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Magnification coronary arteriography: Part II, experimental pathology
clin. Radiol.
(1966) 17, 89-91
MAGNIFICATION CORONARY P A R T II, E X P E R I M E N T A L
ARTERIOGRAPHY: PATHOLOGY
A L L A N L. SIMON,* and R I C H A R D H. GREENSPAN+
From the Department of Radiology, Yale University School of Medicine
Magnification arteriography of the coronary arteries was applied in the detection of stenotic and occlusal disease of the small branches. Allylamine lesions produced in 100 to 600 micron diameter vessels were easily demonstrated and pathologically confirmed. The diagnostic and prognostic significance of small vessel disease is discussed briefly.
FIG. 1A FIG. 1B A--Magnification coronary arteriogram showing allylamine lesions There are multiple narrowmgs m the branches of the right coronary artery (black-white arrows). In addition, there is involvement of the mid left anterior descending branch (white arrow). B--Standard coronary angiogram (done at the same time as (a) with acetylcholine arrest), demonstrating the narrowing of the large vessel only. The fine vessels are not resolved adequately enough to permit evaluanon.
MAGNIFICATION arteriography of the coronary circulation has been proven capable of visualizing the normal arteries to about 250 micron diameter or smaller (Simon and Greenspan, 1965). This subsequent study was undertaken to determine the ability of the method to demonstrate disease in the fine coronary vessels.
Allylamine was chosen because of its ability to produce lesions in the small branches. Waters (1948) showed that intravenous injections of this strong base produced intimal lesions in canine coronary arteries. Severe luminal narrowing by plaques is found, similar to atherosclerosis in humans. The lesions are produced in vessels of *United States Public Health Service Fellow in Cardio- 100 to 600 micron diameter. They have been vascular Radiology, Yale University School of Medicine. documented histologically but could not be tProfessor of Radiology, Yale University School of visualized by conventional methods of coronary Medicine. Supported by Grants from USPHS-HE-05518; USPHS- arteriography (Bloor and Lowman 1963, Lowman HE-5429 and, Grant-in-Aid, New Haven Heart Association. and Bloor 1963). Therefore, this seemed a logical 89
90
CLINICAL
RADIOLOGY
FIG. 2A--Control arterlogram done with magnification techmque. Fro. 2R--Magnification angiogram performed six weeks after allylamine rejections. Note the diffuse narrowing of the right coronary branches and the lack of filling of the 4th generation vessels. There is a complete occlusion at the apex (black-white arrows) with filling of the vessel by the collaterals and obliteration of the mterventricular septal branch (black arrow). Fro. 2c--Section from a branch of the coronary artery (at the white arrow in Fig. B) (4Sx) with extensive intimal narrowing and haemorrhage under the plaque.
were repeated 3 and 6 weeks after the start of injections. One animal was sacrificed at 6 weeks and the heart carefully dissected by a pathologist. Sections were taken from the areas of most severe narrowing as determined angiographically. area of investigation technique.
using
the magnification
METHOD Dogs weighing 10-15 kilograms were the experimental subjects. Preliminary magnification coronary arteriograms were performed. After a 2-3 day delay, a 1 ~ solution of Allylamine in normal saline buffered to ph 7-4 was injected intravenously at a dose of 18 milligrams per Kg., daily for 3 days. This was followed by intravenous injection of 2~o methylcellulose solution every other day for 2 weeks. Magnification arteriograms
RESULTS Three weeks after the Allylamine injections, there is no demonstrable coronary artery disease. However, at 6 weeks, one can see multiple short areas of stenosis in the small third and fourth generation branches of both coronary arteries (Fig. 1). The ventricular branches of the right coronary and the deep interventricular septal branch of the left are especially narrowed. A complete block of the distal anterior descending branch of the left coronary artery near the apex was present in one subject, and the vessel beyond was filled by
MAGNIFICATION
CORONARY
collaterals (Fig. 2, A and B). The normal myocardial 'blush' is not seen, in contrast with the control. Comparison with conventional coronary arteriography was made in one animal with a moderate narrowing of the proximal left anterior descending branch in addition to the multiple small vessel lesions. The large vessel lesion was seen by standard study done under identical conditions, but the diffuse small vessel disease could not be seen (Fig.
1). Gross pathological examination showed diffuse myocardial fibrosis and no major coronary vessel lesion. Microscopic examination using haemotoxylin and eosin stain was also done. Sections taken from the 'stenotie' regions of the vessels showed severe luminal narrowing by subintimal accumulation of maerophages and fibrous tissue (Fig. 2, C). A section from the cardiac apex showed the occluded distal left anterior descending branch with only a microscopic lumen and an early infarct of the myocardium in the area. By direct measurement of the vessel section on the slide and by measurement through the microscope, we determined that vessels with 250 micron diameter lumen are easily seen. The lower limits of visibility still have not been determined.
