Cason B A, Wisneski J A, Neese R A, Stanley W C, Hickey R F, Shnier C B, Gertz E W
Department of Anesthesiology, University of California, San Francisco.
Circulation. 1992 Feb;85(2):828-38. doi: 10.1161/01.cir.85.2.828.
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).
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.
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.
尽管吸氧疗法长期以来一直用于治疗急性心肌缺血，但在不存在低氧血症的情况下，动脉血氧分压升高具有任何有益作用的实验证据并不明确。在本研究中，我们使用了心内膜下心肌缺血的猪模型，以确定动脉高氧对局部心肌收缩功能（超声心动图）、心肌血流分布（微球）和局部心肌糖酵解代谢（碳同位素标记底物）的影响。
在10头家猪中，将左前降支冠状动脉插管，并通过灌注回路中的滚轴泵严格控制该动脉的血流。通过操纵吸入氧浓度（FIO₂）来控制动脉血氧分压。通过将泵流量降低至对照值的50%来诱导低流量心肌缺血，这使局部心内膜收缩期缩短减少至正常的30%-50%。在血流稳定15分钟后，每只动物按随机顺序接受另外两个15分钟的实验阶段：冠状动脉常氧（PO₂ = 90-110 mmHg）和冠状动脉高氧（PO₂大于400 mmHg）。在每个氧合水平，我们测量了局部心肌功能、局部心肌血流和代谢以及心肌需氧量的血流动力学指标。常氧期间的心肌缺血使缺血区的收缩期缩短降至10.9±5.3%。高氧使缺血区收缩期缩短显著增加至15.2±4.6%。在心肌缺血期间，缺血区的心内膜血流降至0.26±0.06 ml·g⁻¹·min⁻¹。在高氧期间，心内膜血流升至0.34±0.10 ml·g⁻¹·min⁻¹。在初始缺血期，心内膜与心外膜血流比值为0.45±0.18，在高氧期升至0.61±0.23。心肌缺血增加了局部葡萄糖摄取、葡萄糖转化为释放的乳酸以及心肌乳酸净释放。在缺血心肌中，冠状动脉高氧降低了化学测量的乳酸生成和同位素测量的乳酸释放，并降低了葡萄糖摄取以及葡萄糖向乳酸的转化。
这些数据首次证明，在急性低流量心肌缺血期间将动脉血氧分压提高至高水平可改善缺血心肌的功能和血流分布，并降低缺血区的糖酵解代谢。收缩功能的改善程度（收缩期缩短绝对增加5%或相对于缺血前值变化25%）与观察到的心内膜下血流增加一致。
