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Singh et al. Myocardial protection in cardiac transplantation

Novitzky et al. [103] performed one of the pioneering series and retrospective audits. However, it also notes
studies in the role of T3 in transplants. One hundred that of the few randomized controlled trials conducted,
and sixteen consecutive potential donors were treated, the number of patients who were hemodynamically
alongside 70 recipients with good immediate cardiac unstable or marginal in other ways, who would have
function in all but 3 patients, who recovered within 24 h possibly benefited from T3 administration was too small
of mechanical circulatory support. They also conducted to exclude a benefit of thyroid hormone in this subgroup.
2 randomized trials in patients undergoing myocardial A randomized trial by Venkateswaran et al. [108] allocated
revascularization on cardiopulmonary bypass, and 80 donors to four treatment groups; A control group,
administration of post-operative T3 therapy was T3 monotherapy, Methylprednisolone monotherapy,
associated with a reduced need for inotropic support and T3 and Methylprednisolone and placebo. Pulmonary
diuretic therapy in the first study and improved cardiac Artery Catheters were used to guide management,
output in the second study. Chen et al. [104] ’s study on with vasopressin infusion commenced while weaning
rat models suggested that T3 can protect myocytes catecholamines at the commencement of blinded trial
against ischemia-induced apoptosis, which may be medication. The study found no difference in outcomes
mediated by Akt signalling. in patients from all 4 groups. They concluded that
detailed donor haemodynamic measurement and
In a study by Jeevanandam et al. [105] , donor hearts management is possibly the most important criteria
with statistically higher filling pressures, lower EF on in increasing the yield of transplantable hearts. In
echocardiograms, and higher inotrope requirements animal models, administration of T3 was shown to
were resuscitated with T3 and compared to normal improve haemodynamic function before and after
donors not receiving T3. All patients survived the transplantation [108-110] .
immediate post-operative period, and at 1 week and
6 months there were no significant differences in However, this has yet to be seen in prospective
systolic blood pressure, diastolic blood pressure, randomized studies in human donors. The stance
heart rate, cardiac index, central venous pressure, taken by most centres in the UK is to replace T3 only
pulmonary capillary wedge pressure, or LVEF on when there is evidence of thyroid hypofunction.
echocardiography. It should also be noted that the
donors also received furosemide and dopamine, both Antidiuretic hormone (arginine-vasopressin)
increasing renal perfusion thereby being partially Antidiuretic hormone is synthesized by magnicellular
responsible for the fall in pre-load and increased mean neurons at the supraoptic and paraventricular nuclei,
arterial pressure [87] . stored in neurosecretory granules in the axons that
project into the posterior pituitary [111,112] . Given its
Novitzky et al. [106] then conducted a retrospective anatomical location, rising intracranial pressures
review on 63,593 donors (2000-2009) who were from the Cushing reflex as described earlier plays a
administered T3/T4. They noted a 12.8% increment part in the depletion of ADH. Yoshioka et al. [113] first
of organs from T3/T4-treated donors compared to described the role of vasopressin and epinephrine vs.
untreated donors (P < 0.0001). In study 2, a 15.3% epinephrine alone in 16 brain-dead patients improving
increase was noted (P < 0.0001). T3/T4 therapy was mean survival from 1 day to 23 days. The rise in ICP
associated with procurement of significantly greater is a cause for neurogenic diabetes insipidus (DI) which
numbers of hearts, lungs, kidneys, pancreases, is very commonly found (in some studies up to 77%
and intestines, but not livers. Multivariate analysis of solid organ donors [113] ), and hormone replacement
indicated a beneficial effect of T3/T4 independent of with vasopressin, an effective treatment for DI, would
other factors (P < 0.0001) [105] . Apart from Novitzky’s have resolved the haemodynamic instability.
work however, there have been mixed reviews on
the efficacy of T3 administration. A recent systematic Blaine et al. [114] noted that aggressive resuscitation
review conducted by Macdonald et al. [107] noted that with crystalloid solutions may instigate intravascular
all case series and retrospective audits reported a to intracellular fluid shifts thus contribute to the
beneficial effect of thyroid hormone administration development of both interstitial and intracellular oedema,
but all seven randomized controlled trials reported no and ultimately result in profound hypoperfusion of
benefit of thyroid hormone administration either alone end organs causing the rejection of the organs for
or in combination with other hormonal therapies. In transplantation. They conducted their study of an animal
four placebo-controlled trials, administration of thyroid model of a brain-dead organ donor, in which polyuria,
hormone had no significant effect on donor cardiac hypernatremia, and hyperosmolality developed.
index (pooled mean difference, 0.15 L/min/m²; 95% Low-dose (2-10 microU/kg/min) vasopressin was
confidence interval -0.18 to 0.48). They noted that there continuously infused to maintain plasma sodium and
was a lack of consideration of confounding factors in case osmolality within normal range over the course of the
222 Vessel Plus ¦ Volume 1 ¦ December 28, 2017