Bioartificial heart: a human-sized porcine model - the way ahead

BACKGROUND: A bioartificial heart is a theoretical alternative to transplantation or mechanical left ventricular support. Native hearts decellularized with preserved architecture and vasculature may provide an acellular tissue platform for organ regeneration. We sought to develop a tissue-engineered whole-heart neoscaffold in human-sized porcine hearts. METHODS: We decellularized porcine hearts (n = 10) by coronary perfusion with ionic detergents in a modified Langendorff circuit. We confirmed decellularization by histology, transmission electron microscopy and fluorescence microscopy, quantified residual DNA by spectrophotometry, and evaluated biomechanical stability with ex-vivo left-ventricular pressure/volume studies, all compared to controls. We then mounted the decellularized porcine hearts in a bioreactor and reseeded them with murine neonatal cardiac cells and human umbilical cord derived endothelial cells (HUVEC) under simulated physiological conditions. RESULTS: Decellularized hearts lacked intracellular components but retained specific collagen fibers, proteoglycan, elastin and mechanical integrity; quantitative DNA analysis demonstrated a significant reduction of DNA compared to controls (82.6+/-3.2 ng DNA/mg tissue vs. 473.2+/-13.4 ng DNA/mg tissue, p<0.05). Recellularized porcine whole-heart neoscaffolds demonstrated re-endothelialization of coronary vasculature and measurable intrinsic myocardial electrical activity at 10 days, with perfused organ culture maintained for up to 3 weeks. CONCLUSIONS: Human-sized decellularized porcine hearts provide a promising tissue-engineering platform that may lead to future clinical strategies in the treatment of heart failure

Ex vivo heart perfusion for increasing organ availability

Background. Heart transplantation still remains the gold standard for patients with end-stage heart failure. Due to the lack of donor organs the use of ex vivo heart perfusion is becoming increasingly more important for reconditioning marginal donor organs. Objective. New developments in the field of ex vivo heart perfusion are presented with an emphasis on the practical application in a donor organ retrieval service. Material andmethods. The utilization of the Organ Care System (OCS, TransMedics, Andover, MA) for evaluation and reconditioning of marginal donor organs is discussed in the light of the substantial shortage of donor organs. Results. Preservation using the OCS can be considered as being equivalent to cold cardioplegia in the clinical application. An OCS heart shows a highly significant reduction in the cold ischemia time so that longer transport times and subsequently greater catchment areas are possible. Extended criteria donors can be conditioned to be suitable donor organs by the professional application of the OCS. Resuscitation of socalled donation after cardiac death (DCD) donor hearts using OCS has been clinically established internationally and the results are very promising. Conclusion. We postulate the standardized application of ex vivo heart perfusion for marginal donor organs to extend the potential donor pool

Minimally invasive strategies for left ventricular assist device implantation

Heart transplantation remains the gold standard for patients with end-stage heart failure. Due to the lack of donor organs the increasing use of left ventricular assist devices (LVAD) has gained a paramount role in heart failure surgery. The conventional technique of LVAD implantation involves median sternotomy and connection to a heart-lung machine. More recent approaches show the progressive development of alternative and less invasive implantation techniques, not least because of the radical downsizing of the pump housing of current generation LVAD systems. As a result of the intrapericardial position of LVADs numerous minimally invasive strategies have already been developed. Moreover, the off-pump implantation technique is increasingly being used in some centers. In this study we present the new developments in the field of minimally invasive LVAD surgery and give an insight into the practical approach. Particular attention is given to appropriate patient selection and critical discussion on the possible advantages and disadvantages of each technique