Autologous fibrin-based tissue-engineered heart valves have demonstrated excellent potential as patient-derived valve replacements. The present pilot study aims to evaluate the structure and mechanical durability of fibrin-based heart valves after implantation in a large-animal model (sheep). Tissue-engineered heart valves were molded using a fibrin scaffold and autologous arterial-derived cells before 28 days of mechanical conditioning. Conditioned valves were subsequently implanted in the pulmonary trunk of the same animals from which the cells were harvested. After 3 months in vivo, explanted valve conduits (n = 4) had remained intact and exhibited native tissue consistency, although leaflets demonstrated insufficiency because of tissue contraction. Routine histology showed remarkable tissue development and cell distribution, along with functional blood vessel ingrowth. A confluent monolayer of endothelial cells was present on the valve surface, as evidenced by scanning electron microscopy and positive von Willebrand factor staining. Immunohistochemistry and extracellular matrix (ECM) assay demonstrated complete resorption of the fibrin scaffold and replacement with ECM proteins. Transmission electron microscopy revealed mature collagen formation and viable, active resident tissue cells. The preliminary findings of implanted fibrin-based tissue-engineered heart valves are encouraging, with excellent tissue remodeling and structural durability after 3 months in vivo. The results from this pilot study highlight the potential for construction of completely "autologous" customized tissue-engineered heart valves based on a patient-derived fibrin scaffold.

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Background Tyrosine kinase inhibitors (TKIs) inhibit the platelet derived growth factor receptor (PDGFR) and gain increasing significance in the therapy of proliferative diseases, e.g. pulmonary arterial hypertension (PAH). Moreover, TKIs relax pulmonary vessels of rats and guinea pigs. So far, it is unknown, whether TKIs exert relaxation in human and murine pulmonary vessels. Thus, we studied the effects of TKIs and the PDGFR-agonist PDGF-BB in precision-cut lung slices (PCLS) from both species. Methods The vascular effects of imatinib (mice/human) or nilotinib (human) were studied in Endothelin-1 (ET-1) pre-constricted pulmonary arteries (PAs) or veins (PVs) by videomicroscopy. Baseline initial vessel area (IVA) was defined as 100%. With regard to TKI-induced relaxation, K + -channel activation was studied in human PAs (PCLS) and imatinib/nilotinib-related changes of cAMP and cGMP were analysed in human PAs/PVs (ELISA). Finally, the contractile potency of PDGF-BB was explored in PCLS (mice/human). Results Murine PCLS: Imatinib (10 μM) relaxed ET-1-pre-constricted PAs to 167% of IVA. Vice versa, 100 nM PDGF-BB contracted PAs to 60% of IVA and pre-treatment with imatinib or amlodipine prevented PDGF-BB-induced contraction. Murine PVs reacted only slightly to imatinib or PDGF-BB. Human PCLS: 100 μM imatinib or nilotinib relaxed ET-1-pre-constricted PAs to 166% or 145% of IVA, respectively, due to the activation of K ATP -, BK Ca 2+ - or K v -channels. In PVs, imatinib exerted only slight relaxation and nilotinib had no effect. Imatinib and nilotinib increased cAMP in human PAs, but not in PVs. In addition, PDGF-BB contracted human PAs/PVs, which was prevented by imatinib. Conclusions TKIs relax pre-constricted PAs/PVs from both, mice and humans. In human PAs, the activation of K + -channels and the generation of cAMP are relevant for TKI-induced relaxation. Vice versa, PDGF-BB contracts PAs/PVs (human/mice) due to PDGFR. In murine PAs, PDGF-BB-induced contraction depends on intracellular calcium. So, PDGFR regulates the tone of PAs/PVs. Since TKIs combine relaxant and antiproliferative effects, they may be promising in therapy of PAH.

Predominantly, standard adult heart lung machines are used for pediatric cardiac surgery, only with individually downsized components. Downsizing is limited, e.g., by the required gas exchange surface. To diminish complications, we developed a new miniaturized heart lung machine (MiniHLM) for neonates, with significantly reduced priming volume and blood contact surface by integration of all major system components in one single device. In particular, a rotary blood pump is centrically integrated into the oxygenator and the cardiotomy reservoir with integrated heat exchanger is directly connected. Thus, tubing is only necessary between patient and MiniHLM. A total priming volume of 102 ml could be achieved for the entire extracorporeal circuit (including arterial/venous line), in contrast to the currently smallest device on the market with 213 ml. In first animal experiments with female New Zealand rabbits, the MiniHLM guaranteed both a sufficient gas exchange and an adequate blood flow; 12 rabbits could successfully be weaned off after 1 hour of aortic clamp time. The first in vitro and in vivo tests confirm the concept of the MiniHLM. Its low priming volume and blood contact surface may significantly reduce complications during heart surgery in neonates.

This study aimed to determine standard left (LV) and right ventricular (RV) transesophageal echocardiographic (TEE) measurements in swine. Additionally, global myocardial work index (GWI) was estimated using pressure-strain loops (PSL). A comprehensive TEE examination was conducted in ten anesthetized, intubated and mechanically ventilated healthy female German landrace swine, weighing 44 to 57 kg. For GWI calculation, we performed LV and RV segmental strain analysis and used invasively measured LV and RV pressure to obtain PSL. The GWI and further myocardial work indices were calculated from the area of the PSL using commercially available software. Furthermore, hemodynamic measurements were obtained using indwelling catheters. We obtained complete standardized baseline values for left and right ventricular dimensions and function. Biplane LV ejection fraction was 63 ± 7 % and the LV end-diastolic volume was 70.5 ± 5.9 ml. Tissue Doppler estimated peak tricuspid annular systolic velocity was 13.1 ± 1.8 cm/s. The Doppler estimated LV and RV stroke volume index were 75.6 ± 7.2 ml/m2 and 76.7 ± 7.8 ml/m2 respectively. Pulsed wave Doppler derived cardiac output correlated well with cardiac output estimated using the thermodilution method (7.0 ± 1.2 l/min vs. 7.0 ± 1.1 l/min, r = 0.812, p = 0.004). The LV global longitudinal strain was -21.3 ± 3.9 % and the RV global longitudinal strain was -15.4 ± 2.5 %. LV GWI was 1885(1281–2121) mmHg*% and 297 ± 62 mmHg*% for the RV. LV global myocardial work efficiency was 82.6 ± 4 % and 83(72–88) % for the RV. TEE offers sufficient morphological, functional and hemodynamic assessment of the heart in swine. Myocardial contractility and mechanics can be reliably evaluated with the non-invasive GWI derived from echocardiography without additional invasive measures.