Our studies allowed us to establish that simulating coarctation of aorta in laboratory animals results in tone reduction of vessels carrying blood to the liver and from it and a subsequent development of their intima atrophy. In spite of that fact the number of vessels containing intimal musculature, muscularelastic sphincters and polypoid pulvini in the arterial bed flow increases and in the major outflowing veins, on the contrary, thinning of their muscular tori takes place. Appearance and functioning in the hepatic vessels of adaptive formations contributes to keeping up homeostasis at the microcirculatory level. With cardiac decompensation decreasing because of venous plethora, hypotonia and atrophy of the intima of the vessels responsible for the blood inflow to the liver and the outflow from it progress. Besides, the number of arteries and the rate of development of arteries with adaptive smooth muscle formations in the arteries, as well as in hepatic veins with muscular tori decreases dramatically. The reason of compensatory reaction failure is a long-term hypoxia leading to vessel and their adaptive formation sclerosis. The consequence of the exhaustion of the above-mentioned mechanisms is development of perisinusoidal fibrosis and depression of the transcapillary metabolism.
Coarctation of aorta is a common and severe congenital heart disease [
The aim of this study is to establish the nature of structural changes in the vessels of the liver in experimental coarctation of aorta and define the role of these changes in the development of the mechanisms of compensation and decompensation in both the organ and the systemic circulation.
Hemodynamic models of coarctation of aorta have been created in 25 puppies by surgical intervention to achieve this goal in the experiment. For this purpose the narrowing of the aorta isthmus was performed by means of a polyethylene stethoscope and in this way the lumen of the vessel was diminished as much as 55% [
In compensated coarctation of aorta there appear marked structural changes in both the inflowing (branches of the hepatic artery and portal vein) and outflowing (branches of the hepatic vein) vessels of the liver. Abrupt blood pressure lowering in the inflowing branches of the hepatic artery is accompanied by lowering of the tone of its arteries. It is manifested by widening of the internal elastic membrane and weakening of its rugae. Morphometric studies make it possible to establish that the thickness of the intima in large, medium arteries and arterioles dicreases 1.4 times and in small arteries 1.5 times (
At the same time the number of arteries with oblique-longitudinal musculature, muscular-elastic sphincters and polypoid pulvini in the liver increases. Oblique-longitudinal musculature is located in the internal vascular membrane and is represented by both separate cells and their bundles (
Gr. | Basin of blood inflow to the liver | ||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|
Arteries | Portal veins of the level of | ||||||||||
Large | Medium | Small | Arterioles | Large arteries | Medium arteries | Small arteries | Arterioles | ||||
C | 24.0 ± 1.1 | 13.2 ± 0.8 | 6.5 ± 0.1 | 3.8 ± 0.09 | 6.0 ± 0.2 | 5.1 ± 0.3 | 4.1 ± 0.2 | 2.8 ± 0.1 | |||
CC | 17.0 ± 0.9 | 9.3 ± 0.3 | 4.3 ± 0.1 | 2.6 ± 0.05 | 3.6 ± 0.1 | 3.1 ± 0.1 | 2.5 ± 0.1 | 2.1 ± 0.1 | |||
pc | <0.001 | <0.001 | <0.001 | <0.001 | <0.001 | <0.001 | <0.001 | <0.001 | |||
CD | 16.9 ± 2.5 | 8.0 ± 0.9 | 3.7 ± 0.1 | 2.2 ± 0.1 | 3.4 ± 0.1 | 2.5 ± 0.3 | 2.0 ± 0.05 | 1.9 ± 0.1 | |||
pc | >0.05 | >0.05 | <0.001 | <0.001 | <0.001 | <0.001 | <0.001 | <0.001 | |||
pcc | <0.001 | <0.001 | <0.001 | <0.001 | >0.05 | <0.001 | <0.001 | >0.05 | |||
Gr. | Basin of blood outflow from the liver | ||||||||||
Hepatic veins | |||||||||||
Large | Medium | Small | Venules | ||||||||
C | 6.2 ± 0.3 | 4.4 ± 0.1 | 3.2 ± 0.1 | 2.7 ± 0.1 | |||||||
CC | 4.0 ± 0.2 | 3.0 ± 0.1 | 2.4 ± 0.1 | 2.1 ± 0.1 | |||||||
pc | <0.001 | <0.001 | <0.001 | <0.001 | |||||||
CD | 3.5 ± 0.4 | 2.5 ± 0.1 | 2.3 ± 0.08 | 2.0 ± 0.05 | |||||||
pc | <0.001 | <0.001 | <0.001 | <0.001 | |||||||
pcc | >0.05 | <0.001 | >0.05 | >0.05 | |||||||
Note: Gr.―group of experiments; C―control figures; CC―compensated coarctation of aorta; CD―decompensated coarctation of aorta; pc―com- parison with the control figures; pcc―comparison with compensated coarctation of aorta.
