The small coronary arteries in alcoholic cardiomyopathy G. E. Burch, M.D. T. D. Giles, M.D. New Orleans, La.
The myocardium is nourished by the smallest blood vessels-capillaries. Blood reaches the capillaries through small arteries. The fact t h a t the interest of cardiologists is presently directed at the large coronary arteries instead of the small ones is understandable since these large arteries, which course along the surface of the heart, are the main channels of the coronary system. They deliver blood to the more peripherally oriented smaller vessels. But these small vessels are dh'ectly involved with supplying the myocardium with blood and, therefore, should not be ignored. Full patency of the large coronary arteries does not necessarily indicate full patency of the small peripheral vessels, nor does a "normal" coronary angiogram exclude disease of the smaller arteries. This fact is too often ignored in clinical practice. This report is concerned with an in vitro study, by x-ray angiographic technic, of the coronary arterial system of two patients with alcoholic cardiomyopathy, with special emphasis on the small peripheral coronary arterial system of the myocardium of both ventricles. Materials and m e t h o d s
One hundred and fifty-eight hearts were collected at autopsy from the New O~leans From the Department of Medicine of Tulane University School of Medicine, the Charity Hospital of Louisiana. and the Veterans Administration Hospital, New Orleans, La. Supported by grant HL-14789 from the National Heart and Lung Institute of the United States Public Health Service. the Rudolph Matas Memorial Fund for the Kate Prewitt Hess Laboratory, the Rowell A. Billups Fund for Research in Heart Disease. and the Feazel Laboratory. Received for publication July 22, 1976. Accepted for publication July 22, 1976. Reprint requests: George E. Burch, M.D.: Tulane University School of Medicine, 1430 Tulane Ave., New Orleans, La. 70112.
October, 1977, Vol. 94, No. 4, pp. 471-478
Veterans Administration Hospital, the Charity Hospital of Louisiana in New Orleans, and from the New Orleans Coroner's Office for the study of the coronary arterial blood vessels. The hearts were collected at random and were all prepared and studied in the same manner. The patients had miscellaneous diseases, not necessarily cardiac disease. Two of the patients had alcoholic cardiomyopathy, and their hearts were studied closely for coronary vasculature and are described in this report. The hearts were fresh and whole and were studied within a few hours of death, never beyond 24 hours after death. The hearts were collected as soon as possible after removal from the body and were immediately washed, and x-ray views of the intact unopened heart were obtained. The two coronary arterial vessels were rinsed with warm normal saline (0.85 per cent NaC1 in H20) at 120 to 150 mm. Hg pressure until the vessels were cleared of all gross evidence of blood, as described previously from this laboratory 1 and by Fulton.'-" ~ The arterial system was then filled with a suspension of 20 per cent Micropaque in 10 per cent formalin at 100 mm. Hg pressure using an injection apparatus as described by Fulton. ~ 3 The hearts were then cooled rapidly in ice and fixed in formalin for 30 to 60 days to allow the formalin to penetrate and fix the entire myocardium with the barium in the coronary arterial system. After fixation in formalin the hearts were thoroughly washed with tap water, cut a n d unrolled, as described by Fulton?-''~ The open ventricles were then exposed to "soft" x-ray, using a Model 6191 Picker industrial machine. Exposure times of 40 to 45 minutes per side with settings of 7 ma. and 28 Kv. were required. Kodak fine grain positive film, 5 by 7 inches, withoutcassettes was used. X-ray stereograms were prepared by x-
American Heart Journal
471
Burch and Giles
raying each heart two times, once with the film angled 3 degrees to the right from the axial ray on an inclined board and once with the film angled 3 degrees to t h e left. 1 The ventricles were then sliced (approximately 5 mmo thick) from apex to base with the knife parallel to the atrioventricular zone. These slices were also x-rayed for stereograms, as described above. P a t i e n t No. 1. H. H., a 60-year-old alcoholic man, was admitted to the V.A. Hospital in New Orleans because of increasing mental confusion and lethargy. The patient had a history of excessive alcohol consumption for more than 30 years. Physical examination on admission to hospital revealed a blood pressure of 150/100 mm. Hg, a pulse rate of 90 beats per minute, a respiratory rate of 20 per minute, and a temperature of 98,6 ~ F. The patient was mentally confused and had a "flapping t r e m o r . " The sclerae were mildly icteric. The remainder of the physical examination was reported as being within normal limits. The electrocardiogram showed sinus tachycardia, left axis deviation, and poor R wave progression from V1 to V3. The T wave was slightly low in Lead I and isoelectric in Lead III. The patient was treated for hepatic coma during the period of hospitalization. However, he failed to respond to treatment and died 21 days after admission. At necropsy, t h e heart weighed 490 Gm. Cardiac measurements were: left ventricular wall thickness, 14 mm.; right ventricular wall thickness, 7 mm.; mitral valve circumference, 85 mm.; tricuspid valve circumference, 87 mm.; aortic valve circumference, 64 mm.; and pulmonic valve circumference, 65 mm. No gross scarring or other lesions were present. Examination of myocardial sections by light microscopy revealed f a t t y infiltration of the right atrial myocardium and mild focal interstitial fibrosis with atrophy of muscle fibers in the left ventricular myocardium. P a t i e n t No. 2. E. K., a 42-year-old man, was admitted to the V.A. Hospital in New Orleans with a long history of alcoholic cirrhosis and, most recently, increasing ascites requiring treatment with diuretics. He was admitted to the hospital because of increasing abdominal swelling, nausea, and vomiting. Physical examination on admission revealed a blood pressure of 100/70 mm. Hg, a pulse rate of 84 beats per minute, and a temperature of 97 ~ F.
