Abrogating myocardial reperfusion injury: novel pharmacological design of a strategy based on antioxidant combination. Data and R code

The main goal of the treatment for acute myocardial infarction is to achieve reperfusion of the affected myocardial tissue, with percutaneous coronary angioplasty being the gold standard procedure. However, this strategy has been associated with an additional heart damage named “lethal reperfusion injury,” which is responsible for up to half of the final infarct size. Among the possible underlying mechanisms that are likely to explain this damage, studies suggest that oxidative stress plays a key role. Although this has not been translated into clinical benefits in most studies, recent preclinical studies reported promising results and a possible synergy with the combined use of vitamin C (VC), N-acetylcysteine (NAC) and deferoxamine (DFO). However, to implement a combined therapy with these drugs for patients requires further studies to understand their pharmacokinetic properties. Available data of the clinical trials have not been validated by overlooking the pharmacokinetics in their design. Therefore, this article presents an update and comparison of the evidence for the efficacy of these administration schemes for each drug in cardioprotection, their pharmacokinetic properties and mechanisms of action for their use against “lethal reperfusion injury.” To achieve a cardioprotective effect by a new pharmacological strategy before the onset of reperfusion, it is helpful to consider pharmacokinetics of each drug. In this regard, to design a fast and short pharmacologic therapeutic strategy, theoretically, VC and DFO concentrations could be modeled by a one-compartment model whereas NAC could be modeled by a three-compartment model with an initial short half-life. 

The pdf file (Data and R code v2.pdf) describes and explains the R code (VC_NAC_DFO.R). The R code imports data from the csv files