Protective Effect of Creatine Elevation against Ischaemia Reperfusion Injury Is Retained in the Presence of Co-Morbidities and during Cardioplegia

• DOI: 10.1371/journal.pone.0146429
• Publication Date: 2016-01-15T02:12:37Z
• Authors: Hannah J. Whittin...; Debra J. McAndrew; Rebecca L. Cross; Stefan Neubauer; Craig A. Lygate
• Keywords: Creatine; Rate pressure product; Creatine kinase

Aims Ischaemic heart disease is most prevalent in the ageing population and often exists with other comorbidities; however majority of laboratory research uses young, healthy animal models. Several recent workshops focus meetings have highlighted importance using clinically relevant models to help aid translation realistic patient populations. We previously shown that mice over-expressing creatine transporter (CrT-OE) elevated intracellular levels are protected against ischaemia-reperfusion injury. Here we test whether elevating retains a cardioprotective effect presence common comorbidities it additive protection afforded by hypothermic cardioplegia. Methods Results CrT-OE wild-type controls were subjected transverse aortic constriction for two weeks induce compensated left ventricular hypertrophy (LVH). Hearts retrogradely perfused Langendorff mode 15 minutes, followed 20 minutes ischaemia 30 reperfusion. hearts exhibited significantly improved functional recovery (Rate pressure product) during reperfusion compared WT littermates (76% baseline vs. 59%, respectively, P = 0.02). Aged mouse (78±5 weeks) also had enhanced following (104% 67%, 0.0007). The high K+ cardioplegic arrest, as used cardiac surgery donor transplant, was further prolonged (90 minutes) 55% seen hearts, Conclusions These observations support development modulators content translatable strategy