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Effects of cardiac lymphatic obstruction on coronary arteries
Effects of cardiac lymphatic obstruction on coronary arteries A study was undertaken to determine whether changes occurred in the coronary arteries of dogs after obstruction of the cardiac lymphatics. Other investigators have described changes in the walls of coronary arteries after cardiac lymphatic obstruction that caused compromise of the lumen. Adult mongrel dogs were subjected to an operation which occluded the cardiac lymphatics. Several days later, a second operation was done to remove specimens of the terminal branches of the coronary arteries. The specimens were studied by light and electron microscopy. There was no gross or microscopic evidence of altered morphology of the coronary arterial walls.
R. Randolph Bradham, M.D.,* Edward F. Parker, M.D.,* William B. Greene, B.S.,** and Gordon R. Hennigar, M.D.,** Charleston, S. C.
An prior investigations in our1 laboratory, the myocardium of the ventricles was found to have a rich lymphatic network. These cardiac lymphatics drain into several efferent collecting trunks that usually follow the pathways of the coronary arteries. Eventually, these terminate in the lymph node usually positioned between the superior vena cava and the ascending aorta. Our-- :i investigations and those of others have been directed toward finding a correlation between insufficiency of lymphatic drainage of the heart and certain cardiac disease states. Jellinek, and associates' described acute changes in the coronary arteries subsequent to obstruction of the efferent cardiac lymphatics. The cardiac lymph nodes were excised and the lymphatics and thoracic duct were ligated, so that a lymphatic congestion of the heart developed. The animals From the Departments of Surgery and Pathology, Medical University of South Carolina, and the Department of Surgery, Roper Hospital, Charleston, S. C. Supported by the John A. Hartford Foundation, Cardiovascular Research Laboratory, Roper Hospital, Charleston, S. C. Received for publication Nov. 29, 1974. *The Departments of Surgery, Medical University of South Carolina and Roper Hospital. **The Department of Pathology, Medical University of South Carolina.
876
were subsequently put to death. These authors' found vacuolization of the endothelium in some coronary vessels and a more or less marked subendothelial plasma imbibition in others. This plasma imbibition was also found in the media. When lymphatic congestion was protracted, muscular necrosis also developed. The process affected the medium-sized and small arteries of the ventricles; thus changes developed mainly in those branches which might play a role in the formation of an eventual collateral circulation. Obstruction of the lymphatics was thought to result in a disturbance of the vascular wall transport. The plasma substances physiologically entering the vascular wall are also prevented from leaving it and ultimately accumulate in it. Plasma imbibition may be absorbed after lymph flow is restored, if no smooth muscle necrosis and resulting fibrinoid necrosis of the vascular wall develop. The subendothelial plasma imbibitions narrow the vascular lumen and contribute to the damage caused by insufficient lymph flow in the cardiac muscle. If these changes do occur and if mechanisms can be identified that cause cardiac lymphatic obstruction in man, a causative
Volume 69 Number 6 June, 1975
Cardiac lymphatic obstruction
Fig. 1. Electron micrograph illustrates a portion of the typical coronary artery ultrastructure found in experimental as well as control animals. In muscular arteries, the subendothelial basement membrane is absent. There is a layer of collagenous reticular fibers between the internal elastic membrane and the endothelial lining. En, Endothelial cell. SM, Smooth muscle cell. E, Internal elastic membrane. Arrows, Collagenous reticular layer.
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The Journal of
878
Bradham et al.
Thoracic and Cardiovascular Surgery
factor for coronary artery disease may emerge. Because of the potential impact of such findings, similar studies were done in our laboratory. Materials and methods Adult mongrel dogs were anesthetized with intravenous sodium pentobarbital. Respiration was controlled via a mechanical respirator, with room air and intermittent positive pressure. The heart was exposed through a right thoracotomy incision. After the pericardium was opened, 1 c.c. of India ink was injected into the walls of the ventricles. The cardiac efferent trunks became apparent within a few minutes, and their course to the cardiac lymph nodes was traced without difficulty. This node (or nodes) was excised, and the efferent trunks were individually ligated. The pericardium and chest were closed and the animal was resuscitated. Three or 4 days later the dog was operated upon again through the same incision after appropriate anesthesia. Extracorporeal circulation was utilized for support. Specimens of the terminal branches of the coronary arteries were then obtained with great care to avoid trauma to the specimen. The specimens were then examined by light and electron microscopy. Tissue blocks were fixed for electron microscopic examination in 4.5 per cent buffered glutaraldehyde for 30 minutes and trimmed by means of a dissecting microscope. The trimmed blocks were left in glutaraldehyde for an additional 60 minutes and then were placed in buffered rinse overnight. The blocks were postfixed in 2 per cent osmium tetroxide the following morning and subsequently were dehydrated and embedded in Epon. Parallel sections of all specimens submitted for electron microscopy were fixed in formalin and processed in paraffin for light microscopy. Thick sections (0.5 JX) were cut and stained with toluidine blue to determine proper orientation. Subsequent thin sections were then stained with uranyl acetate and lead citrate and examined with a Hitochi HU-12 electron microscope.
