Review of selective brain hypothermia in acute ischemic stroke therapy using an intracarotid, closed-loop cooling catheter

Abstract

In acute ischemic stroke patients, selective brain hypothermia is a promising concept aiming at a fast decrease of brain temperature and thus neuroprotection in the acute phase of ischemia. At the same time, the emergence of mechanical thrombectomy (MT) as an effective treatment in large-vessel occlusion opens the door for a combination of neuroprotective approaches in the frame of a neurovascular, catheter-based intervention. In this regard, intracarotid cooling is a very effective energetic approach, using the blood supply to the penumbra as a fast transport vector for heat exchange in affected brain regions. We review the state of development of a novel closed-loop cooling catheter, describing design-related as well as procedural aspects and presenting results from different theoretical and experimental studies. Finally, we compare the concept with two alternative methods: cold saline infusion and extracorporeal blood cooling. We focus on the combination with MT, considering the effect of different and variable perfusion rates on the final goal of a "cold reperfusion" at the time of blood flow restoration.

Ultra-Short Duration Hypothermia Prevents Intracranial Pressure Elevation Following Ischaemic Stroke in Rats

“…In recent years, methods have been well established to achieve rapid cooling in patients using whole-body techniques such as endovascular or skin cooling ( 15 ). Direct brain cooling strategies such as intranasal ( 36 ) and intracarotid cooling ( 37 ) are less well established but are under investigation.…”

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

“…The distal end of the CLCC consists of four balloons with a diameter of 4 mm and a length of 20 mm each, spaced from each other by 4 mm, resulting in a total length of 92 mm. 17 , 19 , 20 Two catheter lumina with an inner diameter of around 1 mm each enable a continuous closed-loop flow of cold saline into and out of the balloons, respectively. The catheter also features a central lumen compatible with a 6 F catheter for MT procedures during cooling, resulting in a 3.4 mm outer diameter (corresponding to an 11 F catheter or to an 8 F sheath).…”

“…Thus, rapid and early endovascular selective brain cooling combined with MT may be an appealing alternative TH approach for neuroprotection in LVO stroke. 4 , 6 , 17 , 18 A recent study including 113 LVO patients demonstrated safety of a combined therapy applying a standard MT plus a short (15 min) intra-arterial (‘selective’) cold saline infusion versus MT alone. 6 Moreover, a trend towards improved functional outcome was observed in the selective TH group.…”

“…We have recently reported preliminary in vitro and in vivo assessment of a closed-loop cooling catheter (CLCC) system for intra-carotid blood cooling 17 , 19 , 20 conceived to provide swift and selective TH in combination with MT for the treatment of LVO stroke. Herein, we aimed to assess feasibility and safety of the CLCC system in an ovine stroke model simulating MT by transient middle cerebral artery occlusion (MCAO).…”

Analysis of microRNA expression in cerebral ischemia/reperfusion after mild therapeutic hypothermia treatment in rats

“…A significant neuroprotection was obtained when hypothermia was started within therapeutic time window of 4 h after reperfusion in rat model (6). Furthermore, in patients with middle cerebral artery infarction, therapeutic hypothermia treatment can significantly reduce intracranial pressure, alleviate cerebral edema, and improve neurological dysfunction (7,8). Furthermore, a number of studies have investigated the potential for combination of mild hypothermia with drug therapy, which was proved to be more effective in protecting neurons than hypothermia alone in an experimental model of cerebral ischemia (6).…”