Cardiovasc Path4 Vol. I, No. 3 July-September 1992:205-210

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Branch Location in the Left Anterior Descending Coronary Artery and Its Relation to the Known Distribution of Early Atherosclerosis N.R.B. Gary, T. Biggs,* and W.A. Seed,* From the Department of Pathology, Papworth Hospital, Cambridge, and the *Department of Medicine, Charing Cross and Westminster Medical School, London

The circumferential and longitudinal locations of branches were determined for 33 left anterior descending coronary arteries (LADS) from persons aged less than 40 years who had died of noncardiovascular causes. In 17, branch location was determined using digitized maps of opened perfusion fixed arteries. In the remainder branch location was measured directly from resin casts of the arteries. Branch location showed a fairly uniform longitudinal distribution throughout the LAD. In the proximal 3 cm of the LAD-the segment known to be principally involved in early atherosclerosis-the results indicate symmetrical distribution of branches, with origins from the posterior and, particularly, both lateral walls. This is in sharp contrast to the known distribution of early atherosclerotic lesions in this area, which occur mainly on the side wall opposite the flow divider separating the circumflex.

This study suggests that these branches are not an important determinant for location of atherosclerosis in this site.

The tendency of the arterial intima to be thickest in regions of branching was described by Rokitansky (1). In the aorta there is evidence that branches are a localizing factor for atherosclerosis (2). Atherosclerotic plaques are more common around the mouths of intercostal arteries and immediately adjacent to the origins of larger vessels, such as the celiac axis. In smaller vessels a distinctive pattern of atherosclerosis is seen in relation to major bifurcations. Several bifurcations have been studied in great detail, including the carotid (3) and left main coronary (4-6). In these sites early atherosclerotic disease in the two daughter vessels of a bifurcation occurs mainly proximally on the outer walls-i.e., on the walls directly opposite and downstream from the main flow divider. This phenomenon is well illustrated in the left anterior descending coronary artery (LAD), where 80% of early atherosclerotic lesions occur in the first 3 cm and most of these are Manuscript received November 8, 1991; accepted February 21. 1992. Address for reprints: Nathaniel Cary, Department of Pathology. Papworth Hospital, Papworth Everard, Cambridgeshire, United Kingdom. 01992

by Elsevier Science Publishing

Co., Inc.

located on the wall distal to and opposite the main flow divider separating the circumflex (4). This study aims to examine whether or not asymmetrical location of smaller branches might contribute to this distribution.

Methods Hearts were obtained at autopsy from persons younger than 40 years who had died of noncardiovascular causes. The longitudinal and circumferential location of branches from 33 LADS were measured. Two methods were used, as described in the following sections. Method 1. Measurements were made from maps of 17 LADS that had been pressure perfused with formalin using a method based on that described by Thomas and Davies (7). A hollow plug is tied into the ascending aorta just above the aortic valve and coronary ostium. Initially the heart is perfused with isotonic saline (0.9 gldl) while suspended in a bath also containing isotonic saline. A physiological perfusion pressure of about 100 mmHg in the main coronary arteries is achieved by positioning the fluid reservoir high enough above the heart to give a saline column of 1054.8807/92/$5,00

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Figure 1. Method of opening the LAD. A. The relationship of the LAD to the left main and circumflex arteries is shown.

B. The artery is opened along its epicardial border with fine

scissors (CUT LINE). This crucial cut therefore defines o”360” when the opened

artery

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out flat.

about 13.5 cm. Fluid going into the aorta through the plug is prevented from entering the left ventricle by the aortic valve, which still remains highly effective after death. The fluid therefore passes into the coronary arterial circulation via the coronary ostia, perfuses the microcirculation, and eventually leaks out into the surrounding fluid of the bath and overflows into another container, from which it is pumped back into the upper reservoir. After 2 to 4 hours the perfusion and bathing fluid is changed to 10% formalin in isotonic saline. This produces fixation of the main coronary arteries that approximates physiological pressure. After about 24 hours the heart is disconnected and stored in formal saline. Subsequently each main coronary artery was opened longitudinally with fine scissors along its pericardial border, starting at the aortic ostium. This opening cut is therefore directly opposite the part of the vessel closest to the myocardium (Fig. 1). The opening cut down the left main artery is continued down the circumflex and left anterior descending branches in a similar manner. Great care was taken in opening the arteries, as this opening cut is crucial in subsequent vessel orientation. Arteries were largely cleaned of surrounding fat

