Selective pulmonary pulsatile perfusion with oxygenated blood during cardiopulmonary bypass attenuates lung tissue inflammation but does not affect circulating cytokine levels

Santini, Francesco; Telesca, Mariassunta; Menon, Tiziano; Mazzi, Paola; Berton, Giorgio; Faggian, Giuseppe; Mazzucco, Alessandro

doi:10.1093/ejcts/ezs199

Cited by 17 publications

(21 citation statements)

References 23 publications

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“…Thus, we used hypothermic LPD solution for pulmonary artery perfusion in this study to reduce those CPB-related adverse effects on lung. Numerous studies have demonstrated that hypothermic pulmonary perfusion can effectively reduce pulmonary metabolic rate, decrease OFR production, and increase plasma colloid osmotic pressure to prevent pulmonary edema [14], [18], [19]. Our results show that pulmonary artery perfusion with TNF-α Ab in hypothermic LPD significantly reduces CPB-induced apoptosis and prevents pulmonary edema.…”

Section: Discussionsupporting

confidence: 55%

Pulmonary Artery Perfusion with Anti-Tumor Necrosis Factor Alpha Antibody Reduces Cardiopulmonary Bypass-Induced Inflammatory Lung Injury in a Rabbit Model

Gao

et al. 2013

PLoS ONE

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Inflammatory lung injury is one of the main complications associated with cardiopulmonary bypass (CPB). Tumor necrosis factor-α (TNF-α) is one of the key factors mediating the CPB-induced inflammatory reactions. Our previous studies have shown that endotracheal administration of anti-tumor necrosis factor-α antibody (TNF-α Ab) produces some beneficial effects on lung in a rabbit CPB model. In this study, we further examined the effects of pulmonary artery perfusion with TNF-α Ab (27 ng/kg) on lung tissue integrity and pulmonary inflammation during CPB and investigated the mechanism underlying the TNF-α Ab-mediated effects in a rabbit model of CPB. Our results from transmission electron microscopy showed that the perfusion with TNF-α Ab alleviated CPB-induced histopathological changes in lung tissue. The perfusion with TNF-α Ab also prevented CPB-induced pulmonary edema and improved oxygenation index. Parameters indicating pulmonary inflammation, including neutrophil count and plasma TNF-α and malondialdehyde (MDA) levels, were significantly reduced during CPB by pulmonary artery perfusion with TNF-α Ab, suggesting that the perfusion with TNF-α Ab reduces CPB-induced pulmonary inflammation. We further investigated the molecular mechanism underlying the protective effects of TNF-α Ab on lung. Our quantitative RT-PCR analysis revealed that pulmonary artery perfusion with TNF-α Ab significantly decreased TNF-α expression in lung tissue during CPB. The apoptotic index in lung tissue and the expression of proteins that play stimulatory roles in apoptosis pathways including the fas ligand (FasL) and Bax were markedly reduced during CPB by the perfusion with TNF-α Ab. In contrast, the expression of Bcl-2, which plays an inhibitory role in apoptosis pathways, was significantly increased during CPB by the perfusion with TNF-α Ab, indicating that the perfusion with TNF-α Ab significantly reduces CPB-induced apoptosis in lung. Thus, our study suggests that pulmonary artery perfusion with TNF-α Ab might be a promising approach for attenuating CPB-induced inflammatory lung injury.

