventions such as mechanical thrombectomy should ideally be studied in large animal models. 9 Moreover, large animal models can be useful to explore opportunities emerging from sophisticated imaging approaches in stroke 10 and related fields. 11…”

The intra‐arterial selective cooling infusion system: A mathematical temperature analysis and in vitro experiments for acute ischemic stroke therapy

“…However, in some of the large animal and non‐human primate studies, the reduction of infarct size and improved functional outcomes induced by selective brain cooling were not statistically different from their control groups, which may ascribe to the small sample size. Therefore, a larger number of subjects might be required to demonstrate the efficacy of this technique 50,51 …”

“…Therefore, a larger number of subjects might be required to demonstrate the efficacy of this technique. 50 , 51 …”

“…Therefore, a larger number of subjects might be required to demonstrate the efficacy of this technique. 50,51 The time to target temperature and the brain temperature from the in vivo and in vitro study is compared in Table 3. The calculation results from the numerical theoretical model in this manuscript were compatible with the brain temperature estimation of rat, monkey, and human during IA-SCAI.…”

The Translational Benefits of Sheep as Large Animal Models of Human Neurological Disorders

“…Temporary MCAo in sheep causes decreased oxygenation of brain tissue which returns to normal levels after reperfusion, resulting in less tissue swelling, neuronal cell death, and white matter injury, and an overall smaller infarct size in the long term ( 109 , 110 ). Modeling acute ischemia in sheep has allowed researchers to develop clinically relevant imaging protocols to determine presence and extent of MCAo, and test early interventions such as therapeutic hypothermia ( 111 , 112 ).…”