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and pinned flat, intimal surface uppermost, on mat black-painted cork boards using fine pins. A small amount of adventitial fat and connective tissue was deliberately left surrounding each vessel so that pins could be placed through this, rather than through the vessel wall itself. Photographs (3.5 mm transparencies) were taken of the arteries with a scale marker and projected onto a Summagraphics digitizing pad. The slide projector was adjusted to achieve an optimum position and magnification of the artery being mapped. The outline of the vessel was then traced onto the digitizing pad using the digitizing cursor, and branch orifices were then mapped. The computer program processed the digitized data concerning vessel outline and branch orifice outline to produce a twice-life-size map on a plotter. Further measurements could be made from the maps or from photocopies of them. Branch location was recorded as a point for smaller branches and as a circle for larger ones. For these larger branches, measurements were made to the center of the circular orifice outline. Longitudinal position was measured from the origin of the LAD to the branch orifice along the central axis of the vessel outline. This consisted of a series of joined, straight-line approximations, rather than a continuous, curving line. Circumferential position was measured assuming that the vessel was circular in transverse section. It was defined looking down the vessel, with 0 to 360 degrees going counterclockwise. A perpendicular line was drawn from the outline edge representing 0 degrees through the center of the branch orifice to the outline edge representing 360 degrees. Circumferential position was then calculated as the distance from the 0 degree edge to the branch divided by the distance from the 0 degree edge to the 360 degree edge measured along the same perpendicular line. This was then converted to a measurement in degrees by multiplying by 360. Method 2. Measurements were made from rigid plastic casts of an additional 16 LADS. These were from a series of casts examined by Nerem and Seed (8) in an analysis of coronary artery geometry. Hearts were obtained at autopsy from the same population that provided the 17 LADS examined in method 1. An aortic plug was tied into position, and the coronary arterial tree was perfused with normal saline at physiological pressure using the method and apparatus described in the method 1 section for formalin perfusion fixation. After thorough perfusion to wash out blood, cardiac shape was approximately restored by placing balloons inflated to physiological volumes within both ventricles, and casting resin (Trylon resin CL201 PA) was injected via a side arm. After injection of resin, the saline pressure head was maintained above the column of injected resin to ensure that the cast was

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method 1 were measured along a straight line approximation to the central axis of the outline map, whereas in method 2 they were measured directly from the cast along the antimyocardial border. Circumferential positions measured in method 1 were calculated to give an actual reading in degrees, whereas in method 2 they were approximations by eye to the nearest 15 to 20 degrees.

Results

Figure 2. Resin cast of left coronary arterial tree made at physiological pressure, approximately life size. The LAD is on the left side.

made at physiological pressure. After the resin had thoroughly hardened, surrounding tissue was removed by immersion in a strong solution of hypochlorite for 1 to 3 days. The cast was then washed and branches were pruned back close to the main vessel (Fig. 2). Longitudinal and circumferential locations of branches from the LAD were measured directly from the casts. A line was drawn along the antimyocardial border of the vessel in a position equivalent to the line of opening of pressure-perfused vessels. Compass dividers were used to measure longitudinal distance downstream from the origin of the LAD along this line. A protractor that could fit over the main vessel was made out of card with 0 to 360 degrees marked on it at 45 degree intervals. As with data derived by the previous method, circumferential branch position was defined looking down the vessel, with 0 to 360 degrees going counterclockwise. The protractor was moved up so that it was immediately proximal to the branch being measured, and the 0 degree mark was lined up with the line drawn on the antimyocardial border of the vessel cast. The angle of branching was then judged by eye reading from the protractor to the nearest 15 to 20 degrees. This method thus produced longitudinal and circumferential branch positions approximately equivalent to those produced by method 1. Some differences would be expected, given that the longitudinal positions in

The combined data for all 33 LADS examined are shown in Figure 3. Each point represents one branch from one main vessel. Because the arteries were of differing lengths, the data more distally is representative of fewer arteries. As would be expected, few branches are located close to the pericardial aspect of the artery (i.e., O-45 degrees and 315-360 degrees). Apart from this no particular pattern is apparent. All LADS examined measured at least 6 cm long, and the combined data for the longitudinal distribution of branches in the first 6 cm are shown in Figure 4, with the longitudinal distribution of early atherosclerotic lesions in this segment for 11 LADS previously described by Fox, James, Morgan, and Seed (4) shown for comparison. Their study used cases similar to this one (persons less than 40 years of age who had died of noncardiovascular causes and drawn from a similar urban population). Early atherosclerotic disease was defined as less than a total of 30 mm2 of purely fatty disease in the LAD (i.e., no fibrous lesions). Figure 5 shows circumferential distribution data for the first 3 cm segment of the LAD, the area principally involved by early atherosclerosis. It can be seen that the two methods of determining branch position give similar results, so it is reasonable to combine the data. The more uniform circumferential distribution of branches seen in the cast data may be explained by the fact that this was the cruder method of estimating the angular position of each branch and consequently smoothed out any peaks and troughs. Using the combined data for this proximal 3 cm segment of the LAD, 49% of branches are located between 0 and 180 degrees and 51% between 181 and 360 degrees. Many of the branches come out of the side walls at 45 to 135 degrees and 225 to 315 degrees (Fig. 6).

