Comparison of the Effects of Adenosine, Inosine, and Their Combination as an Adjunct to Reperfusion in the Treatment of Acute Myocardial Infarction

Abstract

Adenosine and inosine are both key intracellular energy substrates for nucleotide synthesis by salvage pathways, especially during ischemic stress conditions. Additionally they both possess cell protective and cell repair properties. The objective of this study is to detect potential advantages of the combination of adenosine and inosine versus each drug alone, in terms of ventricular function, infarct size reduction and angiogenesis. Myocardial ischemia was created in rodents and treated with adenosine, inosine or their combination. Results of experiments showed that the combination of both drugs significantly reduced infarct size and improved myocardial angiogenesis and ventricular function. The two compounds, while chemically similar, use different intracellular pathways, allowing for complementary biological activities without overlapping. The drug combination at specific 1 : 5 adenosine : inosine dose ratio demonstrated positive cardiologic effects, deserving further evaluation as an adjunct to reperfusion techniques during and after acute coronary syndrome. The association of adenosine and inosine may contribute to reduce myocardial infarction morbidity and mortality rates.

Metabolomic analysis of serum and myocardium in compensated heart failure after myocardial infarction

“…Our findings of increased inosine levels may suggest a metabolic shift towards energy repletion in the face of oxidative stress [26,69]. Inosine can increase energy production through the hypoxanthine-IMP-AMP pathway or through the anaerobic pentose pathway (ribose1P) [61]. An anti-inflammatory role for inosine has also been reported [11,30].…”

Capillary pericytes mediate coronary no-reflow after myocardial ischaemia

“…Control animals received vehicle (saline) infusion. For comparison, in cats 0.5 mg/kg/min is approximately the upper limit ( Portellos et al, 1995 ) for restricting the adenosine-induced fall of blood pressure to less than 10%, in rats a cumulative dose of 3 mg/kg reduced infarct size by 31% ( Shafy et al, 2012 ), and in humans infusing 0.07 mg/kg/min for 3 hr during reperfusion (a cumulative dose of 12.6 mg/kg) reduced infarct size by 57% in the AMISTAD-II trial ( Ross et al, 2005 ), although the REFLO-STEMI trial found no beneficial effect of adenosine ( Nazir et al, 2016 ).…”

An Untargeted Metabolomic Analysis of Lacticaseibacillus (L.) rhamnosus, Lactobacillus (L.) acidophilus, Lactiplantibacillus (L.) plantarum and Limosilactobacillus (L.) reuteri Reveals an Upregulated Production of Inosine from L. rhamnosus

“…Interestingly, this molecule has also a well-known biological role. Indeed, inosine is a key intracellular energy substrate for nucleotide synthesis by salvage pathways and it possesses cell protective activity and cell repair properties [16].…”