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Beta-adrenergic receptor polymorphisms and cardiac graft function in potential organ donors.

ABSTRACT: Prior studies have demonstrated associations between beta-adrenergic receptor (?AR) polymorphisms and left ventricular dysfunction-an important cause of allograft nonutilization for transplantation. We hypothesized that ?AR polymorphisms predispose donor hearts to LV dysfunction after brain death. A total of 1043 organ donors managed from 2001-2006 were initially studied. The following ?AR single nucleotide polymorphisms were genotyped: ?1AR 1165C/G (Arg389Gly), ?1AR 145A/G (Ser49Gly), ?2AR 46G/A (Gly16Arg) and ?2AR 79C/G (Gln27Glu). In multivariable regression analyses, the ?2AR46 SNP was significantly associated with LV systolic dysfunction, with each minor allele additively decreasing the odds for LV ejection fraction <50%. The ?1AR1165 and ?2AR46 SNPs were associated with higher dopamine requirement during the donor management period: donors with the GG and AA genotypes had ORs of 2.64 (95% CI 1.52-4.57) and 2.70 (1.07-2.74) respectively for requiring >10 ?g/kg/min of dopamine compared to those with the CC and GG genotypes. However, no significant associations were found between ?AR SNPs and cardiac dysfunction in 364 donors managed from 2007-2008, perhaps due to changes in donor management, lack of power in this validation cohort, or the absence of a true association. ?AR polymorphisms may be associated with cardiac dysfunction after brain death, but these relationships require further study in independent donor cohorts.

SUBMITTER: Khush KK

PROVIDER: S-EPMC3513582 | biostudies-literature | 2012 Dec

REPOSITORIES: biostudies-literature

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Beta-adrenergic receptor polymorphisms and cardiac graft function in potential organ donors.

Khush K K KK Pawlikowska L L Menza R L RL Goldstein B A BA Hayden V V Nguyen J J Kim H H Poon A A Sapru A A Matthay M A MA Kwok P Y PY Young W L WL Baxter-Lowe L A LA Zaroff J G JG

American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons 20120920 12

Prior studies have demonstrated associations between beta-adrenergic receptor (βAR) polymorphisms and left ventricular dysfunction-an important cause of allograft nonutilization for transplantation. We hypothesized that βAR polymorphisms predispose donor hearts to LV dysfunction after brain death. A total of 1043 organ donors managed from 2001-2006 were initially studied. The following βAR single nucleotide polymorphisms were genotyped: β1AR 1165C/G (Arg389Gly), β1AR 145A/G (Ser49Gly), β2AR 46G/ ...[more]

PMID: 22994654

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Project description:ImportanceThe effectiveness of goal-directed care to reduce loss of brain-dead potential donors to cardiac arrest is unclear.ObjectiveTo evaluate the effectiveness of an evidence-based, goal-directed checklist in the clinical management of brain-dead potential donors in the intensive care unit (ICU).Design, setting, and participantsThe Donation Network to Optimize Organ Recovery Study (DONORS) was an open-label, parallel-group cluster randomized clinical trial in Brazil. Enrollment and follow-up were conducted from June 20, 2017, to November 30, 2019. Hospital ICUs that reported 10 or more brain deaths in the previous 2 years were included. Consecutive brain-dead potential donors in the ICU aged 14 to 90 years with a condition consistent with brain death after the first clinical examination were enrolled. Participants were randomized to either the intervention group or the control group. The intention-to-treat data analysis was conducted from June 15 to August 30, 2020.InterventionsHospital staff in the intervention group were instructed to administer to brain-dead potential donors in the intervention group an evidence-based checklist with 13 clinical goals and 14 corresponding actions to guide care, every 6 hours, from study enrollment to organ retrieval. The control group provided or received usual care.Main outcomes and measuresThe primary outcome was loss of brain-dead potential donors to cardiac arrest at the individual level. A prespecified sensitivity analysis assessed the effect of adherence to the checklist in the intervention group.ResultsAmong the 1771 brain-dead potential donors screened in 63 hospitals, 1535 were included. These patients included 673 males (59.2%) and had a median (IQR) age of 51 (36.3-62.0) years. The main cause of brain injury was stroke (877 [57.1%]), followed by trauma (485 [31.6%]). Of the 63 hospitals, 31 (49.2%) were assigned to the intervention group (743 [48.4%] brain-dead potential donors) and 32 (50.8%) to the control group (792 [51.6%] brain-dead potential donors). Seventy potential donors (9.4%) at intervention hospitals and 117 (14.8%) at control hospitals met the primary outcome (risk ratio [RR], 0.70; 95% CI, 0.46-1.08; P = .11). The primary outcome rate was lower in those with adherence higher than 79.0% than in the control group (5.3% vs 14.8%; RR, 0.41; 95% CI, 0.22-0.78; P = .006).Conclusions and relevanceThis cluster randomized clinical trial was inconclusive in determining whether the overall use of an evidence-based, goal-directed checklist reduced brain-dead potential donor loss to cardiac arrest. The findings suggest that use of such a checklist has limited effectiveness without adherence to the actions recommended in this checklist.Trial registrationClinicalTrials.gov Identifier: NCT03179020.

Dataset Information

Beta-adrenergic receptor polymorphisms and cardiac graft function in potential organ donors.

Publications

Beta-adrenergic receptor polymorphisms and cardiac graft function in potential organ donors.

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