Calcification of epicardial stretches of bridged coronary arteries in man

Journal of Atherosclerosis Research

Elsevier Publishing Company, Amsterdam - Printed in The Netherlands

121

CALCIFICATION OF E P I C A R D I A L S T R E T C H E S OF B R I D G E D CORONARY A R T E R I E S I N MAN

A. ZECHMEISTER Department of Anatomy, School of Medicine J. E. Purkynje, University of Brno, Brno (Czechoslovakia)

(Received September 16th, 1968)

SUMMARY

Calcium deposits in the wall of the anterior descending branch of the left coronary artery were investigated in hearts with myocardial bridges of the ant. descending branch and in hearts without these bridges, i.e., where this branch ran an epicardial course. The results showed the amount of calcium to be twice as high when bridges were present as when they were absent. Increased calcium deposits appear during the course of atheromatosis. The differences in calcification between the bridged and unbridged arteries show the highest degree of statistical significance in the third degree of atheromatosis. Myocardial bridges begin to exercise their effec~ during the 5th decade of life when calcification in the arterial wall is sharply accelerated. The greatest difference between the two groups is seen in the 6th decade. In bridged cases, increased calcium deposit occurs in the sections proximal and distal to the bridge, while the section covered b y the bridge is comparable to the amount of calcium found in all three segments of the unbridged specimens. The position of the bridge was found to influence the amount of calcium deposited, with only bridges lying proximally (distance from bifurcation of the left coronary artery to the proximal edge of the bridge on the ant. descending and circumflex branches, 3.5 cm) having an effect. Muscular bridges lying distally had no influence on the deposits.

INTRODUCTION In the walls of the coronary arteries advanced sclerotic changes are associated with the deposit of minerals, particularly calcium. On occasion, the varying distribution of these deposits can lead to complete vascular occlusion. We had recently investigated the influence exerted b y muscular bridges on the coronary arteries in j . Atheroscler. Res., 1969, 9:121-129

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cholesterol-induced a t h e r o m a t o s i s in dogs la a n d its relation to t h e incidence of a n t e r i o r m y o c a r d i a l infarction in h u m a n s la. W e were now i n t e r e s t e d in w h e t h e r these bridges could, in a n y way, affect t h e d e p o s i t of calcium in the c o r o n a r y wall of t h e h u m a n heart. W e desired in this s t u d y to define t h e q u a n t i t a t i v e differences of calcium deposits in cases where a m y o c a r d i a l b r i d g e was present a n d those where the a r t e r y followed an e p i c a r d i a l course a n d was u n b r i d g e d . MATERIAL AND METHOD The e x p e r i m e n t a l m a t e r i a l - - s u p p l i e d b y t h e Brno I n s t i t u t e of F o r e n s i c M e d i c i n e - - c o n s i s t e d of 82 h e a r t s from 48 male a n d 34 female donors r a n g i n g from 19-87 years, w i t h a 0 - V degree of sclerosis. F o r t y - o n e h e a r t s d i s p l a y i n g m y o c a r d i a l bridges of the c o r o n a r y arteries on t h e ant. descending b r a n c h were o b t a i n e d b y a n a t o m i c a l dissection 12 a n d t h e n a n o t h e r 41, w i t h a p u r e l y e p i c a r d i a l course a n d w i t h o u t m y o c a r d i a l bridges, were sought to serve as controls (Fig. 1). I n selecting t h e controls, o t h e r v a r i a b l e s were t a k e n into a c c o u n t a n d regulated; these included stage of a t h e r o m a t o s i s u n i f o r m to :t: 1~ e v a l u a t e d according to ZECHMEISTER AND KREjZLfI
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Fig. 1. Diagram of the heart, facies sternocostalis cordis, showing portions measured in investigating the degree of calcium deposits in the arterial wall of the anterior descending branch (r. interventricularis ant. a. coronariae cordis sin.). A: the arterial portion before the bridge; B: the portion below the bridge; C: the portion after the bridge. A', B' and C' refer to corresponding portions in the control group and X is X'. J. Atheroscler. Res., 1969, 9:121-129

