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.
Highlights
Oxygen is often administered to patients experiencing uncomplicated ST-segment elevation myocardial infarction (STEMI)
Mice ventilated with either room air or 100% O2 were subject to 40min. coronary ischaemia followed by 120-min. reperfusion, after which the ischaemic area at risk and infarct area were measured
remote ischaemic preconditioning (RIPC) induced using either 2.5- or 5-min. cycles was cardioprotective in mice breathing room air, but not supplementary O2 (Fig. 2B)
Summary
Oxygen is often administered to patients experiencing uncomplicated ST-segment elevation myocardial infarction (STEMI). Whether it is beneficial in this context remains controversial [1, 2]. Remote ischaemic pre- and post-conditioning (RIC) has been investigated as a method of protecting the myocardium against ischaemia and reperfusion injury that occurs during STEMI treated by primary percutaneous coronary intervention or during cardiac surgery [3, 4]. Despite initial promise in the setting of coronary artery bypass graft (CABG) surgery, the outcomes of two recent large clinical trials were neutral [5, 6]. Pilot studies of RIC in the setting of STEMI have shown more consistent benefit and large clinical trials are currently underway [7]. It is important to recognize that a number of factors have been proposed to influence the efficacy of RIC, few of these have been systematically examined in either the clinical or
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