Oxygen Perfusion (Persufflation) of Human Pancreata Enhances Insulin Secretion and Attenuates Islet Proinflammatory Signaling.

BACKGROUND: All human islets used in research and for the clinical treatment of diabetes are subject to ischemic damage during pancreas procurement, preservation, and islet isolation. A major factor influencing islet function is exposure of pancreata to cold ischemia during unavoidable windows of preservation by static cold storage (SCS). Improved preservation methods may prevent this functional deterioration. In the present study, we investigated whether pancreas preservation by gaseous oxygen perfusion (persufflation) better preserved islet function versus SCS. METHODS: Human pancreata were preserved by SCS or by persufflation in combination with SCS. Islets were subsequently isolated, and preparations in each group matched for SCS or total preservation time were compared using dynamic glucose-stimulated insulin secretion as a measure of ß-cell function and RNA sequencing to elucidate transcriptomic changes. RESULTS: Persufflated pancreata had reduced SCS time, which resulted in islets with higher glucose-stimulated insulin secretion compared to islets from SCS only pancreata. RNA sequencing of islets from persufflated pancreata identified reduced inflammatory and greater metabolic gene expression, consistent with expectations of reducing cold ischemic exposure. Portions of these transcriptional responses were not associated with time spent in SCS and were attributable to pancreatic reoxygenation. Furthermore, persufflation extended the total preservation time by 50% without any detectable decline in islet function or viability. CONCLUSIONS: These data demonstrate that pancreas preservation by persufflation rather than SCS before islet isolation reduces inflammatory responses and promotes metabolic pathways in human islets, which results in improved ß cell function.

Submaximal cardiopulmonary exercise testing predicts 90-day survival after liver transplantation.

Liver transplantation has a significant early postoperative mortality rate. An accurate preoperative assessment is essential for minimizing mortality and optimizing limited donor organ resources. This study assessed the feasibility of preoperative submaximal cardiopulmonary exercise testing (CPET) for determining the cardiopulmonary reserve in patients being assessed for liver transplantation and its potential for predicting 90-day posttransplant survival. One hundred eighty-two patients underwent CPET as part of their preoperative assessment for elective liver transplantation. The 90-day mortality rate, critical care length of stay, and hospital length of stay were determined during the prospective posttransplant follow-up. One hundred sixty-five of the 182 patients (91%) successfully completed CPET; this was defined as the ability to determine a submaximal exercise parameter: the anaerobic threshold (AT). Sixty of the 182 patients (33%) underwent liver transplantation, and the mortality rate was 10.0% (6/60). The mean AT value was significantly higher for survivors versus nonsurvivors (12.0 ± 2.4 versus 8.4 ± 1.3 mL/minute/kg, P < 0.001). Logistic regression revealed that AT, donor age, blood transfusions, and fresh frozen plasma transfusions were significant univariate predictors of outcomes. In a multivariate analysis, only AT was retained as a significant predictor of mortality. A receiver operating characteristic curve analysis demonstrated sensitivity and specificity of 90.7% and 83.3%, respectively, with good model accuracy (area under the receiver operating characteristic curve = 0.92, 95% confidence interval = 0.82-0.97, P = 0.001). The optimal AT level for survival was defined to be >9.0 mL/minute/kg. The predictive value was improved when the ideal weight was substituted for the actual body weight of a patient with refractory ascites, even after a correction for the donor's age. In conclusion, the preoperative cardiorespiratory reserve (as defined by CPET) is a sensitive and specific predictor of early survival after liver transplantation. The predictive value of CPET requires further evaluation.