Discussion The longitudinal and circumferential locations of branches from 33 left anterior descending coronary arteries were examined by two independent methods. Both methods used arteries that had either been fixed or had resin casts made at physiological pressure. Previous measurements on coronary artery resin casts

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made at physiological pressure (8) show that the resultant vessel diameters correspond well with those measured at selective coronary angiography in patients with normal coronary arteries (9,lO). The methods showed good agreement and, apart from a relative paucity of branches in the first 1 cm, indicated an fairly even longitudinal distribution of branches. This is in Figure 4. A. The longitudinal distribution of branches is shown in the 33 LADS studied. B. Previously published data (4) concerning the longitudinal distribution of early atherosclerosis in the same segment for 11 LADS are shown for comparison.

sharp contrast to the known distribution of early atherosclerosis, which is confined mainly to the first 3 cm of the LAD (4). The marked tendency for involvement of the proximal LAD compared to the distal artery was also shown for more advanced disease in data derived from the International Atherosclerosis Project (11). In this proximal segment there is also a disparity between the circumferential distribution of branches and that of early atherosclerosis: the branches are evenly distributed between the two side walls, and early atherosclerotic lesions occur mainly on the side wall opposite the flow divider separating the circumflex (4,5,6). This sug-

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Figure 5. The circumferential location of branches in the proximal 3 cm of the LAD. A is data from vessel maps and B is cast data.

gests that these branches are not an important determinant for location of atherosclerosis in the LAD. This finding is not necessarily at odds with the known tendency of early atherosclerotic lesions in the aorta to occur around branch orifices such as the intercostal arteries. There may be major differences in the scale of mechanical and/or fluid mechanical forces acting on these sites. Instead, this finding emphasizes that investigation of the possible role of such forces in atherogenesis should concentrate on the local environment. It may be that in this proximal part of the LAD other localizing influences are present and dominant, e.g., the influence on flow of the bifurcation of left main coronary artery into circumflex and LAD branches.

36 branches /

References 1. Rokitansky C; Day GE, trans. The pathological anatomy of the organs of respiration and circulation (1841-1846). In: A Manual of Pathological Anatomy. London: The New Sydenham Society, 1852;4:261-273. 2. Schwartz CJ. Mitchell JRA. Observations

on the localization of

arterial plaques. Circ Res 1962;11:63-73. 3. Grottum P, Svindland A, Walloe L. Localization of early ather-

osclerotic lesions in the right carotid bifurcation in humans. Acta Pathol, Microbial Immunol Scand[A] 1983;91:65-70. 4. Fox B, James K, Morgan B, Seed A. Distribution

of fatty and fibrous plaques in young human coronary arteries. Atherosclerosis 1982;41:337-347.

5. Svindland

A. The localization of sudanophilic and fibrous plaques in the main left coronary bifurcation. Atherosclerosis 1983;48:139-145.

6. Grottum P, Svindland A, Walloe L. Localization of atheroscle-

rotic lesions in the bifurcation of the main left coronary artery. Atherosclerosis 1983;47:55-62. 7. Thomas AC, Davies MJ. The demonstration

using perfusion fixation. Histopathology

of cardiac pathology 1985:9:5-19.

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Nerem RM, Seed WA. Coronary artery geometry and its fluid mechanical implications. In: Schettler G. Nerem RM, SchmidSchonbein H, Marl H, Diehm C. eds. Fluid Dynamics as a Localising Factor for Atherosclerosis: The Proceedings of a Symposium held at Heidelberg. FRG, June 1982. Berlin: Springer-Verlag, 19835-X Mac Alpin RN, Abbasi AS, Grollman JH, Erber L. Human onary artery size during life. Radiology 1973;308:567-576.

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Viewig WVR, Alpert JS, Hagan AD. Caliber normal coronary arterial anatomy. Cathet 1976: 2:269-280. Montenegro the coronary

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Branch location in the left anterior descending coronary artery and its relation to the known distribution of early atherosclerosis.

The circumferential and longitudinal locations of branches were determined for 33 left anterior descending coronary arteries (LADS) from persons aged ...
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