SURGERY THE EFFECTS OF ADENOSINE ON DUCTUS ARTERIOSUS

先天性心脏病代表了广泛的血流动力学改变 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 动脉导管，因为这是血流的唯一来源， 肺 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） 出生前后动脉导管未闭的维持。 具体而言，本提案的目标是确定：（1）如果 内源性腺苷在调节导管阻力中起作用， 评价氨茶碱和双嘧达莫（药剂）的体内作用 已知减弱和增强腺苷反应） 其中在以下条件下监测导管前和导管后压力以及导管流量 （a）不通风，（B）100% N2通风，和（c） 100%O_2通气;（2）血PO_2、 循环腺苷动脉和静脉血浓度，以及导管 在上述相同条件下的阻力;（3）导管组织是否 腺苷的作用不依赖于循环血浆腺苷， 评价离体灌注导管对O2的反应， 有无氨茶碱和潘生丁;（4）导管组织 腺苷含量在离体灌注导管时，灌注液 用（a）100%N2、（B）10%O2和（c）100%O2鼓泡;（5） 5足核苷酸酶和核苷组织化学定位 用戊二醛原位固定动脉导管， 用特定的单磷酸核苷酸孵育组织， 释放的磷酸盐与铅在反应位点，这可以是 通过电子显微镜检测。 从这一点上获得的信息 该项目不仅将提供关于参与机制的基本数据， 动脉导管关闭，但可能会导致新的合理的 先天性心脏病的治疗方法。

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.