Scaffold-based transplantation of vascular endothelial growth factor-overexpressing stem cells leads to neovascularization in ischemic myocardium but did not show a functional regenerative effect.

The transplantation of skeletal myoblasts (SkM) might improve cardiac function after myocardial infarction via paracrine action. We used scaffold-based cell transfer by using vascular endothelial growth factor (VEGF)-overexpressing myoblasts. Skeletal myoblasts were isolated and expanded from newborn Lewis rats. Cells were transfected with pCINeo-VEGF(121) and seeded on polyurethane (PU) scaffolds. The seeded scaffolds were epicardially implanted in rats 2 weeks after myocardial infarction (group: PU-VEGF-SkM). Before this intervention and 6 weeks later, pressure/volume loops were analyzed followed by histology. Additional study groups (n = 10 per group) were injected with VEGF-overexpressing myoblasts (Inj-VEGF-SkM) or unmodified myoblasts (Inj-SkM) or underwent a sham operation. Overexpression of VEGF was verified in vitro. The transplantation of growth factor producing myoblast-seeded scaffolds resulted in enhanced angiogenesis of ischemically damaged myocardium in vivo. However, the infarction size was not reduced. In group Inj-SkM, hemodynamics remained unchanged. Systolic function as measured by dP/dt(max) was not significantly altered in PU-VEGF-SkM (preinterventionally 2,156 ± 1,222 mmHg vs. postinterventionally 2,134 ± 850 mmHg). Other systolic function and diastolic function parameters as measured by dP/dt(min), tau, and pressure half-time were not restored in groups PU-VEGF-SkM and Inj-VEGF-SkM either. Transplantation of VEGF-overexpressing skeletal myoblasts leads to neovascularization in infarcted hearts. No functional myocardial recovery was observed. Scaffold-based transfer of genetically-modified cells remains a useful tool to study paracrine stem cell action.

Hepatocyte growth factor-transfected skeletal myoblasts to limit the development of postinfarction heart failure.

Stem cells transplanted to an injured heart affect the host myocardium indirectly. The cytokine hepatocyte growth factor (HGF) may play a key role in this paracrine activity. We hypothesized that HGF-overexpressing stem cells would restore cardiac function after myocardial infarction (MI). Because there is a high rate of cell death when injecting the cells intramyocardially, we used scaffold-based cell transfer. Skeletal myoblasts (SkMs) were isolated and expanded from newborn Lewis rats. Cells were transfected with pcDNA3-huHGF and seeded on polyurethane (PU) scaffolds or diluted in medium for cell injection. The seeded scaffolds were transplanted in rats two weeks after MI (group: PU-HGF-SkM) or the infection solution was intramyocardially injected (group: Inj-HGF-SkM). Two groups (Inj-SkM and PU-SkM) have been prepared with untransfected cells and sham group without any cell therapy served as control (n = 10 each group). At the beginning of treatment (baseline) and six weeks later, hemodynamic parameters were assessed. At the end of the study, histological analysis was employed. In sham animals we detected a decrease in systolic and diastolic function during the observation time. Treatment with untransfected myoblasts did not lead to any significant changes in hemodynamic parameters between the intervention and six weeks later. In group PU-HGF-SkM, systolic parameters like dP/dt(max), dP/dt(min) and isovolumic contraction improved significantly from baseline to study end. Some diastolic parameters were inferior as compared to baseline (SB-Ked, pressure half time [PHT], Tau). In group Inj-HGF-SkM, only PHT was impaired as compared to preinterventional values. Histological analysis showed significantly more capillaries in the infarction border zone in groups PU-HGF-SkM than in sham and Inj-SkM group. The infarction size was not affected by the therapy. Transplanting HGF-transfected myoblasts after MI can limit the development of ventricular dysfunction. Scaffold-based therapy in combination with gene therapy accelerates this capacity. This hemodynamic amelioration is accompanied by neovascularization, but not by smaller infarction sizes.

Biventricular cannulation is superior regarding hemodynamics and organ recovery in patients on biventricular assist device support.

