Research Article: Characterization of the intestinal graft in a swine hypotensive after brain death model1

Date Published: January 10, 2020

Publisher: Sociedade Brasileira para o Desenvolvimento da Pesquisa em

Author(s): Linlin Li, Ying Gao, Chunlei Lu, Mingxiao Guo.


To establish a hypotensive brain death pig model and observe the effects of
hypotension on small bowel donors.

The hypotensive brain death model was produced using the modified
intracranial water sac inflation method in ten domestic crossbred pigs.
Effects of hypotensive brain death on small bowel tissue morphology were
evaluated through changes in intestinal tissue pathology, tight junction
protein of the intestinal mucosa and plasma intestinal fatty acid-binding
protein (i-FABP) levels. The pathophysiological mechanism was examined based
on changes in superior mesenteric artery (SMA) blood flow and systemic

After model establishment, SMA blood flow, and the mean arterial pressure
(MAP) significantly decreased, while heart rate increased rapidly and
fluctuated significantly. Small bowel tissue morphology and levels of tight
junction protein of the intestinal mucosa showed that after model
establishment, small bowel tissue injury was gradually aggravated over time
(P<0.05). Plasma i-FABP levels significantly increased after brain death (P<0.05). A hypotensive brain death pig model was successfully established using an improved intracranial water sac inflation method. This method offers a possibility of describing the injury mechanisms more clearly during and after brain death.

Partial Text

Intestinal transplantation (ITx) has become an effective treatment for various
irreversible intestinal failures. However, the number of patients on the waiting
list for small bowel transplantation is larger than the number of available
intestinal donors1. Currently, most small bowel transplantations are from deceased donors
(DDs), while a few come from living donors (LDs)2,3. Nevertheless, cardiac death donors (DCDs) inevitably suffer a period of
warm ischemia before organ donation, which attenuated the graft activity and
clinical success of ITx. Therefore, donors after brain death (DBDs) are an ideal
donor source. However, a series of pathophysiological changes produced by brain
death, especially brain death coupled with circulation instability and extended
hypotension, affect the intestinal quality of DBDs. Poor-quality organs
significantly affect the survival rate and function of transplant organs4,5. The pathophysiological mechanism of the effect of hypotensive brain death
on donor bowels has not been fully elucidated.

The animals were treated humanely by use of protocols that were approved by the
Institutional Animal Use and Care Committee of Linyi People’s Hospital. All
procedures were carried out in accordance with “Principles of laboratory animal
care” (NIH publication No. 85-23, revised in 1985). Ten domestic crossbred pigs of
both sexes, weighing 20-25 kg, were used in the study after a 5- to 7-day
acclimatization. Food and water were provided ad libitum.

Two of the ten animals died from cerebral hemorrhage. The remaining eight animals
completed the establishment of a hypotensive brain death model and survived until
the end of the study.

Intestinal transplantation is an effective treatment for various irreversible
intestinal failures1. DBDs are one of the sources of organs for intestinal transplantation in
most countries3. However, despite progressive improvement in immunosuppression, both the
short- and long-term success rates for transplantation remain substantially inferior
to solid organ, which may be related to the sensitivity of small intestine to
ischemia. Therefore, establishment of a stable, reproducible, and hypotensive animal
model of DBDs is important to understand the effect of brain death on intestinal
donor quality.

A hypotensive brain death pig model was successfully established using an improved
intracranial water sac inflation method. Gut injury was found to be progressively
aggravated under a state of hypotensive brain death. Therefore, it offers the
possibility to describe the injury mechanisms during and after BD, allowing
evaluation of new strategies to ameliorate intestinal quality and patient survival
after intestinal transplantation.




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