Implementation and evaluation of methodology to study myocardial functional parameters using SPECT/CT in an ovine model of acute myocardial infarction: response to mesenchymal stem cell transplantation

Abstract

The potential use of stem cells in repairing damaged myocardium and the ability to assess outcomes has been extensively investigated using small animal models. Sheep have a heart that is similar in size, shape and coronary supply to the human heart and exhibits physiological properties and responses similar to human hearts. This potentially allows the use of diagnostic tools such as Single Photon Emission Computed Tomography/Computed Tomography (SPECT/CT) and other techniques routinely used in the clinical setting that are well established and validated. The aim of this work was to develop appropriate techniques to evaluate the functional consequences of the ovine myocardium following inducement of an acute myocardial infarction and to correlate with response to mesenchymal stem cell transplantation in situ. Several aspects were examined including the most accurate method to measure ejection fraction, optimal imaging times, how to anatomically orientate and reconstruct the in vivo heart to achieve optimal correlation with the post-mortem ex vivo heart and whether creation of normal databases and values would improve accuracy. Evaluation of the reliability and reproducibility of the results included an assessment of myocardial perfusion recovery, ways to accurately measure the size of the infarct using SPECT/CT imaging and methodology to accurately measure reperfusion using readily available software packages. A total of 10 animals completed the full study. An improvement in perfusion and myocardial repair at the peripheral borders of the infarct zone was seen in two of the four sheep following intramyocardial implantation of mesenchymal stems cells and in two of the three intracoronary implantation method sheep with a corresponding increase in LVEF of 6%. These findings correlated with the anatomical findings of prominent or early neovascularisation. To detect a change in perfusion of 12% using a power of 0.9 and 0.8, future studies would need to include 8 and 12 sheep respectively. However for a smaller change of 7%, a much larger number of animals would be needed, being 60 and 80 respectively.