Preconditioning the Human Brain

Koch, Sebastian; Gonzalez, Nestor R.

doi:10.1161/strokeaha.111.000773

Cited by 43 publications

(23 citation statements)

References 68 publications

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“…Remote ischemic conditioning is a powerful innate response to transient ischemia that confers protection against subsequent severe ischemia at distant sites [1]. Several preclinical models have demonstrated that this phenomenon protects against cerebral ischemia [2–5].…”

Section: Discussionmentioning

confidence: 99%

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Matched Cohort Analysis of the Effects of Limb Remote Ischemic Conditioning in Patients with Aneurysmal Subarachnoid Hemorrhage

Laiwalla

Ooi

Liou

et al. 2015

Transl. Stroke Res.

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Background Remote ischemic conditioning (RIC) is a powerful innate response to transient subcritical ischemia that protects against severe ischemic insults at distant sites. We have previously shown the safety and feasibility of limb RIC in aneurysmal subarachnoid hemorrhage (aSAH) patients, along with changes in neurovascular and cerebral metabolism. In this study we aim to detect the potential effect of an established lower-limb conditioning protocol on clinical outcomes of aSAH patients. Methods Neurologic outcome (modified Rankin Scale [mRS]) of patients enrolled in a prospective trial (RIPC-SAH) was measured. A matching algorithm was applied to identify control patients with aSAH from an institutional departmental database. RIC patients underwent 4 lower-limb conditioning sessions, consisting of 4 five-minute cycles per session over nonconsecutive days. Good functional outcome was defined as mRS of 0 to 2. Results The study population consisted of 21 RIC patients and 61 matched controls. There was no significant intergroup difference in age, gender, aneurysm location, clipping versus coiling, Fisher grades, Hunt and Hess grades, or vasospasm. RIC was independently associated with good outcome (OR: 5.17; 95% CI: 1.21–25.02). RIC also showed a trend toward lower incidence of stroke (28.6% vs. 47.5%) and death (4.8% vs. 19.7%). Conclusions Lower-limb RIC following aSAH appears to have a positive effect in the functional outcomes of patients with aSAH. While this effect is consistent with prior preclinical studies, future trials are necessary to conclusively evaluate the effects of RIC for aSAH.

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Section: Discussionmentioning

confidence: 99%

“…Remote ischemic conditioning (RIC) is a powerful endogenous mechanism whereby sublethal episodes of ischemia temporarily protect against subsequent lethal ischemic insults at distant sites [1]. In animal models, RIC of the limb has been shown to be effective in protecting against global and focal cerebral ischemia [2–5].…”

Section: Introductionmentioning

confidence: 99%

Matched Cohort Analysis of the Effects of Limb Remote Ischemic Conditioning in Patients with Aneurysmal Subarachnoid Hemorrhage

Laiwalla

Ooi

Liou

et al. 2015

Transl. Stroke Res.

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“…Following an aSAH there is a well-defined period when patients are at an elevated risk of DIND and may benefit from RIC as a prophylactic measure. 18 Additionally, the controlled conditions and close monitoring afforded by their treatment in the neurocritical care unit were ideal to investigate the safety and feasibility of RIC for aSAH.…”

Section: Discussionmentioning

confidence: 99%

“…17 The rationale for selecting patients with aneurysmal subarachnoid hemorrhage to prevent delayed ischemic neurological deficit (DIND) is based on the well-defined time course of vasospasm and DIND after aneurysmal rupture and has been extensively discussed. 18 In a pilot study, we demonstrated cerebral vascular and metabolic effects of the RIC maneuvers with lower limb ischemia. 19 Finally, to test the hypothesis that RIC by induction of transient lower limb ischemia is a feasible and safe strategy in patients hospitalized for the treatment of aSAH, we present here the results of a prospective phase I clinical trial to test the safety and feasibility of RIC induced by transient lower limb ischemia in patients with aSAH.…”

Section: Introductionmentioning

confidence: 88%

Phase I Clinical Trial for the Feasibility and Safety of Remote Ischemic Conditioning for Aneurysmal Subarachnoid Hemorrhage

et al. 2014

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Background Remote ischemic conditioning (RIC) is a powerful endogenous mechanism whereby a sublethal ischemic stimulus confers a protective benefit against a subsequent severe ischemic insult. RIC has significant potential clinical implications for the prevention of delayed ischemic neurological deficit (DIND) after aneurysmal subarachnoid hemorrhage (aSAH). While RIC has been extensively investigated in animal models, it has not been fully evaluated in humans. Objective To assess the feasibility and safety of RIC for aSAH in a phase I clinical trial. Methods Consecutive patients hospitalized for treatment of an aSAH who met the inclusion/exclusion criteria were approached for consent. Enrolled patients received up to four RIC sessions on non-consecutive days. Primary endpoints were (1) the development of a symptomatic deep venous thrombosis (DVT), bruising or injury to the limb and, (2) request to stop by the patient or surrogate. The secondary endpoints were the development of new neurological deficits or cerebral infarct, demonstrated by brain imaging after enrollment, and neurological deficit and condition at follow-up. Results Twenty patients were enrolled and underwent 76 RIC sessions, 75 of which were completed successfully. One session was discontinued when the patient became confused. No patient developed a DVT or injury to the preconditioned limb. No Patient developed DIND during their enrollment. At follow-up, median modified Rankin Scale was 1 and Glasgow Outcome Score was 5. Conclusion The RIC procedure was well tolerated and did not cause any injury. RIC for aSAH warrants investigation in a subsequent pivotal clinical trial.

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“…In particular, studies suggesting that aging reduces the efficacy of preconditioning 30 are a concern considering that stroke occurrence increases in the elderly. One reason for studying RIPC in subarachnoid hemorrhage is that it generally occurs in younger individuals than ischemic stroke 31 .…”

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confidence: 99%