The absence of lymphatics in normal and atherosclerotic coronary arteries in man: a morphologic study.

It has been suggested by various investigators that the impairment of lymphatic drainage from the coronary arteries may play a role in predisposition to coronary atherosclerosis, the pathogenesis of which is certainly multifactorial. In our study, no lymphatic vessels were found in the walls of the coronary arteries (adventitia, media and intima) in 51 human hearts from patients ranging in ages from 3 months to 83 years with normal coronary arteries, coronary atherosclerosis, and cardiomyopathy. Visualized lymphatics were located solely in the periadventitial area, and these lymphatics were more irregular in hearts from older persons. With injection, histology, and electronmicroscopy methods we could not detect penetration of lymphatics into the wall of coronary trunks in normal as well atherosclerotic arteries. In all coronary arteries studied, and particularly in the atherosclerotic lesions, blood vasa vasorum could be visualized. In the atherosclerotic areas, vasa vasorum (angiogenesis) could be seen penetrating into the media and intima. Many of the thin-walled vasa vasorum could easily be mistaken for lymphatics. The absence of lymphatics draining the epicardial coronary arteries may be a predisposing factor to coronary atherosclerosis.

Morphology of lymphatics in human venous crural ulcers with lipodermatosclerosis.

A morphological evaluation of lymphatic vessels of skin leg ulcers was performed in 39 human subjects with longstanding venous insufficiency and lipodermatosclerosis. Light and electron microscopy demonstrated that the superficial fibrin and inflammatory cell layers and intermediate blood capillary layer of the ulcer bed, which were primarily granulation tissue, did not contain lymphatics. Moreover, lymphatic capillaries were present only sporadically in the transition zone from granulation tissue to the deeper collagenous scar layer of the ulcer. In some instances, in the deepest part of the ulcer bed near the crural fascia, there were one or two thicker lymphatic collectors with valves, which were continuations of collectors from the plantar foot region. Lymphatics were present at the border of the ulcer and in lipodermatosclerotic skin, but the endothelium and muscle lining layer were partially destroyed. Lymphatic capillaries were characterized by open interendothelial junctions in conjunction with subendothelial edema. In lipodermatosclerotic skin, the morphologic changes suggest that absorption of interstitial fluid and lymph is markedly disturbed adjacent to the ulcer bed, which likely contributes to both slow healing and high recurrence of skin ulcers associated with longstanding venous insufficiency.

The morphology of the lymphatics of the coronary arteries in the dog.

On the supposition that pericoronary lymphatics play an important role in the efflux of interstitial fluid from the blood vessel wall, we examined the morphology of pericoronary arterial lymphatics in the dog. After ligation of the principal epicardial drainage lymphatics, after ligation of the left anterior descending coronary artery, after induced pericoronary inflammation and after instillation of India Ink into the pericardial sac using light, dissecting, and electron microscopy. The findings were compared with non-operated (control) dogs. Lymphatic drainage of the coronary arteries is via adventitial lymphatics, which do not penetrate to the media and via periadventitial lymphatics consisting of a subepicardial lymphatic plexus overlying the coronary arteries. The smaller arterioles in the ventricular muscle have many more accompanying lymphatics than do epicardial coronary arteries. In the latter arteries, prelymphatic channels formed by collagen fibers in the media likely transport interstitial fluid to the adventitial and periadventitial lymphatics. Arterial contraction also likely plays a role in propulsion of coronary arterial interstitial fluid towards adventitial lymphatics.

Failure of the canine principal ascending epicardial lymphatic to regenerate after transection.

We transected the principal ascending anterior epicardial cardiac lymphatic in 10 dogs, and after varying time intervals reoperated to look for lymphatic regeneration using dye injection. Photographs and sketches were made to record the findings, and in six dogs serial histologic sections were also examined. In none of the 10 dogs was regeneration of the transected principal cardiac lymphatic detected although small lymphatic collaterals from the distal side of the lymphatic developed in 2 dogs. Further studies are merited to assess the role of lymphatic insufficiency in the development of coronary vasculopathy and chronic rejection after cardiac transplantation and other heart operations (e.g., coronary artery bypass) that may injure lymphatic drainage capacity.

Visualization of the lymphatics of the heart and the mediastinal drainage pathways in the living cynomolgous (Macaca mulatta) monkey.

