Effect of Supersaturated Oxygen Delivery on Infarct Size After Percutaneous Coronary Intervention in Acute Myocardial Infarction

Abstract

Background-Myocardial salvage is often suboptimal after percutaneous coronary intervention in ST-segment elevation myocardial infarction. Posthoc subgroup analysis from a previous trial (AMIHOT I) suggested that intracoronary delivery of supersaturated oxygen (SSO 2 ) may reduce infarct size in patients with large ST-segment elevation myocardial infarction treated early. Methods and Results-A prospective, multicenter trial was performed in which 301 patients with anterior ST-segment elevation myocardial infarction undergoing percutaneous coronary intervention within 6 hours of symptom onset were randomized to a 90-minute intracoronary SSO 2 infusion in the left anterior descending artery infarct territory (nϭ222) or control (nϭ79). The primary efficacy measure was infarct size in the intention-to-treat population (powered for superiority), and the primary safety measure was composite major adverse cardiovascular events at 30 days in the intention-to-treat and per-protocol populations (powered for noninferiority), with Bayesian hierarchical modeling used to allow partial pooling of evidence from AMIHOT I. Among 281 randomized patients with tc-99m-sestamibi single-photon emission computed tomography data in AMIHOT II, median (interquartile range) infarct size was 26.5% (8.5%, 44%) with control compared with 20% (6%, 37%) after SSO 2 . The pooled adjusted infarct size was 25% (7%, 42%) with control compared with 18.5% (3.5%, 34.5%) after SSO 2 (P Wilcoxon ϭ0.02; Bayesian posterior probability of superiority, 96.9%). The Bayesian pooled 30-day mean (ϮSE) rates of major adverse cardiovascular events were 5.0Ϯ1.4% for control and 5.9Ϯ1.4% for SSO 2 by intention-to-treat, and 5.1Ϯ1.5% for control and 4.7Ϯ1.5% for SSO 2 by per-protocol analysis (posterior probability of noninferiority, 99.5% and 99.9%, respectively). Conclusions-Among patients with anterior ST-segment elevation myocardial infarction undergoing percutaneous coronary intervention within 6 hours of symptom onset, infusion of SSO 2 into the left anterior descending artery infarct territory results in a significant reduction in infarct size with noninferior rates of major adverse cardiovascular events at 30 days. Clinical Trial Registration-clinicaltrials.gov Identifier: NCT00175058 (Circ Cardiovasc Intervent. 2009;2:366-375.)

Incidence, Predictors, and Implications of Reinfarction After Primary Percutaneous Coronary Intervention in ST-Segment–Elevation Myocardial Infarction

“…[8][9][10] Therapies to enhance myocardial salvage, such as intravenous β-blockade, intralesional abciximab, systemic hypothermia, and supersaturated oxygen, may therefore be useful to prevent reinfarction. [26][27][28][29] Multivessel disease was also an independent predictor of reinfarction in the present study. A recently reported 465 patient randomized trial suggests that both reinfarction and survival may be reduced by a strategy of complete multivessel revascularization at the time of primary PCI, 30 possibly through treatment of nonculprit vulnerable plaques which are known to be frequent in patients with STEMI.…”

Reperfusion Injury, Microvascular Dysfunction, and Cardioprotection

“…In the bayesian pooled analysis from the 2 trials, supersaturated oxygen therapy was associated with a statistically significant 6.5% reduction in infarct size. 61 As a result, this device is currently undergoing Food and Drug Administration review for approval to reduce infarct size in patients with anterior STEMI undergoing successful primary PCI within 6 hours of symptom onset.…”

Oxygen delivery using engineered microparticles

“…Historically, direct infusion of free oxygen gas into the blood stream has resulted in pulmonary emboli at extremely low infusion rates (i.e., 0.25 mL·kg −1 ·min −1 , corresponding to only 8% of measured oxygen consumption of a healthy human adult) (4,6). Other groups have proposed the use of supersaturated oxygen suspensions to increase oxygen content of injected fluids, although even when the pO 2 reaches ∼1,000 mmHg, solutions only deliver ∼1 mL O 2 ·kg −1 ·h −1 in vivo (7). Another theoretical approach would be to use artificial oxygen carriers to deliver dissolved oxygen to the bloodstream.…”