Sodium thiosulfate mediated cardioprotection against myocardial ischemia-reperfusion injury is defunct in rat heart with co-morbidity of vascular calcification.

Sodium thiosulfate (STS) has shown promising effects in amelioration of myocardial ischemia-reperfusion injury (IR) in a rat model and is clinically useful in the treatment of chronic kidney disease (CKD) associated calciphylaxis. As the prevalence of cardiac complications is higher in CKD, we tested the effectiveness of STS in a rat model of adenine-induced vascular calcification and subjected the heart to IR. We observed an increased infarct size (29%) by TTC staining, lactate dehydrogenase (54%) and creatine kinase (32%) release in the coronary perfusate and altered hemodynamics compared to a normal rat treated with STS and subjected to IR. As functional mitochondria are essential for preserving heart from the detrimental effects of IR, we found that calcification induced mitochondrial dysfunction (reduced RCR->80%, P/O ratio->30%, ΔΨ->10% and swelling- 27%), could not be restored efficiently by STS treatment. Therefore we used nicorandil (mitochondrial potassium channel opener) along with STS as a combination therapy to treat the diseased heart and found an improvement in cardioprotection against IR injury, compared to STS alone. Upon evaluating these hearts, we found that both the cardiac mitochondria namely interfibrillar and subsarcolemmal were functionally well preserved.