A meta-analysis of remote ischaemic conditioning in experimental stroke

Abstract

Remote ischaemic conditioning (RIC) is achieved by repeated transient ischaemia of a distant organ/limb and is neuroprotective in experimental ischaemic stroke. However, the optimal time and methods of administration are unclear. Systematic review identified relevant preclinical studies; two authors independently extracted data on infarct volume, neurological deficit, RIC method (administration time, site, cycle number, length of limb occlusion (dose)), species and quality. Data were analysed using random effects models; results expressed as standardised mean difference (SMD). In 57 publications incorporating 99 experiments (1406 rats, 101 mice, 14 monkeys), RIC reduced lesion volume in transient (SMD −2.0; 95% CI −2.38, −1.61; p < 0.00001) and permanent (SMD −1.54; 95% CI −2.38, −1.61; p < 0.00001) focal models of ischaemia and improved neurological deficit (SMD −1.63; 95% CI −1.97, −1.29, p < 0.00001). In meta-regression, cycle length and number, dose and limb number did not interact with infarct volume, although country and physiological monitoring during anaesthesia did. In all studies, RIC was ineffective if the dose was <10 or ≥50 min. Median study quality was 7 (range 4–9/10); Egger’s test suggested publication bias ( p < 0.001). RIC is most effective in experimental stroke using a dose between 10 and 45 min. Further studies using repeated dosing in animals with co-morbidities are warranted.

Neuroprotection by remote ischemic conditioning in the setting of acute ischemic stroke: a preclinical two-centre study

“…Our two-centre international study is an important step underpinning further research in this direction. The obtained results, showing IS limitation and improvement of functional outcome by RIC, are in agreement with the results of previously published experimentsl studies 20,21 . However, our study was the first one to employ clinically relevant endpoints.…”

“…However, to date, the two completed trials 17 – 19 did not show a benefit in such patients. This may question the results of the numerous single-centre animal studies that demonstrated an infarct-limiting effect of RIC in acute stroke models (reviewed in 20 , 21 ).…”

“…These and subsequent discussions produced guidelines with strong recommendations for the study of potential neuroprotective therapies 23 . In this regard, none of the published experimental studies on the effect of RIC in acute ischemic stroke models 18 , 20 , 21 sufficiently fulfil the requirements of STAIR for effective translational research 22 . Recent meta-analysis of RIC in experimental stroke revealed that the median study quality was only 7 (range 4–9/10) 21 .…”

“…In this regard, none of the published experimental studies on the effect of RIC in acute ischemic stroke models 18 , 20 , 21 sufficiently fulfil the requirements of STAIR for effective translational research 22 . Recent meta-analysis of RIC in experimental stroke revealed that the median study quality was only 7 (range 4–9/10) 21 . Moreover, significant publication bias has been identified ( p < 0.001) 21 , strongly justifying the need for a well-powered and unbiased study.…”

Therapie des akuten ischämischen Schlaganfalls

“…Dem zugrunde liegt unter anderem die Beobachtung, dass Ratten nach transientem bilateralem ACI-Verschluss mit anschließenden weiteren kurzen Okklusionsphasen kleinere Schlaganfälle entwickelten [64]. In der Folge ließ sich zeigen, dass periphere Ischämien denselben oder sogar einen stärkeren Effekt haben und sowohl prä-mehr jedoch auch peri-(RIPerC) und postischämische (RIPostC) Anwendungszeitpunkte effektiv sind [65].…”