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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.

Background: The effects of acute pulmonary embolism (PE) on right ventricular (RV) diastolic function may be one of the determinants of right heart failure. We analysed the parameters of RV diastolic function in a porcine model of PE by the use of phase plane (PP) analysis. In the PP method, a periodic function is plotted such that the function, RV pressure (P), is the abscissa and its time derivative (dP/dt) is the ordinate. Methods: In six anaesthetised open chest pigs, RV pressure-volume (PV) loops were obtained by the conductance catheter technique. Measurements were realised in basal conditions, and repeated 1 hour after injection of coagulated autologous blood clots (0.3g/kg) in the superior vena cava. PV loops and PP loops were constructed with pressure and volume signals. The parameters of RV diastolic function were calculated from the PV and PP loops. Results: End-diastolic pressure and end-diastolic volume increased respectively from 3.40 ± 2.71 to 6.46 ± 2.36 mmHg (mean ± SD, p < 0.05) and from 60.73 ± 9.65 to 80.45 ± 3.72 ml (mean ± SD, p < 0.05), with no significant change in RV compliance (0,19 ±0.14 and 0.19 ± 0.10 ml/mmHg, mean ± SD). RV peak negative dP/dt extended from 0.39 ± 0.08 to 0.65 ± 0.01 mmHg/msec (mean ± SD, p < 0.01). Monoexponential decay time constant (Tau) did not show significant variation (37.85 ± 6.90 to 41.22 ± 13.98 msec, mean ± SD). The RV relaxation curve in the PP graph was nonlinear and was fitted with a quadratic function (dP/dt = A P2+B P+ dP/dt°). The curvilinearity coefficient (A) and the intercept (dP/dt°) did not change significantly but the second constant (B) significantly decreased from -40.30 ± 13.50 to -56.72 ± 11.60 sec-1 (mean ± SD, p < 0.01). Conclusions: As assessed by PP analysis, acute RV pressure overload by PE induces modifications in RV diastolic function. The right ventricle dilates and its diastolic filling pressure increases. Relaxation time constant calculated with monoexponential decay method, that considers linear relaxation of the ventricle, does not significantly changed. The relaxation curve in the PP graph, however, appears modified, as shown by the higher second constant of the fitted quadratic function. This reflects that the relaxation is non-uniform and that the non-uniformity is modified in acute PE in a such way that Tau would increase in early relaxation while it would decrease in late relaxation.