| dc.description.abstract | Current technology has limits organ transport for transplantation to static storage, thereby reducing the reasonable distance of travel. Continuous machine perfusion has been proposed as a viable alternative to improving function and outcome. A series of studies with such a device have been developed to elucidate the method by which optimal results can be achieved.
Adult mongrel dog hearts were established in a device that provided continuous perfusion of oxygenated fluid and enabled precise control of flow rate, oxygenation, and fluid temperature. The first series of experiments sought to determine an optimal flow rate for tissue perfusion at one of six flow rates (5, 10, 15, 20, 25 or 30 mL/min/100 g). The second set of experiments looked at the effects of aortic attachment on tissue perfusion, employing initial high and low pressure, immersion, and valve controls. The next cycle of studies evaluated the influence of flow rate on long term (10 hours) edema buildup and metabolic profile. Evaluations via wet-dry analysis and magnetic resonance spectroscopy were used. The final determination of flow characteristics looked at the effects of the inclination of the heart at different angles with and away from the non-coronary sinus.
Hearts extracted dissolved oxygen continuously throughout perfusion. The MVO2 increased with increasing coronary flow but insignificantly at flows beyond 15 mL/100g/min. Higher pump flow rate correlated with increased tissue perfusate flow, as determined by microsphere analysis. Different modes of attachment led to varying amounts of myocardial oxygen consumption, perfusate flow, and non-nutrient flow. Hearts deployed at low initial flow rate were found to have lower tissue perfusion rates and higher calculated non-nutrient flow than hearts attached at high initial flow rates. For the 10 hour perfusion study, hearts that were found to have high tissue flow had low lactate:alanine ratios, but experienced significant weight gain (34±4%) (p<.01) and had higher myocardial water content. Those with low tissue flow were observed to have significant lactate accumulation with minimal myocardial weight gain over 10 hours (11±4%). Heart inclination testing did not elucidate a definitive angle that would limit tissue perfusion. Control angles (θ = 0°) even displayed limited nutrient flow, despite initial high flow protocol.
Based on these studies it is believed that continuous machine perfusion of the heart can provide better outcomes, longer transport times, and expansion of the donor pool. Two initializing factors are crucial to ensuring the longer term viability of the organ. Starting high pressure flow while attaching the aorta improves valve leaflet apposition. Sequential adjustment to moderate flow rate provides adequate tissue perfusion and minimizes edema development. Heart inclination can affect tissue perfusion due to container and heart size; however, such an adverse outcome is not expected in the clinical device due to the improved design of the container. | en_US |
