Assessment of hemodynamic parameters by transpulmonary thermodilution in orthotopic pig-to baboon cardiac xenotransplantation
Maren Mokelke1,2, Julia Radan1,2, Bruno Reichart1, Ines Buttgereit1, Elisabeth Neumann1,2, Martin Bender1,3, Paolo Brenner1,2, Eckhard Wolf4, Jan-Michael Abicht1,3, Matthias Längin1,3.
1Walter Brendel Centre of Experimental Medicine, LMU Munich, Munich, Germany; 2Department of Cardiac Surgery, University Hospital, LMU Munich, Munich, Germany; 3Department of Anaesthesiology, University Hospital, LMU Munich, Munich, Germany; 4Chair for Molecular Animal Breeding and Biotechnology, LMU Munich, Munich, Germany
Introduction: Reliable intra- and postoperative hemodynamic monitoring is essential for anesthesia and post-operative intensive care. Transpulmonary thermodilution (TPTD) is a minimally invasive and well established technique for monitoring cardiopulmonary parameters and guiding volume and catecholamine therapy.
Method: TPTD measurements (PiCCO®, Pulsion Medical Systems) were taken during orthotopic cardiac xenotransplantation from pig to baboon (n = 14). Genetically engineered pigs (GGTA1KO, hCD46, hTHBD) served as organ donors. According to the applied preservation method of the porcine donor heart, two groups were defined: i) ischemic preservation (IP, n= 5) and ii) continuous non-ischemic perfusion (CP, n = 9). Cardiac output was measured by TPTD and volumetric parameters were calculated as following: global blood flow (cardiac/stroke volume index, CI/SVI), preload (global end-diastolic volume index), afterload (systemic vascular resistance index), contractility (cardiac power index, CPI) and pulmonary edema (extravascular lung water index).
Results: There were significant differences between the IP and CP groups after cardiopulmonary bypass: IP hearts were associated with markedly reduced ventricular function and reduced global blood flow (CI: 3.1 l/min/m2, SVI: 25 ml/m2) in contrast to CP hearts (CI: 4.5 l/min/m2, SVI: 44 ml/m2, p = 0.03 and p = 0.02). In addition, cardiac contractility was diminished in the IP group (CPI 0.5 W/m2) vs. CP group (0.9 W/m2, p = 0.01). There was no evidence for pulmonary edema in both groups (ELWI: IP 11 vs. CP 13 ml/kg, p = not significant). To maintain sufficient blood circulation higher catecholamine doses were required in the IP group. In 3 of 5 cases animals with IP hearts developed primary graft dysfunction within 24 hours. Animals that had received CP hearts maintained stable hemodynamic values, good intra- and postoperative graft function and reached long-term survival for up to half a year.
Conclusion: Regarding overall graft function, continuous non-ischemic perfusion is superior to ischemic preservation and preferable for both preclinical and clinical use. Hemodynamic monitoring by TPTD is useful to identify grafts with exceptional function which facilitate long-term survival. Moreover, TPTD may guide individual treatment of cardiopulmonary insufficiency in the early hours after xenotransplantation experiments.
Supported by the Deutsche Forschungsgemeinschaft (TRR127).