Our interest in the effects of impaired cardiac lymph drainage on coronary atherosclerosis led us to study the cardiac lymphatic anatomy in the monkey, generally considered the ideal experimental animal for examining coronary artery disorders. Short-term and long-term studies to visualize the cardiac lymphatic system and its mediastinal drainage pathways in 14 living monkeys confirmed that the epicardial collecting lymphatic anatomy is comparable to that of man, dog, and pig. These lymphatics, and particular lymphatic drainage to the cardiac lymph node in the right mediastinum, are difficult to visualize, in good part, because lymph uptake of such tracers as India Ink and T1824 blue dye is extremely slow. By modifying our techniques and taking cognizance of the slow lymphatic uptake of the tracers, we have been more successful in visualizing the mediastinal cardiac lymph node. Though our studies confirm that the lymphatic drainage of the monkey heart is similar to that in other mammals, we conclude that the "monkey model" has several drawbacks to study the effects of impaired cardiac lymph flow because of the laborious requirements to visualize successfully the cardiac lymph node. Perhaps the development of new markers would make this lymphatic system more approachable for experimental investigation.

The lymphatic drainage of the parietal pericardium in man.

Parietal pericardial lymphatics were visualized by indirect and direct India ink injections in 35 human cadavers. Studies included examination of cleared specimens under the dissecting microscope and standard light microscopy. The lymphatic vessels of the ventral pericardial surface most often pass along the phrenic nerves cranially to terminate in the anterior right and left and transverse mediastinal nodes, or caudally to the diaphragm or prepericardial lymph nodes. The lymphatics draining the lateral parts of pericardium pass to the anterior mediastinal, tracheobronchial, lateropericardial, prepericardial and posterior mediastinal (juxtaesophageal) lymph nodes. The posterior part of the pericardium drains to the juxtaesophageal and tracheobronchial nodes. Lymphatics from the diaphragmatic part of the pericardium pass to the right lateropericardial and prepericardial, juxtaesophageal and tracheobronchial nodes. The pericardial cupula is anteriorly drained to the anterior mediastinal nodes, and posteriorly to the tracheobronchial nodes. In cleared specimens two networks of lymphatic vessels are seen to surround the pericardial space. On the ventral surface, the lymphatics of the parietal pericardium connect to lymphatics in the pericardial fat and areolar tissue. On the lateral and posterior surfaces, the lymphatics of the parietal pericardium anastomose with lymphatics of the reflected mediastinal pleura. These anatomical observations offer new insights into the mechanisms of turnover of pericardial fluid and into the mechanisms of occurrence of chylopericardium.

Are peripheral lymphatics damaged by high pressure manual massage?

Massage of the foot in men and the hindpaw in dogs was performed by applying external pressures of 70-100 mmHg for a period of one, three, five, and ten minutes with a frequency of 25 strokes per minute. This protocol was performed on individuals without edema, on dogs with experimental lymphedema and men with post-thrombotic venous edema. After ten minutes of forceful massage, focal damage of lymphatics was present. In a group of dogs with lymphedema and men with post-thrombotic venous edema, the alteration of lymphatics was greater than in normal individuals and evident only after 3 to 5 minutes of massage. At first, the forceful massage affected the endothelial lining of the initial lymphatics. Alterations of lymphatic collectors were visible later. The fluid in lymphedema was translocated by massage using high pressure from the interstitium into the lumen of lymphatics by means of the open junctions and by artificial cracks that develop from injury to the lymphatic wall. Vigorous massage in lymphedema also produces loosening of subcutaneous connective tissue, formation of large tissue channels and release of lipid droplets that enter the lymphatics. By this mechanism, massage helps reduce the amount of fat cells in the lymphedematous leg.

The lymphatics of the canine parietal pericardium.

A careful anatomical study of the lymphatic drainage from the parietal pericardium reveals a complicated network that is notably different from that defined by the instillation of markers into the pericardial sac. The pericardial cupola and the posterior (dorsal) area of the parietal pericardium drain directly to the cardiac lymph node in the right upper mediastinum by relatively short lymphatics. The lymphatics of the anterior and lateral areas of the parietal pericardium pass to collecting vessels that travel cranially or caudally along the phrenic nerves. The former traverse specific lymph nodes and then enter the right or left venous angles. The latter pass caudally and then drain to the major collecting systems from the area of the diaphragm.

The efferent cardiac lymphatic pathways in the macaque monkey.

