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韓國人胎兒動脈의 組織化學的檢索

Histochemical studies of fetal arteries of Korean

중앙의학 1963년 5권 1호 p.49 ~ 68
신필수,
소속 상세정보
신필수 (  ) - 연세대학교 의과대학 병리학교실

Abstract


Although innumerous literatures about arteriosclerosis have been piled up, there is no unifying conception about its etiology and pathogenesis at present. Theories and hypothesis proposed or postulated up to now are as follows. However no even single theory is satisfactory to explain the genuine pathogenesis of arteriosclerosis.
1. Senility.
2. Mechanical trauma.
3. Imbibition theory of Virchow and Aschoff.
4. Macrophage theory of Leary, Rannie and Duguid.
5. Inflammatory theory by Winternitz et al.
6. Theory of anoxemia by Hueper.
7. Lipids theory.
8. Diet theory.
9. Heredity and constitution theory.
It is also known that the arteriosclerosis is not only the phenomenon in the aged, but its early form or its antecedent lesion may be found in younger age. Present study is undertaken to investigate whether there is any similar or primordial lesions of arteriosclerosis in fetal life. Surprisingly, several new interesting findings were observed in the aortic arteries of the Korean fetuses.
II. Materials and Methods.
Materials consist of 76 fetuses obtained through artificial abortion, ranging from 2 % months to full term. Distribution of fetuses according to fetal age is as follow
Aortas, coronary arteries, renal arteries, and umbilical arteries of fetus are examined microscopically. Sections of aorta were taken from ascending, thoracic, and abdominal portion, sections of coronary arteries from anterior descending and circumflex branches close to the ostium, sections of the renal arteries from the hilum of the kidney. and sections of the umbilical arteries at any level. Sections were made by paraffin embedding after fixation in 10% formalin. Hematoxylin-Eosin, Periodic-Acid-Schiff staining, and Verhoeff´s elastic staining were made. Sudan IV staining was made in all tissues after frozen section. Microscopic examinations were made following the age of fetuses.
Ⅲ. Results.
Observations were divided in two major findings, normal and abnormal. Both normal and abnormal findings were recorded in aortas, coronary arteries, renal arteries, and umbilical arteries according to different staining and following the age of fetuses.
Normal Findings:
The intima of aortas, coronary arteries, and renal arteries were consisted of single layer of endothelial cells and internal elastic membrane throughout fetal life. Umbilical arteries, however, were lacked in distinct internal elastic membrane. The endothelial cells in early fetal life were tall cuboidal in all four arteries, with evidence of secretory activity in coronary artery, and became low cuboidal and even flattened as the fetal age increases. Well demonstrable internal elastic membrane was observed at 3rd fetal month in aorta, and 31/ month in coronary and renal arteries. The internal elastic membrane was well demarcated, rather uniform, and thin in early fetal life, and then gradually became thicker as the age increases. However, it was several times thicker than elastic fibers in media. It is a continuous membrane, but many small fenestrations, sometime giving impression of chain of interrupted fragments, and it was markedly corrugated, most prominent in renal arteries. No demonstrable connective tissue was noted in intima throughout the fetal life.
The media showed abundance of elastic fibers in aorta even in 2 /2month old fetus, but their outline was rather indistinct at early age and became clearer at later life. The elastic fibers in coronary and renal arteries were rather scanty and very fine in thickness throughout the fetal life, and it was negligible in the umbilical artery. The media of the umbilical artery is consisted of mainly thick layer of smooth muscle which became two distinct layers, inner longitudinal and outer circular from 3rd Letal month. The large portion of the media of the coronary and.
renal arteries also consist mainly of muscular layer.
The intima of aortas, coronary and renal arries was indistinct at early fetal life, then slowly formed by loose ill-outlined thick edematous connective tissue from surrounding mesenchymal tissue. It gradually condensed to become thinner and better defined tunica with coilagenization, and incoporation of fine elastic fibers derived from outer media, as the age of fetuses increases. In aorta, there was definite transformation of inner adventitia into outer media during the early fetal life.
The vasa vasorum of aorta was observed during the fifth fetal month as they branches in or incorporated from adventitia, increasing in numbers and penetrating deeper as the age increases. But even at the full-term fetus, the., did not reach beyond the ⅓of the media.
In several occasions, branching point of arteries from aorta is observed, At the outlet, internal elastic membrane became little thinner and then directly became the internal elastic membrane of branching artery together with endothelial layer, but the elastic fibers of the media emerged and polymerized to become fewer numbers and then formed the media of branching artery. The adventitia continued directly along the meda without notable change.
P.A.S. staining showed exceeding abundant P.A.S. positive materials in the media of the umbilical artery throughout entire fetal life, distributed mainly in muscle cells and fibers, and small amount in granular or fibrillarly form in interstitial area. In aorta, Coronary and renal arteries, PAS. positive -materials were observed in internal elastic membrane, and the media from early fetal life and adventitiai in later fetal life. The P.A.S. positive materials in the media were mostly located in elastic fibers, but also in muscle cells and interstitial area at early life. But in later fetal life, it was mostly noted in elastic fibers.
Sudan IV staining showed no demonstrable sudanopFilic material in all four arteries throughout entire fetal life.
Abnormal findings:
Abnormal findings were observed mostly in aorta. They were limited in the intima and inner media, consisting of proliferative intimal thickening, fraying, splitting, reduplication, and disruption of internal elastic membrane; and rnicrocystic degeneration of inner media.
