Medical Student University of Alberta Fort Saskatchewan, Alberta, Canada
Background: Ex-situ heart perfusion (ESHP) is a technology that seeks to improve donor heart preservation en-route to the recipient via provision of a semi-physiologic, controlled environment for the donor organ. Given the rarity of pediatric donor hearts, optimizing preservation capacity through ESHP is of great interest to expand the donor pool and overcome logistical challenges. However, devices are currently untailored to pediatric donor hearts. Typically, ESHP is conducted at either hypothermic (4-8℃) or normothermic (37℃) temperatures, each with their own benefits and drawbacks, but both requiring active temperature control. Subnormothermic ESHP (sESHP) at room temperature may exhibit the best of both temperature conditions and reduce device complexity, however remains underexplored. We sought to evaluate sESHP of pediatric donor hearts in comparison to traditional cold storage (CS).
METHODS AND RESULTS: The hearts of juvenile Yorkshire pigs (20kg) were procured and subject to either 10 hours of sESHP (n=6) or 6 hours of CS (n=5), after which the hearts were transplanted orthotopically into recipient pigs. The custom sESHP apparatus utilizes a small pump and oxygenator to perfuse the aortic root with a perfusate consistent of 1:1 donor whole blood and modified Krebs-Heinseleit buffer at room temperature. Alternatively, CS hearts were stored at 4 deg C in University of Wisconsin preservation solution. After implant into a recipient animal, hearts from both groups regained acceptable biventricular functionality, confirmed by echocardiogram. Left ventricular ejection fraction (58±3.8% vs. 58±6.6%) and shortening fraction (29.8±2.6% vs. 30±4.3%) was unchanged between groups (p>0.05). Following 2 hours of reperfusion, pigs were euthanized and samples of the ventricles were collected for analysis. Hematoxylin and eosin staining of the ventricles were reviewed by a pathologist blinded to the experimental groups and scored for contraction bands, edema formation, inflammation, and hemorrhage. Despite sESHP hearts being preserved for double the out-of-body time as CS hearts, there were no significant differences in tissue injury scores (reported here as mean ± standard error of the mean (SEM) for sESHP vs. CS): contraction banding (0.3±0.3 vs. 0.4±0.2), edema (1.3±0.2 vs. 1.3±0.2), inflammation (0.8±0.3 vs. 0.7±0.4), or hemorrhage (0±0 vs. 0±0) scores were similar (all p>0.05 via Mann-Whitney U-Test). Immunofluorescence staining for vascular cell adhesion marker (VCAM)-1 qualitatively shows lessened expression in hearts preserved with sESHP, suggesting less inflammation.
Conclusion: sESHP appears to be a viable method to prolong the out-of-body time for pediatric donor hearts, with evidence of non-inferior tissue and functional preservation despite a near doubling of out-of-body time.