472
The sclerae were icteric, and multiple spider angiomata were present on examination of the skin. A Grade II systolic m u r m u r was present at the cardiac apex. The remainder of the physical examination was reported as being within normal limits. Laboratory work on admission revealed a hemoglobin of 11.2 Gm per cent and a hematocrit of 33 per cent. The serum bilirubin was 3.8mg. per cent and the albumin 3.0 Gm per cent. The sodium was 118 mEqo/L. The remainder of the blood chemistries were within normal limits. Chest x-rays were obtained with the patient in the recumbent position, rendering accurate cardiac evaluation impossible. Electrocardiograms revealed diffuse abnormalities of the ST segments and T waves, with some notching and slurring of the QRS complexes, compatible with diffuse myocardial disease. Following admission to the hospital the patient was treated for possible intestinal obstruction. However, he soon began to develop hepatic encephalopathy which was unresponsive to therapy. The patient died 37 days after admission to the hospital. At necropsy, the heart weighed 470 Gin. Cardiac measurements were: left ventricular wall thickness, 19 mm.; right ventricular wall thickness, 8 mm.; mitral valve circumference, 100 mm.; tricuspid valve circumference, 110 mm.; aortic valve circumference, 50 mm.; pulmonic valve circumference, 55 mm. Grossly, the heart was enlarged b u t no other abnormalities were noted. Examination of myocardial sections by light microscopy revealed no specific pathologic findings.
Results Figs. 1 to 7 best illustrate the organization and t h r e e dimensional spatial orientation of the peripheral or small arterial vessels of the myocardium of the ventricles of the two hearts of the patients with alcoholic cardiomyopathy. The small arteries which branch off from the main coronary arterial vessels located on the surface of the heart are spatially oriented in different manners for the free wall of the left ventricle, the free wall of the right ventricle, and the interventricular septum at the apical region of the heart and at the basal regions near the atrioventricular groove. These arterial systems are briefly discussed below.
October, 1977, Vol. 94, No. 4
Small coronary arteries
Fig. 1. Radiographicview of the coronary artery system of the whole heart which is laid open as described by Fulton~to display the vessels.
Free wall of the .left ventricle. The small arteries which penetrate into the left ventricular myocardium branch from the large surface coronary arteries like trunks of trees (Figs. 2, 3, and 4). This tree-like arrangement has been previously described2 -'~ The branches of these "trees" branch dichotomously and connect (anastomose) with the "branches" of the adjacent arterial "trees" located all around them. The trunks (main arteries) Of the surrounding "trees" arespatially oriented as shown in Figs. 2 and 3. The arterial "trees" resemble trees in winter without their leaves (Fig. 5). T h e arterial supply to the papillary muscle system which is attached to the internal surface of the left ventricle has been described in detail previously.7 The observations in these investigations merely confirm the previous findings. Briefly, the finger type of papillary muscle is supplied with a single central artery, T or one "tree," from which small arterial branches are three-dimensionally oriented throughout the papillary muscle (Fig. 4). This central artery originates from the main coronary arterial vessels on the surface of the heart. The papillary muscle which is tethered has a different type of small arterial system. 7 The arterial system for tethered papillary muscles comprises parts of arterial " t r e e s " which stem from the large arteries on the epicardial surface. The arrangement provides for a rich blood supply
American Heart Journal
with an abundance of anastomoses within the entire myocardium of the left ventricle and the papillary muscle system. Each muscle fiber is supplied with a small "twig" of the "trees," terminal vessels in a sense. The subendocardial myocardium and especially the papillary muscles receive their blood supply from the greatest distance-from the aortic origin of the coronary arteries. The trabeculae carneae receive their arterial system as branches of the coronary arterial "trees" which originate from the large epicardial coronary arteries. There is an abundance of anastomoses within the trabeculae carneae. A fairly large coronary artery courses longitudinally along the crest of the trabeculae carneae. This vessel anastomoses with other smaller arteries which originate from the penetrating more vertically oriented "trees." The coronary arterial system at the apical region of the heart is arranged differently from that at the base in the region of the atrioventricular groove (Figs. 1 and 2). At the apical region of the heart there is a tendency for the arteries to form fewer "tree units" and more of a network or mesh of arteries which anastomose with the branches of the anterior and posterior descending coronary arteries, thereby connecting these two descending arteries. This network of arteries located near the epicardial region of the apex
473
Burch a n d Giles
Fig. 2. Radiographic view of the small myocardial arteries in a 5 mm. thick slice of the heart shown in Fig. 1. This slice was cut about midway between the apex and the A-V groove.
ES
:)
Fig. 4. Stereoscopic views of a segment of the myocardium of
Fig. 3. Stereoscopic views of a segment of the myocardium of the free wall of the left ventricle of the same heart as in Figs. 1 and 2, showingthe spatial relationships of the numerous small arteries which supply that segment of the left ventricle.
the anterolateral papillary muscle of the left ventricle, showing the spatial relationships of the numerous small arteries which supply the papillary muscle.
sends p e n e t r a t i n g branches to the e n d o c a r d i a l surface (Figs. 1 and 2). T h e larger vessels t e n d to course parallel with t h e epicardial a n d endocardial surfaces of the h e a r t (Figs. 1 a n d 2). Arteries in t h e region of the a t r i o v e n t r i c u l a r groove also tend to lose the "tree u n i t " f o r m a t i o n . These arteries course parallel with the A-V groove, sending p e n e t r a t i n g b r a n c h e s into the m y o c a r d i u m in a less uniform m a n n e r (Figs. 1 a n d 2). Anastomoses are well developed in the region of the A-V groove.