CALCIFICATION OF EPICARDIAL STRETCHES OF BRIDGED CORONARY ARTERIES

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bridges were used. The coronary artery was excised and relieved of its subepicardial fat thus exposing the myocardial bridge. The width of the bridge was then measured as was the distance from the bifurcation of the left coronary artery on the ant. interventricularis and circumflex branches to the proximal margin of the bridge. The amount of calcium deposit in the arterial wall was determined in the portion immediately below the bridge and in portions, equivalent to it in length, proximal and distal to the bridge; it was then determined in the corresponding portions in the controls. The segments (referred to here as A, B and C, from the bridged arteries, and as A', B' and C' from their unbridged equivalents) were thoroughly washed in distilled water, divided into small pieces, and at a temperature of 105-110~ were dehydrated to a constant weight. The sample was then placed into a boiling solution of 10 ml of concentrated H N 0 3 + concentrated HC1 (1 : 1), and heated until nitrogen peroxide fumes were released. The exact calcium content was then measured by a flame photometer, this method being similar to that employed for estimation of blood calcium. The following results were obtained: (1) the dry weight of segments A, B and C and of the corresponding segments A', B' and C'; (2) the absolute calcium content of segments A, B and C and segments A', B' and C'. Because the length of single segments differed in individual cases, we took the calcium content of 100 mg of dried matter mg Ca/100 mg dried matter as a standard for comparison and calcium content evaluation. The calcium content was determined in all three segments of both bridged and unbridged specimens, i.e., in all 82 specimens. RESULTS

In the 41 bridged specimens the mean calcium value in 100 mg of dried matter

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j . Atheroscler. Res., 1969, 9 : 1 2 1 - 1 2 9

124

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Fig. 3. Degree of calcification of individual arterial segments in the bridged arteries (A, B, C) and in the corresponding segments of the unbridged coronary arteries (A', B', C'). 0-IV: macroscopic degree of atheromatosis with the mean degree of calcium concentration in the artery wall. a m o u n t e d to 2.60 mg Ca; in the u n b r i d g e d specimens it came to only 1.26 mg Ca. The calcium deposit in the bridged arterial segments, therefore, was twice as m u c h as in the u n b r i d g e d ; this means, an increased mineralisation a n d higher degree of sclerosis (Fig. 2). I n bridged specimens there was e s t i m a t e d to be i n segment A 3.88 m g Ca/ 100 m g dried m a t t e r , a n d in segment C 2.03 mg Ca/100 mg dried m a t t e r , which was twice as m u c h as the a m o u n t found in segment B 1.52 mg Ca/100 mg dried m a t t e r . I n the control group calcium c o n t e n t in all three segments was a p p r o x i m a t e l y the

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Fig. 4. Calcium concentration in the wall of bridged and unbridged coronary arteries (r. intezventricularis ant.) during the course of atheromatosis. 0-V: macroscopic degree of atheromatosis (abscissa) with the mean degree of calcium concentration (ordinate) in the artery wall.

J. Agheroscler. Res., 1969, 9:121-129

CALCIFICATION OF EPICARDIAL STRETCHES OF BRIDGED CORONARY ARTERIES

125

same: A', 1.16 mg Ca/100 mg dried matter; B', 1.63 mg Ca/100 mg dried matter; C', 1.04 mg Ca/100 mg dried matter (Fig. 3). These figures approximate the degree of calcification found in the portion under the bridge from the bridged group. It follows, then, that while the bridge does not actually protect the portion below it from the sclerotic process--for the calcium content here is the same as in its corresponding segment (B') from the unbridged artery--there is, in fact, a greater build-up of mineral deposits (sclerosis) in the segments proximal and distal to the bridge. At the same time, the factor of the bridge does not have the same quantitative effect in all cases. The influence exerted on the calcium deposit in the arterial wall during atheromatosis is illustrated in Fig. 4. During the development of the disease there is marked intensification of the calcification in the bridged cases, whereas only a slight increase of calcification is observed in the unbridged sections. The following figure (Fig. 5) shows the greater deposit of calcium in segments A and C of the bridged specimens, whereas the condition of segment B scarcely differs from that of segment B' even in developing atheromatosis. The presence of the bridge caused a higher calcium deposit in the proximal and distal segments in about 50 % of the specimens; a lesser effect was seen to occur where the degree of atheromatosis was lower (0-I; representing about one-third of the specimens) and was enhanced where the degree was higher (IV-V; about two-thirds). Even so, in about one third of the specimens, the bridge, in effect, played no role even where the artery was in an advanced stage of atheromatosis. Med.

