Bethesda, MD Researchers are investigating whether delivery of super-oxygenated blood to ischemic tissues after primary angioplasty may improve outcomes for patients suffering myocardial infarction. Results of a pilot study suggest the approach is at least safe and feasible, and a phase II trial, recently approved by the FDA, will soon be underway.
The approach uses a proprietary system (TherOx AO System®, TherOx, Inc, Irvine, CA) that oxygenates the patient's own blood, creating oxygen levels similar to what might be used in a hyperbaric chamber. The process allows oxygen to remain in solution without the need for it to be under pressure. The "aqueous oxygen" is then delivered directly into newly reperfused myocardium via the catheter after primary angioplasty.
"Essentially what this technology does is provide a local hyperbaric oxygen chamber directed just at the heart, and more specifically, at the area of the myocardial infarction," said Dr Simon R Dixon (William Beaumont Hospital, Royal Oak, MI), who has been involved in the early investigation into this new strategy.
"The technology looks very suitable, is easy to apply in clinical practice, and I think one of the potential hopes is that this therapy may extend the window of opportunity for myocardial salvage by enhancing tissue healing," Dixon told heartwire .
After MI, the residual left ventricular (LV) function is the most important determinant of outcome, he said. Recanalization of the infarct-related artery is done to salvage myocardium in jeopardy, but restoration of flow is too late in some cases to save much heart muscle, Dixon said. For these patients, researchers have been investigating a variety of adjunctive therapies that might aid in myocardial salvage.
Hyperbaric oxygen has been shown to enhance tissue healing, and is used to treat ulcers, wounds, and particularly burns, Dixon said. This new technology aims to use the same mechanism, delivering oxygen in solution to damaged tissues in the heart.
Previously, a barrier to this type of approach has been the fact that to dissolve any gas in water, it is necessary to have the liquid under pressure. Release of the pressure causes the gas to be released, and "bubbles form, like in a soda can," Dixon said. A new proprietary process developed by Dr J Richard Spears (Wayne State University, Detroit, MI) in conjunction with TherOx, allows oxygen to be dissolved in water without microbubble formation.
Spears has shown in preclinical work that infarct size is reduced, myocardial blood flow improved, and that cell morphology in the ischemic area is better preserved with this "hyperoxemic reperfusion" strategy compared to control animals, Dixon said.
During the primary angioplasty procedure, a small amount of the patient's blood is drawn from the opposite femoral artery, and is put through a controller where it is mixed with the aqueous oxygen solution. After the artery is opened, the superoxygenated blood (PO2 600-800 mg Hg) is infused back into the patient's heart over a period of 60-90 minutes.Pilot data promising
In a report that appeared in the February 6, 2002 issue of the Journal of the American College of Cardiology, Dixon and colleagues published results of a multicenter, clinical, pilot trial that included 29 patients undergoing primary angioplasty.
The reperfusion procedure was performed successfully in all cases, with no adverse events seen during either hyperoxemic reperfusion or the in-hospital period. "Although this study was not designed to evaluate the clinical efficacy of hyperoxemic reperfusion, results of the LV analysis suggest this therapy may promote healing and lead to early recovery of function in the infarct zone," the researchers conclude in their paper.
On the strength of their preclinical and pilot data, the FDA granted permission in January 2002 for the company to proceed with a phase 2 clinical study. The AMIHOT trial will be carried out in 10 US centers, under the direction of Dr David O Williams (Rhode Island Hospital) as principal investigator. The first patients have already been enrolled.
In their press release, the company also notes they are pursuing applications for this technology in stroke, cancer therapy, wound treatment, and skin care.
Heartwire from Medscape © 2002
Cite this: Aqueous oxygen delivery after primary angioplasty safe, feasible - Medscape - Mar 01, 2002.