Questions Raised by Coarctation of the Aorta
QUESTIONS RAISED BY COARCTATION OF THE AORTA
Coarctation of the aorta is more than just a curious congenital anomaly; in coarctation lie clues to the role of surface tension of blood, the mechanism whereby cholesterol, though not the basic cause, becomes incorporated in atherosclerotic plaques, the explanation of post stenotic dilatation, the ‘jet’ lesion, compensation for poor perfusion in existing arteries, and the introduction of collateral circulation.
Coarctation and surface tension.
Laplace’s law, expressed by the equation T=PR, mathematically defines the physical factors that influence the load upon arteries (1). Substituting figures in the equation, although some conjecture is inevitable, aids understanding of the physical principles.
The components of the equation are:
(a) ‘T,’ the tension, measured in dynes per cm, is the tangentially acting force contributed by all factors external to the blood-endothelial barrier that withstand blood pressure. Of these, the arterial media plays the major part. The media consists of both elastic tissue and smooth muscle in variable proportions, depending upon the vessel considered. Tension is the force in dynes per cm. required to hold together the sides of an imaginary 1 cm. longitudinal slit in the vessel wall. It is a direct measurement of the load imposed upon that wall, and as such, dictates the degree of wear and tear that localizes atherosclerosis (7).
(b) ‘R’ is the radius of the artery, in cms.
(c) ‘P,’ expressed in dynes/cm2 of water, is the net arterial load which tension ‘T’ opposes.
Although surrounding tissue pressure in most parts of the body is so small as to be negligible (3), there are certain places, e.g. the internal carotid artery surrounded by the bony wall of the carotid canal (fig 1), where surrounding tissue support carries some or even the entire burden. At such sites, the load on the arterial wall is totally or partially removed. If support is total, atherosclerosis does not occur in this segment of vessel; partial relief of the load proportionately inhibits atherogenesis. Hultquist (2), in a study of the carotid artery within its bony canal in 400 cases, found only one with arterial disease. He described this single exception as ‘atypical.’ One suspects the ‘atypical’ case was an embolus, rather than an atherosclerotic plaque. When this protective support is considered in the calculation of tension ‘T’ in the carotid artery within its canal, it yields a figure of zero. If indeed there never is atherosclerosis here, this is proof that mechanical stress is the crucial initiating factor that injures arteries and produces atherosclerosis; the equation T=PR, as expected, then yields a result of zero. If ‘T’ is zero, then no matter what ‘P’ and ‘R’ may be, the load being carried by the canal’s bony wall leaves the arterial wall free of tension, ‘T.’
Other examples of local tissue support that protect from atherosclerosis totally, or in part, include Monckeberg’s medial calcific sclerosis of arteries (4), and the application of silver cuffs around the aorta of the cholesterol-fed rabbit (5). Another example is when the anterior descending coronary artery penetrates the pericardium and lies buried in the supporting myocardium, (in 15% of patients) and is protected from mechanical load ‘T’ (6). The tissue pressure whereby the inguinal ligament lends some support to the external iliac and the femoral artery likewise affords some protection from atherosclerosis (7).
These examples of the influence of local arterial support demonstrate forces opposing the net blood pressure that can favourably influence atherosclerosis throughout the arterial tree. Surface tension of blood is another such protective factor. Blood pressure, by Pascal’s law, operates equally in liquids throughout a closed system. Laplace’s law correlates blood pressure with the radius and the structural quality and the radius of its wall. This law predicts that excessive blood pressure would produce a uniform plaque of atheroma in a tubular configuration throughout the arterial tree. There would be nodular disease superimposed on the tubular, produced by additional factors such as bifurcations, but when hypertension has dwarfed these factors, the distinctive feature is expected to be tubular deposit of cholesterol. In a routine autopsy series of 304 femoral and popliteal arteries, ‘tubular’ atheroma morphologically identified the hypertensives (8).
The commonest localized variation in ‘R’ occurs at bifurcations by a mechanism previously described (7). The carotid sinus (9), with its increased ‘R’ is a powerful stimulus to atheroma. This sinus is a unique physiological aneurysm unrelated to bifurcations, which uses the principles of Laplace’s law to amplify and monitor blood pressure. Unfortunately this vital role is at the expense of the increased vulnerability to atheroma carried by dilatation.
