Thyroid hormone: relevance to xenotransplantation

Abstract

Background It has been well-documented that the level of serum/plasma free triiodothyronine (fT3) falls rapidly following brain death or during certain surgical procedures, e.g., heart surgery carried out on cardiopulmonary bypass. The level in patients following cardiopulmonary bypass usually recovers within 2 days. Methods We have measured serum fT3 in healthy naïve baboons (n=31), healthy naïve monkeys (n=5), and after pig-to-baboon heterotopic heart xenotransplantation (xenoTx) (Group1, n=9), orthotopic liver xenoTx (Group2, n=10), artery patch xenoTx (Group3, n=9), and in monkey-to-monkey heterotopic heart alloTx (Group4, n=5). Results The mean level of fT3 in healthy naïve baboons was 3.1±0.9pg/mL and in healthy naïve monkeys was 2.6±0.3pg/mL. Following pig heart, liver, and artery patch xenoTx and monkey heart alloTx, there was an immediate rapid fall in fT3 level. Recovery of fT3 was more rapid in Groups 3 and 4 than in Groups 1 and 2. In Group1, within 4 days fT3 had recovered, but only to the lower limit of normal range, where it remained throughout follow-up (for up to 42 days). In Group2, no recovery was seen during the 7 days of follow-up. In immunosuppressed baboons with pig patch grafts that received IL-6R blockade (n=2), the fT3 tended to rise higher than in those that received no IL-6R blockade (n=6). Conclusions Following operative procedures, there is a dramatic fall in serum fT3 levels. The persistent low level of fT3 after pig heart and liver xenoTx may be associated with a continuing inflammatory state. We suggest consideration should be given to the replacement of T3 therapy to maintain normal fT3 levels, particularly in nonhuman primates undergoing orthotopic pig heart or liver xenoTx.

Immunological and physiological observations in baboons with life‐supporting genetically engineered pig kidney grafts

“…In contrast, when consumptive coagulopathy was developing in the GroupB recipients, almost no recovery of fT3 was observed, which is consistent with our previous observations. 28 We suggest that D-dimer may also be an indicator of an inflammatory response rather than of a consumptive coagulopathy. 23,25 Variable, but slightly higher than normal D-dimer levels were observed in the long-surviving recipients in GroupA ( Figure 2F).…”

Life‐supporting porcine cardiac xenotransplantation: The Munich study

“…6,7 The much simpler technique of cold static cardioplegia (which would prove advantageous when it becomes possible to transport pig hearts over relatively long distances) may be equally successful if T3 is administered to the recipient before and after graft reperfusion. We have observed significant reductions in plasma free T3 in baboons following either pig heterotopic heart or life-supporting kidney transplantation, 8 which we attribute in part to the systemic inflammatory response that occurs after xenotransplantation, 9,10 and we have documented improved graft function and recipient recovery when T3 has been administered.…”

Xenotransplantation

“…Ezzelarab et al showed that systemic inflammation in xenograft recipients precedes activation of coagulation [66]. Iwase et al measured serum free triiodothyronine (thyroid hormone) as a marker of inflammation in healthy naïve baboons, healthy naïve monkeys, and after pig-to-baboon heterotopic heart xenotransplantation, orthotopic liver xenotransplantation, artery patch xenotransplantation, and in monkey heterotopic heart allotransplantation [67]. They showed that there is a dramatic fall in serum thyroid hormone levels following operative procedures.…”

“…They showed that there is a dramatic fall in serum thyroid hormone levels following operative procedures. A persistent low level of thyroid hormone after pig heart and liver xenotransplantation may be associated with a continuing inflammatory state, which might be corrected with extraneous replacement of thyroid hormone [67]. Other inflammatory states and markers, particularly of extracellular histones, have been discussed with their potential therapeutic regulation in xenotransplantation [68,69].…”