Metformin Alleviates Left Ventricular Diastolic Dysfunction in a Rat Myocardial Ischemia Reperfusion Injury Model

Int J Mol Sci. 2020 Feb 21;21(4):1489. doi: 10.3390/ijms21041489.

Abstract

An increased incidence of myocardial infarction (MI) has recently emerged as the cause of cardiovascular morbidity and mortality worldwide. In this study, cardiac function was investigated in a rat myocardial ischemia/reperfusion (I/R) model using echocardiography. Metformin administration significantly increased ejection fraction and fractional shortening values on Days 3 and 7 when MI occurred, indicating that metformin improved left ventricular systolic function. In the Sham + MET and MI + MET groups, the E' value was significantly different up to Day 3 but not at Day 7. This may mean that left ventricular diastolic function was effectively restored to some extent by Day 7 when metformin was administered. These results suggest that diastolic dysfunction, assessed by echocardiography, does not recover in the early phase of ischemic reperfusion injury in the rat myocardial I/R model. However, administering metformin resulted in recovery in the early phase of ischemic reperfusion injury in this model. Further gene expression profiling of left ventricle tissues revealed that the metformin-treated group had notably attenuated immune and inflammatory profiles. To sum up, a rat myocardial I/R injury model and ultrasound-based assessment of left ventricular systolic and diastolic function can be used in translational research and for the development of new heart failure-related drugs, in addition to evaluating the potential of metformin to improve left ventricular (LV) diastolic function.

Keywords: acute myocardial infarction; coronary artery ligation; diastolic function; myocardial ischemia/reperfusion injury; systolic function.

MeSH terms

  • Animals
  • Disease Models, Animal
  • Echocardiography*
  • Gene Expression Profiling
  • Gene Expression Regulation / drug effects*
  • Male
  • Metformin / pharmacology*
  • Myocardial Reperfusion Injury* / diagnostic imaging
  • Myocardial Reperfusion Injury* / drug therapy
  • Myocardial Reperfusion Injury* / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Ventricular Dysfunction, Left* / diagnostic imaging
  • Ventricular Dysfunction, Left* / drug therapy
  • Ventricular Dysfunction, Left* / metabolism

Substances

  • Metformin