The effect of a microcatheter-based selective intra-arterial hypothermia on hemodynamic changes following transient cerebral ischemia

Chen, Jian; Fredrickson, Vance L; Ding, Yuchuan; Jiang, Lingling; Luo, Yuming; Ji, Xunming

doi:10.1179/1743132814y.0000000451

Cited by 16 publications

(15 citation statements)

References 29 publications

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“…In our experiments we observed an order of magnitude reduction in infarct volume. Infarct volume reductions ranging from 30% to 90% for short duration localized cold fluid infusions have been reported, with the greatest benefits associated with infusions that were initiated before or as close to reperfusion as possible 24 26 27. These benefits were observed over a range of studied target temperatures (30.5–35°C) and treatment durations as short as 5 min but not exceeding 1 hour.…”

Section: Discussionmentioning

confidence: 97%

“…We have shown that localized brain tissue cooling can be quickly and safely achieved with cold saline delivered through an insulated catheter. To date, preclinical models of cold saline infusions have been explored in rodent and non-human primate models 24–27. We sought to demonstrate in a large animal model of temporary MCA occlusion with endovascular occlusion of the MCA (eg, no craniotomy with potential artificial augmentation of localised cooling) effective focal cooling that reduces infarct volume.…”

Section: Discussionmentioning

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: 97%

Section: Discussionmentioning

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 this study, our aim was to investigate the safety and efficacy of cold saline administration early after bleeding started. We used an established intracarotid saline infusion method for rats (Chen et al , 2015 ). We hypothesized that while focal cooling may mitigate injury and edema, cooling and use of heparinized saline may induce coagulopathy, thereby worsening outcome.…”

Section: Introductionmentioning

confidence: 99%

Infusion of Cold Saline into the Carotid Artery Does Not Affect Outcome After Intrastriatal Hemorrhage

Liddle

Prokop

Dirks

et al. 2020

Therapeutic Hypothermia and Temperature Management

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Localized brain hypothermia (HYPO) can be achieved by infusing cold saline into the carotid artery of animals and patients. Studies suggest that HYPO improves behavioral and histological outcomes in focal ischemia models. Given that ischemic stroke and intracerebral hemorrhage (ICH) share pathophysiological overlap, we tested whether cold saline infusion is safe and neuroprotective when given during collagenase-induced ICH. Eighty-five adult male Sprague-Dawley rats were used. Experiment 1 investigated brain and body temperature changes associated with a cold saline infusion paradigm that was scaled from patients according to brain weight and blood volume (3 mL/ 20-minute infusion). Experiment 2 determined whether HYPO aggravated bleeding volume. Experiment 3 investigated if cerebral edema or elemental concentrations were altered by HYPO. We also collected core body temperature and activity data through telemetry. Experiment 4 investigated whether behavioral outcomes (e.g., skilled reaching) and tissue loss were influenced by HYPO. Our HYPO protocol decreased the ipsilateral striatal temperature by *0.20°C (p < 0.001), with no other effects. HYPO did not affect hematoma volume (p = 0.64), cerebral edema (p = 0.34), or elemental concentrations (p = 0.49) at 24 hours post-ICH. Although ICH caused persistent behavioral impairments, HYPO did not improve behavioral outcomes (measured by a neurological deficit scale, cylinder, and the staircase test; p > 0.05 for all). Brain tissue loss was not different between groups on day 28 post-ICH (p = 0.90). Although cold saline infusion appears to be safe in the acute post-ICH period, there was no evidence that this therapy improved outcome. However, our treatment protocol was relatively mild and additional interventions might help improve efficacy. Finally, our findings may also speak to the safety of this cooling approach in focal ischemia where hemorrhagic transformation is a risk; future studies on this issue are needed.

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“…This "luxury reperfusion" has been implicated in post-reperfusion edema formation, the primary cause of death within 1 month of ischemic stroke [45,46]. While hypothermia prevents intracranial-pressure elevations by itself, LEVI provides an additional protective mechanism by washing out vasodilatory metabolites built up during the ischemic period, which minimizes the extent of hyperperfusion-related injury [29,47]. As evidence of this mechanism, fast warm (37°C)-saline LEVI has been shown to signiicantly reduce infarct volumes and improve functional recoveries compared to systemic infusion of warm saline [28].…”

Section: Metabolite Washout and Atenuated Hyper-or Hypoperfusionmentioning

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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The effect of a microcatheter-based selective intra-arterial hypothermia on hemodynamic changes following transient cerebral ischemia

Abstract: Cold saline, when infused directly into the ischemic brain region, can confer robust neuroprotection by reducing immediate post-ischemic hyperperfusion and delayed post-ischemic hypoperfusion.

Cited by 16 publications

References 29 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

Infusion of Cold Saline into the Carotid Artery Does Not Affect Outcome After Intrastriatal Hemorrhage

Hypothermia in Stroke Therapy: Systemic versus Local Application

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