Variations in the material of which the arterial wall is composed, (‘T’ in Laplace’s law), is a major consideration in atherogenesis, and dictates the load the vessel can withstand. Incorporation of locally surrounding tissue pressure in the equation correspondingly reduces factor ‘T’ (7).
Direction of blood flow has no observable influence. The convergence of the left and right vertebral arteries to form the basilar, which in turn bifurcates into the two posterior cerebrals, makes this plain. Here, two adjacent bifurcations have equal degrees of atheroma, despite opposite directions of blood flow (7).
The total energy generated by the heart is both potential and kinetic. Potential energy comprises 99.5 % of the total (3). For this reason, the contribution of kinetic energy, (e.g. shearing forces, and Bernoulli’s principle) is negligible in atherogenesis as long as the system remains closed. Kinetic energy expends itself in blood flow. Transection of the artery opens the system, and kinetic energy becomes the major factor. Besides the importance of this in surgery, there is also relevance to the jet flow in coarctation of the aorta. This scenario resembles that of water under pressure emerging from a garden hose, in which surface tension preserves the cylindrical form of the jet until finally dispersing when surface tension is lost. The degree of constriction influences the velocity and force of the jet.
Just as mechanical factors exerted by factors outside the blood-endothelial barrier oppose the hydrostatic blood pressure within the arterial lumen, surface tension from within this barrier also restrains blood pressure. Surface tension is particularly important, both because of its magnitude, and because of its location at the blood-endothelial barrier. Surface tension from within the barrier assists all the factors counteracting hydrostatic pressure from outside this barrier (i.e. the state of the arterial wall, and the surrounding tissue pressure).
The surface tension of a liquid having several components (such as blood), is the surface tension of the component with the lowest surface tension; by Ellis’ law, this component occupies the surface.
Surface tension is a property of blood, whether in vivo or in vitro. Serum in vitro preserves its surface tension for many hours before decreasing; it thus reflects well the in vivo value (11). The heart pumps blood centrifugally to perfuse tissue at alternating systolic and diastolic pressures; surface tension of blood exerts a constant opposing pressure of about 65 dynes /cm2 of water (11), in both systole and diastole. Because blood pressure drops in diastole, this fixed value of surface tension provides a higher proportion of arterial protection in diastole than in systole.
A blood pressure cuff reading gives the net sum of the opposing forces of hydrostatic pressure and surface tension representative throughout the body; both pressures are expressed in dynes /cm2 of water. Together they make factor ‘P’ of Laplace’s equation. Localized support, such as provided by the carotid canal, while providing important local protection and clues to the understanding of load on arteries in general, being local phenomena, provide no benefit elsewhere.
To mathematically illustrate these principles, where actual numbers are not available, we take the liberty of improvising figures consistent with the context. Blood pressure cuff readings are converted to mean pressures. A BP of 150/90 mms Hg. thus becomes 110 mms Hg. Changing mms of mercury (S.G of mercury taken as 13.6) to dynes /cm2 of water, translates into a mean pressure of about 150 dynes /cm2 of water. By Laplace’s law, this load is withstood by, and is in equilibrium with, the factor ‘T’ of the vessel wall until such time as the material of which the wall is made begins to fail (see Fig 5); then the artery starts to dilate, maintaining the equilibrium with the increasing ‘PR’ until rupture occurs. Fig 5 demonstrates the common, though unexplained, finding in the femoral artery where dilatation to a radius greater than the radius proximally imposes an extra load producing the beginnings of an aneurysm. The ‘T’ value at the dilatation in this case is about 1.6 times greater than in the proximal segment. The predominantly smooth muscle arterial wall is thinned and has the metachromasia of injury. Interestingly, this segment of artery (in Hunter’s canal) is the most vulnerable to atherosclerosis in the entire femoral artery (8).
Were surface tension with its effect of supporting the blood column not included in the net blood pressure measurement, we would be recording an additional unopposed hydrostatic pressure of 65 dynes /cm2 of water. This is approximately equivalent to a mean blood pressure of 43 mms Hg, which when added to the postulated mean pressure used in our former calculation, becomes a total mean pressure of 110 + 43 = 153 mms Hg.