In general, the distribution and spatial orientation of the smaller arterial s y s t e m a n d the large epicardial c o r o n a r y arterial c h a n n e l s in t h e patients with alcoholic c a r d i o m y o p a t h y were normal. Their luminal surfaces were s m o o t h . In general, all the arteries t e n d e d to be slightly dilated in comparison to the n o r m a l arteries, s T h e arterial supply to t h e left ventricle was m u c h richer t h a n t h a t to the right ventricle, as previously reported decades ago by F u l t o n a n d o t h e r s J 3. ~. 3. ~o In spite of d i l a t a t i o n a n d h y p e r -
474
October, 1977, Vol. 94, No. 4
Small coronary arteries
Fig. 5. Diagrammatic reproductions of four representative winter tree configurations selected from the free wall of the left ventricle of injected hearts. The configurations vary considerably.
trophy of the entire heart in alcoholic cardiomyopathy, the arterial system was well distributed throughout the musculature. There were no areas in which the myocardium did not have an abundance of arteries. Right ventricle. The supply of small coronary arteries to the right ventricle is quite different from that to the left ventricle. The small arteries branch off the larger trunks coursing along the surface of t h e heart. The "tree" u n i t s are less numerous and less well developed. The vessels tend to course more parallel to the epicardial and endocardial surfaces of the right ventricular wall. The supply of small arteries is less rich in compar-
American Heart Journal
ison to that for the left ventricle. However, the longitudinally coursing small arteries are more tortuous and spiral, apparently to accommodate the changes in size of the right ventricle during the cardiac cycle and l t o compensate for the absence of we!l-developed "tree units" (Fig. 6). The small arteries connect with those of the left ventricle at the apex within the septum and at the interventricular groove or any point where the two ventricles are in direct contact {Figs. 1 and
2). From the small arteries, extremely numerous fine hair,like arteries branch off parallel to each other and course perpendicular to the epicardial
475
Burch and Giles
Fig. 6. Stereoscopicviewsof a segmentof the free wall of the right ventricle of the same heart as in Figs. 1 and 2, showing the spatialorientationof the smallarteriessupplyingthe right ventricular myocardium. surface of the right ventricle. These m a n y fine arteries produce a brush-like appearance (Fig. 2), not observed in the left ventricle. T h e numerous well-developed trabeculae carneae of the right ventricle have a supply of small arteries comparable to t h a t in the left ventricle. But, here, as well as in the papillary muscle of the right ventricle, the small arteries are not as numerous. The small arteries anastomose freely to ensure a good collateral Circulation. General remarks
The arterial supply to the myocardium of the two patients with alcoholic cardiomyopathy was extremely good. No arteriosclerotic plaques were present, a situation quite different from the hearts of patients with ischemic cardi0myopathy. In fact, the normal arterial distribution to the heart is readily studied in the hearts of patients with alcoholic cardiomyopathy. Previous investigators have commented on the remarkable absence of atherosclerotic changes in the large coronary arteries of patients with alcoholism in
476
Fig. 7. Stereoscopic views of the septum of the slice of myocardiumshown in F/g. 2. The main arterial trunks course parallel to the endocardial surfaces through the septum. Consult text for details. general i' and with alcoholic cardiomyopathy in particular.,2. 13 For example, a postmortem study of the hearts of 97 alcoholic patients revealed no coronary atherosclerosis in 36 (37 per cent), a slight atherosclerosis in 49 (51 per cent), moderate changes in 6 (6 per cent), and marked changes in 6 (6 per cent)." Necropsy findings in 10 patients with primary myocardial disease, most of whom w6re alcoholics, revealed absence of arteriosclerosis in five hearts, negligible or mild arteriosclerosis iri two, and moderate arteriosclerosis in three patients. 1-~ Some reports have described changes in small branches of the coronary arteries composed of "subintimal plaques of homogeneous, reddish, smudgy material. ''13 However, these changes were observed in patients with far: advanced cardiomyopathy, whereas the patients in our study had relatively early disease. Thus, it would seem t h a t pathology of the small coronary arteries is not necessary for the development of alcoholic cardiomyopathy: This study revealed the coronary circulatory "tree" unit which was described over 30 years ago by Gross and KugeP a n d m o r e recently by Fulton/-. 3 Careful consideration of these three-
October, 1977, Vol. 94, No. 4
Small coronary arteries
dimensional units clearly reveals how ideal they are for a structure such as the heart which contracts and dilates about 75 times or more per minute continuously for many years. This spatial organization was well developed with fully patent vessels in our two patients with alcoholic cardiomyopathy. There was no evidence of destruction or interruption of the small coronary arteries in these patients. In spite of the dilated and hypertrophied state of the two ventricles, the small coronary arteries reached the subendocardial myocardium and the myocardium of the papillary muscles and the trabeculae carneae. Thus, the abnormal T waves recorded from these patients could not have been produced by disease of the small coronary arteries as far as this study is concerned. As the ventricles dilated and extended, the small coronary arteries reached out further. This growth of the arterial system is not only interesting b u t challenges one's imagination as to the mechanism and stimuli responsible for the growth and extension of the coronary arterial system into the greater mass of myocardium which was also centrifugally displaced with dilatation. The tree-like circulatory units are interesting and intriguing. For convenience they will be called "tree units." Their architectural and functional beauty can only be appreciated from a careful study of the stereoscopic photographs of the injected vessels (Figs. 3, 4, and 6). This is simple if one imagines the free wall of the left ventricle to be lying flat with the epicardial surface on a table and the endocardial surface directed upward. The vessels would then resemble an orchard of evenly planted or spatially oriented trees with the tips of their branches touching each other. With little imagination and with a knowledge of the microcirculation of the myocardium, it is easy to visualize the manner in which the tips of the branches of t h e trees supply blood to the arterioles, capillaries and vessels and small microcirculatory anastomoses. The branches, there, fore, interconnect to provide an effective collateral circulation should the trunk to any tree become obstructed. This "tree orchard" orientation makes it possible for the myocardium to contract and dilate without necessarily kinking or obstructing the lumen of the small coronary arteries or traumatizing their walls excessively. This spatial morphologic arrangement and orientation is not only extremely interesting and
American Heart Journal
unique b u t necessary to assure least trauma to the vessels. The interconnecting and anastomotic relationships were so extensive that arrest of flow in one circulatory "tree" unit could occur and blood would still be supplied to the ischemic unit by means of anastomoses with several immediately adjacent units. This tree pattern is highly developed in the left ventricle (Figs. 2 and 3). I t i s less well developed near the A-V groove, in the area of the apex, and in the right ventricle (Figs. 2 and 6). Figs. 1, 2, 3, 4, and 6 readily reveal how these "trees" with their branches and the arteries in the trabeculae carneae make it possible for the arteries to fold, i.e., for the branches of the trees to move centripetally toward the main trunk of the trees during cardiac systole and to unfold or spread out centrifugally during diastole of the ventricles. This spatial orientation and architect u r e of the coronary arterial system is quite unique and serves the purpose of maintaining adequate arterial supply to the myocardium without being injured or traumatized in spite of trillions of cardiac contractions and dilatations. The supply of small arteries to the right ventricle is not nearly as luxurious as that for the left side of the septum and free wall of the left ventricle, nor are the tree formations and spatial orientations nearly as well developed (Figs. 2 and 6). The arteries in the right ventricular myocardium are tortuous and coil as they do in the left ventricle and possibly even more so, since changes in the wall size during the cardiac cycle have to depend mainly on such non-linear courses of the arteries and less upon the morphology of "tree" configurations. The circulation of the septum is also rather interesting. Large arteries penetrate the septum at about one-third of its thickness from the right ventricle o r two-thirds from the endocardial surface of the left ventricle. The arterial supply to the left side (two-thirds) of the septum is richer than that to the right side (one-third). The "tree" type of arterial distribution is predominantly to the left side of the septum. On the right side of the septum the branching, distribution, and spatial orientation of the arteries are more like that of the free wall of the right ventricle (Fig. 7). Thus, these anatomic arterial patterns indicate that a large part (two-thirds) of the septal myocardium does "belong" to the left ventricle and a smaller part (one-third) "belongs" to the right ventricle.