Eleven animals were studied, and specimens were obtained from 3 control animals under similar conditions but without prior obstruction of the cardiac lymphatics. Results There was no gross dilatation of the cardiac lymphatic network on the surface of the heart. The sites of injection of India ink were still apparent, and some of the efferent trunks still contained the ink. Light microscopy revealed normal coronary arterial walls in all animals. There was no evidence of any compromise of the arterial wall on electron microscopy. No collection of plasma between the endothelium and the lamina elastica interna was seen. Fig. 1 is typical of the morphology of the specimens of both experimental and control animals. The cells in the blood vessel wall appear normal, and the plasma membranes of adjacent cells are coapted well. Comment The cardiac lymphatic network is significant and must serve the heart as do the lymphatics of other organs. It would seem logical that prevention of lymphatic drainage of the heart would cause changes that might be detrimental to function of the organ. In a previous study, we:i could find no alteration in appearance and only minimal and insignificant changes in morphology of the atrioventricular valves following cardiac lymphatic obstruction. In another study, only minimal changes have been found in the endocardium by electron microscopy after interruption of the cardiac lymphatics.5 Summary Mongrel dogs were subjected to obstruction of the cardiac lymphatics and subsequent microscopic examination of coronary arterial structure. There was no gross or microscopic evidence of altered morphology of the coronary arterial walls. It can be theorized that obstruction of the cardiac
Volume 69 Number 6
Cardiac lymphatic obstruction
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June, 1975
lymphatics is not a factor in coronary artery atherosclerosis. REFERENCES 1 Bradham, R. R., Parker, E. F., Barrington, B. A., Jr., Webb, C. M., and Stallworth, J. M.: The Cardiac Lymphatics, Ann. Surg. 171: 899, 1970. 2 Bradham, R. R„ and Parker, E. F.: The Cardiac Lymphatics: Collective Review, Ann. Thorac. Surg. 15: 527, 1973.
3 Bradham, R. R., Parker, E. F., and Greene, W. B.: Lymphatics of the Atrioventricular Valves, Arch. Surg. 106: 210, 1973. 4 Jellinek, H., Gabor, G., Solti, F., and Veress, B.: The Problem of the Coronary Changes Due to Disturbance of Vascular Wall Permeability, Angiology 18: 179, 1967. 5 Parker, E. F., Bradham, R. R., Hennigar, G. R., and Greene, W. B.: Effects of Obstruction of Cardiac Lymphatics, i. THORAC. CARDIOVASC. SURG. 69: 390,
1975.
R. Randolph Bradham, M.D.,* Edward F. Parker, M.D.,* William B. Greene, B.S.,** and Gordon R. Hennigar, M.D.,** Charleston, S. C.
An prior investigations in our1 laboratory, the myocardium of the ventricles was found to have a rich lymphatic network. These cardiac lymphatics drain into several efferent collecting trunks that usually follow the pathways of the coronary arteries. Eventually, these terminate in the lymph node usually positioned between the superior vena cava and the ascending aorta. Our-- :i investigations and those of others have been directed toward finding a correlation between insufficiency of lymphatic drainage of the heart and certain cardiac disease states. Jellinek, and associates' described acute changes in the coronary arteries subsequent to obstruction of the efferent cardiac lymphatics. The cardiac lymph nodes were excised and the lymphatics and thoracic duct were ligated, so that a lymphatic congestion of the heart developed. The animals From the Departments of Surgery and Pathology, Medical University of South Carolina, and the Department of Surgery, Roper Hospital, Charleston, S. C. Supported by the John A. Hartford Foundation, Cardiovascular Research Laboratory, Roper Hospital, Charleston, S. C. Received for publication Nov. 29, 1974. *The Departments of Surgery, Medical University of South Carolina and Roper Hospital. **The Department of Pathology, Medical University of South Carolina.
876
were subsequently put to death. These authors' found vacuolization of the endothelium in some coronary vessels and a more or less marked subendothelial plasma imbibition in others. This plasma imbibition was also found in the media. When lymphatic congestion was protracted, muscular necrosis also developed. The process affected the medium-sized and small arteries of the ventricles; thus changes developed mainly in those branches which might play a role in the formation of an eventual collateral circulation. Obstruction of the lymphatics was thought to result in a disturbance of the vascular wall transport. The plasma substances physiologically entering the vascular wall are also prevented from leaving it and ultimately accumulate in it. Plasma imbibition may be absorbed after lymph flow is restored, if no smooth muscle necrosis and resulting fibrinoid necrosis of the vascular wall develop. The subendothelial plasma imbibitions narrow the vascular lumen and contribute to the damage caused by insufficient lymph flow in the cardiac muscle. If these changes do occur and if mechanisms can be identified that cause cardiac lymphatic obstruction in man, a causative
Volume 69 Number 6 June, 1975
Cardiac lymphatic obstruction
Fig. 1. Electron micrograph illustrates a portion of the typical coronary artery ultrastructure found in experimental as well as control animals. In muscular arteries, the subendothelial basement membrane is absent. There is a layer of collagenous reticular fibers between the internal elastic membrane and the endothelial lining. En, Endothelial cell. SM, Smooth muscle cell. E, Internal elastic membrane. Arrows, Collagenous reticular layer.