ARTERIOGRAPHY:
PART
I1
91
disease, therefore, escapes detection by conventional methods. Much speculation has been made over the significance of small vessel disease. Postmortem angiography of hearts with coronary artery disease has shown a large percentage involved by diffuse small vessel narrowing coincident with major artery obstruction (Niles and Dotter 1963, Swedlund et al., 1962). This diffuse disease has been implicated as a factor which would inhibit the development of collaterals and is thought by many to be responsible for the failures of endarterectomy (Thal et al., 1958, Swedlund et al., 1962). Selective coronary catheterization and cineradiography gives much dynamic information and is the best method for localizing surgical lesions. We feel magnification coronary arteriography should be performed in addition to the conventional study for significant vascular detail is added and lesions of the peripheral branches can be detected. Acknowledgments.--Our thanks is given to Mr. Henry Gautot, R.T., M.S.R. for his technical assistance. We are indebted to Levin Waters, M.D., who performed the pathology, and for his encouragement. Department of Radiology, Yale University School of Medicine, 789 Howard Avenue, New Haven 4, Connecticut.
DISCUSSION The allylamine-induced short and severe stenoses were easily demonstrated by magnification arteriography regardless of the size of the vessel. Conventional arteriography performed with rapid serial filming during cardiac arrest and coronary artery injection was capable of visualizing only the major coronary branches. Diffuse small vessel
REFERENCES BLOOR,C. M., & LOWMAN,R. M. (1963). Radiology 81,770. LOWMAN,R. M., & BLOOR,C. M. (1963). Radiology 81,778. NILES, N. R., & DOTTER,C. T. (1963). Circulation 28, 190 S~MON,A. L., & GREEYSVAN(1965). Clin. Radiol., 16, 414. SWEDLUND,H. A. et al. (1962). Circulation 25, 292. THAL, A. P. et al. (1958). J A M A 168, 2104. WATERS,L. L. (1948). Am. Heart J. 35, 212.
BOOK REVIEW Studies in the Pathology of Radiation Disease. By N. A.
KRAYEVSKH(1957). English Translation (1965). Pergamon Press. Pp. 219. Price £5. This monograph is strictly concerned with the morphological changes observed in organs after exposure to ionizing radiation. The naked eye and histological changes which can be seen in experimental animals are surveyed and each chapter is devoted to a different organ or system. This well
produced and illustrated English translation has appeared 7 years after the original publication and this delay does detract from the value of the book at this time. Also, physical dose and pathological change are often inadequately related. Reference is made to work performed in all parts of the world, but the contributions of Professor Krayevskii and his colleagues dominate in the book. Ttus volume will therefore be of interest more as an account of Russian work and opinion than as a general review of the subject. S, DISCHE
(1966) 17, 89-91
MAGNIFICATION CORONARY P A R T II, E X P E R I M E N T A L
ARTERIOGRAPHY: PATHOLOGY
A L L A N L. SIMON,* and R I C H A R D H. GREENSPAN+
From the Department of Radiology, Yale University School of Medicine
Magnification arteriography of the coronary arteries was applied in the detection of stenotic and occlusal disease of the small branches. Allylamine lesions produced in 100 to 600 micron diameter vessels were easily demonstrated and pathologically confirmed. The diagnostic and prognostic significance of small vessel disease is discussed briefly.
FIG. 1A FIG. 1B A--Magnification coronary arteriogram showing allylamine lesions There are multiple narrowmgs m the branches of the right coronary artery (black-white arrows). In addition, there is involvement of the mid left anterior descending branch (white arrow). B--Standard coronary angiogram (done at the same time as (a) with acetylcholine arrest), demonstrating the narrowing of the large vessel only. The fine vessels are not resolved adequately enough to permit evaluanon.
MAGNIFICATION arteriography of the coronary circulation has been proven capable of visualizing the normal arteries to about 250 micron diameter or smaller (Simon and Greenspan, 1965). This subsequent study was undertaken to determine the ability of the method to demonstrate disease in the fine coronary vessels.
Allylamine was chosen because of its ability to produce lesions in the small branches. Waters (1948) showed that intravenous injections of this strong base produced intimal lesions in canine coronary arteries. Severe luminal narrowing by plaques is found, similar to atherosclerosis in humans. The lesions are produced in vessels of *United States Public Health Service Fellow in Cardio- 100 to 600 micron diameter. They have been vascular Radiology, Yale University School of Medicine. documented histologically but could not be tProfessor of Radiology, Yale University School of visualized by conventional methods of coronary Medicine. Supported by Grants from USPHS-HE-05518; USPHS- arteriography (Bloor and Lowman 1963, Lowman HE-5429 and, Grant-in-Aid, New Haven Heart Association. and Bloor 1963). Therefore, this seemed a logical 89
90
CLINICAL
RADIOLOGY
FIG. 2A--Control arterlogram done with magnification techmque. Fro. 2R--Magnification angiogram performed six weeks after allylamine rejections. Note the diffuse narrowing of the right coronary branches and the lack of filling of the 4th generation vessels. There is a complete occlusion at the apex (black-white arrows) with filling of the vessel by the collaterals and obliteration of the mterventricular septal branch (black arrow). Fro. 2c--Section from a branch of the coronary artery (at the white arrow in Fig. B) (4Sx) with extensive intimal narrowing and haemorrhage under the plaque.
