A study of method for enhancement of perfusion flow in experimental cerebral ischemia--Part 1. Effects of hypercapnia (author's transl))

Abstract

In terms of increase of perfusion flow into an area of ischemia, carbon dioxide must be one of the most promising candidates, even though complete agreement has still not been obtained. A controversial, but attractive point in this field is that there is a discrepancy between experimental results obtained by beta-emitting 85Kr and gamma-emitting 133Xe clearance techniques. To resolve this discrepancy in the results from the two isotopes, the experiment of this series were undertaken and our first report clarified that between 45 and 55 mmHg of arterial carbon dioxide pressure (PaCO2), microregional cerebral blood flow (rCBF), measured with both the 85Kr and 133Xe clearance techniques, increased significantly. However, in the same study, as PaCO2 was elevated above this level, there was a remarkable dissociation in rCBF change as measured by each isotope. The cortical blood flow measured with 85Kr clearance method decreased and conversely, global miniregional cerebral blood flow measured by 133Xe continued to increase steadily. In our first report, occurrence of subpial hemorrhage, extravasation of dye and increase of brain volume were considered as possible factors contributing to decrease in cortical blood flow by 85Kr clearance following a stage of its definite increase. In that report, the former two factors were analyzed in detail. Since cerebrovascular occlusive disease in humans tends to produce intracranial hypertension of varying degrees, depending upon secondary brain edema, the elevation of intracranial pressure by inhalation of carbon dioxide must be carefully investigated. If two methods of management, increase of perfusion flow by inhalation of carbon dioxide and reduction of increased brain volume by infusion of hypertonic solution are compatible on treatment and are capable of extending the range of PaCO2 which permits an increase of cortical blood flow measured with 85Kr clearance, an application of carbon dioxide to humans will be much safer and its therapeutic indication will be much wider. Therefore, Part 2 of our experiments was done with administration of 20% mannitol solution, using the same materials and methods as in the previous experiment and a comparison of the results with and without mannitol was made. In results, between 45 and 55 mmHg of PaCO2, cortical blood flow measured with the 85Kr clearance method, increased significantly with a gradual decline at PaCO2 higher than this level, which was very similar to the previous work done without mannitol. With the combined use of these two agents, subpial hemorrhage of more marked degree was observed at a PaCO2 above 65 mmHg with extravasation of dye appearing at lower PaCO2 level than with hypercapnia alone. The use of mannitol combined with hypercapnia appeared to be harmful.