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Introduction: Orthotopic cardiac xenotransplantation has seen notable improvement, leading to the first compassionate use in 2022. However, it remains challenging to define the clinical application of cardiac xenotransplantation, including the back-up strategy in case of xenograft failure. In this regard, the heterotopic thoracic technique could be an alternative to the orthotopic procedure. We present hemodynamic data of heterotopic thoracic pig-to-baboon transplantation experiments, focusing on perioperative xenograft dysfunction and xenograft overgrowth., Methods: We used 17 genetically modified piglets as donors for heterotopic thoracic xenogeneic cardiac transplantation into captive-bred baboons. In all animals, pressure probes were implanted in the graft's left ventricle and the recipient's ascending aorta and hemodynamic data (graft pressure, aortic pressure and recipient's heart rate) were recorded continuously., Results: Aortic pressures and heart rates of the recipients' hearts were postoperatively stable in all experiments. After reperfusion, three grafts presented with low left ventricular pressure indicating perioperative cardiac dysfunction (PCXD). These animals recovered from PCXD within 48 h under support of the recipient's heart and there was no difference in survival compared to the other 14 ones. After 48 h, graft pressure increased up to 200 mmHg in all 17 animals with two different time-patterns. This led to a progressive gradient between graft and aortic pressure. With increasing gradient, the grafts stopped contributing to cardiac output. Grafts showed a marked weight increase from implantation to explantation., Conclusion: The heterotopic thoracic cardiac xenotransplantation technique is a possible method to overcome PCXD in early clinical trials and an experimental tool to get a better understanding of PCXD. The peculiar hemodynamic situation of increasing graft pressure but missing graft's output indicates outflow tract obstruction due to cardiac overgrowth. The heterotopic thoracic technique should be successful when using current strategies of immunosuppression, organ preservation and donor pigs with smaller body and organ size., (© 2024 The Authors. Xenotransplantation published by John Wiley & Sons Ltd.)

Background: Whilst macrohemodynamic function of porcine xenografts transplanted into baboons has been assessed perioperatively, the ability of the xenograft to maintain systemic microcirculatory perfusion has not been investigated after pig-to-baboon xenotransplantation so far., Methods: We investigated the sublingual microcirculation of six baboons undergoing orthotopic transplantation of hCD46-transgenic pig hearts using orthogonal polarization spectral imaging. Microvascular measurements were performed after induction of anesthesia, in the early phase of cardiopulmonary bypass (CPB), during reperfusion of the porcine heart and 1 h after the xenograft had resumed its life-supporting function. Microvascular blood flow was analyzed semiquantitatively and the number of visualized cell-to-cell interactions was counted., Results: The proportion of continuously perfused microvessels was 97 (96 to 97) % at baseline and 95 (94 to 97) % in the early phase of CPB. It decreased significantly (P < 0.05) during CPB to 89 (84 to 91), and alterations were still present (P < 0.05) when CPB was terminated and the xenograft had taken over systemic perfusion 83 (81 to 85) %. The microcirculatory changes correlated with the lactate levels (y = 18.1-0.18 x; r(2) = 0.55; P < 0.001), but no correlation with macrohemodynamic parameters was found., Conclusion: Microvascular blood flow is altered after orthotopic pig-to-baboon heart transplantation, despite systemic hemodynamic parameters being well maintained by the porcine xenograft. These changes are moderate but persist after termination of CPB. Further studies need to elucidate whether these changes are transient or add to the mortality associated with cardiac xenotransplantation., (© 2011 John Wiley & Sons A/S.)

Background: Transpulmonary thermodilution is well established as a tool for in‐depth hemodynamic monitoring of critically ill patients during surgical procedures and intensive care. It permits easy assessment of graft function following cardiac transplantation and guides post‐operative volume and catecholamine therapy. Since no pulmonary catheter is needed, transpulmonary thermodilution could be useful in experimental cardiac pig‐to‐baboon xenotransplantation. However, normal values for healthy animals have not yet been reported. Here, we present data from piglets and baboons before xenotransplantation experiments and highlight differences between the two species and human reference values. Methods: Transpulmonary thermodilution from baboons (body weight 10‐34 kg) and piglets (body weight 10‐38kg) were analyzed. Measurements were taken in steady state after induction of general anesthesia before surgical procedures commenced. Cardiac index (CI), mean arterial pressure (MAP), systemic vascular resistance index (SVRI), parameters quantifying cardiac filling (global end‐diastolic volume index, GEDI), and pulmonary edema (extravascular lung water, ELWI) were assessed. Results: Preload, afterload, and contractility parameters clearly correlated with total body weight or body surface area. Baboons had lower CI values than weight‐matched piglets (4.2 ± 0.9l/min/m2 vs 5.3 ± 1.0/min/m2, P <.01). MAP and SVRI were higher in baboons than piglets (MAP: 99 ± 22 mm Hg vs 62 ± 11 mm Hg, P <.01; SVRI: 1823 ± 581 dyn*s/cm5*m2 vs 827 ± 204 dyn*s/cm5*m2, P <.01). GEDI and ELWI did differ significantly between both species, but measurements were within similar ranges (GEDI: 523 ± 103 mL/m2 vs 433 ± 78 mL/m2, P <.01; ELWI: 10 ± 3 mL/kg vs 11 ± 2 mL/kg, P <.01). Regarding adult human reference values, CI was similar to both baboons and piglets, but all other parameters were different. Conclusions: Parameters of preload, afterload, and contractility differ between baboons and piglets. In particular, baboons have a much higher afterload than piglets, which might be instrumental in causing perioperative xenograft dysfunction and post‐operative myocardial hypertrophy after orthotopic pig‐to‐baboon cardiac xenotransplantation. Most transpulmonary thermodilution‐derived parameters obtained from healthy piglets and baboons lie outside the reference ranges for humans, so human normal values should not be used to guide treatment in those animals. Our data provide reference values as a basis for developing algorithms for perioperative hemodynamic management in pig‐to‐baboon cardiac xenotransplantation. [ABSTRACT FROM AUTHOR]