Kind of group | Dlinnik of the nucleus in µm | Diameter of the nucleus in µm | Area of the nucleus in µm2 | Volume of the nucleus in µm3 | Number of cells |
---|---|---|---|---|---|
C | 7.6 ± 0.10 | 4.1 ± 0.60 | 24.6 ± 0.60 | 72.4 ± 3.30 | 9.7 ± 0.80 |
CC | 5.6 ± 0.09 | 2.7 ± 0.02 | 11.9 ± 0.20 | 22.6 ± 1.00 | 5.1 ± 0.10 |
pc | <0.001 | <0.001 | <0.001 | <0.001 | <0.001 |
CD | 5.5 ± 0.2 | 2.7 ± 0.1 | 11.7 ± 0.20 | 22.0 ± 1.0 | 3.7 ± 0.20 |
pc | >0.05 | >0.05 | >0.05 | >0.05 | <0.001 |
pcc | <0.001 | <0.001 | <0.001 | <0.001 | <0.001 |
Note: C―control; CC―compensated coarctation of aorta; CD―decompensated coarctation of aorta; pc―comparison with the control figures; pcc― comparison with compensated coarctation of aorta.
Our calculations show that among large arteries and arterioles the number of vessels with oblique-longitudinal smooth muscles increases 3-fold, and at the level of medium and small arteries―1.5 and 18 times, respectively. Muscular-elastic sphincters represent formations that surround the ostia of lateral branches of arteries all along the perimeter and at the longitudinal section of such a branch they look like one torus or two tori coming out into the lumen of the main vessel (
Considerable structural changes in coarctation of aorta take place not only in the arteries of the liver but also in the branches of the portal vein located nearby. Elastic membrane winding of these vessels becomes less marked and testifies to their tone lowering. The portal vein wall noticeably thins out regardless of their caliber. In the veins of the large, medium and small arteries level it decreases 1.6 times, and in the veins of arteriole level―1.3 times (
In the sinusoids of the liver histological and electromicroscopical changes appear to be minimal. The vessels seem to be a little dilated but structurally they hardly differ from those in the control group. Immunohistological examination doesn’t reveal CD34 expression in the sinusoids, the fact indicating the integrity of their basal phenystril membrane.
In the vessels belonging to the vascular bed system responsible for the blood outflow from the liver (hepatic veins) we observed marked structural changes. Their large and medium branches wall thickness decreased 1.5 times and that of small veins and venules―1.3 times (
In the case of decompensated coarctation of aorta morphological changes in the vascular system of the liver are more marked. The inner elastic membrane of the arteries not only becomes smooth, but unevenly wears out as well, testifying a high degree of hypotension. Atrophic changes of middle coat of the liver arteries occur to be more pronounced than in the previous series of experiments, which quantitatively proves morphometry findings. In addition, wall thickness of arterioles and small arteries decreases 1.7 times, medium ones―1.6 times, and large ones―1.4 times (see
Apart from the enumerated facts, this experimental series has shown arteries reconstructed according to locked type more rarely. For example, the amount of vessels (arterioles and small arteries) with intimal muscular structure decreases 3 and 9 times compared to compensated coarctation. Muscular-elastic sphincters show scle- rosis and hyalinosis. These structures amount arterioles and small arteries, compared to the animals in the 1st observation group, becomes 1.5 and 4 times less. Polypoid formations in liver bloodstream never occur in the series of dogs. Connective tissue growth is marked against the background of smooth muscles atrophy in many arteries middle coat.
There are not only changes in rugosity in the branches of the portal vein, but also pronounced wearing out of elastic plates. The middle coat thickness of these vessels decreases in the veins compared to small and medium arteries level 2 times, in the veins compared to arterioles level―1.5 times, in the veins compared to large arteries level―1.8 times.
