357 Comparative effects on LV performance, arterial hemodynamics and ventriculo-arterial coupling of two models of coronary artery occlusioninpigs

Abstract

Introduction: Human embryonic stem cells (hES) have emerged as an attractive and promising new therapeutic approach for treatment of heart diseases. The aim of this study was to evaluate in rats with acute myocardial infarction (MI): 1) effects of myocardial transplantation of undifferentiated hES on left ventricular (LV) function and morphology and 2) to determine whether potential improvement in LV function requires the presence of hES in the myocardium. Methods:Male Sprague-Dawley rats∼200 g were used. MI was induced by cryo-injury (protocol 1) and by ligation of left coronary artery (protocol 2). These procedures resulted in anterior MI engaging ∼30-40% of left ventricle (LV). In the protocol 1, the rats were randomized into two groups: rats with MI treated with vehicle (n = 8) and rats with MI treated with 1 million hES cells (n = 8). Rats treated with hES cells received cyclosporine (5 mg/kg/d). The hES cells were suspended in 0,05 ml buffer and transplanted by intramyocardial injection into the viable myocardium close to the infracted area directly after cryo-injury. The rats were followed for 1 week. In order to evaluate hypothetical paracrine effects of hES, in the protocol 2, the rats were randomised into three groups: rats with MI treated with vehicle (n = 4), rats with MI treated with cell medium (n = 6) and rats with MI treated with supernatant extracted from hES cell culture (n = 6). The animals received i.p. injections 3 times/week during 4 weeks. All animals were investigated with transthoracal echocardiography, continuous ECG and LV catheterization. Post-mortem, the hearts were evaluated histologically. Results: In the protocol 1 neither deaths nor arrhythmias occurred in the rats treated with hES cells. dP/dT was similar in both groups. There were no signs of abnormal tissue growth at the site of hES cell engraftment after one week. There was no difference in the indices of LV systolic function while diastolic function was significantly improved in the hES rats (p < 0.05). hES were detected in 1/8 rats in the infarcted area. In the protocol 2, no difference was found between the groups in indices of LV function and morphology after 4 weeks of treatment. Conclusion: Transplantation of undifferentiated hES cells have positive effect on LV diastolic function in the rat model of acute MI. This effect requires the presence of hES in the tissue. The use of hES may be an important approach for cardio-reparation and reconstitution of normal cardiac structure and function in the future.