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Fig. 5. C a l c i u m c o n c e n t r a t i o n in t h e s e p a r a t e s e g m e n t s of t h e b r i d g e d a n d u n b r i d g e d c o r o n a r y arteries d u r i n g t h e course of a t h e r o m a t o s i s . Prox.: p r o x i m a l s e g m e n t ( - - , A ; - - -, A'); m e d . : medial segment (--, B; - - - , B'); dist.: distal s e g m e n t ( - - , C; - - - , C'). O-V: macroscopic degree of a t h e r o m a t o s i s (abscissa) w i t h t h e m e a n degree of c a l c i u m c o n c e n t r a t i o n (ordinate) in t h e a r t e r y wall.

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A. ZECHMEISTER

Up to the age of 40, the calcium deposit in the anterior descending branch (Fig. 6) of both bridged and unbridged arteries is low, but within the next decade (40-50 years) a sharp incline takes place which, in contrast to the earlier years, manifests itself in the bridged cases. Fig. 7 again illustrates that the influence of the

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Fig. 6. Influence of age on calcification in bridged ( . . . . ) a n d u n b r i d g e d ( . . . . . ) c o r o n a r y arteries. 0-V: m a c r o s c o p i c degree of a t h e r o m a t o s i s w i t h t h e m e a n degree of c a l c i u m c o n c e n t r a t i o n in t h e a r t e r y wall.

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Fig. 7. C a l c i u m c o n c e n t r a t i o n in t h e c o r o n a r y a r t e r y wall d u r i n g t h e course of age. Prox. : p r o x i m a l segments (--, A; ---, A'); med.: m e d i a l s e g m e n t s ( - - , B; - - - , B'); dist.: distal s e g m e n t s (--, C; - - - , C'). 0 - V : m a c r o s c o p i c degree of a t h e r o m a t o s i s w i t h t h e m e a n degree of c a l c i u m c o n c e n t r a t i o n in t h e a r t e r y wall.

.]'. Atheroscler. Res., 1969, 9 : 1 2 1 - 1 2 9

CALCIFICATION OF EPICARDIAL STRETCHES OF BRIDGED CORONARY ARTERIES

127

bridge over the coronary artery is expressed in the intensified calcification of the artery in the segments proximal and distal to the bridge. The influence exercised by the myocardial bridge depends partly upon its position across the anterior descending branch. Only a myocardial bridge lying proximally produces uneven distribution of calcium. The influence of bridges with a mean distance of 3.5 cm from the left coronary bifurcation to the ant. descending branch and to the circumflex branch, proved to be statistically significant in the uneven distribution of calcium. Bridges lying distally show no apparent effect upon calcium deposit. DISCUSSION

