Brain death effects on lung microvasculature in an experimental model of lung donor

Abstract

Objective: Brain death (BD) triggers important hemodynamic and inflammatory alterations, compromising the viability of organs suitable for transplantation. To better understand the microcirculatory alterations in donor lungs caused by BD. The present study investigated the pulmonary microcirculation in a rodent model of BD via intravital microscopy. Methods: Male Wistar rats were anaesthetized and mechanically ventilated. They were trepanned and BD was induced through the increase in intracranial pressure. As control group, sham-operated (SH) rats were trepanned only. In both groups, expiratory O 2 and CO 2 were monitored and after three hours, a thoracotomy was performed, and a window was created to observe the lung surface using an epi-fluorescence intravital microscopy. Lung expression of intercellular adhesion molecule (ICAM)-1 and endothelial nitric oxide synthase (eNOS) was evaluated by immunohistochemistry, and cytokines were measured in lung samples. Results: Three hours after the surgical procedures, pulmonary perfusion was 73% in the SH group. On the other hand, BD animals showed an important decrease in organ perfusion to 28% (p = 0.036). Lung microcirculatory compromise after BD induction was associated with an augmentation of the number of leukocytes recruited to lung tissue, and with a reduction in eNOS expression and an increase in ICAM-1 expression on lung endothelial cells. BD rats showed higher values of expiratory O 2 and lower values of CO 2 in comparison with SH animals after three hours of monitoring. Conclusion: Data presented showed that BD triggers an important hypoperfusion and inflammation in the lungs, compromising the donor pulmonary microcirculation.

Tacrolimus Prevents Mechanical and Humoral Alterations in Brain Death–induced Lung Injury in Pigs

“…Hemodynamic and inflammatory alterations after brain death contribute to vascular endothelial dysfunction (39). Here, we showed decreased endothelial Tie2 receptor in the lung and increased concentrations of glycocalyx components in serum, strongly suggesting endothelial injury after brain death.…”

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

“…We used an investigation time of 3 h, which is usually the standard time for microcirculatory studies in this model [10,12]. However, the coagulation phenomenon is installed immediately after BD induction and the perfusion compromise is maintained [11]. Although the evaluation of the female rats only on the proestrus phase of the cycle (higher estradiol concentration) could be seen as a limitation, this approach allowed us to focus on estradiol effects in coagulation.…”

“…Previous studies have pointed to microcirculatory changes in male rats subjected to BD, suggesting that hypoperfusion could reduce the viability of various organs [5–11]. In female rats, the initially high estradiol concentration before BD and elevated expression of eNOS seemed to favour the maintenance of microvascular perfusion/flow [12].…”

Avaliação funcional e inflamatória de pulmões submetidos ao tratamento com solução salina hipertônica em modelo de morte encefálica

“…Na análise do LBA, não observamos efeito da SSH entre os grupos, por outro lado, no tecido pulmonar, notamos expressivo aumento dos níveis de TNF-α no grupo ME, corroborando com os resultados encontrados por Nepomuceno e colaboradores, que demonstraram redução dos valores de TNF-α no tecido pulmonar, utilizando como tratamento a SSH em modelo de doador para transplante com choque hemorrágico42 . Outro estudo recentemente publicado e com metodologia semelhante à utilizada neste trabalho, mostrou níveis de TNFα aumentados no tecido pulmonar no grupo submetido à ME, sugerindo que determinados processos inflamatórios observados sejam desencadeados por traumas correlacionados à própria ME85 . Neste cenário, Mitra e colaboradores, através de estudo "in vitro" por meio de cultura celular, utilizando combinação de citocinas pró-inflamatórias TNF-α, IL-1β e IFN-γ em meio contendo SSH, demonstraram o efeito benéfico da SSH e seu protagonismo em atenuar a resposta pró-inflamatória, diminuindo a expressão das citocinas avaliadas86 .…”