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J Cell Mol Med. 2017 Oct;21(10):2426-2431. doi: 10.1111/jcmm.13164. Epub 2017 Apr 4.

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

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The Hatter Cardiovascular Institute, University College London, London, UK.
Magnus Sciences, University College London, London, UK.


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.


blood flow; bradykinin; cardioprotection; ischaemia; oxygen; preconditioning; reactive hyperaemia; remote preconditioning; reperfusion; ventilation

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