Although
oxygen inhalation therapy has long been used in the treatment of acute
myocardial ischemia, experimental evidence that increased arterial PO2 has any beneficial effect in the absence of
hypoxemia is equivocal. In this study, we used a swine model of subendocardial
myocardial ischemia to determine the effects of arterial
hyperoxia on regional myocardial contractile function (sonomicrometry), myocardial blood flow distribution (
microspheres), and regional myocardial glycolytic metabolism (
carbon isotope-labeled substrates).
METHODS AND RESULTS: In 10 domestic swine, the left anterior descending coronary artery was cannulated and flow to this artery was strictly controlled via a roller pump in the perfusion circuit. Arterial PO2 was controlled by manipulating inspired
oxygen concentration (FIO2). Low-flow
myocardial ischemia was induced by reducing pump flow to 50% of the control value, which diminished regional endocardial systolic shortening to 30-50% of normal. After a 15-minute period of flow stability, each animal was exposed in randomized order to two additional 15-minute experimental periods: coronary normoxia (PO2 = 90-110 mm Hg) and coronary
hyperoxia (PO2 greater than 400 mm Hg). At each level of oxygenation, we measured regional myocardial function, regional myocardial blood flow and metabolism, and hemodynamic indexes of myocardial
oxygen demand.
Myocardial ischemia during normoxia reduced systolic shortening to 10.9 +/- 5.3% in the ischemic zone.
Hyperoxia increased ischemic zone systolic shortening substantially to 15.2 +/- 4.6%. During
myocardial ischemia, endocardial blood flow was decreased to 0.26 +/- 0.06 ml.g-1.min-1 in the ischemic zone. During
hyperoxia, endocardial blood flow rose to 0.34 +/- 0.10 ml.g-1.m-1. The endocardial: epicardial flow ratio was 0.45 +/- 0.18 in the initial
ischemia period and rose to 0.61 +/- 0.23 in the hyperoxic period.
Myocardial ischemia increased regional uptake of
glucose, conversion of
glucose to released
lactate, and net myocardial
lactate release. In the ischemic myocardium, coronary
hyperoxia decreased both chemically measured
lactate production and isotopically measured
lactate release and decreased
glucose extraction and the conversion of
glucose to
lactate.
CONCLUSIONS: These data demonstrate for the first time that increasing arterial PO2 to high levels during acute low-flow
myocardial ischemia improves both function and flow distribution in the ischemic myocardium and decreases glycolytic metabolism in the ischemic zone. The degree of improvement in contractile function (5% absolute increase in systolic shortening or 25% change normalized to preischemic values) is consistent with the observed increase in subendocardial blood flow.