Morphodynamics and pathology of blood vessels II. Morphodynamic study of constriction of umbilical blood vessels and its application to coronary artery disease

The morphodynamic changes of the umbilical artery from full distension to total occlusion Within 45 seconds of delivery is very striking. On gross examination, the constricted artery shows a small, round, outer contour and reduced external diameter. On microscopic examination, it shows a small, compressed or completely obliterated lumen with an irregular wavy luminal outline, plump endothelial cells with ovoid nuclei, remodeling of the inner muscle layer with smooth muscle cells reoriented towards the luminal center, wrinkled elastic fibrils dispersed in the inner muscle layer and/or wrinkled thick internal elastic lamina, contracted smooth muscle cells with plump cellular outline and squeezed nuclear deformity, and thickened muscle bundles. A total occlusion of the umbilical arterial lumen is accomplished by maximal contraction of smooth muscle cells in the outer muscle layer. This contraction creates thick muscle bundles, generates a constrictive force to reduce the outer circumference and external diameter, and then causes the inward projection of the inner muscle layer to obliterate the lumen. The morphological changes of smooth muscle cells and the remodeling of the arterial wall by muscle contraction and constriction can also be found in the coronary arteries of patients who died of occlusive coronary artery disease. Coronary artery constriction or spasm can cause (1) remodeling of soft atheromatous plaques, resulting in nonthromboric occlusion; (2) volcano-like eruption of soft atheromatous plaques, resulting in thrombus formation; and (3) tearing of the nonatherosclerotic arterial wall, resulting in dissection and compressive hematoma in the arterial wall. Presented in part at the 30th Annual Meeting, International College of Angiology, Amsterdam, The Netherlands, June 1988 Correspondence to: Ching-Shen Lin, M.D., Department of Pathology (Box 1194), The Mount Sinai Medical Center, One Gustav L. Levy Place, New York, NY 10029-6574 Introduction Artery spasm implies a transient or prolonged constriction of the arterial lumen by contraction of vascular smooth muscle cells. Clinically, coronary artery spasm (CAS) can be demonstrated in angiograms. The CAS can develop spontaneously, can be induced by ergonovine and other vasoconstrictors, and can be relieved by nitroglycerin and other vasodilators. The myocardial ischemic effects of CAS can be reflected in electrocardiograms and demonstrated by thallium scan [1]. Clinically, CAS can lead to artery thrombosis, myocardial infarction, or death [2,3]. CAS has been seen and palpated by Kattus [4] during coronary artery bypass surgery. In a discussion of the causal relationship between coronary artery spasm and angina pectoris in 1935, Saphir et al. [5] stated, "From the point of view of the morphologist, nothing can be said for or against spasm of the coronary arteries as the cause of angina pectoris because evidence cannot be obtained of the existence of spasm in the gross or histologic picture. " Currently it is believed that CAS cannot be demonstrated grossly and histologically by pathologists [6]. In three autopsy reports [7-9] of patients who had angiographically documented CAS, gross and histological findings indicative of CAS were not documented. We believe that morphological evidence of persistent or irreducible constriction can be found at autopsy. We first studied case 6 in 1977 and obtained morphological evidence of constriction as a cause of plaque rupture. Subsequently we have attempted to illustrate and interpret the morphological changes of coronary atherosclerosis with thrombotic occlusion by using a dynamic process [10,11] and have shown morphological evidence of CAS [11]. Subsequent to initial study presenting a morphodynamic interpretation of acute coronary thrombosis, with special reference to volcano-l ike eruption of atheromatous plaque caused by coronary artery constriction or spasm [11], we studied umbilical arteries and have demonstrated gross and histological evidence of contraction of vascular smooth 120 C. -S. Lin et al.: Constriction of Umbilical Blood Vessels and Coronary Artery Disease C. -S. Linet al.: Constriction of Umbilical Blood Vessels and Coronary Artery Disease 121 muscle cells and constriction of the umbilical artery with total occlusion of the lumen. On the basis of these observations, we