Early Intracoronary N-Acetylcysteine During Primary PCI in STEMI: A Pilot Randomized Trial of Reperfusion Injury Biomarkers and Functional Recovery

The standard reperfusion strategy for patients with ST-segment elevation myocardial infarction is primary percutaneous coronary intervention. While PPCI restores epicardial coronary blood flow and limits ischemic myocardial injury, the process of reperfusion itself may contribute to additional myocardial damage through myocardial ischemia-reperfusion injury. It is mediated through several interacting mechanisms including generation of reactive oxygen species, lipid peroxidation, inflammatory activation, endothelial dysfunction, mitochondrial injury, calcium overload, and programmed cell death.

N-acetylcysteine is an antioxidant with a thiol group and a glutathione precursor which may have cardioprotective effects in ischemia-reperfusion. NAC may reduce oxidative stress by donating thiols, by repleting intracellular glutathione, and by modulating reactive oxygen species . It may also modulate pathways involved in inflammation and apoptosis that are activated during early myocardial reperfusion. Prior studies in the clinical setting of NAC in acute myocardial infarction have largely been administered orally or intravenously. Evidence is limited for direct intracoronary delivery of NAC during PPCI.

This is a pilot, randomized, double-blind, placebo-controlled trial of early intracoronary NAC administration in STEMI patients undergoing PPCI. Eligible patients are adults undergoing PPCI for STEMI who give written informed consent. Participants will be randomized 1:1 to intracoronary NAC or intracoronary placebo in addition to standard PPCI and guideline-directed medical therapy.

In the intervention arm intracoronary NAC is given at a dose of 480 mg diluted in 10 mL normal saline. NAC is administered as early as possible during reperfusion after guidewire crossing when any antegrade coronary flow has been established. If crossing the guidewire alone does not restore flow, NAC is given after initial balloon dilatation when minimal flow is obtained. Solution is delivered through a microcatheter positioned proximal to the culprit lesion over 10 minutes. In the control arm, participants receive an intracoronary placebo of 10 mL normal saline by the same method and duration. The placebo solution appears and has the same volume as the NAC solution to maintain the blinding.

The primary end point was change in serum malondialdehyde from baseline to 24 h after PPCI. Circulating marker of oxidative stress and lipid peroxidation in early reperfusion. MDA . Secondary mechanistic end points are change from baseline to 24 hours after PPCI in high-sensitivity troponin I, interleukin-6, and caspase-3. High-sensitivity troponin I is used as a marker for release of the biomarker of myocardial injury, interleukin-6 as a marker for inflammatory response, and caspase-3 as a marker related to apoptosis.

Secondary functional end points are global longitudinal strain and metabolic equivalents from the six-minute walk test. Two-dimensional speckle-tracking echocardiography is used to measure global longitudinal strain at admission, discharge and 6 months after admission. Functional capacity was measured by the six-minute walk test at discharge and at 6 months, and the walking distance was expressed in metabolic equivalents.

This trial is intended to provide mechanistic and hypothesis-generating evidence regarding whether early intracoronary NAC during PPCI can attenuate reperfusion injury biomarker responses and support functional recovery signals in STEMI patients.