Hyperoxic ventilation exacerbates lung reperfusion injury

Ellman, Peter I.; Alvis, Jeffrey S.; Tache-Leon, Carlos; Singh, Ramesh; Reece, T. Brett; Kern, John A.; Tribble, Curtis G.; Krön, Irving L.

doi:10.1016/j.jtcvs.2005.06.037

Cited by 24 publications

(11 citation statements)

References 22 publications

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“…The primary definition of grade 3 PGD at 48 or 72 hours after transplant was associated with a relative risk (RR) of 4.8 (95% CI, 3.3-7.0; P , 0.001) for death within 90 days of transplant compared with those without grade 3 PGD and an ARI of 18% (95% CI, 12-24). Grade 3 PGD was associated with a significantly increased 1-year mortality (RR, 3.0; 95% CI, 2.3-3.9; P , 0.001) compared with those without grade 3 PGD, and an ARI of 23% (95% CI, [15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30]. Although the magnitude of the association between grade 3 PGD and mortality was attenuated when the alternate definition of any grade 3 PGD within 72 hours was used in the sensitivity analyses, the association remained significant at 90 days (RR, 3.5; 95% CI, 2.3-5.1; P , 0.001) and 1 year (RR, 2.5; 95% CI, 1.9-3.3; P , 0.001) (see Table E6).…”

Section: Resultsmentioning

confidence: 99%

“…Cold ischemia of the allograft followed by reperfusion results in a significant oxidative burst (26), which may overwhelm cellular antioxidant pathways and lead to cellular necrosis and apoptosis, production of proinflammatory cytokines, and worsening edema and gas exchange in animal models (27). Although we attempted to determine the FI O 2 for each subject before allograft reperfusion, we appreciate that FI O 2 is a dynamic variable, which may have been confounded by patient needs during the surgical procedure.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Clinical Risk Factors for Primary Graft Dysfunction after Lung Transplantation

Diamond

Lee

Kawut

et al. 2013

Am J Respir Crit Care Med

551

361

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Rationale: Primary graft dysfunction (PGD) is the main cause of early morbidity and mortality after lung transplantation. Previous studies have yielded conflicting results for PGD risk factors. Objectives: We sought to identify donor, recipient, and perioperative risk factors for PGD. Methods: We performed a 10-center prospective cohort study enrolled between March 2002 and December 2010 (the Lung Transplant Outcomes Group). The primary outcome was International Society for Heart and Lung Transplantation grade 3 PGD at 48 or 72 hours posttransplant. The association of potential risk factors with PGD was analyzed using multivariable conditional logistic regression. Measurements and Main Results: A total of 1,255 patients from 10 centers were enrolled; 211 subjects (16.8%) developed grade 3 PGD. In multivariable models, independent risk factors for PGD were any history of donor smoking (odds ratio [OR], 1.8; 95% confidence interval [CI], 1.2-2.6; P ¼ 0.002); FI O 2 during allograft reperfusion (OR, 1.1 per 10% increase in FI O 2 ; 95% CI, 1.0-1.2; P ¼ 0.01); single lung transplant (OR, 2; 95% CI, 1.2-3.3; P ¼ 0.008); use of cardiopulmonary bypass (OR, 3.4; 95% CI, 2.2-5.3; P , 0.001); overweight (OR, 1.8; 95% CI, 1.2-2.7; P ¼ 0.01) and obese (OR, 2.3; 95% CI, 1.3-3.9; P ¼ 0.004) recipient body mass index; preoperative sarcoidosis (OR, 2.5; 95% CI, 1.1-5.6; P ¼ 0.03) or pulmonary arterial hypertension (OR, 3.5; 95% CI, 1.6-7.7; P ¼ 0.002); and mean pulmonary artery pressure (OR, 1.3 per 10 mm Hg increase; 95% CI, 1.1-1.5; P , 0.001). PGD was significantly associated with 90-day (relative risk, 4.8; absolute risk increase, 18%; P , 0.001) and 1-year (relative risk, 3; absolute risk increase, 23%; P , 0.001) mortality. Conclusions: We identified grade 3 PGD risk factors, several of which are potentially modifiable and should be prioritized for future research aimed at preventative strategies. Clinical trial registered with www.clinicaltrials.gov (NCT 00552357). What This Study Adds to the FieldWe performed a multicenter, prospective cohort study of 1,255 lung transplant recipients across 10 US transplant centers. We identified receipt of an organ from a donor with any smoking history, elevated FI O 2 during allograft reperfusion, preoperative sarcoidosis or pulmonary arterial hypertension, use of cardiopulmonary bypass, single lung transplant, large-volume blood product transfusion, elevated pulmonary arterial pressures, and overweight or obese recipient body habitus as risk factors for grade 3 PGD. Several of these risk factors are potentially modifiable, and thus may suggest preventative strategies, whereas other risk factors should be prioritized for future mechanistic research efforts.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Clinical Risk Factors for Primary Graft Dysfunction after Lung Transplantation

Diamond

Lee

Kawut

et al. 2013

Am J Respir Crit Care Med

551

361

View full text Add to dashboard Cite

show abstract

“…Our laboratory has shown that hyperoxic ventilation exacerbates lung reperfusion injury, suggesting that the lowest possible tension of inspired oxygen should be used during reperfusion. 14 These studies suggest that controlled ventilation or perfusion is beneficial after lung ischemia. To date, no study has investigated ventilation and perfusion applied in combination during a post-transplantation reperfusion model.…”

mentioning

confidence: 99%

Attenuation of Lung Reperfusion Injury by Modified Ventilation and Reperfusion Techniques

Singh

Laubach

Ellman

et al. 2006

The Journal of Heart and Lung Transplantation

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“…At the time of reperfusion there is a generation of free radicals partially due to the buildup of xanthine and the conversion of xanthine reductase to xanthine oxidase. This production of toxic metabolites, potentially exacerbated by hyperoxic oxygen delivery, leads to lung inflammation and IR injury [19]. IR injury is then thought to occur in a two hit process, with donor macrophages initiating the early injury and initiating the early inflammatory cascade, followed by the recruitment of recipient neutrophils and lymphocytes [20,21].…”

Section: Discussionmentioning

confidence: 99%