History of Cardioplegia in a Nutshell
Rapid cardiac arrest before cardiac surgery, and therefore the concept
of cardioplegia, with a hyperkalaemic solution was introduced by Melrose
et al. in 1955, and it enabled better post-ischaemic recovery of
myocardial function compared to mere aortic cross
clamping(3). However, it also led
to [Ca2+]I overload, and Hearse et
al. found that myocardial damage was related to ATP depletion along with
this
[Ca2+]I overload(4). Hence,
Hearse proposed three components of myocardial protection by
cardioplegia during cardiac surgery: (a) rapid diastolic cardiac arrest
to conserve energy by [Na+]I and
[Ca2+]I depletion, extracellular
K+ and Mg2+ elevation and infusion
of local anaesthetic agents or Ca2+ antagonists, (b)
hypothermia to slow down cellular metabolic demands, and (c) application
of substances (i.e. oxygen, energy substrates etc.) to prevent or
reverse IR injury(5). These principles now form the
foundation for most cardioplegic solutions.
Bretschneider et al. developed Custodiol, an intracellular crystalloid
cardioplegic solution which is Ca2+-free with a low
Na+ concentration to reduce the
Na+ gradient causing the loss of action potential
(AP) and consequently inducing cardiac arrest(6). In
comparison, Hearse introduced an optimal extracellular crystalloid
cardioplegic solution, called the St. Thomas’ Hospital solution, which
mainly relies on depolarised hyperkalemic (16mM) arrest. In addition,
Lolley et al. developed glucose cardioplegic solutions containing
insulin and K+ to enhance ATP production during I-R,
which was later found to reduce myocardial injuries in animal models of
I-R(7).
Cold blood cardioplegia was proposed by Buckberg et al. to arrest,
perfuse then reperfuse the myocardium with different compositions
of hyperkalaemic crystalloid cardioplegic solution mixed with blood in a
1:4 ratio(8). Calafiore et al. later introduced warm
blood cardioplegia containing
K+/Mg2+ which provides myocardial
protection when applied continuously(9).
Cardioplegic delivery can be anterograde, retrograde or combined.
Anterograde delivery involves running the cardioplegia solution down the
coronary arteries and supplying the myocardium in the same fashion that
blood normally does. In retrograde cardioplegia however, the flow of
solution is administered in a retrograde manner, and it is indicated in
cases such as critical coronary stenosis or when anterograde delivery
does not provide sufficient cardioplegic solution to the myocardium
distal to the occlusion(10). Despite the extensive
study of cardioplegia solutions over the last decades
(Fig.1 ), the ideal myocardial protection method during
cardiac surgery is still uncertain.