Translation of methodology used in human myocardial imaging to a sheep model of acute myocardial infarction

Pre-clinical investigation of stem cells for repairing damaged myocardium predominantly used rodents, however large animals have cardiac circulation closely resembling the human heart. The aim of this study was to evaluate whether SPECT/CT myocardial perfusion imaging [MPI] could be used for assessing sheep myocardium following an acute myocardial infarction [MI] and response to intervention. 18 sheep enrolled in a pilot study to evaluate [[99m]Tc]-sestamibi MPI at baseline, post-MI and after therapy. Modifications to the standard MPI protocols were developed. All data was reconstructed with OSEM using CT-derived attenuation and scatter correction. Standard analyses were performed and inter-observer agreement were measured using Kappa [k]. Power determined the sample sizes needed to show statistically significant changes due to intervention. Ten sheep completed the full protocol. Data processed were performed using pre-existing hardware and software used in human MPI scanning. No improvement in perfusion was seen in the control group, however improvements of 15% - 35% were seen after intra-myocardial stem cell administration. Inter-observer agreement was excellent [k=0.89]. Using a target power of 0.9, 28 sheep were required to detect a 10-12% change in perfusion. Study demonstrates the suitability of large animal models for imaging with standard MPI protocols and it's feasibility with a manageable number of animals. These protocols could be translated into humans to study the efficacy of stem cell therapy in heart regeneration and repair

REMODELLING OF CARDIAC COLLAGEN IN CHRONIC HEART FAILURE AND ITS RELATIONSHIP TO CARDIAC FUNCTION / 解放军医学杂志

To study cardiac function in an ovine model of chronic heart failure in relation to cardiac collagen and its phenotype, 11 sheep were developed into chronic heart failure by sequential microembolisation. Cardiac collagen contents and phenotypes were determined after hemodynamic evaluation at 6 months. The results showed that collagen contents and type Ⅰ /type Ⅲ collagen ratio in the left ventricle were increased significantly in heart failure group as compared with those in the normal group. Collagen concentration in left ventricle correlated significantly to left ventricular ejection fraction, left ventricular end diastolic pressure, dP/dt min , left ventricular diastolic diameter, and diastolic interventricular septum thickness.Our conclusion is increase in collagen content and type Ⅰ/Ⅲ collagen ratio may be partly responsible for the reduction of cardiac function seen in this model of heart failure.