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Background— In patients with sickle cell trait or disease, reduced life expectancy and a tendency for complications are believed to negatively affect likelihood of survival after open heart surgery. The aim of this study was to review retrospectively the perioperative results of patients undergoing cardiac surgery at our institution. Methods and Results— Between January 1995 and December 2006, 47 patients with either sickle cell disease or sickle cell trait underwent open heart surgery at our institution. The average age of the 29 male and 18 female patients was 20 years. Patient outcomes were analyzed through the use of the institutional database. Clinical and echocardiographic follow-up was complete in all patients except 3, with a mean follow-up period of 46 months. Current status could be confirmed in 32 patients. The most common operations included the treatment of congenital and valvular heart diseases. There were no coronary artery bypass grafting procedures. Average weight of the patients was 45 kg. Exchange transfusion was performed both preoperatively and during surgery. Mean preoperative hemoglobin S concentration was 30.4±3.2% and decreased to 8.1±2.6% while on pump. Average on-pump hematocrit value was 25.4±3.7%; in the postoperative period, it increased to 32.7±4.9%. Mean cardiopulmonary bypass and cross-clamp times were 95 and 69 minutes, respectively. None of the patients had sickling crisis or acidosis. Postoperative complications included exploration for hemorrhage in 3 patients (6.4%), stroke in 2 patients (4.3%), renal failure in 2 patients (4.3%), and prolonged ventilation in 1 patient (2.1%). Average hospital stay was 8.3 days (range, 4 to 27 days). Early in-hospital death occurred in 1 patient (2.1%); currently, 31 patients (66%) remain alive and free of cardiac symptoms. Conclusion— Heart valve surgery and surgery for congenital heart diseases can be performed safely in patients with sickle cell disease or sickle cell trait with acceptable outcome and survival rates.

Bone marrow-derived mesenchymal stem cells (MSCs) are multipotent cells characterized by their selfrenewal and differentiation potential. Accumulating clinical and preclinical evidence indicate MSCs are a promising cell source for regenerative medical therapies. However, undesirable immortalization, spontaneous transformation, and tumorigenic potential from long-term cultured MSCs have been reported in human and mouse. We report rat MSCs isolated from young donors could undergo transformation in early passage culture. We aimed to characterize the transformed population and determine their therapeutic effects after intracardiac transplantation in the infarcted myocardium. MSCs were isolated from bone marrow of Lewis rats according to standard protocols and cultured under standard conditions. Phenotype of growing cells was assessed by flow cytometry. Following acute myocardial infarction in rats, cells were delivered by intracardiac injection. Cardiac functions were assessed by pressure-volume loops. Infarction size and pathologic effects were evaluated after 6 weeks. The abnormal colonies were detected in culture as early at passage 3. They were noted to appear as distinctly different morphology from typical MSCs, which changed from a normal elongated spindle shape to a compact abnormal morphology. They exhibited rapid cell proliferation. Some subclones lost contact inhibition of cell division and formed multilayer aggregates. Chromosomal instability was detected. They were devoid of surface markers CD29, CD44, CD90, and CD117. Furthermore, there was no significant improvement on infarction size and cardiac function 6 weeks after cell transplantation. Our study highlights the need for establishment of biosafety criteria in regulating cultureexpanded MSCs to achieve the full clinical therapeutic benefits.

MNB-mediated gene delivery could comprise a promising method for gene delivery to the lung and the heart.