In ten postmortem hearts of the Macaque monkey (M. mulatta), the coronary lymphatics were visualized using an India ink suspension in 2% gelatin. The left coronary lymphatic initially passed to the dorsal surface of the aortic arch. In five hearts, this lymphatic went directly to the cardiac lymph node, whereas in the others, it first ascended to the left superior tracheobronchial node and then interconnected with the cardiac lymph node. The right coronary lymphatic usually passed in front of the ascending aorta and common arterial (brachiocephalic) trunk and entered the cardiac lymph node. In two hearts, however, the right coronary lymphatic first ascended to an anterior transverse mediastinal node and from here lymphatics joined the cardiac lymph node. Those lymphatics that passed cephalad from the cardiac lymph node to the right anterior mediastinal nodes and the right paratracheal nodes ultimately emptied into the right venous angle. Those lymphatics that passed cephalad from the cardiac lymph node to the anterior transverse mediastinal nodes ultimately emptied into the left venous angle. In five other Macaque monkeys (M. mulatta and M. fascicularis) after marker injection (T1824 blue dye and micropulverized barium sulfate) into the living heart or pericardium, lymphatic drainage beyond the base of the heart could not be demonstrated. Whereas postmortem morphologic studies suggest that the monkey coronary lymphatic system is amenable to obstruction by removal of the cardiac lymph node and interruption of its adjacent lymphatic connections, effective methods for visualizing the mediastinal lymphatic collecting system in the living monkey must be developed before experimental cardiac lymphatic ablation can be accomplished in this species.

How lymph is drained away from the human papillary muscle: anatomical conditions.

The lymphatic and venous bed was evaluated in 42 human heart papillary muscles. The lymphatics form networks in the superficial and deep layers of the subendocardium and in the myocardium of the papillary muscles. In the apical area, the subendocardial lymphatics gradually merge with the fine myocardial, developing arcades at the origins of chordae tendineae. Thicker myocardial lymphatics leave the area passing along the connective tissue septa, often in close vicinity to the blood vessels. The injection method failed to reveal deep lymphatics in the connective tissue of chordae tendineae. Lymphovenous anastomoses were disclosed in the papillary muscle. The possible morphological pathways for lymphatic drainage of the papillary muscle are as follows: (1) the lymphatic bed subendocardial and myocardial, joining on the ventricular wall bed at the muscle base, and (2) lymphovenous anastomoses, passing along from the myocardial and subendocardial lymphatic bed into the ventricular wall veins and the sinus coronarius system, or into the thebesian veins and further directly into the heart ventricles.

Morphology of the region of the coronary sinus in respect to coronary sinus rhythm.

The arterial supply to the region of the coronary sinus and the interatrial septum was examined in 18 normal canine hearts. In 13 of a further 18 dogs, coronary sinus rhythm was evoked by the ligation of atrial arteries, subsequent to which the arteries were visualized by injection of latex. A stable coronary sinus rhythm is evoked by producing ischaemia in an extensive area of the right atrium, including the sinus node, the interatrial septum and Bachmann's bundle, but preserving from ischaemia the posteroinferior part of the right atrium. Microscopical examination of the hearts with coronary sinus rhythm, and comparison with 9 control hearts, failed to demonstrate any morphological centre, in the form of nodal cells, which might have been responsible for the abnormal rhythm. In the posterior part of the right atrium, the ischaemic changes failed to affect the approaches of the atrioventricular node. The approaches were predominantly composed of cells poor in myofibrils mixed to a variable degree with cells of the working myocardium. We discuss the possibilities of the development of coronary sinus rhythm and "circus movement" with regard to the participation of the approaches to the atrioventricular node.

Arterial supply of the region of the coronary sinus in man.

Patterns of arterial supply to the atria were studied with respect to the coronary sinus region in 60 human hearts obtained from patients with a negative cardiac history and in 2 hearts with ECG-demonstrated coronary sinus rhythm. The atria, including the interatrial septum, were supplied by the right (40%) or left (30%) or both (30%) sinuatrial arteries which, however, did not reach as far as the posterior margin of the oval fossa and the coronary sinus. The region of the coronary sinus with the Eustachian ridge received direct branches from the trunk of the right (41%) or left (11%) coronary artery or both (48%) in the adjacent part of the coronary sulcus. Possible development of the 'coronary sinus rhythm' on the basis of multifocal damage of the sinuatrial arteries is discussed.

Light microscopy of the lymphatics of the human atrial wall and lymphatic drainage of supraventricular pacemakers.

