Brain Microemboli During Cardiopulmonary Bypass

Moody, Dixon

Abstract

At least 79% of patients will have mild, moderate or severe intellectual dysfunction following surgery assisted by cardiopulmonary bypass (CPB). Although some suspect microemboli to be the etiologic agent causing this brain dysfunction, little objective evidence confirming the presence of emboli is reported with the most recent techniques of cardiac surgery. Recently, small capillary and arteriolar dilatations (SCADs) have been found in autopsy brains shortly after CPB irrespective of whether the membrane of bubble type of oxygenator was employed. These SCADs are probably the site of iatrogenic emboli (air, fat or some other material dissolved out by the solvents used in the preparation), and the vascular lumen remains fixed in a dilated or aneurysmal state after preparation for microvascular analysis. SCADs range in size from 10 mu m to 40 mu m, a size that lodges in the smallest vessels of the microvasculature, and they have been found in numbers that might be expected to cause subtle neurological dysfunction. SCADs have been found blocking 0.4% of the capillaries, but the larger ones blocking the 40-50 mu m system arterioles are believed to be more dangerous. Therefore, the outcome of surgery requiring CPB may be improved if the hundreds of thousands of these microemboli can be eliminated, but first their etiology must be established. A unique histochemical technique revealed the SCADs initially; it is also appropriate for their further quantification and characterization. The native alkaline phosphatase (AP) ectoenzyme, present in the endothelial plasma cell membrane of small arteries, arterioles, and capillaries, but not in veins or large arteries, is used to precipitate black lead sulfide salt in these structures. This histochemical technique is superior to injection techniques or stains of intravascular contents because it avoids artifacts of injection such as rupture and incomplete filling and loss of the stain at the cut surface of the tissue. More important for this proposal, one screening for small emboli, there is no possibility the SCADs have been injected artifactually during tissue preparation because nothing is injected at this stage, neither in fixation nor in staining. The AP histochemical technique also allows counterstaining of the background neural tissue with a variety of stains in the case of 100 mu m celloidin sections. This study will focus tightly on these SCADs to determine (1) their etiology, and (2) if they are clinically significant. The brains from non- surviving humans enrolled in Projects 1 and 2, will be examined in order to quantify the SCADs and to correlate their accumulation with the technical CPB conditions and the subjects' neurological outcome. Finally, we will quantify the SCADs in muscle and skin and correlate with 1) the accumulation of SCADs in the brains of non-surviving humans and, 2) postoperative neuropsychological testing in surviving patients in order to develop a surrogate for brain tissue in future studies aimed at reducing brain microemboli.