Blood transfusion of the donor is associated with stage 3 primary graft dysfunction after lung transplantation.

BACKGROUND: The first aim of this study was to assess the association between stage 3 PGD and pre-donation blood transfusion of the donor. The secondary objectives were to assess the epidemiology of donor transfusion and the outcome of LT recipients according to donor transfusion status and massive donor transfusion status. METHODS: This was an observational, prospective, single-center study. The results are expressed as absolute numbers, percentages, medians, and interquartile ranges. Statistical analyses were performed using Chi squared, Fischer's exact tests, and Mann-Whitney U tests (P < .05 was considered significant). A multivariate analysis was performed. RESULTS: Between January 2016 and February 2019, 147 patients were included in the analysis. PGD was observed in 79 (54%) patients, 45 (31%) of whom had stage 3 PGD. Pre-donation blood transfusion was administered in 48 (33%) donors (median of 3[1-9] packed red cells (PRCs)). On multivariate analysis, stage 3 PGD was significantly associated with donor blood transfusion (OR 2.69, IC (1.14-6.38), P = .024). Mortality at days 28 and 90 was not significantly different according to the pre-donation transfusion status of the donor. CONCLUSION: Pre-donation blood transfusion is associated with stage 3 PGD occurrence after LT. Transfusion data of the donor should be included in donor lung assessment.

Interaction between PGI2 and ET-1 pathways in vascular smooth muscle from Group-III pulmonary hypertension patients.

Pulmonary hypertension (PH) is characterized by an elevation of mean pulmonary artery pressure and it is classified into five groups. Among these groups, PH Group-III is defined as PH due to lung disease or hypoxia. Prostacyclin (PGI2) analogues (iloprost, treprostinil) and endothelin-1 (ET-1) receptor antagonists (ERA) (used alone or in combination) are therapies used for treating PH. The mechanisms underlying the positive/negative effects of combination treatment are not well documented, and in this study, we tested the hypothesis that the combination of a PGI2 analogue (iloprost, treprostinil) and an ERA may be more effective than either drug alone to treat vasculopathies observed in PH Group-III patients. Using Western blotting, ETA and ETB receptor expression were determined in human pulmonary artery (HPA) preparations derived from control and PH Group-III patients, and the physiologic impact of altered expression ratios was assessed by measuring ET-1 induced contraction of ex vivo HPA and human pulmonary veins (HPV) in an isolated organ bath system. In addition, the effects of single agent or combination treatments with a PGI2 analogue and an ERA on ET-1 release and HPA smooth muscle cells (hPASMCs) proliferation were determined by ELISA and MTT techniques, respectively. Our results indicate that the increased ETA/ETB receptor expression ratio in HPA derived from PH Group-III patients is primarily governed by a greatly depressed ETB receptor expression. However, contractions induced by ET-1 are not impacted in HPA and HPV derived from PH Group-III patients as compared to controls. Also, we found that the combination of an ETA receptor antagonist (BQ123) with iloprost provides greater inhibition of hPASMCs proliferation (-48±14% control; -32±06% PH) than either agent alone. Of note, while the ETB receptor antagonist (BQ788) increases ET-1 production from PH Group-III patients' preparations (HPA, parenchyma), even under these more proliferative conditions, iloprost and treprostinil are still effective to inhibit hPASMCs proliferation (-22/-24%). Our findings may provide new insights for the treatment of PH Group-III by combining a PGI2 analogue and a selective ETA receptor antagonist.