Sex-related differences in lung inflammation after brain death

Breithaupt‐Faloppa, Ana Cristina; Ferreira, Sueli Gomes; Kudo, Guilherme Konishi; Armstrong, Roberto; Tavares-de-Lima, Wothan; Silva, Luiz Fernando Ferraz da; Sannomiya, Paulina; Moreira, Luíz Felipe Pinho

doi:10.1016/j.jss.2015.09.018

Cited by 14 publications

(31 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Human and animal studies, mainly in heart and kidney transplantation, have demonstrated a multitude of injurious processes and pathways activated by BD. 34,39,43 However, despite these studies, the BD model has largely been underutilized in LTx studies. Studies in rodents confirm our findings that BD induces the development of a proinflammatory state 44 that has the potential to adversely affect posttransplant outcomes.…”

Section: Donor Brain Death Significantly Exacerbates Lung Allograftmentioning

confidence: 99%

Donor pretreatment with nebulized complement C3a receptor antagonist mitigates brain-death induced immunological injury post–lung transplant

Cheng

Patel

Lei

et al. 2018

American Journal of Transplantation

View full text Add to dashboard Cite

Donor brain death (BD) is an inherent part of lung transplantation (LTx) and a key contributor to ischemia-reperfusion injury (IRI). Complement activation occurs as a consequence of BD in other solid organ Tx and exacerbates IRI, but the role of complement in LTx has not been investigated. Here, we investigate the utility of delivering nebulized C3a receptor antagonist (C3aRA) pretransplant to BD donor lungs in order to reduce post-LTx IRI. BD was induced in Balb/c donors, and lungs nebulized with C3aRA or vehicle 30 minutes prior to lung procurement. Lungs were then cold stored for 18 hours before transplantation into C57Bl/6 recipients. Donor lungs from living donors (LD) were removed and similarly stored. At 6 hours and 5 days post-LTx, recipients of BD donor lungs had exacerbated IRI and acute rejection (AR), respectively, compared to recipients receiving LD lungs, as determined by increased histopathological injury, immune cells, and cytokine levels. A single pretransplant nebulized dose of C3aRA to the donor significantly reduced IRI as compared to vehicle-treated BD donors, and returned IRI and AR grades to that seen following LD LTx. These data demonstrate a role for complement inhibition in the amelioration of IRI post-LTx in the context of donor BD.

show abstract

Section: Donor Brain Death Significantly Exacerbates Lung Allograftmentioning

confidence: 99%

Donor pretreatment with nebulized complement C3a receptor antagonist mitigates brain-death induced immunological injury post–lung transplant

Cheng

Patel

Lei

et al. 2018

American Journal of Transplantation

View full text Add to dashboard Cite

show abstract

“…In pathological conditions, the extent of platelet deposition can contribute to occlusive thrombus formation and thrombocytopenia is reported to lead to increased permeability of systemic and pulmonary vessels in several models and to be associated with vascular leak in clinical conditions [16]. Although previous results showed higher microvascular permeability in female animals after BD [17], the analysis of platelets presence in the lung tissue did not show differences among groups. However, study from Cleary et al [18] showed adhesion of platelets in the lung microvasculature in an inflammatory response induced by LPS that was not associated with thrombus formation, occurring through mechanisms distinct from those mediating neutrophil recruitment or the occurrence of pulmonary emboli.…”

Section: Discussionmentioning

confidence: 76%

The influence of female sex hormones on lung inflammation after brain death ‐ an experimental study

et al. 2019

Self Cite

View full text Add to dashboard Cite

Summary Organ donor's age negatively influences graft survival of organs, increasing risk of complications. Aging occurs in both men and women; however, the menopause marks a decrease in sex hormones and a sudden increase in the process of vascular aging. We investigated sex hormones' influence on the lung inflammatory process induced by BD in female rats. Wistar rats were grouped as: female rats from high estradiol to heat period (non‐OVx) and ovariectomized (OVx) female rats. Ovariectomy was carried out 10 days before BD. BD was induced using intracranial balloon rapid inflation. Serum hormones and inflammatory mediators were quantified, leukocytes and platelets counted and lung samples were collected for RT‐PCR, immunohistochemical, and histological analysis. Female sex hormones and corticosterone were reduced 6 h after BD in non‐OVx group. The infiltration of leukocytes in female non‐OVx lungs was higher compared to OVx. G‐CSF, VEGF, and CINC‐1 were found increased in non‐OVx group serum in comparison to OVx. Lung mediators were increased in non‐OVx rats compared to controls. The acute reduction of sex hormones induced by BD appears to have a worse effect on lung inflammation than a reduction that has happened over a prolonged period of time, allowing a physiological adaptation prior to BD.

show abstract

“…It is important to consider that platelet activity may be negatively modulated by substances such as NO which is released by several cells [29]. As mentioned earlier, female rats present a higher inflammatory response after BD and higher iNOS and eNOS expression than male rats [12,13]. Srihirun et al [30] showed that there is an inverse correlation between nitrite levels in the blood and ADP-induced platelet aggregation.…”

Section: Discussionmentioning

confidence: 99%

“…Along with hypoperfusion, BD leads to the activation of the inflammatory pathways and reduction in hormone synthesis and release [9,13]. BD‐generated inflammatory response is higher in female animals, occurring in parallel with the acute reduction in female sex hormone concentration [12,13].…”

Section: Discussionmentioning

confidence: 99%

Sex differences in the coagulation process and microvascular perfusion induced by brain death in rats

et al. 2020

Self Cite

View full text Add to dashboard Cite

Summary Brain death (BD) leads to a systemic inflammation associated with the activation of coagulation, which could be related to decreased microcirculatory perfusion. Evidence shows that females exhibit higher platelet aggregability than males. Thus, we investigated sex differences in platelets, coagulation and microcirculatory compromise after BD. BD was induced in male and female (proestrus) Wistar rats. After 3 h, we evaluated: (i) intravital microscopy to evaluate mesenteric perfusion and leucocyte infiltration; (ii) platelet aggregation assay; (iii) rotational thromboelastometry; and (iv) Serum NOx‐. Female rats maintained the mesenteric perfusion, whereas male reduced percentage of perfused vessels. Male BD presented higher platelet aggregation than the controls. In contrast, female BD had lower platelet aggregation than the control. Thromboelastometry indicated a reduction in clot firmness with increased clotting time in the female group compared with the male group. Serum NOx‐ level in female BD was higher than that in the male BD and female control. There is sex dimorphism in platelet function and clotting process, which are altered in different ways by BD. Thus, it is possible to connect the reduction in microcirculatory perfusion in males to intravascular microthrombi formation and the maintenance of perfusion in females to a higher inflammatory response and NO synthesis.

show abstract

Sex-related differences in lung inflammation after brain death

Cited by 14 publications

References 35 publications

Donor pretreatment with nebulized complement C3a receptor antagonist mitigates brain-death induced immunological injury post–lung transplant

Donor pretreatment with nebulized complement C3a receptor antagonist mitigates brain-death induced immunological injury post–lung transplant

The influence of female sex hormones on lung inflammation after brain death ‐ an experimental study

Sex differences in the coagulation process and microvascular perfusion induced by brain death in rats

Contact Info

Product

Resources

About