Response by Chen et al to Letter Regarding Article, “Endovascular Hypothermia in Acute Ischemic Stroke: A Pilot Study of Selective Intra-Arterial Cold Saline Infusion”

Chen, Jian; Ding, Yuchuan; Ji, Xunming

doi:10.1161/strokeaha.116.014786

Cited by 45 publications

(81 citation statements)

References 5 publications

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“…The rapid induction and short duration make simple cold fluid infusions attractive for MT adjunctive studies and are currently being explored in humans. A recent pilot study in 26 patients studied the feasibility of selective intra-arterial TH in association with MT 19. Cold saline was infused through standard catheters for 5 min prior to MT (pre-cool) and an additional 10 min following clot removal (post-cool).…”

Section: Discussionmentioning

confidence: 99%

“…However, the length of time to deep TH is limited by a whole-body cooling approach. To address these issues, localized delivery of cold fluids through standard catheters has been explored 19 20. Recently published clinical work is encouraging, showing the potential for infarct reduction, motivating a larger randomized controlled trial to further evaluate efficacy 21…”

Section: Introductionmentioning

confidence: 99%

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Focal cooling of brain parenchyma in a transient large vessel occlusion model: proof-of-concept

Caroff

King

Mitchell

et al. 2019

J NeuroIntervent Surg

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IntroductionThe neuroprotective benefit of therapeutic hypothermia (TH) has been demonstrated, but systemic side effects and time required to achieve effective TH in acute ischemic stroke (AIS) care limits clinical use. We investigate rapid and localized cooling using a novel insulated catheter in an ischemia-reperfusion model.MethodsIn phase I (n=4), cold saline was delivered to the canine internal carotid artery via an insulated catheter. Temperature was measured using intracerebral thermocouples. The coolant flow rate was varied to meet a target temperature of 31–32°C in the hemisphere infused. In phase II (n=8), a temporary middle cerebral artery occlusion was created. Five dogs underwent localized TH at the optimal flow rate from phase I, and the remaining animals were untreated controls. Cooling was initiated 5 min before recanalization and continued for an additional 20 min following 45 min of occlusion duration. The outcome was infarct volume and neurological function.ResultsIpsilateral tissue cooling rates were 2.2±2.5°C/min at a flow rate of 20–40 mL/min with an observed minimum of 23.8°C. Tissue cooling was localized to the ipsilateral side of the infusion with little impact on temperatures of the core or contralateral hemisphere of the brain. In phase II, animals tolerated TH with minimal systemic impact. Infarct volume in treated animals was 0.2±0.2 cm3, which was smaller than in sham animals (3.8±1.0 cm3) as well as six untreated historical control animals (4.0±2.8 cm3) (p=0.013).ConclusionsProof-of-concept data show that localised brain TH can be quickly and safely achieved through a novel insulated catheter. The small infarct volumes suggest potential benefit for this approach.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Focal cooling of brain parenchyma in a transient large vessel occlusion model: proof-of-concept

Caroff

King

Mitchell

et al. 2019

J NeuroIntervent Surg

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“…In a more recent pilot study, 26 patients underwent intraarterial endovascular cooling within 8 hours of intraarterial recanalization. 13 This therapy did reduce brain temperature by at least 2°C with no obvious complications. The Intravascular Cooling in the Treatment of Stroke (ICTuS) 2 trial results were recently published; 50 however, only 120 patients of the intended 1600 were enrolled before the study was stopped.…”

Section: Hypothermiamentioning

confidence: 80%

Experimental neuroprotection in ischemic stroke: a concise review

Rajah

Ding

2017

FOC

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Acute ischemic stroke (AIS) is a leading cause of disability and death worldwide. To date, intravenous tissue plasminogen activator and mechanical thrombectomy have been standards of care for AIS. There have been many advances in diagnostic imaging and endovascular devices for AIS; however, most neuroprotective therapies seem to remain largely in the preclinical phase. While many neuroprotective therapies have been identified in experimental models, none are currently used routinely to treat stroke patients. This review seeks to summarize clinical studies pertaining to neuroprotection, as well as the different preclinical neuroprotective therapies, their presumed mechanisms of action, and their future applications in stroke patients.

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“…In nine human patients with partially or completely treated cerebrovascular diseases undergoing diagnostic cerebral angiogram, 7°C LEVI at ~33 mL/min for 10-13 min was able to reduce jugular venous blood temperature (a proxy for brain temperature) by 0.84°C while reducing rectal temperature by 0.15°C and having no signiicant efects on vital signs. LEVI was also recently implemented in patients actively undergoing ischemic stroke (within 8 h of symptom onset), which conirmed the safety and feasibility of the procedure [25]. The neuroprotective eicacy of LEVI, however, remains to be established in a clinical seting.…”

Section: Hypothermia Via Local Endovascular Infusionmentioning

confidence: 99%

“…This allows for more rapid achievement of target temperatures and permits greater speciicity of hypothermia while avoiding the side efects of systemic cooling. During these procedures, an infusion microcatheter, guided to the site of the lesion via the guide catheter over a microguidewire, is advanced distally to the site of occlusion, and cold saline is perfused [25] for a variable length of time, usually from 5 to 30 min. The logistics of actually performing LEVI in humans are relatively simple, as this is a normal part of performing endovascular interventions for many neuroendovascular surgeons [26].…”

Section: Hypothermia Via Local Endovascular Infusionmentioning

confidence: 99%

Hypothermia in Stroke Therapy: Systemic versus Local Application

Huber¹,

Duan²,

Chandra³

et al. 2017

Hypoxia and Human Diseases

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Presently, there are no efective, widely applicable therapies for ischemic stroke. There is strong clinical evidence for the neuroprotective beneits of hypothermia, and surfacecooling methods have been utilized for decades in the treatment of cerebral ischemia during cardiac arrest, but complications with hypothermia induction have hindered its clinical acceptance in ischemic stroke therapy. Recently, the microcatheter-based local endovascular infusion (LEVI) of cold saline directly to the infarct site has been proposed as a solution to the drawbacks of surface cooling. The safety and eicacy of LEVI in rat models have been established, and implementation in larger animals has been similarly encouraging. A recent pilot study even established the safety of LEVI in humans. This review seeks to outline the major research on LEVI, discusses the mechanisms that mediate its superior neuroprotection over surface and systemic cooling, and identiies areas that warrant further investigation. While LEVI features improvements on surface cooling, its core mechanisms of neuroprotection are still largely shared with therapeutic hypothermia in general. As such, the mechanisms of hypothermia-based neuroprotection are discussed as well.

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Response by Chen et al to Letter Regarding Article, “Endovascular Hypothermia in Acute Ischemic Stroke: A Pilot Study of Selective Intra-Arterial Cold Saline Infusion”

Cited by 45 publications

References 5 publications

Focal cooling of brain parenchyma in a transient large vessel occlusion model: proof-of-concept

Focal cooling of brain parenchyma in a transient large vessel occlusion model: proof-of-concept

Experimental neuroprotection in ischemic stroke: a concise review

Hypothermia in Stroke Therapy: Systemic versus Local Application

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