477
Burch and Giles
T h e s e p t u m , t h e r e f o r e , is n o t e n t i r e l y left v e n t r i c ular myocardium. T h e arterial s u p p l y to t h e f a t of t h e s u r f a c e o f the h e a r t is a c h i e v e d b y m e a n s o f m a n y v e r y small hair-like arteries w h i c h e x t e n d v e r t i c a l l y f r o m t h e large vessels to t h e e p i c a r d i a l e p i t h e l i u m (Fig. 2).
Summary T h e small c o r o n a r y arteries o f t w o p a t i e n t s with alcoholic c a r d i o m y o p a t h y were s t u d i e d b y m e a n s of fine p a r t i c l e b a r i u m i n j e c t i o n a n d soft xr a y technic. T h e s p a t i a l a r c h i t e c t u r e o f t h e s e small arteries w h i c h p e n e t r a t e d i n t o t h e d e p t h o f t h e right a n d left v e n t r i c u l a r m y o c a r d i u m w e r e normal. Their lumina were somewhat dilated and their l u m i n a l s u r f a c e s were s m o o t h . T h e " t r e e c i r c u l a t o r y u n i t s " were described f r o m this s t u d y a n d were f o u n d to be n o r m a l . T h e left v e n t r i c u l a r m y o c a r d i u m was r i c h l y s u p p l i e d w i t h s m a l l arteries, w h e r e a s t h e m y o c a r d i u m o f t h e r i g h t ventricle w a s n o t so r i c h l y supplied. T h e m y o c a r d i u m of t h e p a p i l l a r y m u s c l e s a n d t h e t r a b e c u l a e c a r n e a e of t h e left ventricle also h a d a g o o d s u p p l y of small arteries, as did t h e r e m o t e e n d o cardial m y o c a r d i a l a p p e n d a g e s . N u m e r o u s fine hair-like arteries e x t e n d e d t o t h e e p i c a r d i a l myocardium of the right ventricle to form a brush-like a p p e a r a n c e .
REFERENCES 1. Hale, A. R., and Reed, A. F.: Studies in cerebral circulation: Methods for the qualitative and quantitative study of human cerebral blood vessels, AM. HEART J. 66:226, 1963.
478
2. Fulton, W. F. M.: Arterial anastomoses in the coronary circulation. I. Anatomical features in normal and diseased hearts demonstrated by stereoarteriography, Scot. Med. J. 8:420, 1963. 3. Fulton, W. F. M.: The coronary arteries: Arteriography, microanatomy, and pathogenesis of obliterative coronary artery disease, Springfield, Ill., 1965, Charles C Thomas, Publisher. 4. Crainichianu, A.: Anatomische Studien fiber die Coronaraterien und experimenteUe Untersuchungen fiber ihre Durchg~ingigkeit, Virchows Arch. Pathol. Anat. 238:1, 1922. 5. Gross, L., and Kugel, M. A.: The arterial blood vascular distribution to the left and right ventricles of the human heart, AM. HEARTJ. 9:165, 1933. 6. Burch, G. E., and Giles, T. D.: Interesting peculiarities of the spatial dynamic architecture of the coronary arteries, AM. HEARTJ. 85:140, 1973. 7. Ranganathan, N., and Burch, G. E.: Gross morphology and arterial supply of the papillary muscles of the left ventricle of man, AM. HEARTJ. 77:506, 1969. 8. Baroldi, G., and Scomazzoni, G.: Coronary circulation in the normal and the pathologic heart, Superintendent of Documents, U. S. Government Printing Office, Washington, D. C., 1967. 9. Spalteholz, W,: Die Arterien der Herzwand. Anatomische Untersuchungen an Menschenund Tierherzen, Leipzig, 1924, S. Hirzel. 10. Estes, E., Jr., Entman, M. L., Dixon, H. B., II, and Hackel, D. B.: The vascular supply of the left ventricular wall: Anatomic observations, plus a hypothesis regarding acute events in coronary artery disease, AM. HEART J. 71:58, 1966. 11. Schenk, E. A., and Cohen, J.: The heart in chronic alcoholism: Clinical and pathologic findings, Pathol. Microbiol. 35:96, 1970. 12. Massumi, R. A., Rios, J. C., Gooch, A. S., Nutter, D., De Vita, V. T., and Datlow, D. W.: Primary myocardial disease: Report of fifty cases and review of the subject, Circulation 31:19, 1965. 13. Pintar, K., Wolanskyj, B. M., and Gubbay, E. R.: Alcoholic cardiomyopathy, Can. Med. Assoc. J. 93:103, 1965.