Reports in the literature by authors who have observed the influence of muscular bridges on the unequally developing sclerotic process are contradictory so far. GEIRINGER4 was the first to point out that in the arterial portion below the bridge, termed by him the "mural" portion, the character of the human intima does not change, while the portions proximal and distal to the bridge, the "epicardial" portions, become thickened with advancing age. EDWARDS et al. 2 and KALUg5 were the first to investigate the possible implications of muscular bridges over the coronary arteries in the pathogenesis of coronary occlusions and myocardial infarction. The results of both these authors have shown that the degree of atheromatosis proximal to the bridge is not directly dependent upon the bridge itself. POLA~EK7 investigated the condition of the intima and found a significant thickening of this coat before the bridge and the frequent occurrence of vascular occlusion and myocardial infarct in hearts with myocardial bridges. The results of the present study conform with those of GEIRINGER4 and POL/~EK 7 in verifying the significance of muscular bridges in the unequal development of the sclerotic process in the coronary arteries in atheromatosis. In control cases, however, the calcium concentration in the arterial wall remains the same in both bridged and unbridged arteries, i.e., arteries running an epicardial course. This adverse effect was also shown in atheromatosis in dogs. In "normal" dogs 10, no effect from bridges was found in the arteries; but in cholesterol-induced atheromatosis in dogs, the bridges again caused unequal development of the sclerotic changes in the arterial wall which were most apparent before the myocardial bridge in the main trunk; in the small branches ramifying before the bridge, this even led to complete occlusion 13. Similarly, in humans 12 not suffering from atheromatosis or in less advanced (stages I-III) cases of atheromatosis, no marked changes were found and the incidence of ant. myocardial infarction was not greater in bridged cases than in unbridged. In bridged cases with a higher degree of atheromatosis (IV-V), the incidence of myocardial infarction was high, the difference being statistically significant. The method generally employed for evaluation and determination of the atheromatotic changes in the arterial segments (i.e., the segments proximal, below and distal to the bridge), whether it be in macroscopic or microscopic investigation, J. Atheroscler. Res., 1969, 9:121-129

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A. ZECHMEISTER

c a n n o t give a c o m p l e t e l y true (objective) p i c t u r e of t h e degree of a t h e r o m a t o s i s existing in these i n d i v i d u a l segments. F o r this reason, an a t t e m p t was m a d e to establish t h e degree of a t h e r o m a t o s i s b y a q u a n t i t a t i v e m e t h o d which would give a precise expression of t h e differences in t h e segments: a s t a t i s t i c a l e v a l u a t i o n a n d also a c o m p a r i s o n b e t w e e n a wider series of specimens. F u r t h e r m o r e , while the results refute t h e s u p p o s i t i o n of GEIRINGER4 a n d POL2{~EK7 t h a t t h e u n d e r l y i n g section of t h e a r t e r y is p r o t e c t e d b y t h e bridge, a m o r e a d v a n c e d degree of a t h e r o m a t o s i s is in fact f o u n d in t h e sections p r o x i m a l a n d d i s t a l to it t h a n in t h e b r i d g e d section itself. I n o t h e r words, t h e degree of a t h e r o m a t o s i s in this l a t t e r p o r t i o n is a l m o s t i d e n t i c a l w i t h t h e e q u i v a l e n t portions in t h e u n b r i d g e d a r t e r y of t h e controls, i.e., in t h e a r t e r y r u n n i n g epicardially. E x p e r i e n c e gained b y o b s e r v a t i o n of t h e c o r o n a r y a r t e r y in dogs in vivo m a y serve to e x p l a i n t h e increased d e p o s i t of calcium before a n d b e h i n d t h e m y o c a r d i a l bridges. I t was seen t h a t in t h e presence of a m y o c a r d i a l bridge, changes m a y be b r o u g h t a b o u t in the course of t h e a r t e r y a n d in t h e c h a r a c t e r of its l u m e n which are affected d u r i n g c a r d i a c actionl,3,6,8, 9. D u r i n g systole, t h e m y o c a r d i a l b r i d g e forces t h e p o r t i o n of t h e ant. descending b r a n c h l y i n g i m m e d i a t e l y below it into t h e shape of a V, a n d d e p e n d i n g u p o n the pressure e x e r t e d b y t h e bridge, t h e wall of the vessel at this site is liable to become flattened. These m o r p h o l o g i c a l changes in t h e course a n d l u m e n of t h e a r t e r y can result in a l t e r e d h a e m o d y n a m i c s in t h e i n d i v i d u a l a r t e r i a l portions, a n d this v e r y d i s t u r b a n c e m i g h t l e a d to the b u i l d i n g u p of calcium a n d t h e v a r i a t i o n s in the sclerotic process in general. ACKNOWLEDGEMENTS

T h e a u t h o r wishes to t h a n k Mr. M. B ~ r t l for t e c h n i c a l help w i t h t h e a n a l y t i c a l m e t h o d a n d Dr. M. Stejfov~ from t h e Central L a b o r a t o r y of t h e Medical School, U n i v e r s i t y of Brno, for excellent t e c h n i c a l assistance.

