Evaluation of the cardioprotective effect of remote ischaemicpreconditioning in acute coronary syndrome patients and its correlation with vitamin D

Acute coronary syndrome (ACS) is an emergency condition where timely reperfusion therapy would

help to save the infarct size. Remote ischemic preconditioning (RIPC) has been put forward as a

promising cardioprotective strategy for patients with ischemic heart disease (IHD) that involves the

induction of brief and intermittent cycles of ischemia and reperfusion in a distant organ (Pryds et al.,

2019). Different endogenous substances like adenosine, bradykinin and calcitonin gene-related peptide

(CGRP) which have been reported to produce cardioprotection during I/R injury are released during

preconditioning (Hausenloy DJ et al. 2008). The substances generated in the remote organ during RIPC may pass via the blood and upon reaching the myocardium activate intracellular signalling pathways.

These may include adenosine, erythropoietin, MicroRNAs, Nitrite, CGRP, apolipoprotein A1, amino

acids, glucagon-like peptide and extracellular vesicles (Billah et al., 2019). Several clinical reports have

revealed that RIPC (prior, during, or following myocardial reperfusion) can reduce the myocardial

infarct size, increase myocardial salvage, and prevent clinical adverse events happening in patients

(Stiermaier et al., 2019). In India studies done by Sundeep et al., 2015 have shown that RIPC, leads to

a significant reduction in the incidence of PCI-related MI. Another study by Suresh et al., 2020 have

shown that PCI in patients with ACS could provide protection against ischemia-reperfusion injury.

However, the studies related to the cardioprotective effect of RIPC have come up with conflicting

results. In one of the studies , it showed that RIPC did not reduce troponin release, improve

hemodynamics, or enhance organ protection (Rahman et al., 2010). A study conducted by Prasad A et

al. 2013 did not support an adjunctive role for remote IP in low- to moderate-risk patients undergoing

percutaneous coronary intervention (PCI). It had been observed that remote ischemic preconditioning

did not reduce myocardial or kidney injury during cardiac surgery and this type of therapy is unlikely

to substantially improve patient- important outcomes in cardiac surgery (Walsh M et al. 2016).

Vitamin D, on the other hand, is known to be a major cause of IHD and is a prevailing global health

concern. Low vitamin D levels have been linked to an increased risk of myocardial infarction (MI),

stroke, CVD mortality, and heart failure in case-control and other prospective epidemiologic studies

(Kheiri et al., 2018). An I/R injury model was induced by left coronary artery ligation in Sprague-

Dawley rats (in vivo) and Langendorff perfusion of isolated hearts (in vitro). It demonstrates that

vitamin D plays a protective role against myocardial injury by inhibiting inflammation through

repressing the RhoA/ROCK/NF-κB pathway (Qian X et al.2019). It was demonstrated that treatment of

vitamin D markedly improved left ventricular function (LVF) in mice, and reduced plasma level of cTn-

I as a marker of cardiac injury. Moreover, the effects of vitamin D was associated with attenuations in

both chemokine and cytokines expression following I/R, that accompanied by down-regulation of

activation of ERK1-2 pathway (Yousif NG et al.2017). There have been various previous clinical

studies which have shown the protective effect of vitamin D on I/R injury by maintaining the ejection

fraction and limiting the infarct size which may help in decreasing the morbidity and mortality in the

population. Furthermore, it has been reported that vitamin D administration in people suffering from

IHD confers cardioprotection in terms of decreased cardiac injury markers i.e. troponin, CK-MB and

decrease the release of inflammatory markers (IL 6, IL 8, IL 10, IL-33, CRP, interferon (IFN)-γ).

Therefore, here the question arises if vitamin D supplementation shows a protective effect in I/R injury

during coronary intervention; does that mean that vitamin D deficient people are more prone to I/R

injury? Moreover, if preconditioning is given in vitamin D deficient patients will it compromise the

cardioprotective effect of pre-conditioning. Although there is evidence that vitamin D is associated with

heart disease, however, no information is available regarding 25- hydroxyvitamin D3 (Vit D) and remote ischemic preconditioning (RIPC). Furthermore, literature reports that the cardioprotective effect

of preconditioning shows diversity from person to person with some being non-responsive so does that

mean those people would be vitamin D deficient. Therefore, the present study has been designed to

evaluate the cardioprotective effect of remote ischemic preconditioning in ACS patients and correlate

it with serum vitamin D levels.