Background The perioperative phase of preclinical cardiac xenotransplantations significantly affects the experimental outcome. Moderate or even severe hemodynamic and respiratory impairment occurs frequently in baboons after receiving a cardiac transplant. The perioperative management of such postoperative instability is very demanding, especially in the experimental setting. We compared perioperative changes of hemodynamic and laboratory findings during orthotopic and heterotopic thoracic cardiac xenotransplantations and describe our monitoring, treatment and intensive care. Methods Twenty-eight pig-to-baboon cardiac xenotransplantations were performed using either the orthotopic ( oHTx, n=5) or heterotopic thoracic (ht HTx; n=23) technique. In both techniques, cardioplegia and an intraoperative cardiopulmonary bypass ( CPB) were required. Preoperatively, intensive care (eg, transfusions, catecholamine therapy) was provided and fast extubation was targeted. A central venous catheter, a femoral arterial thermodilution catheter, a telemetric pressure transmitter and transthoracic echocardiography were used to monitor the animal. Baboon jackets with a tethering system were used to continuously apply medication postoperatively and permit blood sampling, also after extubation of the animal and transfer into the cage. Perioperative survival, hemodynamics, catecholamine doses, respiratory function and weaning from respirator were compared. Perioperative organ damage was evaluated based on laboratory findings 12 hours after transplantation. Results Recipients could be weaned from CPB in the 20 ht HTx and all five oHTx experiments, and three ht HTx procedures were terminated during the operation. The time of cardiopulmonary bypass was significantly lower in the heterotopic group ( oHTx median 171 [157-193] minutes; ht HTx median 144 [100-190] minutes; P=.02). In 17 ht HTx procedures, no inotropics were used, whereas epinephrine had to be administered in four of the five oHTx experiments; the mean time of catecholamine support was longer in the oHTx group ( oHTx 972±348 minutes vs ht HTx 111±92 minutes; P<.01). After ht HTx, weaning off the respirator was possible in 19 of 20 cases (one died due to pneumothorax). After oHTx, three of the five baboons could be weaned off the respirator; in these cases, the arterial saturation was higher compared with the extubated baboons after ht HTx ( oHTx 99±1% vs ht HTx 91±4%, P=.01). Intraoperative blood loss was similar between the two groups, and hemostasis was impaired after all procedures, but relevant postoperative bleeding never occurred. Conclusion Intensive intra- and postoperative monitoring and care is required in both transplantation techniques as a requirement for successful weaning from CPB and respirator. After ht HTx, the animals needed less catecholamines and were hemodynamically more stable. Even though pulmonary function was often impaired after ht HTx, weaning from the respirator and extubation was more successful in this group. [ABSTRACT FROM AUTHOR]

Background: Only limited data are available on the physiological functional compatibility of cardiac xenografts after orthotopic pig to baboon transplantation (oXHTx). Thus we investigated hemodynamic parameters including cardiac output (CO) before and after oXHTx. Methods: Orthotopic xenogeneic heart transplantation from nine hDAF transgeneic piglets to baboons was performed. We used femoral arterial thermodilution for the invasive assessment of CO and stroke volume. Results: Baseline CO of the baboons after induction of anesthesia was 1.36 (1.0–1.9) l/min. 30 to 60 min after termination of the cardiopulmonary bypass, CO of the cardiac xenograft was significantly increased to 1.72 (1.3–2.1) l/min (P < 0.01). The stroke volumes of the baboon heart before transplantation and the cardiac xenograft was comparable [14.9 (11–26) vs. 11.8 (10–23) ml]. Thus the higher CO was achieved by an increase in heart rate after oXHTx [75.0 (69–110) vs. 140.0 (77–180)/min; P < 0.01]. Despite the increased CO, oxygen delivery was reduced [256 (251–354) vs. 227 (172–477) ml/min; P < 0.01] due to the inevitable hemodilution during the cardiopulmonary bypass and the blood loss caused by the surgical procedures. Conclusion: Our results demonstrate that in the early phase after orthotopic transplantation of hDAF pig hearts to baboons, cardiac function of the donor heart is maintained and exceeds baseline CO. However, in the early intraoperative phase this was only possible by using inotropic substances and vasopressors due to the inevitable blood loss and dilution by the priming of the bypass circuit. [ABSTRACT FROM AUTHOR]