Background: Remote myocardial function is crucial for post-ischemic outcome beyond infarct size reduction. Echocardiographic assessment of left ventricular function has shown a decreased strain in remote myocardium after acute myocardial infarction (AMI). In mice with diet-induced obesity (DIO), baseline conditions are altered with reduced longitudinal strain. However, the impact of AMI in this setting on remote myocardial function has not been evaluated. In this study, we investigated functional remote myocardial outcome in DIO mice by murine myocardial strain analysis.

Methods: Mice were treated with high-fat diet (EF Bio-Serv #F1850 mod. 24% sucrose HF 35.85% lard) for 24 weeks. Functional assessment of myocardial function was conducted at the end of diet by strain analysis including longitudinal, circumferential, and radial strain (MS 400, VEVO 3100, VisualSonicsInc®., Toronto, Canada; analysis of peak strain [%], time to peak [ms], strain rate [1/s]). Mice were transferred to ischemia/reperfusion induced by transient ligation of the left-anterior descending artery for the duration of 30 minutes. After reperfusion of 24 hours, re-assessment of post-ischemic myocardial function separated into segments of infarcted area and remote myocardium was conducted. Worsening of strain and time-to-peak were calculated in percent of baseline in these segments. Ratio paired t-test and unpaired t-test was conducted to compare groups, p<0.05 was considered significant.

Results: Prior to AMI, DIO treated mice showed reduced global longitudinal strain compared to NCD (NCD -15.77±3,0% vs. DIO -11.93±2.9%, p=0.0061). Global circumferential strain was equal (NCD -22.46±5.3% vs. DIO -24.14±4.3%, p=0.4254). After AMI, DIO mice had more intense worsening of circumferential and radial strain in the remote segments compared to worsening of NCD mice (in percent of baseline; circumferential - NCD 96.5±20.4% vs. DIO 68.58±15.35%, p=0.0159; radial – NCD 82.23±22.3% vs. DIO 51.62±17.0%, p=0.0113). In the infarcted area, worsening did not differ between groups (in percent of baseline; circumferential – NCD 70.72±23.6% vs. DIO 52.47±13.81%, p=0.1102; radial – NCD 63.96±21.45% vs. DIO 70.93±26.7%, p=0.5906). Worsening of longitudinal strain was equal both in the remote and infarct zone.

Conclusion: In this study, we could demonstrate that DIO mice show more intense decrease of remote radial and circumferential strain on top to the already weaker longitudinal function prior to AMI. This might play a role in the worse post-ischemic outcome after AMI in DM patients. Therapeutic targets are needed to improve myocardial function in the remote area in order to improve ischemic heart failure in diabetic patients.