October, 1977, Vol. 94, No. 4
The myocardium is nourished by the smallest blood vessels-capillaries. Blood reaches the capillaries through small arteries. The fact t h a t the interest of cardiologists is presently directed at the large coronary arteries instead of the small ones is understandable since these large arteries, which course along the surface of the heart, are the main channels of the coronary system. They deliver blood to the more peripherally oriented smaller vessels. But these small vessels are dh'ectly involved with supplying the myocardium with blood and, therefore, should not be ignored. Full patency of the large coronary arteries does not necessarily indicate full patency of the small peripheral vessels, nor does a "normal" coronary angiogram exclude disease of the smaller arteries. This fact is too often ignored in clinical practice. This report is concerned with an in vitro study, by x-ray angiographic technic, of the coronary arterial system of two patients with alcoholic cardiomyopathy, with special emphasis on the small peripheral coronary arterial system of the myocardium of both ventricles. Materials and m e t h o d s
One hundred and fifty-eight hearts were collected at autopsy from the New O~leans From the Department of Medicine of Tulane University School of Medicine, the Charity Hospital of Louisiana. and the Veterans Administration Hospital, New Orleans, La. Supported by grant HL-14789 from the National Heart and Lung Institute of the United States Public Health Service. the Rudolph Matas Memorial Fund for the Kate Prewitt Hess Laboratory, the Rowell A. Billups Fund for Research in Heart Disease. and the Feazel Laboratory. Received for publication July 22, 1976. Accepted for publication July 22, 1976. Reprint requests: George E. Burch, M.D.: Tulane University School of Medicine, 1430 Tulane Ave., New Orleans, La. 70112.
October, 1977, Vol. 94, No. 4, pp. 471-478
Veterans Administration Hospital, the Charity Hospital of Louisiana in New Orleans, and from the New Orleans Coroner's Office for the study of the coronary arterial blood vessels. The hearts were collected at random and were all prepared and studied in the same manner. The patients had miscellaneous diseases, not necessarily cardiac disease. Two of the patients had alcoholic cardiomyopathy, and their hearts were studied closely for coronary vasculature and are described in this report. The hearts were fresh and whole and were studied within a few hours of death, never beyond 24 hours after death. The hearts were collected as soon as possible after removal from the body and were immediately washed, and x-ray views of the intact unopened heart were obtained. The two coronary arterial vessels were rinsed with warm normal saline (0.85 per cent NaC1 in H20) at 120 to 150 mm. Hg pressure until the vessels were cleared of all gross evidence of blood, as described previously from this laboratory 1 and by Fulton.'-" ~ The arterial system was then filled with a suspension of 20 per cent Micropaque in 10 per cent formalin at 100 mm. Hg pressure using an injection apparatus as described by Fulton. ~ 3 The hearts were then cooled rapidly in ice and fixed in formalin for 30 to 60 days to allow the formalin to penetrate and fix the entire myocardium with the barium in the coronary arterial system. After fixation in formalin the hearts were thoroughly washed with tap water, cut a n d unrolled, as described by Fulton?-''~ The open ventricles were then exposed to "soft" x-ray, using a Model 6191 Picker industrial machine. Exposure times of 40 to 45 minutes per side with settings of 7 ma. and 28 Kv. were required. Kodak fine grain positive film, 5 by 7 inches, withoutcassettes was used. X-ray stereograms were prepared by x-
American Heart Journal
471
Burch and Giles
raying each heart two times, once with the film angled 3 degrees to the right from the axial ray on an inclined board and once with the film angled 3 degrees to t h e left. 1 The ventricles were then sliced (approximately 5 mmo thick) from apex to base with the knife parallel to the atrioventricular zone. These slices were also x-rayed for stereograms, as described above. P a t i e n t No. 1. H. H., a 60-year-old alcoholic man, was admitted to the V.A. Hospital in New Orleans because of increasing mental confusion and lethargy. The patient had a history of excessive alcohol consumption for more than 30 years. Physical examination on admission to hospital revealed a blood pressure of 150/100 mm. Hg, a pulse rate of 90 beats per minute, a respiratory rate of 20 per minute, and a temperature of 98,6 ~ F. The patient was mentally confused and had a "flapping t r e m o r . " The sclerae were mildly icteric. The remainder of the physical examination was reported as being within normal limits. The electrocardiogram showed sinus tachycardia, left axis deviation, and poor R wave progression from V1 to V3. The T wave was slightly low in Lead I and isoelectric in Lead III. The patient was treated for hepatic coma during the period of hospitalization. However, he failed to respond to treatment and died 21 days after admission. At necropsy, t h e heart weighed 490 Gm. Cardiac measurements were: left ventricular wall thickness, 14 mm.; right ventricular wall thickness, 7 mm.; mitral valve circumference, 85 mm.; tricuspid valve circumference, 87 mm.; aortic valve circumference, 64 mm.; and pulmonic valve circumference, 65 mm. No gross scarring or other lesions were present. Examination of myocardial sections by light microscopy revealed f a t t y infiltration of the right atrial myocardium and mild focal interstitial fibrosis with atrophy of muscle fibers in the left ventricular myocardium. P a t i e n t No. 2. E. K., a 42-year-old man, was admitted to the V.A. Hospital in New Orleans with a long history of alcoholic cirrhosis and, most recently, increasing ascites requiring treatment with diuretics. He was admitted to the hospital because of increasing abdominal swelling, nausea, and vomiting. Physical examination on admission revealed a blood pressure of 100/70 mm. Hg, a pulse rate of 84 beats per minute, and a temperature of 97 ~ F.
