The extracellular cardiac purine metabolome in sepsis

The total cardiac purine metabolome includes all of the adenine and guanine nucleoside and nucleosides and related molecules involved throughout the intracellular and extracellular compartments and various cell types in the heart. In considering purines as molecules involved in autocrine and paracrine communication, effective interstitial concentrations of the nucleoside adenosine, or purine metabolites, are of greatest interest. These molecules arise from the complex interactions between cardiac-specific cell types, including fibroblasts and myocytes, and noncardiac cells, such as tissue-resident macrophages and other immune cells that have vascular access. In the interstitial environment, adenosine can regulate vascular resistance, contractile function, and immunochemical interactions. The breakdown of purines can produce reactive oxygen species that also influence autocrine and paracrine interactions. A central enzyme in this paradigm, adenosine deaminase, is a pivotal molecule in regulating the balance between pro-inflammatory and anti-inflammatory signaling cascades. A new role for adenosine deaminase as an allosteric regulator of relevant membrane proteins has yet to be explored in the heart.