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Section: Discussionsupporting

confidence: 55%

Pulmonary Artery Perfusion with Anti-Tumor Necrosis Factor Alpha Antibody Reduces Cardiopulmonary Bypass-Induced Inflammatory Lung Injury in a Rabbit Model

Gao

et al. 2013

PLoS ONE

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“…As reported in animal studies, [13][14][15][16] small randomised trials and observational studies in infants 18 19 and adults, [22][23][24][25] we have now evaluated and confirmed in a clinical setting with adult patients with COPD, that pulmonary artery perfusion with oxygenated blood during CPB results in a higher postoperative oxygenation. This was obtained without an increased incidence of complications or significant prolongation of the surgical procedure.…”

Section: Discussionmentioning

confidence: 53%

“…It has now been confirmed in several animal models that bronchial artery blood flow is decreased substantially during CPB, and although exposure to CPB alone is enough to cause pulmonary injury, concomitant cessation of pulmonary artery flow contributes significantly to the development of postoperative pulmonary dysfunction. [9][10][11][12] The results of animals studies, [13][14][15][16] small randomised trials in infants with congenital heart disease 17-20 and inconclusive minor randomised trials and observational studies in adults [21][22][23][24][25] indicates that pulmonary artery perfusion with normothermic oxygenated blood preserves postoperative oxygenation. Further, lung transplantation experiences has shown that pulmonary artery perfusion with a hypothermic preservation solution protects the lungs from warm ischaemic injury during storage and transplantation.…”

Section: Introductionmentioning

confidence: 99%

Pulmonary artery perfusion versus no pulmonary perfusion during cardiopulmonary bypass in patients with COPD: a randomised clinical trial

et al. 2016

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IntroductionAbsence of pulmonary perfusion during cardiopulmonary bypass (CPB) may be associated with reduced postoperative oxygenation. Effects of active pulmonary artery perfusion were explored in patients with chronic obstructive pulmonary disease (COPD) undergoing cardiac surgery.Methods90 patients were randomised to receive pulmonary artery perfusion during CPB with either oxygenated blood (n=30) or histidine-tryptophan-ketoglutarate (HTK) solution (n=29) compared with no pulmonary perfusion (n=31). The coprimary outcomes were the inverse oxygenation index compared at 21 hours after starting CPB and longitudinally in a mixed-effects model (MEM). Secondary outcomes were tracheal intubation time, serious adverse events, mortality, days alive outside the intensive care unit (ICU) and outside the hospital.Results21 hours after starting CPB patients receiving pulmonary artery perfusion with normothermic oxygenated blood had a higher oxygenation index compared with no pulmonary perfusion (mean difference (MD) 0.94; 95% CI 0.05 to 1.83; p=0.04). The blood group had also a higher oxygenation index both longitudinally (MEM, p=0.009) and at 21 hours (MD 0.99; CI 0.29 to 1.69; p=0.007) compared with the HTK group. The latest result corresponds to a difference in the arterial partial pressure of oxygen of 23 mm Hg with a median fraction of inspired oxygen of 0.32. Yet the blood or HTK groups did not demonstrate a longitudinally higher oxygenation index compared with no pulmonary perfusion (MEM, p=0.57 and 0.17). Similarly, at 21 hours there was no difference in the oxygenation index between the HTK group and those no pulmonary perfusion (MD 0.06; 95% CI −0.73 to 0.86; p=0.87). There were no statistical significant differences between the groups for the secondary outcomes.DiscussionPulmonary artery perfusion with normothermic oxygenated blood during cardiopulmonary bypass appears to improve postoperative oxygenation in patients with COPD undergoing cardiac surgery. Pulmonary artery perfusion with hypothermic HTK solution does not seem to improve postoperative oxygenation.Trial registration numberNCT01614951; Pre-results.

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“…Clinical studies in settings resembling our study are less sanguine. Selective continuous pulmonary artery perfusion flows of 7 ml/kg/min, comparable to those used in our study, in low-risk adult patients during on-bypass coronary revascularization resulted in no significant clinical benefits (14, 15) despite slightly improved pulmonary perfusion indices and decreased pulmonary tissue inflammatory cytokine production. Importantly, Kiessling et al (5) reported an absence of clinical benefits despite small trends toward decreased pulmonary tissue-generated inflammatory markers in a study of intermittent selective pulmonary perfusion in high-risk pulmonary patients undergoing on-bypass coronary revascularization.…”