472
The sclerae were icteric, and multiple spider angiomata were present on examination of the skin. A Grade II systolic m u r m u r was present at the cardiac apex. The remainder of the physical examination was reported as being within normal limits. Laboratory work on admission revealed a hemoglobin of 11.2 Gm per cent and a hematocrit of 33 per cent. The serum bilirubin was 3.8mg. per cent and the albumin 3.0 Gm per cent. The sodium was 118 mEqo/L. The remainder of the blood chemistries were within normal limits. Chest x-rays were obtained with the patient in the recumbent position, rendering accurate cardiac evaluation impossible. Electrocardiograms revealed diffuse abnormalities of the ST segments and T waves, with some notching and slurring of the QRS complexes, compatible with diffuse myocardial disease. Following admission to the hospital the patient was treated for possible intestinal obstruction. However, he soon began to develop hepatic encephalopathy which was unresponsive to therapy. The patient died 37 days after admission to the hospital. At necropsy, the heart weighed 470 Gin. Cardiac measurements were: left ventricular wall thickness, 19 mm.; right ventricular wall thickness, 8 mm.; mitral valve circumference, 100 mm.; tricuspid valve circumference, 110 mm.; aortic valve circumference, 50 mm.; pulmonic valve circumference, 55 mm. Grossly, the heart was enlarged b u t no other abnormalities were noted. Examination of myocardial sections by light microscopy revealed no specific pathologic findings.
Results Figs. 1 to 7 best illustrate the organization and t h r e e dimensional spatial orientation of the peripheral or small arterial vessels of the myocardium of the ventricles of the two hearts of the patients with alcoholic cardiomyopathy. The small arteries which branch off from the main coronary arterial vessels located on the surface of the heart are spatially oriented in different manners for the free wall of the left ventricle, the free wall of the right ventricle, and the interventricular septum at the apical region of the heart and at the basal regions near the atrioventricular groove. These arterial systems are briefly discussed below.
October, 1977, Vol. 94, No. 4
Small coronary arteries
Fig. 1. Radiographicview of the coronary artery system of the whole heart which is laid open as described by Fulton~to display the vessels.
Free wall of the .left ventricle. The small arteries which penetrate into the left ventricular myocardium branch from the large surface coronary arteries like trunks of trees (Figs. 2, 3, and 4). This tree-like arrangement has been previously described2 -'~ The branches of these "trees" branch dichotomously and connect (anastomose) with the "branches" of the adjacent arterial "trees" located all around them. The trunks (main arteries) Of the surrounding "trees" arespatially oriented as shown in Figs. 2 and 3. The arterial "trees" resemble trees in winter without their leaves (Fig. 5). T h e arterial supply to the papillary muscle system which is attached to the internal surface of the left ventricle has been described in detail previously.7 The observations in these investigations merely confirm the previous findings. Briefly, the finger type of papillary muscle is supplied with a single central artery, T or one "tree," from which small arterial branches are three-dimensionally oriented throughout the papillary muscle (Fig. 4). This central artery originates from the main coronary arterial vessels on the surface of the heart. The papillary muscle which is tethered has a different type of small arterial system. 7 The arterial system for tethered papillary muscles comprises parts of arterial " t r e e s " which stem from the large arteries on the epicardial surface. The arrangement provides for a rich blood supply
American Heart Journal
with an abundance of anastomoses within the entire myocardium of the left ventricle and the papillary muscle system. Each muscle fiber is supplied with a small "twig" of the "trees," terminal vessels in a sense. The subendocardial myocardium and especially the papillary muscles receive their blood supply from the greatest distance-from the aortic origin of the coronary arteries. The trabeculae carneae receive their arterial system as branches of the coronary arterial "trees" which originate from the large epicardial coronary arteries. There is an abundance of anastomoses within the trabeculae carneae. A fairly large coronary artery courses longitudinally along the crest of the trabeculae carneae. This vessel anastomoses with other smaller arteries which originate from the penetrating more vertically oriented "trees." The coronary arterial system at the apical region of the heart is arranged differently from that at the base in the region of the atrioventricular groove (Figs. 1 and 2). At the apical region of the heart there is a tendency for the arteries to form fewer "tree units" and more of a network or mesh of arteries which anastomose with the branches of the anterior and posterior descending coronary arteries, thereby connecting these two descending arteries. This network of arteries located near the epicardial region of the apex
473
Burch a n d Giles
Fig. 2. Radiographic view of the small myocardial arteries in a 5 mm. thick slice of the heart shown in Fig. 1. This slice was cut about midway between the apex and the A-V groove.
ES
:)
Fig. 4. Stereoscopic views of a segment of the myocardium of
Fig. 3. Stereoscopic views of a segment of the myocardium of the free wall of the left ventricle of the same heart as in Figs. 1 and 2, showingthe spatial relationships of the numerous small arteries which supply that segment of the left ventricle.
the anterolateral papillary muscle of the left ventricle, showing the spatial relationships of the numerous small arteries which supply the papillary muscle.
sends p e n e t r a t i n g branches to the e n d o c a r d i a l surface (Figs. 1 and 2). T h e larger vessels t e n d to course parallel with t h e epicardial a n d endocardial surfaces of the h e a r t (Figs. 1 a n d 2). Arteries in t h e region of the a t r i o v e n t r i c u l a r groove also tend to lose the "tree u n i t " f o r m a t i o n . These arteries course parallel with the A-V groove, sending p e n e t r a t i n g b r a n c h e s into the m y o c a r d i u m in a less uniform m a n n e r (Figs. 1 a n d 2). Anastomoses are well developed in the region of the A-V groove.
