Investigating the physiology of normothermic ex vivo heart perfusion in an isolated slaughterhouse porcine model used for device testing and training

Abstract

BackgroundThe PhysioHeart™ is a mature acute platform, based isolated slaughterhouse hearts and able to validate cardiac devices and techniques in working mode. Despite perfusion, myocardial edema and time-dependent function degradation are reported. Therefore, monitoring several variables is necessary to identify which of these should be controlled to preserve the heart function. This study presents biochemical, electrophysiological and hemodynamic changes in the PhysioHeart™ to understand the pitfalls of ex vivo slaughterhouse heart hemoperfusion.MethodsSeven porcine hearts were harvested, arrested and revived using the PhysioHeart™. Cardiac output, SaO2, glucose and pH were maintained at physiological levels. Blood analyses were performed hourly and unipolar epicardial electrograms (UEG), pressures and flows were recorded to assess the physiological performance.ResultsNormal cardiac performance was attained in terms of mean cardiac output (5.1 ± 1.7 l/min) and pressures but deteriorated over time. Across the experiments, homeostasis was maintained for 171.4 ± 54 min, osmolarity and blood electrolytes increased significantly between 10 and 80%, heart weight increased by 144 ± 41 g, free fatty acids (− 60%), glucose and lactate diminished, ammonia increased by 273 ± 76% and myocardial necrosis and UEG alterations appeared and aggravated. Progressively deteriorating electrophysiological and hemodynamic functions can be explained by reperfusion injury, waste product intoxication (i.e. hyperammonemia), lack of essential nutrients, ion imbalances and cardiac necrosis as a consequence of hepatological and nephrological plasma clearance absence.ConclusionsThe PhysioHeart™ is an acute model, suitable for cardiac device and therapy assessment, which can precede conventional animal studies. However, observations indicate that ex vivo slaughterhouse hearts resemble cardiac physiology of deteriorating hearts in a multi-organ failure situation and signalize the need for plasma clearance during perfusion to attenuate time-dependent function degradation. The presented study therefore provides an in-dept understanding of the sources and reasons causing the cardiac function loss, as a first step for future effort to prolong cardiac perfusion in the PhysioHeart™. These findings could be also of potential interest for other cardiac platforms.

Inflammation and Oxidative Stress in the Context of Extracorporeal Cardiac and Pulmonary Support

“…In ESOP, there has been an ongoing effort to replace the blood-based perfusates with acellular ones, aiming to eliminate dependence on donor blood and the problems associated with banked blood as well as bypass hemolysis and related problems (82)(83)(84). Kappler et al have shown that during four-hour ESHP in a porcine model, the free hemoglobin in the perfusate increased throughout the perfusion by approximately 0.02 mmol/L per hour (85).…”

Production of living myocardial slices from circulatory death hearts after ex vivo heart perfusion

“…Similarly, slaughterhouse hearts are obtained after circulatory death and it appears that these hearts also need normothermic reperfusion before viable LMS can be produced. Hence, slaughterhouse hearts present a clinically relevant model for DCD transplantations while decreasing unnecessary animal experimentation 3 and providing an unlimited supply of tissue for biomimetic examination using LMS.…”

Use of 3D anatomical models in mock circulatory loops for cardiac medical device testing

“…To expand their testing applications, MCLs have been combined with ex vivo hearts. This allows to assess additional features of the MD as hemocompatibility, the fitting with the anatomical site of interest, and the biochemical and electrophysiological changes the MD elicits on the heart 7–9 . Despite the clear advantages of testing a MD on a beating heart, this combined MCLs‐ex vivo testing technique presents some limitations.…”