Erythropoietin (EPO) protects the myocardium from ischaemic injury and promotes beneficial remodelling. We assessed the therapeutic efficacy of intracardiac EPO injection and EPO-mediated stem cell homing in a rat myocardial infarction (MI) model. Following MI, EPO (3000 U/kg) or saline was delivered by intracardiac injection. Compared to myocardial infarction control group (MIC), EPO significantly improved left ventricular function (n= 11–14, P< 0.05) and decreased right ventricular wall stress (n= 8, P< 0.05) assessed by pressure-volume loops after 6 weeks. MI-EPO hearts exhibited smaller infarction size (20.1 ± 1.1%versus 27.8 ± 1.2%; n= 6–8, P< 0.001) and greater capillary density (338.5 ± 14.7 versus 259.8 ± 9.2 vessels per mm; n= 6–8, P< 0.001) than MIC hearts. Direct EPO injection reduced post-MI myocardial apoptosis by approximately 41% (0.27 ± 0.03%versus 0.42 ± 0.03%; n= 6, P= 0.005). The chemoattractant SDF-1 was up-regulated significantly assessed by quantitative realtime PCR and immunohistology. c-Kit+ and CD34+ stem cells were significantly more numerous in MI-EPO than in MIC at 24 hrs in peripheral blood (n= 7, P< 0.05) and 48 hrs in the infarcted hearts (n= 6, P< 0.001). Further, the mRNAs of Akt, eNOS and EPO receptor were significantly enhanced in MI-EPO hearts (n= 7, P< 0.05). Intracardiac EPO injection restores myocardial functions following MI, which may attribute to the improved early recruitment of c-Kit+ and CD34+ stem cells via the enhanced expression of chemoattractant SDF-1.

Stentless bioprostheses have been considered to achieve superior hemodynamics over stented bioprostheses for aortic valve replacement with improved long-term performance. We observed severe thrombocytopenia in patients who received the Sorin Freedom Solo aortic stentless pericardial bioprosthesis within the first days after implantation. Absolute and relative platelet counts within 2 weeks after implantation of either a stentless (Sorin Freedom Solo) or a stented (Sorin Mitroflow) bovine pericardial bioprosthesis were compared in a matched-pairs analysis in 40 patients. Except the preoperative values, absolute platelet count was higher at all time points in the Mitroflow group. In the Mitroflow group, the mean platelet count moderately dropped to a minimum of 60% of the initial value on POD 3 and fully recovered by POD 8. In the Freedom Solo group, platelet loss was significantly more severe (minimum relative value 25% on POD 4) with no recovery during follow-up (60% on POD 13). Eight patients of the Freedom Solo group experienced a critical platelet drop towards <20% of their initial values, in five of them absolute numbers decreased below 30,000/microl. No bleeding complications or other morbidity occurred. Attention should focus on the platelet count after implantation of the Freedom Solo bioprosthesis, especially in patients who are supposed to receive platelet inhibitors. However, the described phenomenon remains unexplained.

We aimed to evaluate the feasibility and efficacy of autologous umbilical cord blood mononuclear cell (UCMNC) transplantation on right ventricular (RV) function in a novel model of chronic RV volume overload. Four-month-old sheep (n = 20) were randomized into cell (n = 10) and control groups (n = 10). After assessment of baseline RV function by the conductance catheter method, a transannular patch (TAP) was sutured to the right ventricular outflow tract (RVOT). Following infundibulotomy the ring of the pulmonary valve was transected without cardiopulmonary bypass. UCMNC implantation (8.22 +/- 6.28 x 10(7)) in the cell group and medium injection in the control group were performed into the RV myocardium around the TAP. UCMNCs were cultured for 2 weeks after fluorescence-activated cell sorting (FACS) analysis for CD34 antigen. Transthoracic echocardiography (TTE) and computed tomography were performed after 6 weeks and 3 months, respectively. RV function was assessed 3 months postoperatively before the hearts were excised for immunohistological examinations. FACS analysis revealed 1.2 +/- 0.22% CD34(+) cells within the isolated UCMNCs from which AcLDL(+) endothelial cells were cultured in vitro. All animals survived surgery. TTE revealed grade II-III pulmonary regurgitation in both groups. Pressure-volume loops under dobutamine stress showed significantly improved RV diastolic function in the cell group (dP/dt(min): p = 0.043; E(ed): p = 0.009). CD31 staining indicated a significantly enhanced number of microvessels in the region of UCMNC implantation in the cell group (p < 0.001). No adverse tissue changes were observed. TAP augmentation and pulmonary annulus distortion without cardiopulmonary bypass constitutes a valid large animal model mimicking the surgical repair of tetralogy of Fallot. Our results indicate that the chronically volume-overloaded RV profits from autologous UCMNC implantation by enhanced diastolic properties with a probable underlying mechanism of increased angiogenesis.

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