In general, the distribution and spatial orientation of the smaller arterial s y s t e m a n d the large epicardial c o r o n a r y arterial c h a n n e l s in t h e patients with alcoholic c a r d i o m y o p a t h y were normal. Their luminal surfaces were s m o o t h . In general, all the arteries t e n d e d to be slightly dilated in comparison to the n o r m a l arteries, s T h e arterial supply to t h e left ventricle was m u c h richer t h a n t h a t to the right ventricle, as previously reported decades ago by F u l t o n a n d o t h e r s J 3. ~. 3. ~o In spite of d i l a t a t i o n a n d h y p e r -
474
October, 1977, Vol. 94, No. 4
Small coronary arteries
Fig. 5. Diagrammatic reproductions of four representative winter tree configurations selected from the free wall of the left ventricle of injected hearts. The configurations vary considerably.
trophy of the entire heart in alcoholic cardiomyopathy, the arterial system was well distributed throughout the musculature. There were no areas in which the myocardium did not have an abundance of arteries. Right ventricle. The supply of small coronary arteries to the right ventricle is quite different from that to the left ventricle. The small arteries branch off the larger trunks coursing along the surface of t h e heart. The "tree" u n i t s are less numerous and less well developed. The vessels tend to course more parallel to the epicardial and endocardial surfaces of the right ventricular wall. The supply of small arteries is less rich in compar-
American Heart Journal
ison to that for the left ventricle. However, the longitudinally coursing small arteries are more tortuous and spiral, apparently to accommodate the changes in size of the right ventricle during the cardiac cycle and l t o compensate for the absence of we!l-developed "tree units" (Fig. 6). The small arteries connect with those of the left ventricle at the apex within the septum and at the interventricular groove or any point where the two ventricles are in direct contact {Figs. 1 and
2). From the small arteries, extremely numerous fine hair,like arteries branch off parallel to each other and course perpendicular to the epicardial
475
Burch and Giles
Fig. 6. Stereoscopicviewsof a segmentof the free wall of the right ventricle of the same heart as in Figs. 1 and 2, showing the spatialorientationof the smallarteriessupplyingthe right ventricular myocardium. surface of the right ventricle. These m a n y fine arteries produce a brush-like appearance (Fig. 2), not observed in the left ventricle. T h e numerous well-developed trabeculae carneae of the right ventricle have a supply of small arteries comparable to t h a t in the left ventricle. But, here, as well as in the papillary muscle of the right ventricle, the small arteries are not as numerous. The small arteries anastomose freely to ensure a good collateral Circulation. General remarks
The arterial supply to the myocardium of the two patients with alcoholic cardiomyopathy was extremely good. No arteriosclerotic plaques were present, a situation quite different from the hearts of patients with ischemic cardi0myopathy. In fact, the normal arterial distribution to the heart is readily studied in the hearts of patients with alcoholic cardiomyopathy. Previous investigators have commented on the remarkable absence of atherosclerotic changes in the large coronary arteries of patients with alcoholism in
476
Fig. 7. Stereoscopic views of the septum of the slice of myocardiumshown in F/g. 2. The main arterial trunks course parallel to the endocardial surfaces through the septum. Consult text for details. general i' and with alcoholic cardiomyopathy in particular.,2. 13 For example, a postmortem study of the hearts of 97 alcoholic patients revealed no coronary atherosclerosis in 36 (37 per cent), a slight atherosclerosis in 49 (51 per cent), moderate changes in 6 (6 per cent), and marked changes in 6 (6 per cent)." Necropsy findings in 10 patients with primary myocardial disease, most of whom w6re alcoholics, revealed absence of arteriosclerosis in five hearts, negligible or mild arteriosclerosis iri two, and moderate arteriosclerosis in three patients. 1-~ Some reports have described changes in small branches of the coronary arteries composed of "subintimal plaques of homogeneous, reddish, smudgy material. ''13 However, these changes were observed in patients with far: advanced cardiomyopathy, whereas the patients in our study had relatively early disease. Thus, it would seem t h a t pathology of the small coronary arteries is not necessary for the development of alcoholic cardiomyopathy: This study revealed the coronary circulatory "tree" unit which was described over 30 years ago by Gross and KugeP a n d m o r e recently by Fulton/-. 3 Careful consideration of these three-
October, 1977, Vol. 94, No. 4
Small coronary arteries
dimensional units clearly reveals how ideal they are for a structure such as the heart which contracts and dilates about 75 times or more per minute continuously for many years. This spatial organization was well developed with fully patent vessels in our two patients with alcoholic cardiomyopathy. There was no evidence of destruction or interruption of the small coronary arteries in these patients. In spite of the dilated and hypertrophied state of the two ventricles, the small coronary arteries reached the subendocardial myocardium and the myocardium of the papillary muscles and the trabeculae carneae. Thus, the abnormal T waves recorded from these patients could not have been produced by disease of the small coronary arteries as far as this study is concerned. As the ventricles dilated and extended, the small coronary arteries reached out further. This growth of the arterial system is not only interesting b u t challenges one's imagination as to the mechanism and stimuli responsible for the growth and extension of the coronary arterial system into the greater mass of myocardium which was also centrifugally displaced with dilatation. The tree-like circulatory units are interesting and intriguing. For convenience they will be called "tree units." Their architectural and functional beauty can only be appreciated from a careful study of the stereoscopic photographs of the injected vessels (Figs. 3, 4, and 6). This is simple if one imagines the free wall of the left ventricle to be lying flat with the epicardial surface on a table and the endocardial surface directed upward. The vessels would then resemble an orchard of evenly planted or spatially oriented trees with the tips of their branches touching each other. With little imagination and with a knowledge of the microcirculation of the myocardium, it is easy to visualize the manner in which the tips of the branches of t h e trees supply blood to the arterioles, capillaries and vessels and small microcirculatory anastomoses. The branches, there, fore, interconnect to provide an effective collateral circulation should the trunk to any tree become obstructed. This "tree orchard" orientation makes it possible for the myocardium to contract and dilate without necessarily kinking or obstructing the lumen of the small coronary arteries or traumatizing their walls excessively. This spatial morphologic arrangement and orientation is not only extremely interesting and
American Heart Journal
unique b u t necessary to assure least trauma to the vessels. The interconnecting and anastomotic relationships were so extensive that arrest of flow in one circulatory "tree" unit could occur and blood would still be supplied to the ischemic unit by means of anastomoses with several immediately adjacent units. This tree pattern is highly developed in the left ventricle (Figs. 2 and 3). I t i s less well developed near the A-V groove, in the area of the apex, and in the right ventricle (Figs. 2 and 6). Figs. 1, 2, 3, 4, and 6 readily reveal how these "trees" with their branches and the arteries in the trabeculae carneae make it possible for the arteries to fold, i.e., for the branches of the trees to move centripetally toward the main trunk of the trees during cardiac systole and to unfold or spread out centrifugally during diastole of the ventricles. This spatial orientation and architect u r e of the coronary arterial system is quite unique and serves the purpose of maintaining adequate arterial supply to the myocardium without being injured or traumatized in spite of trillions of cardiac contractions and dilatations. The supply of small arteries to the right ventricle is not nearly as luxurious as that for the left side of the septum and free wall of the left ventricle, nor are the tree formations and spatial orientations nearly as well developed (Figs. 2 and 6). The arteries in the right ventricular myocardium are tortuous and coil as they do in the left ventricle and possibly even more so, since changes in the wall size during the cardiac cycle have to depend mainly on such non-linear courses of the arteries and less upon the morphology of "tree" configurations. The circulation of the septum is also rather interesting. Large arteries penetrate the septum at about one-third of its thickness from the right ventricle o r two-thirds from the endocardial surface of the left ventricle. The arterial supply to the left side (two-thirds) of the septum is richer than that to the right side (one-third). The "tree" type of arterial distribution is predominantly to the left side of the septum. On the right side of the septum the branching, distribution, and spatial orientation of the arteries are more like that of the free wall of the right ventricle (Fig. 7). Thus, these anatomic arterial patterns indicate that a large part (two-thirds) of the septal myocardium does "belong" to the left ventricle and a smaller part (one-third) "belongs" to the right ventricle.
