SURGERY THE EFFECTS OF ADENOSINE ON DUCTUS ARTERIOSUS

先天性心脏病是一种广泛的血流动力学改变。 会影响肺和心脏功能。在某些形式的 先天性心脏病，婴儿的存活取决于通畅性 动脉导管，因为这是唯一的血流来源 肺部。这样做的长期目标是确定什么角色，如果有的话， 腺苷(一种内源性释放的血管活性腺嘌呤核苷)起作用 出生前后动脉导管未闭的维持。 具体地说，本提案的目标是确定：(1) 内源性腺苷通过以下途径调节导管阻力 氨茶碱和潘生丁的体内药效评价 已知可减弱和增强腺苷反应) 其中导管前后的压力和导管的流动是在 (A)不通风，(B)100%氮气通风，和(C) (2)血氧饱和度与血氧饱和度的关系。 动脉和静脉循环中的腺苷浓度和导管 阻力；(3)导管组织是否 腺苷通过以下途径发挥独立于循环血浆腺苷的作用 评价离体血流管对氧的反应 有无氨茶碱和潘生丁；(4)导管组织 当灌流液被灌流时，离体灌流导管中的腺苷含量 用(A)100%氮气、(B)10%O2和(C)100%O2；(5) 5英尺核苷酸酶和核苷的组织化学定位 通过用戊二醛原位固定动脉导管来进行磷酸化， 用特定的单磷酸核苷酸孵育组织，并捕获 在反应部位与铅一起释放的磷酸盐，可以是 通过电子显微镜检测到的。从这一点上获得的信息 项目不仅将提供有关 动脉导管的闭合，但很可能导致新的理性 治疗某些形式的先天性心脏病的方法。

Congenital heart disease represents a wide spectrum of altered hemodynamics which affect pulmonary and cardiac function. In certain forms of congenital heart disease, survival of infants is dependent upon patency of the ductus arteriosus as this represents the only source of blood flow to the lungs. The long-term goals of this are to determine what role, if any, adenosine (an endogenously released vasoactive adenine nucleoside) plays in the maintenance of patent ductus arteriosus before and after birth. Specifically, the objectives of this proposal are to determine: (1) if endogenous adenosine plays a role in modulating ductal resistance by evaluating in vivo the effects of aminophylline and dipyridamole (agents known to attenuate and potentiate the adenosine response) in the fetal lamb in which pre- and post-ductal pressures and ductal flow are monitored under conditions of (a) nonventilation, (b) ventilation with 100% N2, and (c) ventilation with 100% O2; (2) the relationship between blood PO2, circulating adenosine arterial and venous blood concentrations, and ductal resistance under the same conditions as above; (3) whether ductal tissue adenosine plays a role independent of circulating plasma adenosine by evaluating the response of the isolated perfused ductus to O2 in the presence and absence of aminophylline and dipyridamole; (4) ductal tissue adenosine content in the isolated perfused ductus when the perfusate is bubbled with (a) 100% N2, (b) 10% O2, and (c) 100% O2; (5) the histochemical localization of 5 feet-nucleotidase and nucleoside phosphorylase by fixing the ductus arteriosus in situ with glutaraldehyde, incubating the tissue with specific monophosphate nucleotides, and trapping the released phosphate with lead at the site of reaction, which can be detected by electron microscopy. The information to be gained from this project will not only provide basic data on the mechanisms involved in the closure of the ductus arteriosus, but may well lead to new rational approaches for the treatment of certain forms of congenital heart disease.