Chronic myocardial and coronary arterial effects of intracoronary supersaturated oxygen therapy in swine with normal and ischemic-reperfused myocardium.

The study assessed chronic myocardial, coronary and systemic effects of intracoronary supersaturated oxygen (SSO2) therapy. Left anterior descending coronary arteries of 40 swine were stented and randomized to 90-min selective intracoronary infusion of SSO2 (pO2 760-1000 mmHg) or normoxemic saline. In 20 out of 40 animals, SSO2 delivery followed a 60-min balloon occlusion to induce myocardial infarction (MI). In both normal and MI models, intracoronary treatment with hyperoxemic SSO2 therapy showed no evidence of coronary thrombosis. There were no biologically relevant differences between treatments at either time point in regard to coronary intervention site healing and neointimal growth. No signs of any myocardial or systemic toxicity were observed after 7 or 30 days. A trend was observed toward reduced incidence of microscopic MI scars and reduced infarct size in histopathology, as well as toward better recovery of echocardiographically evaluated global and regional contractility at 30 days. No treatment related infarcts or thromboemboli were observed in the downstream organs.

Update on Cardioprotective Strategies for STEMI: Focus on Supersaturated Oxygen Delivery.

Despite the fact that door-to-balloon times have been greatly reduced, the rates of death and the incidence of heart failure in patients with ST-segment elevation myocardial infarction (MI) have plateaued. There is still an unmet need to further reduce MI size in the reperfusion era. Most adjunctive therapies to enhance myocardial salvage have failed, but some have shown promise. Currently, the only adjunctive therapy in a pivotal trial that has demonstrated reductions in infarct size is localized delivery of supersaturated oxygen (SSO2) therapy. This review provides background on prior infarct size reduction efforts. The authors describe the preclinical data that shows the effectiveness of SSO2 in reducing MI size, improving regional myocardial blood flow and cardiac function, and reducing adverse left ventricular remodeling-presumably by reducing patchy areas of residual ischemia within the reperfused risk zone. Potential mechanisms by which SSO2 is beneficial are described, including the delivery of high levels of dissolved oxygen through plasma to ischemic, but viable, vascular and myocardial cells, thus allowing their survival and function. The authors then describe the SSO2 clinical trials, demonstrating that in patients with anterior ST-segment elevation MI, SSO2 therapy safely and effectively reduces infarct size, improves cardiac function, and reduces adverse left ventricular remodeling.

Development and Characterization of Broadly Cross-reactive Monoclonal Antibodies Against All Known Ebolavirus Species.

As of 25 March 2015, the largest recorded outbreak of Ebola virus infection is ongoing, with almost 25 000 cases and >10 000 deaths. There are 5 genetically and antigenically distinct species within the genus Ebolavirus. Limited cross-reactivity and protection is observed between these 5 Ebolavirus species, which complicates vaccine development. However, on the basis of sequence homology between the 5 Ebolavirus species, we hypothesize that conserved epitopes are present on the viral glycoprotein (GP), which can be targeted by antibodies. In the current study, a panel of mouse monoclonal antibodies was isolated and characterized using an enzyme-linked immunosorbent assay (ELISA) to determine cross-reactivity, avidity, and competition for epitope binding; Western blot analysis was also performed. Four monoclonal antibodies were identified by ELISA as cross-reacting with the GPs of all 5 Ebolavirus species. The identification of cross-reactive antibodies that bind the GPs of all known Ebolavirus species will give us important insight into the presence of conserved epitopes on the viral GP. These data will be crucial for the development of novel therapeutics and diagnostic assays.

Topical oxygen emulsion: a novel wound therapy.

OBJECTIVE: To investigate the use of a topical oxygen emulsion (TOE), consisting of a supersaturated oxygen suspension using perfluorocarbon components, on second-degree burns and partial-thickness wounds. DESIGN: Oxygen is a required substance for various aspects of wound repair, and increased oxygen tension in a wound has been shown to stimulate phagocytosis and to reduce the incidence of wound infection. Second-degree burns and partial-thickness wounds were created on the backs of specific pathogen-free pigs. Wounds were then randomly assigned to 1 of the following treatment groups: TOE, TOE vehicle, or air-exposed control. MAIN OUTCOME MEASURE: Wounds were assessed for complete epithelialization using a salt-split technique. RESULTS: The TOE was able to significantly (P = .001) enhance the rate of epithelialization compared with both vehicle and untreated control. These data suggest that topical oxygen may be beneficial for acute and burn wounds. CONCLUSIONS: The results obtained from this double-blind, control, in vivo study demonstrate that TOE can significantly enhance the rate of epithelialization of partial-thickness excisional wounds and second-degree burns. These findings could have considerable clinical implications for patients with surgical and burn wounds by providing functional skin at an earlier date to act as a barrier against environmental factors, such as bacteria invasion. Other types of wounds may also benefit from this therapy (eg, chronic wounds and surgical incisions). Additional studies, including clinical studies, are warranted.

