Page 231 - Read Online

Singh et al. Myocardial protection in cardiac transplantation

of loading conditions, endothelial dysfunction and to the control group and the all-cause mortality was
impairment of coronary blood flow [126] . assessed over 1.54 (SD 1.22) years and was lower with
remote ischaemic preconditioning than without (ratio
Nicolas-Robin et al. [127] looked at GKI infusion in 0.27, 95% CI 0.08-0.98, P = 0.046) [137] . Hong et al. [140]
comparison to dobutamine for in DBD donors. They however failed to demonstrate any difference between
found that a GKI infusion significantly improved the the groups but it should be noted that he included RIC
systolic dysfunction comparably to dobutamine without with PostC in 1280 patients and had a much broader
its inherent side effects of peripheral vasodilation, composite of outcomes. Hong’s group also failed to
potential arrhythmogenesis, and tachycardia. This was record any biomarkers, limiting the end-points to solely
thought to be possibly due to an adaptive hibernating clinical outcomes.
state of the myocardium to reduce myocardial oxygen
demand, thereby allowing a longer period of ischaemia Sachdeva et al. [141] noted no subsequent benefit in both
without necrosis [128] . Hence the rationale behind GKI remote preconditioning and postconditioning alone
infusion is by replenishing the energy supply of the or in combination and observed that they failed to
failing heart, by switching metabolism from oxidation attenuate infarct size in an anesthetized rat model with
of fatty acids (glycogenolysis) to oxidation of glucose myocardial infarction. There was also no recovery of
(glycolysis) and lactate [129] . This allows restoration of LV dysfunction induced by ischemia-reperfusion injury.
calcium homeostasis and replenishment of glycogen
stores by increasing the rate of ATP [130] . Although GKI However, the recently concluded randomized
was not shown to improve mortality in acute myocardial LipsiaConditioning [142] trial studied the effects of RIC
infarction as mentioned above, there may be a role for and PostC revealed conflicting evidence to this. Using
it in the ischaemic myocardium. cardiac magnetic resonance to quantify myocardial
injury, they showed that combined intra-hospital RIC
Cottin et al. [131] demonstrated that their cohort of patients and PostC significantly increases myocardial salvage
with heart failure (Ejection Fraction < 45%), GKI infusion when compared with conventional PCI, whereas PostC
reduced Wall Motion Score Index and increased alone failed to demonstrate a cardioprotective effect in
ejection fraction significantly in their small study. Similar STEMI patients undergoing primary PCI.
findings were noted in several other studies, including a
reduction in BNP concentrations [132-135] . Another article by Pichot et al. [143] however revealed

PostC had a significant effect in reducing myocardial
ISCHAEMIC CONDITIONING injury independently of traditional cardiovascular risk
factors in patients with STEMI.
Reperfusion injury is postulated to be a key
contributing factor for primary graft dysfunction, thus Ischaemic conditioning has garnered a lot of interest in
the role of ischaemic conditioning whilst still in its recent times with almost 500 articles published every
trialling phase may be of benefit. The lack of evidence year, and 53 clinical trials (phase I to IV) available
of benefit in large scale studies such as RIPheart [136] on PubMed. Of these 37 clinical trials are specific
and ERICCA [137] clarified that this intervention does not to cardiac surgery alone [144] . A lot of the RIC data in
confer any benefits to patients undergoing CABG. other studies have focused on biomarkers of cardiac
injury and not outcomes, which were the endpoints for
Animal models have shown potential benefits and both RIPheart and ERICCA. To date, no adequately
cardioprotective mechanisms, but while biochemical powered and randomised trial has looked at the effect
improvements were noted by the ERICCA trial of RIC and PostC in transplantation, and given the
(reduced troponin levels), its relevance remains to be recent findings of large trials in CABGs, an adequately
seen. Remote ischaemic preconditioning (RIC) and powered trial in transplant cannot be justified. The
remote ischaemic post conditioning (PostC) work negative results have generated more discussion and
on the premise that brief episodes of ischemia and questions with better discourse into methodology. For
reperfusion to the remote organ protect the heart by example, in Kottenberg et al. [145] ’s study, propofol was
a paracrine or neural-reflex mechanism while avoiding a potential confounding factor. Propofol interferes with
additional stress on the heart itself [138] . the activation of the signal transducer and activator
of transcription 5 (STAT5) pathway. A recent study
Thielmann et al. [139] conducted the first single centre by Kleinbongard et al. [146] looking at confounders that
randomised, double blind controlled trial of RIC in 329 may affect the efficacy of RIC found that patients
patients from 2008-2012. They found a significantly with an aortic cross-clamp time of < 56 min had no
lower troponin level (cTnI) in the RIC group compared protection by RIC whereas there was solid protection

224 Vessel Plus ¦ Volume 1 ¦ December 28, 2017