The proliferative intimal thickening was observed in 10 fetuses, 3 in 5th month, 6 in 7th month, and 1 in 9th month. The involvement was mostly sectal and protruding into the lumen, and consisted of fibrous connective tissue.
The fraying of internal elastic membrane was observed in 6 fetuses, 2 in 5th month, 1 in 6th month, and 3 in 6th month. Four of them were associated with intimal thickening.
The splitting of internal elastic membrane were observed in 3 fetuses, 1 in 6½ month, 2 in 7½ month. They did. not associate with intimal thickening or fraying of internal elastic membrane.
The reduplication of internal elastic membrane was found in only one fetus, 7½ month in association with splitting of the membrane.
The disruption of internal elastic membrane was observed in 4 fetuses, 2 in 7-th month, one in 7½ month, and one in 8th month.
The microcystic degeneration of the media was observed in 11 fetuses, 2 in 5th fetal month, 3 in 6th, 5 in 7th, and 1 in 9th fetal month. They were found at subintimal part of inner media as irregular spindle shaped, isolated or communicated each other. The contents were stained faintly basophilic amorphous by hematoxylin and eosin staining, and negative by P.A.S., elastic, and Sudan stainings.
The elastic fibers of the media at the lesion became thinner, frayed´, disrupted, and separated widely between each other.
In only one fetus, 7½ month, focal calcification in the media of coronary artery was observed. Otherwise, no notable abnormal findings were found in coronary arteries.
Three fetuses showed acute non-specific inflammatory reaction of the umbilical artery with early thrombosis in the lumen, 1 in 5th month, 1 in 6 month, and I in 7%2 month. One fetus showed single umbilical artery beside inflammation, 5th fetal month.
No abnomal findings were observed in renal arteries.
I. Discussion.
Surprisingly high frequency of abnormal findings are observed in aorta during fetal life. These are consisted of proliferative intimal thickening, disturbances of internal elastic membrane such as fraying, splitting, reduplication and disruption, and microcystic degeneration of inner media. These are exceedingly interesting findings in view of that they are quite similar to various stages of arteriosclerosis observed in neonatal and adult life. These lesions are found only in aorta in present investigation. And the only lesion found in coronary arteries was focal calcification of media in one fetus. Moon (1957) found rupture of internal elastic membrane in two instances among 24 fetuses in his histochemical investigation of coronary arteries, and higher frequency of early arteriosclerotic lesions in coronary arteries among 52 infants of 0 to two years old. Oruenwald, (1949), Tolman (1 950) and Cochrane and Browden (1954) observed degenerative changes in coronary arteries of still-born fetuses. Moon and Rinehart (1952) also observed simultaneous deposition of mucopolysacchari.le at the area of proliferative intimal thickening by colloidal iron staining method. However, the P.A.S. staining in present investigation did not necessarily associated with intimal change. This discrepancy is probably due to difference of staining between P.A.S. and colloidal iron staining.
Apparently P.A.S. staining failed to demonstrate acid mucopolysaccharide as evidenced by negative staining of Wharton´s jelly in umbilical cord. The most prominent alteration of internal elastic membrane in the lesion what the author thought to be early arteriosclerotic change in present study well accord with previous reports by Wolkoff,(1923), Ehrich, de la Chappelle, and Cohn,(1931) Fox,(1933) Gross, Epstein, and Kugel,(1934), Blumenthal, Lansing. and Gray,(1950), Moon and Rinehar"t,(1952), Lindsay, Chaikoff, and Gilmore,(1952), Lansing, Rosenthal, and Dempsey,(1952), Moon(1957) who have emphasized that the most important change in pathogenesis of arteriosclerosis is degeneration of internal elastic membrane.
Microystic degeneration of inner media in present investigation is reminiscent of those of idiopathic cystic degeneration of media in adult aorta, and perhaps this is an antecedent lesion of cystic medial necrosis. McKusick (1958) reported that the medial cystic degeneration is a cause of dissecting aneurysm and he tried to investigate its genetic nature. In this connection, further investigation of microcystic change of inner media of the aorta in fetal life may throw light in pathogenesis of dissecting aneurysm of the aorta.
Three instances of acute inflammatory changes in the umbilical artery may have been resulted from the infection of amniotic fluid.
In view of sparsity of report on normal histochemical structures of major arteries during the fetal life following the age of fetus, in spite of many reports on genetic aspect of these arteries in embryology, author believes that the present report on normal developmental course of structure of major arteries during fetal life will merit to guide in future investigation.
V. Conclusions.
1. Histochemical and morphological investigations of aorta, coronary, renal and umbilical arteries of 76 fetuses, ranging from 21/2 fetal month to full-term, are made following the age of fetuses, and results are described.
2. P.A.S. positive substance was most abundantly found in the media of umbilical artery, moderate degree in intima and media of renal artery and aorta, and somewhat lesser degree in coronary arteries. These substances were thought to be neutral mucopolysaccharide in nature.
3. Rather high incidence of lesions reminiscent of those of arteriosclerosis in adult were observed in aorta. They were proliferative intimal thickening, fraying, splitting, reduplication, and rupture of internal elastic membrane. These were thought to be antecedent or primordial lesions of arteriosclerosis in neonatal and adult life. The most prominent changes were alterations of internal elasitc membrane and its significance in the genesis of arteriosclerosis was discussed.
4. In eleven instances, microcystic degeneration of inner media were observed, and the possible relationship between cystic medial necrosis of adult and causal relationship to dissecting aneurysm was discussed.
5. None of 76 fetuses showed demonstrable lipids deposition in examined arterial wall. But focal medial calcification was observed in coronary artery of one fetus. Three cases of umbilical arteritis were rather incidental findings and thought to be due to infection of amniotic fluid.

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