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T he patent ductus arteriosus (PDA) is a vascular structure that connects the proximal descending aorta to the roof of the main pulmonary artery near the origin of the left branch pulmonary artery. This essential fetal structure normally closes spontaneously after birth. After the first few weeks of life, persistence of ductal patency is abnormal. The physiological impact and clinical significance of the PDA depend largely on its size and the underlying cardiovascular status of the patient. The PDA may be "silent" (not evident clinically but diagnosed incidentally by echocardiography done for a different reason), small, moderate, or large. Regardless of the size, complications may arise, and it is important for both pediatric and adult cardiologists to have an understanding of the pathophysiology, clinical implications, and management of PDA. EmbryologyThe ductus arteriosus is a normal and essential fetal structure that becomes abnormal if it remains patent after the neonatal period. In normal cardiovascular development, the proximal portions of the sixth pair of embryonic aortic arches persist as the proximal branch pulmonary arteries, and the distal portion of the left sixth arch persists as the ductus arteriosus, connecting the left pulmonary artery with the left dorsal aorta (Figure 1). Normally, the distal right sixth aortic arch loses its connection to the dorsal aorta and degenerates. This transformation is complete by 8 weeks of fetal life. Normal Physiology Fetal CirculationWhereas Ϸ65% of the fetal cardiac output is from the right ventricle, only 5% to 10% passes through the lungs. 1,2 The preponderance of right ventricular output passes through the ductus arteriosus into the descending aorta. The fetal ductus arteriosus is thus an important structure that is essential for normal fetal development, permitting right ventricular output to be diverted away from the high-resistance pulmonary circulation. Premature constriction or closure may lead to right heart failure, resulting in fetal hydrops. 3 Histology and Mechanisms of Normal ClosureGrossly, the constitution of the fetal ductus arteriosus appears to be similar to the contiguous main pulmonary artery and descending aorta; there are important histological differences, however. 4 -9 Whereas the mediae of surrounding aorta and pulmonary artery are composed mainly of circumferentially arranged layers of elastic fibers, the media of the ductus arteriosus is composed of longitudinally and spirally arranged layers of smooth muscle fibers within loose, concentric layers of elastic tissue. The intima of the ductus arteriosus is thickened and irregular, with abundant mucoid material, sometimes referred to as intimal cushions.Fetal patency of the ductus arteriosus is controlled by many factors, the most important of which are relatively low fetal oxygen tension 10 and cyclooxygenase-mediated products of arachidonic acid metabolism (primarily prostaglandin [PGE 2 ] and prostacyclin [PGI 2 ]). 11 Locally produced and circulating PGE 2 and PGI 2 in the fetus cau...

Previous studies suggested that tetrodotoxin, a poison from the puffer fish, blocks conduction of nerve and muscle through its rather selective inhibition of the sodium-carrying mechanism. In order to verify this hypothesis, observations have been made of sodium and potassium currents in the lobster giant axons treated with tetrodotoxin by means of the sucrose-gap voltageclamp technique. Tetrodotoxin at concentrations of 1 X I0 -~ to 5 X 10 -9 gm/ml blocked the action potential but had no effect on the resting potential. Partial or complete recovery might have occurred on washing with normal medium. The increase in sodium conductance normally occurring upon depolarization was very effectively suppressed when the action potential was blocked after tetrodotoxin, while the delayed increase in potassium conductance underwent no change. It is concluded that tetrodotoxin, at very low concentrations, blocks the action potential production through its selective inhibition of the sodium-carrying mechanism while keeping the potassium-carrying mechanism intact.Tetrodotoxin is the active principle of the puffer poison which has long been a matter of interest because the puffer fish is one of the major sea foods in Japan. It blocks peripheral nerve and muscle conduction as well as the central nervous system at very low concentrations (Fleisher, Killos, and

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Measurements of the potassium current in the squid axon membrane have been made, after changes of the membrane potential to the sodium potential of Hodgkin and Huxley (HH), from near the resting potential, from depolarizations of various durations and amplitudes, and from hyperpolarizations of up to 150 mv. The potassium currents I given by I = I(infinity) {1 - exp [- (t + t(0))/tau]}(25), where t(0) is determined by the initial conditions, represent the new data and approximate the HH functions in the regions for which they are adequate. A corresponding modification for the sodium current does not appear necessary. The results support the HH assumptions of the independence of the potassium and sodium currents, the dependence of the potassium current upon a single parameter determined by the membrane potential, and the expression of this parameter by a first order differential equation, and, although the results drastically modify the analytical expressions, they very considerably extend the range of apparent validity of these assumptions. The delay in the potassium current after severe hyperpolarization is used to estimate a potassium ion mobility in the membrane as 10(-5) of its value in aqueous solutions.

In this multi-institutional cohort, the incidence of AE is higher among interventional compared to diagnostic cases, and is very low among biopsy cases. Equitable comparisons among institutions will require the development and application of risk adjustment methods.

Conduction of impulses in myelinated axons has been studied by a new method of computer simulation. The contributions of nodal and internodal characteristics and parameters were examined. Surprisingly, the conduction velocity, theta, was found to be quite insensitive to the nodal area or the exact description of its excitable processes. The conduction velocity also is relatively insensitive to the internodal length but much more sensitive to the myelin capacitance and axoplasm conductance. Qualitative change in theta with temperature depended on which temperature-sensitive parameters were included in the simulation.

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