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Critical warm ischemia time point for cardiac donation after circulatory death.

ABSTRACT: Donation after circulatory death (DCD) represents a promising opportunity to overcome the relative shortage of donors for heart transplantation. However, the necessary period of warm ischemia is a concern. This study aims to determine the critical warm ischemia time based on in vivo biochemical changes. Sixteen DCD non-cardiac donors, without cardiovascular disease, underwent serial endomyocardial biopsies immediately before withdrawal of life-sustaining therapy (WLST), at circulatory arrest (CA) and every 2 min thereafter. Samples were processed into representative pools to assess calcium homeostasis, mitochondrial function and cellular viability. Compared to baseline, no significant deterioration was observed in any studied parameter at the time of CA (median: 9 min; IQR: 7-13 min; range: 4-19 min). Ten min after CA, phosphorylation of cAMP-dependent protein kinase-A on Thr197 and SERCA2 decreased markedly; and parallelly, mitochondrial complex II and IV activities decreased, and caspase 3/7 activity raised significantly. These results did not differ when donors with higher WLST to CA times (≥9 min) were analyzed separately. In human cardiomyocytes, the period from WLST to CA and the first 10 min after CA were not associated with a significant compromise in cellular function or viability. These findings may help to incorporate DCD into heart transplant programs.

SUBMITTER: Sanchez-Camara S

PROVIDER: S-EPMC9303247 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:ObjectiveDespite growing evidence of comparable outcomes in recipients of donation after circulatory death and donation after brain death donor lungs, donation after circulatory death allografts continue to be underused nationally. We examined predictors of nonuse.MethodsAll donors who donated at least 1 organ for transplantation between 2005 and 2019 were identified in the United Network for Organ Sharing registry and stratified by donation type. The primary outcome of interest was use of pulmonary allografts. Organ disposition and refusal reasons were evaluated. Multivariable regression modeling was used to assess the relationship between donor factors and use.ResultsA total of 15,458 donation after circulatory death donors met inclusion criteria. Of 30,916 lungs, 3.7% (1158) were used for transplantation and 72.8% were discarded primarily due to poor organ function. Consent was not requested in 8.4% of donation after circulatory death offers with donation after circulatory death being the leading reason (73.4%). Nonuse was associated with smoking history (P < .001), clinical infection with a blood source (12% vs 7.4%, P = .001), and lower PaO2/FiO2 ratio (median 230 vs 423, P < .001). In multivariable regression, those with PaO2/FiO2 ratio less than 250 were least likely to be transplanted (adjusted odds ratio, 0.03; P < .001), followed by cigarette use (0.28, P < .001), and donor age >50 (0.75, P = .031). Recent transplant era was associated with significantly increased use (adjusted odds ratio, 2.28; P < .001).ConclusionsNontransplantation of donation after circulatory death lungs was associated with potentially modifiable predonation factors, including organ procurement organizations' consenting behavior, and donor factors, including hypoxemia. Interventions to increase consent and standardize donation after circulatory death donor management, including selective use of ex vivo lung perfusion in the setting of hypoxemia, may increase use and the donor pool.

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Critical warm ischemia time point for cardiac donation after circulatory death.

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