After injection of Indian ink stained 2% gelatine in 42 human hearts the lymph drainage of the regions of supraventricular cardiac pacemakers and the patterns of the lymphatic vascular bed in the atrial wall were studied. From the sites of the pacemakers the lymph is drained into the tracheobronchial nodes in 100%. Only two of those regions are drained through additional pathways, namely the SAN region into the anterior mediastinal node situated at the azygos vein and the coronary sinus area into the anterior mediastinal lateropericardiac nodes. In the cleared specimens as microscopically the epicardial lymph vessels produce polygonal superficial network; oblique anastomoses of that network run into the deeper layers of subepicardial tissue where they join with deep irregular lymphatic network. Deep subepicardial lymph vessels are often accompanied by veins and nerves. The course of most of myocardial lymph vessels follows the position of muscle cells. In the connective septa these vessels join to form larger trunks and open into the subepicardial vessels.

Morphological study of M. anococcygeus in male and female rats.

In the rat, m. anococcygeus appears as a paired smooth muscle. In the males the muscle divides into a dorsal and ventral part. The ventral parts from both sides embrace the rectum ventrocaudally, they join in front of the rectum and proceed in the septum scroti in a fan-like manner. The dorsal part of the muscle in males and the whole muscle in the females proceed caudally along the lateral gut circumference, gradually developing a fibromuscular plate, a cord adjoining the rectal wall. Caudally from the junction of MA, the longitudinal gut musculature is more abundant in the plate area, appearing as if extracted in the form of a longitudinal column. Directed towards the anus, a frontally oriented septum is formed from connective tissue emerging from the columns. The morphology of the muscle as described here permits to assume that MA in the females and its dorsal part in the males operates as a levator ani, the ventral part of the muscle in males operating as a levator - retractor scroti.

Musculus sphincter ani externus in the rat.

M. sphincter ani externus (MSAE) in the rat appears as a circular ring 1-1.25 mm in height and 250-350 microns thick, completed by a plate composed of longitudinal musculature in its posterior third. The main structures serving for the structural arrangement of MSAE are columns composed of longitudinal smooth musculature of the gut lining the posterior third of the anal circumference. Ventrally to the columns there are several structures in the MSAE showing fluent mutal transitions, namely the horshoe-like pars profunda, the ring-shaped pars superficialis and the pars subcutanea. The ends of the fibres of the horshoe shaped pars profunda join with the columns and pass along longitudinally to gradually replace the smooth musculature. The extension of the longitudinal muscle fibres of the columns upon the dorsal circumference leads to the development of the dorsal plate of MSAE. Some of the fibres of MSAE cross each other ventrally in the pars profunda and pars subcutanea, as well as dorsally in the pars subcutanea and in the area of longitudinally oriented fibres. Some fibres of MSAE are also fixed to the surrounding structures.

Light microscopy of sinoatrial node ischaemia.

Ischaemia of the sinoatrial node (SAN) region was produced in 57 dogs by obstructing the sinoatrial nodal artery by injecting it with various media. In the light microscope ischaemia of the nodal cells resulted in myocytolysis. The cells were oedematous, with a distinctly cleared cytoplasm and cytoplasmic vacuolization. Macrophages penetrated into the nodal cells. Myocytolysis resulted either in disintegration of the cell membrane and the nucleus or in atrophy of nodal cells. The damaged cells were gradually replaced with collagenous connective tissue. Ischaemic changes in the light microscope appeared between hours 3 to 24 after the onset of ischaemia and continued to develop for a period of 4 to 5 weeks showing a variable intensity in different areas of the SAN region. The process became virtually stabilized between months 1 to 7. The degree of ischaemia was most probably responsible for the fact that changes of various degree--myocytolysis, atrophy and fibrosis--were present simultaneously. The preservation of ganglion cells in ischaemic tissue is discussed.

Lymph vessels of the transplanted kidney.

Lymph vessels were evaluated in 20 transplanted canine kidneys. Prior to the occurrence of morphological rejection changes, transplants with good blood flow rates show areas with dilated but, less frequently, also undilated lymph vessels. In transplants with the presence of a rejection infiltrate and a decrease of the blood flow rate of 21-50% the lymph vessels may be focally dilated or, in contrast, narrowed by the cells of the rejection infiltrate. Numerous vesicles and vacuoles can be seen within the cytoplasm of endothelial cells. Interendothelial junctions may be occasionally open, the walls of endothelial cells become attenuated, and disintegration of the cell membrane is followed by a focal destruction of the wall and the development of defects. Cells of the rejection infiltrate penetrate through the gaps in the wall of the lymph vessels. The possible mechanism of the disintegration is discussed in this paper.