The sinusoids of liver lobes appear to be extremely plethoric. Electronograpms show thickening of their basal membranes, collagen deposition in dilated perisinusoidal space (perisinusoidal fibrosis), causing continuous basal membrane formation, similar to that of capillaries in other organs. The electronographic microscopy findings are proved by immunohistochemical research, defining the expression of CD34. In decompensated coarctation of aorta, compared to the compensated one, and as a result of sclerosis, continuous basic membrane formation and perisinusoidal fibrosis, endothelium actively expresses CD34 (
Marked plephora is noted in the bloodstream from the liver, as opposed to the dogs with compensated coarctation. Media thickness in venules and small liver veins decreases 1.4 times, in medium and large ones―1.8 times (
Thus, the research has shown that coarctation of aorta simulated in the experiment is followed by the formation of pronounced structural changes in the vascular system of the liver. In compensated coarctation of aorta the blood inflow to this organ under lowered pressure leads to hypotension and dilatation of the inflowing vessels. Due to decreased hemodynamic load the walls of arteries and portal veins of different size wear out and undergo atrophy. The phenomena are based on their media leiomyocytes decrease in number and size, which can be considered an adjustment. As a result of new conditions of blood circulation the amount of arteries, containing bundles of oblique and longitudinal smooth myocytes, muscular-elastic sphincters and polypoid formations is increasing. According to our research and literature findings such formations sometimes occur in the bloodstream of control animals [
on contraction of the muscular tori and its discharge into the systemic circulation on their relaxation. In our opi- nion, depositing function of the liver in coarctation of aorta is decreased as otherwise its proper functioning would lead to the decrease of the blood supply in the arterial systemic circulation, where persistent hypotension has set in. Morphologically this decrease means atrophy of muscular tori. Thus, the function of the adjustment structures, situated on different sides of the sinusoids (bundles of intimal musculature, muscular sphincters and polypoid pulvini―on one side and muscular tori of the veins―on the other side) is essentially different. In afferent vessels they regulate the flow of blood on the organ (liver) level, in the vessels carrying blood from the liver they regulate the volume of blood in systemic circulation.
According to our research, structural changes in the hepatic vessels are considerably different in compensated and decompensated defect. This is directly associated with the differences in the degree of blood supply disorders. Decompensated coarctation of aorta is manifested by the left ventricular cardiac insufficiency which causes congestion of blood in pulmonary circulation and pulmonary edema of hemodynamic genesis. Insufficiency of the left chambers of the heart is accompanied by contractile function impairment of the right chamber as well; that is why all the animals at the stage of decompensation demonstrated venous plephora. Venous haemostasia causes dramatic dilatation of veins carrying blood from the liver and sinusoids. Tissue metabolism dysfunction at the sinusoid level creates the increase of hypoxia, the fact that causes even greater than in compensated co- arctation, tone lowering of the afferent vessels and more pronounced atrophic changes in their medium mem- brane. Animals with decompensated defect show substantial structural changes of afferent liver vessels, thus morphologically reflecting sinusoidal homeostasis failure. These are to be observed in the fact that the number of arteries with intimal musculature, muscular-elastic sphincters and polypoid pulvini is considerably less in this series of experiments than in the animals of the first one. Adjustment structures show sclerotic changes, causing their functional failure, that is inability to regulate the impaired hemodynamics of the organ. Besides, smooth muscles sclerotic formations not only fail to regulate the organ circulation but also form a mechanical obstacle in the arterial bloodstream, jutting out into the lumen of the arteries. The same reaction is to be found in the veins carrying blood from the liver where atrophy and sclerosis of the muscular tori of Mautner-Pick veins alongside with the lowering of their contractile properties takes place, the fact contributing to the venous con- gestion development. Enumerated changes reflect the exhaustion of compensatory reactions of the liver vessels and their inability to protect the microcirculatory system from blood overflow. In the latter there develops peri- sinusoidal fibrosis, thickening and formation of sinusoids continuous basal membranes, which causes transca- pillary exchange decrease, aggravating hypoxia and creating a vicious circle. Obviously, adjustment insuffi- ciency is an unavoidable consequence of a higher level sclerotic changes in the liver vessels and their regulating structures in decompensated coarctation. All these facts serve as a basis for the forthcoming liver dysfunction.
1) Simulating coarctation of aorta in experimental animals is accompanied by the liver circulatory impairment that is revealed in the decrease of the blood supply to this organ with the subsequent development of a complex of adjustment changes in the vessels as well as that of pathological changes.
2) Adjustment changes in the vessels carrying blood to the liver and from it in the compensated stage are seen in vasodepression, decrease of the degree of smooth muscles development, as well as in greater intensity of de- velopment of adjustment structures regulating the blood supply in the microcirculatory system.
3) The transition of compensated defect to decompensated one is not only associated with even greater vaso- depression, the vessels medium membrane atrophy but also with a considerable involution of adjustment struc- tures that have been formed before. In decompensated coarctation of aorta atrophy of smooth muscles is ac- companied by such pathological changes as excrescence of rough fibrous connective tissue. Sclerosis affects not only arterial and venous walls but their adjustment formations as well, the fact transforming the latter into hardly- contractible structures preventing the flow of blood.
4) The development of the liver hemocirculatory disorders, along with the development of cardiac decom- pensation and sclerosis of vessels, results in sinusoids capillarization, negatively affecting the organ functioning.