Distinctive effect of anesthetics on the effect of limb remote ischemic postconditioning following ischemic stroke

Abstract

Limb remote ischemic postconditioning (LRIP) has been reported as an effective method to reduce the induced experimental stroke damage after ischemic reperfusion (IR) injury. Studies suggest that anesthetics used during induction of ischemic stroke can reduce IR injury, which could affect the actual mechanisms of neuroprotection by LRIP. This study focuses on the comparative effects of anesthetics such as isoflurane and ketamine-xylazine on ischemic injury when used during LRIP. Adult C57BL/6 mice were anesthetized by isoflurane or halothane, and transient middle cerebral artery occlusion (MCAO) was induced through insertion of the filament. Under isoflurane or ketamine-xylazine anesthesia, LRIP was performed after 90 min of reperfusion by carrying out three cycles of 5 min ischemia/5 min reperfusion of the bilateral hind limbs for one session per day for a total of 3 days. Results showed that the use of different anesthetics-isoflurane or ketamine-xylazine-during LRIP had no effects on body weight. However, LRIP was able to improve neurological function as observed by the neurological deficit score in ischemic mice. Interestingly, the neurological deficit in the group where ketamine-xylazine was used was better than the group where isoflurane was used during LRIP. Furthermore, the LRIP was able to prolong the period of the ischemic mice on the rotarod and this effect was more significant in the groups where ketamine-xylazine was used during LRIP. Moreover, LRIP significantly attenuated the infarction volume; however, this effect was independent of the anesthetic used during LRIP. From these results, we conclude that ischemic mice that were subjected to LRIP under ketamine-xylazine anesthesia had better neurological deficit outcomes after stroke.

Translational challenges of remote ischemic conditioning in ischemic stroke – a systematic review

“…Anesthetics were used during MCAO in all studies; most used chloral hydrate, 17–21,25–28 eight used isoflurane, 1,3,10,11,22–24,30 and two used the structural isomer enflurane 2,29 . One study used isoflurane and halothane during the MCAO to determine if either had additional effects on the outcomes of RIPostC 24 . Sodium pentobarbital was used prior to inducing RIPostC/sham procedures in two studies, but the type of anesthesia used was not reported 15,16 .…”

“…One study initiated RIPostC at 12 h, 24 h, and 5 days after MCAO, and applied it up to three times with variable time intervals to investigate very delayed post‐conditioning 23 . Two studies tested consecutive RIPostC; one initiated the protocol for 90 min and applied RIC for a total of four sessions during the following 72 h 24 and another initiated RIC at 48 h after reperfusion and applied it daily for 21 consecutive days 21 . In two studies testing the combination of RIPerC and RIPostC for 7 or 14 days, the RIPostC regime started 24 h after the MCAO 15,16 …”

“…Complete limb ischemia was confirmed using monitoring or Doppler ultrasound equipment to detect the loss of pulse or flow 1,2,25–29 or clinical evaluation 3,11,17–19,21,30 . More than one‐third of the studies omitted how adequate ischemia was ensured 10,15,16,20,22–24,31 …”

“…Nine studies did not inform on randomization to groups 1,10,11,15–17,20,21,31 . Most studies reported blinding was applied for parts of the data analysis 1,3,10,11,15–24,26–31 …”

“…Testing effects of delayed conditioning is perhaps more interesting for future treatment because not all arrive in a timely fashion or are eligible for revascularization therapy. Unfortunately, the few studies that tested a delayed application of RIC all applied different RIC protocols, leaving their conclusions unconfirmed 1,15,16,21–24 . Studies testing and confirming the effect of delayed RIC from animal studies, could have huge translational potential and become important in clinical treatment.…”