Section: Discussionmentioning

confidence: 57%

“…Even such well-established concepts as the deleterious effects of inflammatory cytokines still await their correlation with specific clinical end-points. While Siepe et al (20) attributed the protective effects of pulmonary perfusion during CPB to the decreased pulmonary tissue expression and blood concentration of inflammatory cytokines, such as IL-6, IL-8, IL-10, and TNF-α, and others (5, 15, 19) could not reproduce these effects. Likewise, despite avoidance of CPB, pulmonary atelectasis and activation of inflammatory cascades associated with pulmonary ischemia–reperfusion injury, off-bypass technique of coronary revascularization offers only a modest clinical impact on pulmonary outcomes in patients with severe pulmonary disease (21–23).…”

Section: Discussionmentioning

confidence: 99%

Pulmonary Perfusion and Ventilation during Cardiopulmonary Bypass Are Not Associated with Improved Postoperative Outcomes after Cardiac Surgery

Rodriguez-Blanco

Gologorsky

Salerno

et al. 2016

Front. Cardiovasc. Med.

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ObjectivesClinical trials of either pulmonary perfusion or ventilation during cardiopulmonary bypass (CBP) are equivocal. We hypothesized that to achieve significant improvement in outcomes both interventions had to be concurrent.DesignRetrospective case–control study.SettingsMajor academic tertiary referral medical center.ParticipantsTwo hundred seventy-four consecutive patients who underwent open heart surgery with CBP 2009–2013.InterventionsThe outcomes of 86 patients who received pulmonary perfusion and ventilation during CBP were retrospectively compared to the control group of 188 patients.Measurements and main resultsRespiratory complications rates were similar in both groups (33.7 vs. 33.5%), as were the rates of postoperative pneumonia (4.7 vs. 4.3%), pleural effusions (13.9 vs. 12.2%), and re-intubations (9.3 vs. 9.1%). Rates of adverse postoperative cardiac events including ventricular tachycardia (9.3 vs. 8.5%) and atrial fibrillation (33.7 vs. 28.2%) were equivalent in both groups. Incidence of sepsis (8.1 vs. 5.3%), postoperative stroke (2.3 vs. 2.1%), acute kidney injury (2.3 vs. 3.7%), and renal failure (5.8 vs. 3.7%) was likewise comparable. Despite similar transfusion requirements, coagulopathy (12.8 vs. 5.3%, p = 0.031) and the need for mediastinal re-exploration (17.4 vs. 9.6%, p = 0.0633) were observed more frequently in the pulmonary perfusion and ventilation group, but the difference did not reach the statistical significance. Intensive care unit (ICU) and hospital stays, and the ICU readmission rates (7.0 vs. 8.0%) were similar in both groups.ConclusionSimultaneous pulmonary perfusion and ventilation during CBP were not associated with improved clinical outcomes.

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Selective pulmonary pulsatile perfusion with oxygenated blood during cardiopulmonary bypass attenuates lung tissue inflammation but does not affect circulating cytokine levels

Abstract: sPPP attenuates alveolar inflammation, as demonstrated by the lower neutrophilic/lymphocytic alveolar infiltration, and the secretion of anti-inflammatory rather than proinflammatory mediators.

Cited by 17 publications

References 23 publications

Pulmonary Artery Perfusion with Anti-Tumor Necrosis Factor Alpha Antibody Reduces Cardiopulmonary Bypass-Induced Inflammatory Lung Injury in a Rabbit Model

Pulmonary Artery Perfusion with Anti-Tumor Necrosis Factor Alpha Antibody Reduces Cardiopulmonary Bypass-Induced Inflammatory Lung Injury in a Rabbit Model

Pulmonary artery perfusion versus no pulmonary perfusion during cardiopulmonary bypass in patients with COPD: a randomised clinical trial

Pulmonary Perfusion and Ventilation during Cardiopulmonary Bypass Are Not Associated with Improved Postoperative Outcomes after Cardiac Surgery

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