877
The Journal of
878
Bradham et al.
Thoracic and Cardiovascular Surgery
factor for coronary artery disease may emerge. Because of the potential impact of such findings, similar studies were done in our laboratory. Materials and methods Adult mongrel dogs were anesthetized with intravenous sodium pentobarbital. Respiration was controlled via a mechanical respirator, with room air and intermittent positive pressure. The heart was exposed through a right thoracotomy incision. After the pericardium was opened, 1 c.c. of India ink was injected into the walls of the ventricles. The cardiac efferent trunks became apparent within a few minutes, and their course to the cardiac lymph nodes was traced without difficulty. This node (or nodes) was excised, and the efferent trunks were individually ligated. The pericardium and chest were closed and the animal was resuscitated. Three or 4 days later the dog was operated upon again through the same incision after appropriate anesthesia. Extracorporeal circulation was utilized for support. Specimens of the terminal branches of the coronary arteries were then obtained with great care to avoid trauma to the specimen. The specimens were then examined by light and electron microscopy. Tissue blocks were fixed for electron microscopic examination in 4.5 per cent buffered glutaraldehyde for 30 minutes and trimmed by means of a dissecting microscope. The trimmed blocks were left in glutaraldehyde for an additional 60 minutes and then were placed in buffered rinse overnight. The blocks were postfixed in 2 per cent osmium tetroxide the following morning and subsequently were dehydrated and embedded in Epon. Parallel sections of all specimens submitted for electron microscopy were fixed in formalin and processed in paraffin for light microscopy. Thick sections (0.5 JX) were cut and stained with toluidine blue to determine proper orientation. Subsequent thin sections were then stained with uranyl acetate and lead citrate and examined with a Hitochi HU-12 electron microscope.
Eleven animals were studied, and specimens were obtained from 3 control animals under similar conditions but without prior obstruction of the cardiac lymphatics. Results There was no gross dilatation of the cardiac lymphatic network on the surface of the heart. The sites of injection of India ink were still apparent, and some of the efferent trunks still contained the ink. Light microscopy revealed normal coronary arterial walls in all animals. There was no evidence of any compromise of the arterial wall on electron microscopy. No collection of plasma between the endothelium and the lamina elastica interna was seen. Fig. 1 is typical of the morphology of the specimens of both experimental and control animals. The cells in the blood vessel wall appear normal, and the plasma membranes of adjacent cells are coapted well. Comment The cardiac lymphatic network is significant and must serve the heart as do the lymphatics of other organs. It would seem logical that prevention of lymphatic drainage of the heart would cause changes that might be detrimental to function of the organ. In a previous study, we:i could find no alteration in appearance and only minimal and insignificant changes in morphology of the atrioventricular valves following cardiac lymphatic obstruction. In another study, only minimal changes have been found in the endocardium by electron microscopy after interruption of the cardiac lymphatics.5 Summary Mongrel dogs were subjected to obstruction of the cardiac lymphatics and subsequent microscopic examination of coronary arterial structure. There was no gross or microscopic evidence of altered morphology of the coronary arterial walls. It can be theorized that obstruction of the cardiac
Volume 69 Number 6
Cardiac lymphatic obstruction
879
June, 1975
lymphatics is not a factor in coronary artery atherosclerosis. REFERENCES 1 Bradham, R. R., Parker, E. F., Barrington, B. A., Jr., Webb, C. M., and Stallworth, J. M.: The Cardiac Lymphatics, Ann. Surg. 171: 899, 1970. 2 Bradham, R. R„ and Parker, E. F.: The Cardiac Lymphatics: Collective Review, Ann. Thorac. Surg. 15: 527, 1973.
3 Bradham, R. R., Parker, E. F., and Greene, W. B.: Lymphatics of the Atrioventricular Valves, Arch. Surg. 106: 210, 1973. 4 Jellinek, H., Gabor, G., Solti, F., and Veress, B.: The Problem of the Coronary Changes Due to Disturbance of Vascular Wall Permeability, Angiology 18: 179, 1967. 5 Parker, E. F., Bradham, R. R., Hennigar, G. R., and Greene, W. B.: Effects of Obstruction of Cardiac Lymphatics, i. THORAC. CARDIOVASC. SURG. 69: 390,
1975.