BACKGROUND: Adequate pump flow is a prerequisite for recovery of end-organ failure and outcome in patients treated with a biventricular assist device (BiVAD). We hypothesized that hemodynamics and organ recovery would improve after biventricular, apical cannulation compared with right atrial cannulation. METHODS: Between 2003 and 2009, we treated 31 patients (21 men, 10 women; mean age, of 43 ± 15 years) with a paracorporeal BiVAD (Thoratec BVAD, Pleasanton, CA). In 15 of 31 patients, the inflow cannula of the right VAD (RVAD) was positioned inside the right ventricle (RV) through the RV apex (biapical) instead of the right atrium (conventional). We analyzed pump flow, driving pressure, and vacuum of the Thoratec driving console and recovery of kidney (creatinine, blood urea nitrogen) and liver function (bilirubin). RESULTS: Mean duration of BiVAD support was 84 ± 72 days. BiVAD weaning was successful in 4 of 31 patients (13%), 12 underwent cardiac transplantation (39%), and 15 (48%) died. We observed significantly higher pump flow of the LVAD and RVAD in patients after biapical cannulation compared with those with conventional cannulation (LVAD, 5.6 ± 0.4 vs 5.1 ± 0.3 liters/min, p = 0.002; and RVAD: 4.9 ± 0.3 vs 4.2 ± 0.3 liters/min, p < 0.001). This superior circulatory support correlated with faster recovery of kidney function. CONCLUSION: Cardiac support with a BiVAD is hemodynamically more effective after biventricular apical cannulation compared with conventional right atrial cannulation. Consequently, higher pump flow results in better end-organ recovery using biapical cannulation.

Implantation of a catheter-based self-expanding pulmonary valve in congenital heart surgery: results of a pilot study.

OBJECTIVE: Dilatation of RV outflow after surgical patch repair represents a problem for seating a percutaneous valve. We present the data of a new catheter-based, self-expanding tissue valve with a diameter up to 31 mm. METHODS: 7 Patients (median 9 years, range 2 to 24 years) with severe PR due to RV outflow tract dilatation after patch repair or percutaneous procedures were treated with a catheter-based, self-expanding porcine pulmonary valve (Biointegral®). Valve diameter ranged between 15 and 29 mm. Maximum follow-up was 40 months. Patients were postoperatively assessed on day 1 and 6 months after the procedure, including physical examination, 12 lead electrocardiography and cross-sectional echocardiography with color Doppler. RESULTS: Valve implantation was successful in all patients. Implantation was performed using three different routes: RVOT after partial sternotomy, pulmonary artery after mini-thoracotomy, or via the RV apex. Median follow-up was 25 months (5-40) identifying no significant morbidity and no death. Echocardiography revealed competent valves, no paravalvular leaks, no valve migration and no significant gradient in the RVOT. CONCLUSION: The new, self-expanding, catheter-based pulmonary valve is easy to implant via an antegrade (RVOT, RV) or retrograde approach (PA) even in dilated RV outflow tracts. The procedure can be done without CPB under echocardiographic guidance.

Scaffold-based transplantation of akt1-overexpressing skeletal myoblasts: functional regeneration is associated with angiogenesis and reduced infarction size.

Myoblast-based therapy can improve cardiac function after infarction and is conventionally performed by direct injection. A scaffold-based transfer could overcome injection-associated problems. In upgrading this approach we transplanted skeletal myoblasts (SkM) overexpressing the prosurvival gene Akt1. SkM were transfected with pcDNA3-huda-Akt1 and seeded on polyurethane scaffolds. These scaffolds were transplanted in rats 2 weeks after myocardial infarction. Hemodynamics were analyzed before therapy and 6 weeks later. Infarction size and capillary density were performed thereafter. Additional groups received injections of Akt1-transfected or untransfected myoblasts, scaffolds seeded with untransfected myoblasts, or sham operation. Deterioration of global systolic left ventricular function could be inhibited by all therapeutic approaches. In addition, transplantation of Akt1-transfected cells, either scaffold-based or injected, was superior with regard to systolic properties of the left ventricular wall. This effect was accompanied by smaller infarction sizes and angiogenesis. Scaffolds with untransfected myoblasts yielded also smaller infarctions than injections of untransfected myoblasts. Both Akt groups profited with regard to dP/dt(min). In contrast, other diastolic parameters pointed at impaired relaxation and stiffer myocardium especially in the Akt1-scaffold group. In conclusion, SkM overexpressing Akt1 can maintain myocardial function after infarction, reduce infarction size, and induce neovascularization. Scaffold-based cell transfer does not augment this reverse remodeling capacity.

Sternum augmentation with bovine bone substitute in the neonate.

Delayed chest closure may be mandatory after heart surgery to treat a congenital disorder. Sternal closure can be challenging, even when a staged closure procedure has been performed. We present 2 case reports of a sternal augmentation technique in neonates using bovine bone substitute. Staged chest closure was mandatory because of cardiomediastinal disproportion in the first patient, and hemodynamic deterioration followed by an extracorporeal assist device in the second patient. We succeeded in closing the chests in these 2 neonates using this augmentation technique. To the best of our knowledge, these are the first 2 reports of this type of sternum augmentation technique in neonates.