were repeated 3 and 6 weeks after the start of injections. One animal was sacrificed at 6 weeks and the heart carefully dissected by a pathologist. Sections were taken from the areas of most severe narrowing as determined angiographically. area of investigation technique.
using
the magnification
METHOD Dogs weighing 10-15 kilograms were the experimental subjects. Preliminary magnification coronary arteriograms were performed. After a 2-3 day delay, a 1 ~ solution of Allylamine in normal saline buffered to ph 7-4 was injected intravenously at a dose of 18 milligrams per Kg., daily for 3 days. This was followed by intravenous injection of 2~o methylcellulose solution every other day for 2 weeks. Magnification arteriograms
RESULTS Three weeks after the Allylamine injections, there is no demonstrable coronary artery disease. However, at 6 weeks, one can see multiple short areas of stenosis in the small third and fourth generation branches of both coronary arteries (Fig. 1). The ventricular branches of the right coronary and the deep interventricular septal branch of the left are especially narrowed. A complete block of the distal anterior descending branch of the left coronary artery near the apex was present in one subject, and the vessel beyond was filled by
MAGNIFICATION
CORONARY
collaterals (Fig. 2, A and B). The normal myocardial 'blush' is not seen, in contrast with the control. Comparison with conventional coronary arteriography was made in one animal with a moderate narrowing of the proximal left anterior descending branch in addition to the multiple small vessel lesions. The large vessel lesion was seen by standard study done under identical conditions, but the diffuse small vessel disease could not be seen (Fig.
1). Gross pathological examination showed diffuse myocardial fibrosis and no major coronary vessel lesion. Microscopic examination using haemotoxylin and eosin stain was also done. Sections taken from the 'stenotie' regions of the vessels showed severe luminal narrowing by subintimal accumulation of maerophages and fibrous tissue (Fig. 2, C). A section from the cardiac apex showed the occluded distal left anterior descending branch with only a microscopic lumen and an early infarct of the myocardium in the area. By direct measurement of the vessel section on the slide and by measurement through the microscope, we determined that vessels with 250 micron diameter lumen are easily seen. The lower limits of visibility still have not been determined.
ARTERIOGRAPHY:
PART
I1
91
disease, therefore, escapes detection by conventional methods. Much speculation has been made over the significance of small vessel disease. Postmortem angiography of hearts with coronary artery disease has shown a large percentage involved by diffuse small vessel narrowing coincident with major artery obstruction (Niles and Dotter 1963, Swedlund et al., 1962). This diffuse disease has been implicated as a factor which would inhibit the development of collaterals and is thought by many to be responsible for the failures of endarterectomy (Thal et al., 1958, Swedlund et al., 1962). Selective coronary catheterization and cineradiography gives much dynamic information and is the best method for localizing surgical lesions. We feel magnification coronary arteriography should be performed in addition to the conventional study for significant vascular detail is added and lesions of the peripheral branches can be detected. Acknowledgments.--Our thanks is given to Mr. Henry Gautot, R.T., M.S.R. for his technical assistance. We are indebted to Levin Waters, M.D., who performed the pathology, and for his encouragement. Department of Radiology, Yale University School of Medicine, 789 Howard Avenue, New Haven 4, Connecticut.
DISCUSSION The allylamine-induced short and severe stenoses were easily demonstrated by magnification arteriography regardless of the size of the vessel. Conventional arteriography performed with rapid serial filming during cardiac arrest and coronary artery injection was capable of visualizing only the major coronary branches. Diffuse small vessel
REFERENCES BLOOR,C. M., & LOWMAN,R. M. (1963). Radiology 81,770. LOWMAN,R. M., & BLOOR,C. M. (1963). Radiology 81,778. NILES, N. R., & DOTTER,C. T. (1963). Circulation 28, 190 S~MON,A. L., & GREEYSVAN(1965). Clin. Radiol., 16, 414. SWEDLUND,H. A. et al. (1962). Circulation 25, 292. THAL, A. P. et al. (1958). J A M A 168, 2104. WATERS,L. L. (1948). Am. Heart J. 35, 212.
BOOK REVIEW Studies in the Pathology of Radiation Disease. By N. A.
KRAYEVSKH(1957). English Translation (1965). Pergamon Press. Pp. 219. Price £5. This monograph is strictly concerned with the morphological changes observed in organs after exposure to ionizing radiation. The naked eye and histological changes which can be seen in experimental animals are surveyed and each chapter is devoted to a different organ or system. This well
produced and illustrated English translation has appeared 7 years after the original publication and this delay does detract from the value of the book at this time. Also, physical dose and pathological change are often inadequately related. Reference is made to work performed in all parts of the world, but the contributions of Professor Krayevskii and his colleagues dominate in the book. Ttus volume will therefore be of interest more as an account of Russian work and opinion than as a general review of the subject. S, DISCHE