Koppany Sarai’s research while affiliated with University of Freiburg and other places

An 8-year-old (35 kg) boy presented with progressive right ventricular outflow tract enlargement (28 mm) and progressive tricuspid regurgitation after transannular repair of tetralogy of Fallot and was scheduled for pulmonary valve replacement. To spare reoperation on full sternotomy, a transverse mini-thoracotomy through the third intercostal space was used to implant an injectable 29-mm stented porcine valve directly through an incision of the pulmonary artery bifurcation. The procedure was performed while rapid ventricular pacing and right ventricular unload by a short running femorally implanted cardiopulmonary bypass. The stented valve was fixed with three single sutures to avoid embolization. The interventional result was well with full competence of the valve. The boy was discharged at day 4 after the procedure.

The pig heart is an ideal graft for orthotopic cardiac xenotransplantation regarding its physiological attributes and ready availability. Although single clinical attempts have been performed since the 1960s, details concerning the surgical technique of pig-to-human transplantation have never been reported. The present investigation should verify which anatomical differences between humans and pigs require special care in cardiac xenotransplantation. We transplanted four pig hearts into human thoraces after autopsy. Implantation was performed using both the biatrial (modified Shumway) and bicaval techniques. The implanted hearts were not perfused. The four-legged walk of the pig implies a more transverse heart position and therefore a different outflow-angle of the great vessels. Accordingly, the thin-walled pulmonary artery and the superior vena cava (in bicaval technique) tend to kink and narrow. A special feature of porcine anatomy is the left azygous vein that empties into the coronary sinus. It must be ligated before the implantation. Keeping the porcine anatomical particularities in mind, technical problems in pig-to-human heart transplantation can be avoided. The anastomosis of the pulmonary artery requires special care. By using the biatrial technique surgeons can prevent imminent stenoses of the caval vein anastomoses.

In-vivo explants in pigs are well-established to investigate myocardial function directly after transplantation. However, there is no functional data available for a longer time period after transplantation. We have established a pig model to investigate myocardial function 24 hours after orthotopic transplantation. Orthotopic cardiac transplantations (HTx) in pigs were performed with a postoperative observation period of 24 hours (n = 6). To analyze myocardial function after transplantation, hemodynamical parameters (Swan-Ganz- and impedance-catheter data) as well as tissue and blood samples were obtained. Regional myocardial blood flow (RMBF) was assessed using fluorescent microspheres. The impedance-catheter parameters demonstrated a preserved contractility in both ventricles 24 hours post-transplantation. In contrast, cardiac output 24 hours after HTx was diminished by 50% as compared to the preoperative value. Conversely, pulmonary vascular resistance increased significantly. The RMBF was increased in both ventricles. Metabolic and histological analyses indicate myocardial recovery 24 hours after HTx with no irreversible damage. For the first time, we were able to establish a porcine model to investigate myocardial function 24 hours after heart transplantation. While the contractility of the transplanted hearts was well-preserved, impaired cardiac output was going along with an increase in pulmonary vascular resistance. Using this clinical relevant model, improvements of human cardiac transplantation and post-transplant contractile dysfunction, especially, could be investigated.

Background Acute right ventricular failure (RVF) is a common and life-threatening complication after heart transplantation (HTx). Novel strategies are required to improve myocardial protection and prevent acute RVF, which is observed commonly in recipients with pulmonary hypertension. We used a minimally invasive mechanical circulatory support (MCS) in combination with a new technique for myocardial protection for prophylaxis and treatment of RVF after HTx. Methods Pig hearts (n=16) were perfused with Bretschneider’s HTK solution supplemented with adenosine and the Na+-H+-exchange inhibitor HOE 642 (cariproide) before excision. After cold storage in Bretschneider solution at 4 °C for 24 h hearts were transplanted orthotopically and controlled reperfusion with substrate-enriched, leukocyte-depleted blood cardioplegia (BCP) was begun. During implantation intermittent BCP, supplemented with adenosine and HOE 642 as well, was given after each completed anastomosis. After transplantation hearts were perfused with pure blood for 20 minutes before cross-clamp was released. After the implantation of the right ventricular microaxial pump “Impella” cessation of cardiopulmonary bypass was attempted. Right ventricular MCS was maintained for 5 h . Thereafter MCS was stepwise reduced. Results 14 hearts could be weaned from cardiopulmonary bypass. No initial graft failure was observed. Because of methodical problems (bleeding, lung or renal failure) only 5 hearts could be weaned from MCS. Right ventricular MCS with “Impella” proved its reliabilitiy over 5 h of support and maintained stable hemodynamics providing a flow of 2.5–4 l/min. Preload recruitable stroke work (PRSW), dp/dtmax and dp/dtmin measured 1 h after weaning from MCS remained unchanged compared to baseline. Cardiac output was significantly reduced presumably due to the increased pulmonary vascular resistance. Histological examination revealed only decent myocardial damage. Discussion The use of the microaxial pump “Impella” after HTx could enable a new therapeutic strategy for prevention and treatment of acute RVF. The mortality rate of this complication would decrease. The application of modified myocardial protection technique combined with minimally invasive MCS to the clinical practice would encourage the liberalization of donor and recipient criteria and even the transplantation of marginal donor hearts.