REFERENCES I ]3LOOR, C. M. AND 1{. M. LOWMANN, Myocardial bridges in coronary angiography, Amer. Heart J., 1963, 65: 195-199. 2 EDWARDS, J. C., C. ]3URNSIDES, R. L. SWARM AND A. I. LANSING, Arteriosclerosis in the intramural and extramural portions of coronary arteries in the human heart, Circulation, 1956, 13: 235-241. 3 ELI~KA, O., V. SKOP AND O. HAMET, Bends in the coronary arteries after removal of muscle bridges, Acta radiol. (Stockh.), 1968, 7: 470-480. 4 GEIRINGER, E., The mural coronary, Miner. Heart J., 1951, 41: 359-468. 5 KALU~, M., Vztah aterosklerosy a ischemick35ch zm~n srde~nlch ke svalov3~m mflstkflm koron~rnfch arterif, Acta Univ. Carol. Med. (Praha), 1963, 7: 605-610. 6 LOWMANN, R. M. AND M. C. BLOOR, Angiography of the intramural coronary segments in experiment in animals, Acta radiol. (Stockh.), 1962, 57: 24-30. 7 POL~EK, P., Relation of myocardial bridges and loops on the coronary arteries to coronary occlusions, Amer. Heart J., 1961, 61: 44-52. 8 POL~EK, P., L. STENHART, J. ENDRYS AND J. VYSLOU~IL, Muscular bridges and loops over coronary arteries in coronariograms, Cs. Morfol., 1962, 10: 251-258. 9 PORSTMANN, V~. AND J. IWIG, Die intramurale Koronararterie im Angiogramm, Fortschr. ROntgenstr., 1960, 92: 129-133. J. Atheroscler. Res., 1969, 9:121-129

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10 ZECHMEISTER, A., Macroscopic a n d microscopic o b s e r v a t i o n s of m u s c u l a r (myocardial) b r i d g e s

a n d loops over c o r o n a r y arteries of dogs, Folia morph. (Praha), 1965, 1 3 : 1 - 1 1 . 11 ZECHMEISTER, A. AND P. POLACEK, T h e incidence of m y o c a r d i a l bridges a n d loops in r e l a t i o n

to t h e v a r i o u s t y p e s of ramification of t h e c o r o n a r y arteries, Folia. morph. (Praha), 1967, 15: 34-44. 12 ZECHMEISTER, A. ANn Z. KREJZLiK, M e t h o d i s c h b e d i n g t e Differenzen der U n t e r s u c h u n g s r e s u l t a t e fiber die M y o k a r d b r f i e k e n u n d -schlingen, Scr. reed. Fac. Med. Brun., 1967, 40: 27-36. 13 ZECHMEISTER, A., T h e influence of m y o c a r d i a l bridges on t h e wall of t h e c o r o n a r y arteries d u r i n g e x p e r i m e n t a l cholesterol atherosclerosis in dogs, I n p r e p a r a t i o n . 14 ZECHMEISTER, A. AND Z. KREJZLfK, A u f t r e t e n des V o r d e r w a n d i n f a r k t e s u n t e r b e s o n d e r e r Beriicksichtigung seines V e r h a l t e n s zu M y o k a r d b r f i c k e n fiber d e m R a m u s intervelltricularis a n t e r i o r der A r t e r i a c o r o n a r i a cordis sinistra, Zbl. allg. Path. path. Anat., 1968, 111: 391-401.

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