477
Burch and Giles
T h e s e p t u m , t h e r e f o r e , is n o t e n t i r e l y left v e n t r i c ular myocardium. T h e arterial s u p p l y to t h e f a t of t h e s u r f a c e o f the h e a r t is a c h i e v e d b y m e a n s o f m a n y v e r y small hair-like arteries w h i c h e x t e n d v e r t i c a l l y f r o m t h e large vessels to t h e e p i c a r d i a l e p i t h e l i u m (Fig. 2).
Summary T h e small c o r o n a r y arteries o f t w o p a t i e n t s with alcoholic c a r d i o m y o p a t h y were s t u d i e d b y m e a n s of fine p a r t i c l e b a r i u m i n j e c t i o n a n d soft xr a y technic. T h e s p a t i a l a r c h i t e c t u r e o f t h e s e small arteries w h i c h p e n e t r a t e d i n t o t h e d e p t h o f t h e right a n d left v e n t r i c u l a r m y o c a r d i u m w e r e normal. Their lumina were somewhat dilated and their l u m i n a l s u r f a c e s were s m o o t h . T h e " t r e e c i r c u l a t o r y u n i t s " were described f r o m this s t u d y a n d were f o u n d to be n o r m a l . T h e left v e n t r i c u l a r m y o c a r d i u m was r i c h l y s u p p l i e d w i t h s m a l l arteries, w h e r e a s t h e m y o c a r d i u m o f t h e r i g h t ventricle w a s n o t so r i c h l y supplied. T h e m y o c a r d i u m of t h e p a p i l l a r y m u s c l e s a n d t h e t r a b e c u l a e c a r n e a e of t h e left ventricle also h a d a g o o d s u p p l y of small arteries, as did t h e r e m o t e e n d o cardial m y o c a r d i a l a p p e n d a g e s . N u m e r o u s fine hair-like arteries e x t e n d e d t o t h e e p i c a r d i a l myocardium of the right ventricle to form a brush-like a p p e a r a n c e .
REFERENCES 1. Hale, A. R., and Reed, A. F.: Studies in cerebral circulation: Methods for the qualitative and quantitative study of human cerebral blood vessels, AM. HEART J. 66:226, 1963.
478
2. Fulton, W. F. M.: Arterial anastomoses in the coronary circulation. I. Anatomical features in normal and diseased hearts demonstrated by stereoarteriography, Scot. Med. J. 8:420, 1963. 3. Fulton, W. F. M.: The coronary arteries: Arteriography, microanatomy, and pathogenesis of obliterative coronary artery disease, Springfield, Ill., 1965, Charles C Thomas, Publisher. 4. Crainichianu, A.: Anatomische Studien fiber die Coronaraterien und experimenteUe Untersuchungen fiber ihre Durchg~ingigkeit, Virchows Arch. Pathol. Anat. 238:1, 1922. 5. Gross, L., and Kugel, M. A.: The arterial blood vascular distribution to the left and right ventricles of the human heart, AM. HEARTJ. 9:165, 1933. 6. Burch, G. E., and Giles, T. D.: Interesting peculiarities of the spatial dynamic architecture of the coronary arteries, AM. HEARTJ. 85:140, 1973. 7. Ranganathan, N., and Burch, G. E.: Gross morphology and arterial supply of the papillary muscles of the left ventricle of man, AM. HEARTJ. 77:506, 1969. 8. Baroldi, G., and Scomazzoni, G.: Coronary circulation in the normal and the pathologic heart, Superintendent of Documents, U. S. Government Printing Office, Washington, D. C., 1967. 9. Spalteholz, W,: Die Arterien der Herzwand. Anatomische Untersuchungen an Menschenund Tierherzen, Leipzig, 1924, S. Hirzel. 10. Estes, E., Jr., Entman, M. L., Dixon, H. B., II, and Hackel, D. B.: The vascular supply of the left ventricular wall: Anatomic observations, plus a hypothesis regarding acute events in coronary artery disease, AM. HEART J. 71:58, 1966. 11. Schenk, E. A., and Cohen, J.: The heart in chronic alcoholism: Clinical and pathologic findings, Pathol. Microbiol. 35:96, 1970. 12. Massumi, R. A., Rios, J. C., Gooch, A. S., Nutter, D., De Vita, V. T., and Datlow, D. W.: Primary myocardial disease: Report of fifty cases and review of the subject, Circulation 31:19, 1965. 13. Pintar, K., Wolanskyj, B. M., and Gubbay, E. R.: Alcoholic cardiomyopathy, Can. Med. Assoc. J. 93:103, 1965.
October, 1977, Vol. 94, No. 4