can apply the morphological changes of smooth muscle cells and the architectural changes of the wall of the umbilical artery and vein by muscle contraction and constriction to better understand occlusive coronary artery disease. Specifically, we can now explain (1) the mechanism of acute nonthrombotic atheromatous occlusion, (2) volcanolike rupture of soft atheromatous plaque with thrombosis, (3) spontaneous tear of nonatherosclerotic arterial wail with dissection and compressive hematoma in arterial wall, (4) failure of thrombus retrieval [12], and (5) failure of response to nitroglycerin or thrombolytic agents in many patients with myocardial infarction [13]. Three autopsy reports of patients who died from angiographically documented CAS are also reviewed for comparison with the constricted umbilical arteries. Herein the term morphodynamics is defined by morphological changes caused by force, mainly generated from contraction of smooth muscle cells. Morphological evidence for vasoconstriction or CAS is proposed. Materials and Methods Two normal umbilical cords were studied prior to separation from the newborns at delivery; the cords were simultaneously clamped in two separate areas with surgical clamps. We designated the segments between the surgical clamps as "the pressurized, distended segments". All specimens were fixed in 4% neutral buffered formalin for 48 hours. The fixed cords were then cross-sectioned perpendicular to the long axis of the blood vessels. Four tissue blocks were taken from each distended segment, and 7 tissue blocks from each constricted segment. In total. 11 tissue blocks were taken from each cord for paraffin preparation. Areas of focal constriction, so-called Fold of Hoboken, from the distended arterial segment of the second cord were also cut transversely and longitudinally. Before submission to the paraffin process, the blood clots in the umbilical vessels were drained out with tap water. The paraffin blocks were cut serially at 5 txm and stained with hematoxylin and eosin, Masson's trichrome, and elastica van Gieson's stains. Two hundred placentas with nonpressurized cords, Fig. l. The first umbilical cord (UC) from a full-term normal vaginal delivery. (A) Fresh spiral cord, a middle segment of the UC is clamped before separation from the newborn and shows indentations with Folds of Hoboken (arrows). (B) Low power histological view of cross-sections of UC, $2. and $3 are from the clamped, pressurized segment and contain one vein (V) and one artery (A1) distended with blood pressure and one constricted artery (A2). S I and $4 are from the nonpressurized segment and contain two constricted and occluded arteries (A1 & A2) and a severely constricted vein (V). Note contracted muscle bundles (*) in the outer layer of welPdistended vascular wall of $2-3 (hematoxylin and eosin stain 3x). (C) Micrographs of transitional morphological changes of nuclei of SMCs from distension to severe contraction. Grade 1 indicates a straight, thin, long nucleus of distended SMC, and grades 2, 3, and 4 passively squeezed nuclei of mildly, moderately, and severely contracted SMCs, respectively. Note bars indicating distended nuclear length: grade 3, 40% shortened, and grade 4, 70% shortened. (hematoxylin and eosin stain, lower right, oil immersion 750x, others 300x). (D) and (E) Elastica van Gieson's stain of the distended (S2AI) and constricted arteries, respectively. The distended artery has a large lumen, smooth luminal and external outline, thin wall and inconspicuous elastic fibrils in the inner muscle layer. The constricted artery has a small round external outline, a small irregular lumen, thick wall, and irregularly condensed elastic fibrils in the inner muscle layer. The star areas are magnified. Note a large arrow indicating condensed elastic fibrils forming wrinkled elastic lamina, medium-sized arrow indicating laminated condensed fibrils, and small arrows indicating thin fibrils (D upper and E upper 13x, D lower 400x, E lower 50x). which were submitted to surgical pathology for routine examination, were studied fl)r comparison with the distended blood vessels, and one of the constricted umbilical arteries was distended with formalin fixative by hand pressure infusion for comparison study. The umbilical cords from three stillborn fetuses and five premature newborns were also studied. The method of examination of the atherosclerotic coronary arteries at autopsy has been described in a previous report [11].