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Ventilation strategy has a major influence on remote ischaemic preconditioning in mice.

ABSTRACT: Whether oxygen should be administered acutely during ST-segment elevation myocardial infarction is debated. Despite this controversy, the possible influence of supplementary oxygen on animal models of ischaemia-reperfusion injury or cardioprotection is rarely considered. We used an in vivo mouse model of ischaemia and reperfusion to investigate the effect of ventilation with room air versus 100% oxygen. The coronary artery of anaesthetized mice was occluded for 40 min. followed by 2-hrs reperfusion. Infarct size was measured by tetrazolium staining and expressed as a percentage of area at risk, determined using Evan's blue. Unexpectedly, infarct size in mice ventilated with 100% oxygen was significantly smaller than in those ventilated with room air (33 ± 5% versus 46 ± 3%; n = 6; P < 0.01). We tested a standard protocol of 3 × 5 min. cycles of remote ischaemic preconditioning (RIPC) and found this was unable to protect mice ventilated with 100% oxygen. RIPC protocols using 2.5- or 10-min. occlusion were similarly ineffective in mice ventilated with oxygen. Similar disparate results were obtained with direct cardiac ischaemic preconditioning. In contrast, pharmacological protection using bradykinin administered at reperfusion was effective even in mice ventilated with 100% oxygen, reducing infarct size from 33 ± 5% to 21 ± 3% (n = 4-6; P < 0.01). Laser speckle contrast imaging of blood flow and direct pO₂ measurements were made in the hindlimb, but these measurements did not correlate with protection. In conclusion, ventilation protocol can have a major influence on infarct size and ischaemic preconditioning protocols in mice.

SUBMITTER: Davidson SM

PROVIDER: S-EPMC5618711 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature

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Ventilation strategy has a major influence on remote ischaemic preconditioning in mice.

Davidson Sean M SM He Zhenhe Z Dyson Alex A Bromage Daniel I DI Yellon Derek M DM

Journal of cellular and molecular medicine 20170404 10

Whether oxygen should be administered acutely during ST-segment elevation myocardial infarction is debated. Despite this controversy, the possible influence of supplementary oxygen on animal models of ischaemia-reperfusion injury or cardioprotection is rarely considered. We used an in vivo mouse model of ischaemia and reperfusion to investigate the effect of ventilation with room air versus 100% oxygen. The coronary artery of anaesthetized mice was occluded for 40 min. followed by 2-hrs reperfus ...[more]

PMID: 28374972

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Project description:IntroductionCerebral small vessel disease (cSVD) accounts for 20%-25% of strokes and is the most common cause of vascular cognitive impairment (VCI). In an animal VCI model, inducing brief periods of limb ischaemia-reperfusion reduces subsequent ischaemic brain injury with remote and local protective effects, with hindlimb remote ischaemic conditioning (RIC) improving cerebral blood flow, decreasing white-matter injury and improving cognition. Small human trials suggest RIC is safe and may prevent recurrent strokes. It remains unclear what doses of chronic daily RIC are tolerable and safe, whether effects persist after treatment cessation, and what parameters are optimal for treatment response.Methods and analysisThis prospective, open-label, randomised controlled trial (RCT) with blinded end point assessment and run-in period, will recruit 24 participants, randomised to one of two RIC intensity groups: one arm treated once daily or one arm twice daily for 30 consecutive days. RIC will consistent of 4 cycles of blood pressure cuff inflation to 200 mm Hg for 5 min followed by 5 min deflation (total 35 min). Selection criteria include: age 60-85 years, evidence of cSVD on brain CT/MRI, Montreal Cognitive Assessment (MoCA) score 13-24 and preserved basic activities of living. Outcomes will be assessed at 30 days and 90 days (60 days after ceasing treatment). The primary outcome is adherence (completing ≥80% of sessions). Secondary safety/tolerability outcomes include the per cent of sessions completed and pain/discomfort scores from patient diaries. Efficacy outcomes include changes in cerebral blood flow (per arterial spin-label MRI), white-matter hyperintensity volume, diffusion tensor imaging, MoCA and Trail-Making tests.Ethics and disseminationResearch Ethics Board approval has been obtained. The results will provide information on feasibility, dose, adherence, tolerability and outcome measures that will help design a phase IIb RCT of RIC, with the potential to prevent VCI. Results will be disseminated through peer-reviewed publications, organisations and meetings.Trial registration numberNCT04109963.

Project description:BackgroundVascular surgery patients have reduced tissues` blood supply, which may lead to mitochondrial dysfunction and accumulation of acylcarnitines (ACs). It has been suggested that remote ischaemic preconditioning (RIPC) has its organ protective effect via promoting mitochondrial function. The aim of this study was to evaluate the effect of RIPC on the profile of ACs in the vascular surgery patients.MethodsThis is a randomised, sham-controlled, double-blinded, single-centre study. Patients undergoing open surgical repair of abdominal aortic aneurysm, surgical lower limb revascularisation surgery or carotid endarterectomy were recruited non-consecutively. The RIPC protocol consisting of 4 cycles of 5 min of ischaemia, followed by 5 min of reperfusion, was applied. A blood pressure cuff was used for RIPC or a sham procedure. Blood was collected preoperatively and approximately 24 h postoperatively. The profile of ACs was analysed using the AbsoluteIDQp180 kit (Biocrates Life Sciences AG, Innsbruck, Austria).ResultsNinety-eight patients were recruited and randomised into the study groups and 45 patients from the RIPC group and 47 patients from the sham group were included in final analysis. There was a statistically significant difference between the groups regarding the changes in C3-OH (p = 0.023)-there was a decrease (- 0.007 µmol/L, ± 0.020 µmol/L, p = 0.0233) in the RIPC group and increase (0.002 µmol/L, ± 0.015 µmol/L, p = 0.481) in the sham group. Additionally, a decrease from baseline to 24 h after surgery (p < 0.05) was detected both in the sham and the RIPC group in the levels of following ACs: C2, C8, C10, C10:1, C12, C12:1, C14:1, C14:2, C16, C16:1, C18, C18:1, C18:2. In the sham group, there was an increase (p < 0.05) in the levels of C0 (carnitine) and a decrease in the level of C18:1-OH. In the RIPC group, a decrease (p < 0.05) was noted in the levels of C3-OH, C3-DC (C4-OH), C6:1, C9, C10:2.ConclusionsIt can be concluded that RIPC may have an effect on the levels of ACs and might therefore have protective effects on mitochondria in the vascular surgery patients. Further larger studies conducted on homogenous populations are needed to make more definite conclusions about the effect of RIPC on the metabolism of ACs.Trial registrationClinicalTrials.gov database, NCT02689414. Registered 24 February 2016-Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT02689414.

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Ventilation strategy has a major influence on remote ischaemic preconditioning in mice.

Publications

Ventilation strategy has a major influence on remote ischaemic preconditioning in mice.

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