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Hyperoxemic Perfusion for Treatment of Reperfusion Microvascular Ischemia in Patients with Myocardial Infarction

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Abstract

In patients with acute myocardial infarction (AMI) primary angioplasty and stent placement is a more effective and better tolerated treatment than thrombolysis, and therefore, when logistics allow, this treatment is preferred and routinely used. However, successful reopening of an occluded coronary artery does not necessarily lead to recovery of left ventricular (LV) function. Post-AMI reduction in contractile function and ventricular remodeling may result in heart failure.There is evidence that reduced contractile function in the infarct zone is related to poor microvascular perfusion even after normalization of large-vessel flow by angiographic criteria following coronary recanalization. Failure to re-establish adequate tissue perfusion may be because of reperfusion injury, ischemia-induced microvascular damage, and plugging of the microcirculation by thrombus and plaque during mechanical recanalization. Experimental data support the hypothesis that reperfusion microvascular ischemia contributes to myocardial tissue injury over a prolonged time period.

Hyperbaric oxygen therapy (HBO) attenuates microvascular dysfunction and reperfusion microvascular ischemia, as demonstrated in both experimental models and patients with AMI. However, treating patients in an HBO chamber or with a conventional oxygenator is impractical and difficult.

Aqueous oxygen (AO) is a newly developed solution containing extremely high oxygen concentrations (1–3ml O2/mL saline). The AO system mixes AO solution with a patient’s blood from an arterial puncture and delivers the hyperoxemic blood to targeted ischemic myocardium via an infusion catheter for regional correction of hypoxemia and production of hyperoxemia. The system precisely controls the level of pO2 without clinically significant microbubble formation.

Hyperoxemic coronary infusion of AO in experimental models of AMI improved LV function and reduced infarct size compared with normoxemic controls, very likely as a result of microvascular blood flow improvement. The first clinical experiences with intracoronary infusion of AO solution demonstrated the therapy to be a safe and well tolerated in the setting of AMI after successful primary percutaneous transluminal coronary angioplasty. Its use was associated with significant progressive improvement in LV function as measured by ejection fraction and wall motion score index. Interestingly, such improvement was primarily due to functional recovery of infarct zone contractility. A larger randomized trial is currently underway to define the role of hyperoxemic coronary infusion in patients with AMI.

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Acknowledgements

I give special thanks to the dedicated scientists and engineers at TherOx, Inc., Irvine, California, US, who developed the Aqueous Oxygen™ System. I am indebted particularly to Paul J. Zalesky, Ph.D. and Linda D’Abate for their invaluable collaboration. No sources of funding were used to assist in the preparation of this manuscript. The author has no conflicts of interest that are directly relevant to the content of this manuscript.

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  1. Centro Cardiologico “Monzino” IRCCS, Institute of Cardiology, University of Milan, Via Parea, 4, Milan, 20138, Italy

    Antonio L. Bartorelli

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Bartorelli, A.L. Hyperoxemic Perfusion for Treatment of Reperfusion Microvascular Ischemia in Patients with Myocardial Infarction. Am J Cardiovasc Drugs 3, 253–263 (2003). https://doi.org/10.2165/00129784-200303040-00004

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