Myocardial Infarct Size Reduction Provided by Local and Remote Ischaemic Preconditioning: References Values from the Hatter Cardiovascular Institute

Abstract

To accurately estimate the effect size of both local or classic ischaemic preconditioning (IPC) and remote ischaemic preconditioning (RIPC) using a pooling data set of 91 animals. We combined all the available mouse data collected from our Institute over the last 3 years regarding (i) local IPC (4 cycles of 5 min of global ischaemia/reperfusion injury, IRI, followed by 35-min ischaemia and 2-h reperfusion) in the Langendorff-isolated perfused mouse heart model and (ii) RIPC (3 cycles of 5 min of limb occlusion followed by 40-min ischaemia and 2-h reperfusion) in the in vivo mouse model. Five independent experiments containing 27 control and 29 IPC mice were used to estimate the overall (i) local IPC effect, which reduced infarct size in the ex-vivo setting by a mean difference of 24.1\% (95\% CI 19.5, 28.6\%) when compared to untreated controls (P < 0.001) and for (ii) RIPC, three independent experiments including data for 16 control and 19 RIPC mice were used to estimate that RIPC diminished infarct size in the in-vivo setting by a mean difference of 20.8\% (95\% CI 14.7, 26.9\%) when compared to controls (P < 0.001). Using a significant animal dataset, we found that local IPC reduces myocardial infarct size by 24.1\% and RIPC by 20.8\% in the ex vivo and in vivo mouse models of IRI, respectively. These differences may be used as reference values to either establish positive controls or to determine by how much myocardial infarct size can be reduced by novel cardioprotective interventions following an IRI insult.