Brain-dead Pigs Research Articles

Glucose-insulin-potassium (GIK) prevents derangement of myocardial metabolism in brain-dead pigs

Brain death is associated with neuroendocrine changes resulting in reduced myocardial glycogen content. The purpose of this study was to investigate the effects of glucose-insulin-potassium (GIK), on myocardial metabolism in brain-dead pigs. Sixteen brain-dead pigs were given GIK infusion (n = 8), or Ringer solution (n = 8). At end-point (7 h post brain death) arterial concentrations and myocardial arteriovenous (a-v) concentration differences of glucose, lactate and free fatty acids (FFA) were assessed, and myocardial biopsy specimens were taken from the right atrium and left ventricle. Biopsies were also taken from five normal pigs. Myocardial glycogen content in the GIK group was significantly higher compared to the control group, but comparable to the non-brain-dead animals. There was a higher and significant myocardial uptake of glucose and lactate in the GIK group compared to the controls. Plasma levels of FFA were significantly lower in the GIK group, and the myocardial uptake of FFA was 5 times higher in the control group compared to the GIK group. There were no significant differences in hemodynamic variables among the groups. In conclusion, intravenous supply of GIK to brain-dead pigs results in increased myocardial glycogen content and seems to prevent abnormal myocardial metabolism, which may have clinical implications for the myocardial protection of donor hearts.

The influence of thyroid hormone replacement in a porcine brain death model.

This study was conducted to determine whether the administration of tri-iodothyronine (T3) to brain-dead donor pigs would improve hemodynamic instability, serum levels of thyroid hormones, or the outcome of transplantation of donor livers. Brain death was caused in young pigs (25-38 kg) by rapid inflation of an intracranially implanted balloon catheter. The animals were maintained on a ventilator and frequent measurements of acid/base balance, electrolytes, and glucose were made. At the end of 16 hr, livers were removed and implanted into prepared recipients. Serum-free tri-iodothyronine fell to zero at the end of 16 hr, and there was a 4-6-fold decline in free thyroxine (T4). The levels of serum reverse T3 (rT3) however, increased up to 6-fold. In animals treated with tri-iodothyronine 2 micrograms/hr, the serum levels of free T3 and T4 were not changed but the levels of serum reverse T3 (rT3) increased further. There were no apparent correlations between any hemodynamic parameter and serum thyroid hormone levels in the donors. After the liver transplants, recipients could be divided into those that survived longer than 6 days and those that did not. Although there were significant differences in the plasma levels of alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase, there was no correlation between survival and whether the donor had received tri-iodothyronine. Although other hormones, including insulin and cortisol, may also be necessary, there is no indication from these studies that the administration of tri-iodothyronine to brain-dead donors of liver grafts benefits the serum hormone levels in the donors or the subsequent survival of the recipients.

Improved cardiac function following hormonal therapy in brain dead pigs: Relevance to organ donation

Deterioration of function in brain dead baboons is associated with depletion of both myocardial energy stores and certain circulating hormones, notably thyroxine, cortisol, and insulin. We have therefore investigated the effect of the administration of these three hormones to the brain dead pig; their value has been assessed on both the freshly excised and stored donor heart. Brain death was induced by ligation of the two arteries to the upper part of the body which arise from the aortic arch. Storage of selected hearts was by continuous hypothermic perfusion for 20 to 24 hr. Hearts were biopsied for estimation of adenosine triphosphate, creatine phosphate, lactate, and glycogen, and were subsequently functionally tested. Six groups of pigs were studied. Hearts were tested from control pigs which had not undergone brain death (A1), from brain dead pigs which had received intravenous fluid and inotropic support for 4 hr (B1), and from brain dead pigs which had in addition received 2 hr of hormonal therapy (thyroxine 2 μg cortisol 100 mg, and insulin 5–10 IU hourly) (C1). A further 3 groups (A2-C2) underwent management identical to A1-C1, but in addition the hearts were stored for 24 hr. Brain death in pigs was followed by a consumption of myocardial energy stores, despite anaerobic glycolysis; this was associated with reduced myocardial function. The administration of hormones to the brain dead pig led to some replenishment of myocardial energy and glycogen reserves and reduction in lactate, with associated improvement in hemodynamic function. A period of hypothermic perfusion storage appeared to reverse the anaerobic metabolism occurring in the heart in the nonhormonally treated brain dead animal, though not in the hormonally treated animal, and led to replenishment of glycogen reserves in nontreated animals. The observation that both better function and an increase in myocardial energy stores occurred in hormonally treated, stored hearts, even though perfusate lactate dehydrogenase rose to significantly higher levels during hypothermic perfusion storage, and tissue lactate levels remained high, suggests that thyroxine promotes both aerobic and anaerobic metabolism in brain dead animals.

The effects of brain death and 24 hours’ storage by hypothermic perfusion on donor heart function in the pig

The effects on the myocardium of the agonal period and subsequent management have been studied in the pig. Acute ischemia of the brain led to major temporary hemodynamic changes. Brain death, with or without hemodynamic support of the circulation, led to a significant reduction in subsequent myocardial function, associated with some depletion of the myocardial high-energy phosphate and glycogen reserves, although the rate of this depletion was reduced by anaerobic glycolysis. Although 24 hours' storage by continuous hypothermic perfusion of hearts taken from control animals led to only a minimal reduction in myocardial function, storage increased the reduction in function associated with brain death when intravenous fluid and dobutamine support had been given to maintain the brain dead pig in a normotensive state. Storage, however, reduced the anaerobic metabolism seen in hearts functioning in hypotensive brain dead pigs and led to replenishment of the glycogen stores.