Echocardiographic assessment of left ventricular function in ex situ heart perfusion using pump-supported and passive afterload working mode: a pilot study

Ex situ heart perfusion (ESHP) has been developed to decrease cold ischemia time and allow metabolic assessment of donor hearts prior to transplantation. Current clinical ESHP systems preserve the heart in an unloaded condition and only evaluate the cardiac metabolic profile. In this pilot study we performed echocardiographic functional assessment using two alternative systems for left ventricular (LV) loading: pump supported afterload working mode (SAM) and passive afterload working modes (PAM). Six hearts were procured from male Yorkshire pigs. During cold ischemia, hearts were mounted on our custom made ESHP circuit and a 3D-printed enclosure for the performance of echocardiography with a standard TEE probe. Following perfusion with Langherdorf mode of the unloaded heart, the system was switched into different working modes to allow LV loading and functional assessment: pump supported (SAM) and passive (PAM). Echocardiographic assessment of left ventricular function in the donor hearts was performed in vivo and at 1 h of ESHP with SAM, after 4.5 h with PAM and after 5.5 h with SAM. We obtained good quality epicardial echocardiographic images at all time points allowing a comprehensive LV systolic assessment. All indices showed a decrease in LV systolic function throughout the trial with the biggest drop after heart harvesting. We demonstrated the feasibility of echocardiographic functional assessment during ESHP and two different working modes. The expected LV systolic dysfunction consisted of a reduction in EF, FAC, FS, and strain throughout the experiment with the most significant decrease after harvesting.

Donor Death Category Is an Effect Modifier Between Cold Ischemia Time and Post-transplant Graft Function in Deceased-Donor Kidney Transplant Recipients

Objectives: We aimed to analyze the effect of cold ischemia time (CIT) on post-transplant graft function through mixed-effect model analysis to reduce the bias caused by paired mate kidneys.Methods: We reviewed all kidney transplantation records from 2015 to 2019 at our center. After applying the exclusion criteria, 561 cases were included for analysis. All donor characteristics, preservation and matching information, and recipient characteristics were collected. Transplant outcomes included delayed graft function (DGF) and estimated glomerular filtration rate (eGFR). Generalized linear mixed models were applied for analysis. We also explored potential effect modifiers, namely, donor death category, expanded criteria donors, and donor death causes.Results: Among the 561 cases, 79 DGF recipients developed DGF, and 15 recipients who died after surgery were excluded from the eGFR estimation. The median stable eGFR of the 546 recipients was 60.39 (47.63, 76.97) ml/min/1.73 m2. After adjusting for confounding covariates, CIT had a negative impact on DGF incidence [odds ratio = 1.149 (1.006, 1.313), P = 0.041]. In the evaluation of the impact on eGFR, the regression showed that CIT had no significant correlation with eGFR [β = −0.287 (−0.625, 0.051), P = 0.096]. When exploring potential effect modifiers, only the death category showed a significant interaction with CIT in the effect on eGFR (Pinteraction = 0.027). In the donation after brain death (DBD) group, CIT had no significant effect on eGFR [β = 0.135 (−0.433, 0.702), P = 0.642]. In the donation after circulatory death/donation after brain death followed by circulatory death (DCD/DBCD) group, CIT had a significantly negative effect on eGFR [β= −0.700 (−1.196, −0.204), P = 0.006]. Compared to a CIT of 0–6 h, a CIT of 6–8 or 8–12 h did not decrease the post-transplant eGFR. CIT over 12 h (12–16 h or over 16 h) significantly decreased eGFR. With the increase in CIT, the regenerated eGFR worsened (Ptrend = 0.011).Conclusion: Considering the effect of paired mate kidneys, the risk of DGF increased with prolonged CIT. The donor death category was an effect modifier between CIT and eGFR. Prolonged CIT did not reduce the eGFR level in recipients from DBDs but significantly decreased the eGFR in recipients from DCDs/DBCDs. This result indicates the potential biological interaction between CIT and donor death category.

Number of Donor Renal Arteries and Early Outcomes After Deceased Donor Kidney Transplantation

Background: Anatomical abnormalities increase the risk of deceased donor kidney discard but their impact on transplant outcomes is understudied. We sought to determine the impact of multiple donor renal arteries on early outcomes after deceased donor kidney transplantation. Methods: For this retrospective cohort study, we identified 1443 kidneys from 832 deceased donors with ≥1 kidney transplanted at our center (2006-2016). We compared the odds of delayed graft function and 90-day graft failure using logistic regression. To reduce potential selection bias, we then repeated the analysis using a paired-kidney cohort including kidney pairs from 162 donors with 1 single-artery kidney and 1 multi-artery kidney. Results: Of 1443 kidneys included, 319 (22%) had multiple arteries. Multi-artery kidneys experienced longer cold ischemia time, but other characteristics were similar between groups. Delayed graft function (50% multi-artery vs 45% one artery, p=0.07) and 90-day graft failure (3% vs 3%, p=0.83) were similar between groups before and after adjusting for donor and recipient characteristics. In the paired kidney analysis, cold ischemia time was significantly longer for multi-artery kidneys compared to single-artery kidneys from the same donor (33.5 versus 26.1 hours, p<0.001), but delayed graft function and 90-day graft failure were again similar between groups. Conclusions: Compared to single-artery deceased donor kidneys, those with multiple renal arteries are harder to place but experience similar delayed graft function and early graft failure.

Lung Inflation With Hydrogen During the Cold Ischemia Phase Alleviates Lung Ischemia-Reperfusion Injury by Inhibiting Pyroptosis in Rats

Background: Lung inflation with hydrogen is an effective method to protect donor lungs from lung ischemia-reperfusion injury (IRI). This study aimed to examine the effect of lung inflation with 3% hydrogen during the cold ischemia phase on pyroptosis in lung grafts of rats.Methods: Adult male Wistar rats were randomly divided into the sham group, the control group, the oxygen (O2) group, and the hydrogen (H2) group. The sham group underwent thoracotomy but no lung transplantation. In the control group, the donor lungs were deflated for 2 h. In the O2 and H2 groups, the donor lungs were inflated with 40% O2 + 60% N2 and 3% H2 + 40% O2 + 57% N2, respectively, at 10 ml/kg, and the gas was replaced every 20 min during the cold ischemia phase for 2 h. Two hours after orthotopic lung transplantation, the recipients were euthanized.Results: Compared with the control group, the O2 and H2 groups improved oxygenation indices, decreases the inflammatory response and oxidative stress, reduced lung injury, and improved pressure-volume (P-V) curves. H2 had a better protective effect than O2. Furthermore, the levels of the pyroptosis-related proteins selective nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3), cysteinyl aspartate specific proteinase (caspase)-1 p20, and the N-terminal of gasdermin D (GSDMD-N) were decreased in the H2 group.Conclusion: Lung inflation with 3% hydrogen during the cold ischemia phase inhibited the inflammatory response, oxidative stress, and pyroptosis and improved the function of the graft. Inhibiting reactive oxygen species (ROS) production may be the main mechanism of the antipyroptotic effect of hydrogen.