CAPILLARY HEMATOCRIT AND GAS EXCHANGE

该提案的主要目标是确定 毛细血管中的线性红细胞密度（droc）对扩散气体转运的影响 组织.毛细血管线红细胞密度，毛细血管的指标 红细胞压积，在不同的条件下可以在3倍范围内迅速变化， 条件然而，它在气体交换中的确切作用目前尚不清楚。 对两栖动物皮肤的研究将确定：1）扩散的依赖性 在不同表皮厚度下DROC上穿过表皮的气体通量， 2)毛细血管内红细胞间距的异质性及其影响 这种不均匀性对扩散气体输送的影响，以及3）对 用无基质替代红细胞的组织扩散能力 血红蛋白溶液这将通过测试以下内容来实现 青蛙皮肤上的假说：1）droc的变化影响组织扩散 在低droc下的CO容量（DtCO）大于在高droc下的。2)如表皮 厚度增加，droc的变化对DtCO的影响较小。3)的 毛细血管红细胞间距的异质性是 DtCO。4)用无基质血红蛋白溶液置换红细胞 5）随着表皮厚度的增加，红细胞被替换， 无基质血红蛋白溶液对DtCO的影响较小。六、 数学模型结合现实的几何形状和解决有限 元素分析可以描述穿过两栖动物皮肤的扩散气体通量。 所有实验均在麻醉（氨基甲酸乙酯）两栖动物上进行。CO 将通过质谱法测量穿过小块皮肤的通量， 计算DTCO。与此同时，微循环 将在具有荧光的皮肤的相同区域上测量参数。 视频显微镜： 毛细血管细胞间距，灌注毛细血管密度，红细胞流速 和毛细血管体积。在检验假设1-3时，~~将被改变， 血液稀释和血液浓缩。在假设4和假设5的检验中，红色 细胞将被人类血红蛋白交叉的无基质溶液所取代， 连接在阿尔法链之间这种血红蛋白被用来 作为血液替代品。不同种类的两栖动物 将测试和比较表皮厚度。 对两栖动物皮肤的研究将提供独特的信息 有助于理解哺乳动物气体交换的基本问题， 由于大多数的复杂性， 组织中这项研究的结果将使我们更好地了解 1）毛细血管红细胞压积的意义和非常大的， 快速变化，发生在这个参数，和2）的精确影响， 血液代用品对扩散性气体运输的影响。

The primary goal of this proposal is to determine the precise effect of the lineal red cell density in capillaries (droc) on diffusive gas transport in tissue. Capillary lineal red cell density, an index of capillary tube hematocrit, can vary rapidly over a 3-fold range under different conditions. However, its precise role in gas exchange is presently unclear. Studies on amphibian skin will determine: 1) the dependence of diffusive gas flux across the epidermis on droc at different epidermal thicknesses, 2)the heterogeneity in red cell spacing within capillaries and the effects of this heterogeneity on diffusive gas transport, and 3) the effect on tissue diffusing capacity of replacing red cells with a stroma-free hemoglobin solution. This will be accomplished by testing the following hypotheses on frog skin: 1) Changes in droc affect the tissue diffusing capacity to CO (DtCO) more at low droc than at high droc. 2) As epidermal thickness increases, changes in droc have less effect on DtCO. 3) The heterogeneity of capillary red cell spacing is an important determinant of DtCO. 4) Replacement of red cells with a stroma-free hemoglobin solution augments D,CO. 5) As epidermal thickness increases, replacing red cells with a stroma-free hemoglobin solution has less effect on DtCO. 6) Mathematical models incorporating realistic geometries and solved by finite element analysis can describe diffusive gas flux across amphibian skin. All experiments will be performed on anesthetized (urethane) amphibians. CO flux will be measured across a small patch of skin by mass spectrometry for calculation of DtCO. Simultaneously, the following microcirculatory parameters will be measured on the same region of skin with fluorescent video microscopy: droc, capillary cell spacing, perfused capillary density, red cell velocity and capillary volume. In testing Hypotheses 1-3, ~~ will be altered by hemodilution and hemoconcentration. In testing Hypotheses 4 and 5, red cells will be replaced by a stroma-free solution of human hemoglobin cross- linked between the alpha chains. This hemoglobin has been used experimentally as a blood substitute. Different amphibians with a variety of epidermal thicknesses will be tested and compared. This investigation of amphibian skin will provide unique information helpful to the understanding of basic issues in mammalian gas exchange that have not been experimentally accessible because of the complexity of most tissues. The results of this research will lead to a better understanding of 1) the significance of capillary hematocrit and the very large and rapid changes that occur in this parameter, and 2) the precise effects of blood substitutes on diffusive gas transport.