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Singh et al. Myocardial protection in cardiac transplantation

Table 3: Modified Maastricht Classification of DCD [76] was performed at Papworth Hospital [80] . While it is
Classification Descriptions quoted that this may potentially increase the donor pool
I Dead on arrival and have not been resuscitated by about 25% in the UK alone, several ethical issues
II Unsuccessfully resuscitated arise from DCD heart procurement. These include the
III Typical controlled DCD, with planned cardiac definition of death. While the needs and feelings of
arrest the donors and their families are noted, organ viability
IV Planned DBD that suddenly arrest during or should be maintained and maximized. Organ donation
after the brain death determination [81]
DCD: donor after circulatory death; DBD: donations following brain in itself should not be the reason for donor death .
death
Another point noted by the Australian group was the
by the Maastricht group [Table 3] [76] . potential use of OCS for resuscitating marginal donors.
An estimated 60% of hearts offered are rejected for
Of these, type I, II and IV are regarded uncontrolled transplantation and the introduction of OCS may
DCD. For these donors, cardiopulmonary resuscitation therefore on paper at least, increase the number of
is typically conducted until organ recovery procedures suitable organs [82] .
are employed.
HORMONAL THERAPY
Iyer et al. [77] conducted a porcine orthotopic heart
transplant using a DCD asphyxia model. Following 30 min As alluded to, the increasing recipient waiting list
of warm ischaemia, the hearts were allocated to has led to the recruitment of so-called “marginal”
either OCS preservation of SOC with Celsior solution. donors. Brain death usually succeeds a period of
Following preservation, the OCS group demonstrated variable intracranial pressure in which the term
acceptable lactate profiles and all hearts out of this “coning” is often used. The classic Cushing’s reflex
group were successfully transplanted whereas none
of the hearts in the SOC group could be weaned off of increased blood pressure and reduced heart rate
bypass. is often discernible through monitoring and can lead
to deleterious effects on multiple organ systems if

Dhital et al. [78] then piloted the first case series of not managed appropriately. There is a compensatory
Maastrict group III DCD cardiac transplants at St arterial hypertension and bradycardia (Cushing’s
Vincent’s Hospital (Australia) using the OCS. The reflex) that is followed by sympathetic stimulation with
3 recipients (2 men and 1 woman; mean age 52 vasoconstriction, raised systemic vascular resistance
years) received the transplants. After periods of and tachycardia (a triad called the catecholamine
warm ischaemia < 30 min, ex-vivo perfusion was storm) [83] . There is a redistribution of blood volume that
done with the OCS device to resuscitate, assess, prompts visceral ischaemia and in one study, revealed
and transport the donor hearts. Of these patients, 1 that myocardial injury occurs in 20-25% of DBD
required mechanical circulatory support for 72 h post- donors [84] , with echocardiographic imaging of cardiac
operatively, with all 3 patients showing normal cardiac dysfunction evident in up to 40% of DBD donors [85] .
function within a week post-transplantation. Follow up Following this catecholamine storm phenomena, there
data shows patients are still making a good recovery is a profound hypotension that results from a reduction
at 176, 91, and 77 days after transplantation.The in sympathetic tone and peripheral vasodilation
cohort included a fourth donor, a trauma victim, who causing mass hypoperfusion of all organs, potentially
was excluded as the warm ischaemic time was > 30 resulting in more organ dysfunction [86] .
min (which did not meet the inclusion criteria).
Cooper et al. [87] and Novitzky et al. [88] noted that
DCD donation however was not pioneered by this group. several animal model studies carried out in South
In fact the first ever cardiac transplant by Barnard was Africa in the 1980s demonstrated the catecholamine
a DCD heart. Boucek et al. [79] highlighted the first case storm phenomena followed by profound hypotension
series of DCD donations in the paediatric population occurred with reduction in cortisol, insulin, thyroid, and
owing to the higher waiting list mortality compared to antidiuretic hormone levels, a switch from aerobic to
adults. They successfully performed 3 transplants in anaerobic metabolism and increases in inflammation
the paediatric population and found no late deaths (3.5 markers and cytokines. Hormonal replacement
years post-operatively) with functional and immunologic resulted in recovery of cardiac function in both
outcomes similar to those of controls. experimental animals and humans, thus protecting
the donor organs. Registry multivariate studies
In March 2015, the first DCD heart transplant in Europe on hormonal treatment of brain-dead donors also

220 Vessel Plus ¦ Volume 1 ¦ December 28, 2017