Potential for Myocardial Salvage Utilizing Direct Intracoronary Infusion of Aqueous Oxygen


David G. Rizik, MD, Denise A. Dowler, BSN, Joanne M. Saczynski, MSN, Bernard J. Villegas, MD, Simon Dixon, MD

Clinical Presentation. A 52-year-old male with a history of tobacco use, hypertension and hypercholesterolemia presented to the emergency room with 6 hours of “chest pressure radiating to the neck and jaw.” Associated dyspnea, diaphoresis and nausea were noted at the time of presentation. Initial electrocardiogram (Figure 1a) demonstrated unequivocal evidence of an inferior myocardial injury pattern. He was triaged to urgent catheterization laboratory intervention.

Diagnostic coronary angiography (Figure 2a) revealed a total occlusion of the right coronary artery (RCA) in its proximal segment. Figure 2B demonstrates the angiographic results following primary stenting of the RCA. Direct intracoronary infusion of aqueous oxygen (TherOx, Irvine, Calif.) as a part of the AMIHOT trial followed percutaneous coronary intervention (PCI) (the patient was randomized as part of the AMIHOT trial after a detailed informed consent). The total duration of direct intracoronary infusion of aqueous oxygen (AO) as mandated by protocol was 90 minutes following PCI.

Following PCI and intracoronary infusion of AO directly in the culprit vessel, amelioration of chest discomfort as well as resolution of electrocardiographic changes were noted. The patient was discharged 2 days later on appropriate antiplatelet therapy.

Two weeks following discharge, myocardial perfusion imaging revealed a minimal defect of the inferior wall. This represented less than 1% of the left ventricle. Gated images demonstrated an end-diastolic volume of 141 ml, an end-systolic volume of 55 ml and an ejection fraction of 61%.

Discussion. Left ventricular systolic function has been demonstrated to be a vital prognostic determinant of survival, irrespective of reperfusion strategy utilized in the setting of acute myocardial infarction.1–7 Reduction of infarct size and preservation of myocardium have both been attributed to early and sustained culprit vessel patency. However, the angiographic appearance of successful restoration of coronary flow has been an inconsistent marker of adequate myocardial reperfusion.8–16

It has also been determined that simply achieving brisk TIMI flow in the culprit vessel may be an inadequate or inconsistent marker for recovery of regional wall motion.17 Reperfusion injury and other pathologic microvascular mechanisms (including distal embolization) are the prime culprits for incomplete recovery of ventricular function in the weeks following an ischemic insult.18–20 It is important to point out that published reports have shown that the deleterious effects related to focal regions of microvascular impairment and ischemia may be attenuated by the local delivery of AO and the resultant achievement of hyperoxemic conditions at the microvascular level.21

At a macroscopic level, TherOx AO therapy delivers hyperoxemic blood (760–1000 Hg pO2) at a coronary blood flow rate (75 cc/min) into the culprit vessel for a period of 90 minutes. Figure 4a shows schematically the potential for “clustering” of cellular elements associated with microvascular engorgement and capillary edema. It is clear that this may occur despite the presence of angiographically normal epicardial flow and lead to the no-reflow condition. With the local delivery of AO and conversion to a potentially hyperoxemic state (Figure 4b), flow may be partially restored to the “engorged” microcirculation. With a sustained hyperoxemic microvascular environment (Figure 4c), the potential for amelioration of capillary edema and improved tissue perfusion exists.

Spears and colleagues have reported their histopathologic observations of microvascular injury22 in swine myocardium following experimental ischemia. Figures 5a and 5b represent transmission electron microscopy of swine myocardium at 3 hours following reperfusion. The presence of prominent endothelial cell (EC) edema, numerous mitochondrial inclusion bodies and myocyte contracture were associated with autoreperfusion alone as seen in Figure 5a. Endothelial cell edema and myocyte contracture were conspicuously absent in Figure 5b, following autoreperfusion concomitant with AO hyperoxemic perfusion.

The current case presentation demonstrates the potential practical benefits of intracoronary AO in the acute setting. Moreover, it serves to clinically correlate those histopathologic observations earlier discussed. Whether the administration of intracoronary AO is practical in a broad, unselected population of acute ST-elevation myocardial infarction patients remains to be more fully explored. The current AMIHOT trial is designed to test this developing technology in order to determine whether AO in combination with angioplasty can be safely administered and consistently produce improved left ventricular function as compared to angioplasty alone. The results of this ongoing randomized trial are expected to lend further insight into its practical application.

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