Hyperbaric oxygen solution infused into the anterior interventricular vein at reperfusion reduces infarct size in swine.

This study was designed to test the hypothesis that raising myocardial O2 via diffusion of a hyperbaric oxygen solution (AO) administered through the anterior interventricular vein (AIV) will reduce infarct size by reducing reperfusion injury associated with reduced neutrophil activation. In three pilot open-chest swine experiments, myocardial tissue Po2 was monitored using an oxygen probe during coronary occlusion (Occl) and reperfusion (Rep). One control experiment had no AIV infusion; a second control received arterial blood drawn from the femoral artery infused into the AIV during Rep. In a third open-chest experiment, AO mixed with arterial blood was infused through the AIV at Rep. In controls, tissue Po2 in the risk region (RR) rose early in Rep and then fell to Occl levels, whereas in AO-treated animals, myocardial Po2 remained above baseline. The following three groups of five swine then underwent 60 min of left anterior descending coronary artery Occl and Rep: 1) arterial blood infused at Rep as controls (Con), 2) AO infused beginning 30 min after Rep (AO 30 min), and 3) AO infused immediately at Rep (AO 0 min). There were no differences among the three groups in hemodynamics or myocardial blood flow during baseline (BL) or Occl or in RR size. However, endocardial blood flow was significantly higher in RR during Rep in AO 0 min vs. control and AO 30 min (P=0.01). Both infarct size (IS) as %heart and IS as %RR were lower in AO 0 min compared with Con and AO 30 min (P <0.01 for both), and myeloperoxidase values were lower for epicardial (P <0.001), midmyocardial (P=0.03), and endocardial (P <0.001) layers in AO 0 min. AO infused into the AIV immediately at Rep diffuses into the RR and reduces IS by reducing Rep injury associated with neutrophil activation.

Aqueous oxygen hyperbaric reperfusion in a porcine model of myocardial infarction.

OBJECTIVES: The purpose of the study was to test the hypothesis that intracoronary aqueous oxygen (AO) hyperbaric reperfusion reduces myocardial injury after prolonged coronary occlusion. Background. Attenuation of ischemia/reperfusion injury by the use of hyperbaric oxygen (HBO) administered during reperfusion has been demonstrated for a wide variety of tissues, including myocardium. We have recently developed a more practical, catheter-based, site-specific method for delivery of oxygen at hyperbaric levels with aqueous oxygen infusion. METHODS: Following a 60-minute balloon occlusion of the left anterior descending coronary artery in swine, intracoronary AO hyperoxemic perfusion (50 mL blood/minute; 1.5 mL AO/minute; mean pO2 = 834 104 mmHg) was performed for 90 minutes after a 15-minute period of normoxemic autoreperfusion (physiologic reperfusion). Control groups consisted of autoreperfusion alone; active normoxemic perfusion (50 mL/minute) for 90 minutes; and hyperoxemic perfusion with a hollow fiber oxygenator (HFO) for 90 minutes. Results. A significant improvement in left ventricular ejection fraction was noted by ventriculography at 105 minutes of reperfusion (ANOVA, p < 0.05), compared to the 15-minute autoreperfusion period, only in the AO and HFO groups. Mean percent infarct size (area of necrosis)/(area at risk), quantitative post-mortem hemorrhage score, and myocardial myeloperoxidase levels at 3 hours of reperfusion were significantly less in the AO group (ANOVA, p < 0.05), but not in the HFO group, compared to normoxemic groups. Conclusions. The results demonstrate that intracoronary hyperbaric reperfusion with AO, but not with a membrane oxygenator, attenuates myocardial ischemia/reperfusion injury.