Dataset Information

Glutathione infusion before primary percutaneous coronary intervention: a randomised controlled pilot study.

ABSTRACT:

Objective

In the setting of reperfused ST-elevation myocardial infarction (STEMI), increased production of reactive oxygen species (ROS) contributes to reperfusion injury. Among ROS, hydrogen peroxide (H₂O₂) showed toxic effects on human cardiomyocytes and may induce microcirculatory impairment. Glutathione (GSH) is a water-soluble tripeptide with a potent oxidant scavenging activity. We hypothesised that the infusion of GSH before acute reoxygenation might counteract the deleterious effects of increased H₂O₂ generation on myocardium.

Methods

Fifty consecutive patients with STEMI, scheduled to undergo primary angioplasty, were randomly assigned, before intervention, to receive an infusion of GSH (2500?mg/25?mL over 10?min), followed by drug administration at the same doses at 24, 48 and 72?hours elapsing time or placebo. Peripheral blood samples were obtained before and at the end of the procedure, as well as after 5 days. H₂O₂ production, 8-iso-prostaglandin F2? (PGF2?) formation, H₂O₂ breakdown activity (HBA) and nitric oxide (NO) bioavailability were determined. Serum cardiactroponin T (cTpT) was measured at admission and up to 5 days.

Results

Following acute reperfusion, a significant reduction of H₂O₂ production (p=0.0015) and 8-iso-PGF2? levels (p=0.0003), as well as a significant increase in HBA (p<0.0001)and NO bioavailability (p=0.035), was found in the GSH group as compared with placebo. In treated patients, attenuated production of H₂O₂ persisted up to 5 days from the index procedure (p=0.009) and these changes was linked to those of the cTpT levels (r=0.41, p=0.023).

Conclusion

The prophylactic and prolonged infusion of GSH seems to determine a rapid onset and persistent blunting of H₂O₂ generation improving myocardial cell survival. Nevertheless, a larger trial, adequately powered for evaluation of clinical endpoints, is ongoing to confirm the current finding.

Trial registration number

EUDRACT 2014-00448625; Pre-results.

SUBMITTER: Tanzilli G

PROVIDER: S-EPMC6701599 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature

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Publications

Glutathione infusion before primary percutaneous coronary intervention: a randomised controlled pilot study.

Tanzilli Gaetano G Truscelli Giovanni G Arrivi Alessio A Carnevale Roberto R Placanica Attilio A Viceconte Nicola N Raparelli Valeria V Mele Rita R Cammisotto Vittoria V Nocella Cristina C Barillà Francesco F Lucisano Luigi L Pennacchi Mauro M Granatelli Antonino A Dominici Marcello M Basili Stefania S Gaudio Carlo C Mangieri Enrico E

BMJ open 20190808 8

<h4>Objective</h4>In the setting of reperfused ST-elevation myocardial infarction (STEMI), increased production of reactive oxygen species (ROS) contributes to reperfusion injury. Among ROS, hydrogen peroxide (H<sub>2</sub>O<sub>2</sub>) showed toxic effects on human cardiomyocytes and may induce microcirculatory impairment. Glutathione (GSH) is a water-soluble tripeptide with a potent oxidant scavenging activity. We hypothesised that the infusion of GSH before acute reoxygenation might countera ...[more]

PMID: 31399448

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Project description:BackgroundPrimary percutaneous coronary intervention (PPCI) has been widely recognized as the preferred treatment for ST-segment-elevation myocardial infarction (STEMI). However, substantial numbers of STEMI patients cannot receive timely PPCI. Early fibrinolysis followed by routine percutaneous coronary intervention (FPCI) has been proposed as an effective and safe alternative for eligible patients. To date, few studies have compared FPCI with PPCI in terms of microvascular reperfusion. This study aimed to evaluate the microvascular function of FPCI and PPCI.MethodsSTEMI patients at the Peking University First Hospital and Miyun Hospital were enrolled in this retrospective study between January 2015 to December 2020. Microvascular function documented by the coronary angiography-derived index of microvascular resistance (caIMR) was measured at the final angiogram after revascularization. The primary end point was the caIMR of the culprit vessels. The secondary end points were in-hospital and follow-up major adverse cardiovascular events (MACE), including cardiovascular death, non-fatal recurrent myocardial infarction, target-vessel revascularization (TVR), and non-fatal stroke/transient ischemic attacks (TIA). Details of the adverse clinical events were obtained from telephone interviews and electronic medical record systems until January 2022.ResultsIn total, 496 STEMI patients were enrolled in this cross-sectional retrospective study. Of these patients, 81 underwent FPCI, and 415 underwent PPCI. At the baseline, the PPCI patients had a higher-risk profile than the FPCI patients. The time from symptom onset to reperfusion therapy was significantly shorter in the FPCI group than the PPCI group (median 3.0 vs. 4.5 hours; P<0.001). The caIMR was significantly lower in the FPCI group than the PPCI group (median 20.34 vs. 40.33; P<0.001). The median follow-up duration was 4.1 years. During the follow-up period, the rate of MACE was lower in the FPCI group than the PPCI group [7 (10.1%) vs. 82 (20.8%), P=0.048]. After propensity score matching to adjust for the imbalances at the baseline, the caIMR remained significant and the clinical outcomes did not differ significantly between the two groups.ConclusionsIn eligible STEMI patients, clinically successful FPCI may be associated with better microvascular reperfusion and comparable clinical outcomes as compared with PPCI.

Dataset Information

Glutathione infusion before primary percutaneous coronary intervention: a randomised controlled pilot study.

Objective

Methods

Results

Conclusion

Trial registration number

Publications

Glutathione infusion before primary percutaneous coronary intervention: a randomised controlled pilot study.

Similar Datasets

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