How do you study blue

See associated article on page 105. C yanosis is perhaps one of the most impressive signs one can note on physical examination. The ability of the human body to adapt to function satisfactorily—well in many cases—in the setting of an arterial oxygen saturation of under 80% is remarkable. Since cyanosis is oftentimes a secondary phenomenon of congenital heart disease and since congenital heart disease producing cyanosis will usually require cardiac surgery, it seems prudent to evaluate the impact of cardiopulmonary bypass on the heart that has been subject to low oxygen tension for a prolonged period. This is certainly not a new concept or subject of experimentation as there are many studies reported in the literature using different models of acute and chronic hypoxemia in an attempt at studying “blue.” There are many variables in these studies, including the model used to produce hypoxemia, the age at which it commenced, the duration before experimental study, the consistency of the hypoxemia, the animal species, and the precise nature of the experimental design evaluating myocardial response to the setting of cardiac surgery. There is conflicting evidence regarding the impact of chronic cyanosis on outcome from cardiac surgery, although most agree that it does have a deleterious effect overall. On the surface it seems counterintuitive, but there is a growing body of evidence that oxygen itself might be an underlying toxin. Ideally, cyanosis should be evaluated in isolation absent any other factors. There are basically two general experimental models. One is to place an animal in a low oxygen tension environment for a prolonged period and then perform the studies. The other is to create a right-to-left shunt of significant magnitude as to produce low systemic oxygen saturations. Another issue in designing experimental models has to do with timing. Should the hypoxemia begin soon after birth, before maturation of the myocardium, or does it make any difference? How long should the animals remain hypoxic before study? There are problems inherent in both general types of experimental models and with timing. It is very difficult to keep an animal in a low oxygen tension environment continuously from birth onward. These animals will need to nurse for the first few days or weeks of life, and it is unlikely that the mother can be safely kept in this environment. Bringing the animals out several times per day likely will negate the impact of the hypoxic environment for the replication of a clinically relevant state of cyanosis. Creating surgical shunts is a high-risk operation in newly born animals and introduces potential hemodynamic factors that might confound the experiments where the control animals have normal hearts. It is not completely clear what constitutes complete maturation of the myocardium and when it occurs in any one animal species. Furthermore, children with congenital heart disease—particularly cyanotic congenital heart disease—may not “mature” at the same time as children with normal hearts. The study from Corno and associates is another attempt at evaluating the impact of reoxygenation on the myocardium of chronically hypoxic Sprague-Dawley rats. They found evidence of deleterious effects of the reoxygenation process on myocardial function and metabolism. This experiment is fairly simple and straightforward. Animals are kept hypoxic continuously beginning at 5 weeks of life, even while the hearts are stabilized on the Langendorff preparation before seeing hyperoxic blood. These investigators have done a meticulous job of maintaining a strictly hypoxic environment for their experimental animals in an effort to eliminate any effect of even brief exposure to normoxia. Changes in systolic and diastolic function of the chronically hypoxic hearts occur precisely when exposed to hyperoxic From Washington University School of Medicine, St Louis, Mo.