Surface tension is totally abolished by turbulence and by disruption of the blood-endotheilal barrier. Local damage to the latter persists until repaired or replaced (see Figs 4b and 6a). In coarctation of the aorta, turbulence is always present. The constriction of coarctation produces a high velocity jet (the velocity dependent on the degree of constriction), converting much of the potential energy to kinetic. The narrow high velocity jet, with its decreased potential energy component, produces a degree of ‘opening’ of the formerly ‘closed’ system, almost like a hemorrhage. The great increase in kinetic energy of the jet introduces a significant shearing force which damages the aortic wall where it strikes. Turbulence immediately develops and abolishes the 65 dynes /cm2 of water that has been restraining blood pressure. The net effect is to increase the blood pressure by 65 dynes /cm2, augmenting the pressure of the dispersed jet. Guessing at what this final pressure might be is difficult but for our hypothetical calculation we assign an arbitrary figure of 150 dynes / cm2 for the total. The ‘shearing’ force of the jet is significant, and Bellet and Gelfand quote Abbot’s report of an incidence of rupture in 33 of 200 cases of coarctation (12).
Adjusting Laplace’s equation of T=PR to calculate the expected ‘R’ in this hypothetical case of coarctation with its aortic ‘R’ proximal to the coarctation of 1 cm, the equation becomes: R=T/P. The shearing force has increased ‘T’ greatly and we assign a value of 250 dynes / cm for it, so that for a pressure of 150 dynes /cm2 the radius of the aorta would now be 1.66 cms at the post stenotic dilatation. This is consistent with the actual degree of post stenotic dilatation clinically encountered.
As the blood moves on from turbulence to normal flow, surface tension is restored and hydrostatic pressure falls. It is once more a closed system, but at greatly reduced hydrostatic pressure, merging with the collateral circulation that by-passed the coarctation, together perfuse the lower extremities with normal surface tension. With this restraint once again added, the lower limb blood pressure is low and the femoral pulses are often not palpable.
Conclusion #1: The protection provided to the internal carotid artery by the bony wall of the carotid canal entirely bears the load of blood pressure and prevents arterial injury. No atheroma occurs at the site, proving that damage done by excessive arterial load is a basic requirement for atherogenesis. Surface tension significantly opposes blood pressure, and provides a protective effect upon the arterial wall and the blood-endothelial barrier. The paradoxical feature of coarctation (and in fact any severe arterial stenosis) is that while arterial constriction results in weak or absent distal pulses, the aorta immediately distal to the stenosis dilates. This is perplexing, but can be explained. The impact of the local kinetic energy of the jet striking the opposing aortic wall exerts a strong shearing effect, damaging it and becomes turbulent. In the turbulence, surface tension which has been opposing blood pressure, is abruptly lost, allowing about 65 dynes /cm2 of additional pressure at the point where the jet strikes. This extra force greatly increases ‘T’ of Laplace’s law, and though the constriction has reduced blood pressure somewhat, this is outweighed by the loss of surface tension that normally restrains the blood pressure.
Transfer of blood cholesterol to the arterial intima follows Ellis’ law.
At the point of impact, where turbulence has abolished surface tension, Ellis’ law has been violated. At this turbulent site, no longer does the blood component with the lowest surface tension occupy the position in immediate contact with the arterial endothelium; instead turbulence creates a homogenized mixture of all the blood ingredients. This is the situation in coarctation of the aorta. In this homogenized mixture, cholesterol has lost its superficial position at the perimeter of flow. No longer is there easy access of cholesterol through the interendothelial cement. Entry to the arterial intimal ground substance to form cholesterol plaque is now denied. It is not that the shearing force of the jet has not well prepared the aortic wall to receive and bind cholesterol. The problem is that cholesterol, with Ellis’ law invalidated, just cannot reach this site, and the blood, homogenized by turbulence, yields little or no cholesterol for deposition. There is no atherosclerosis; instead the ‘jet lesion’ of coarctation is a target- shaped area of medial atrophy, not a cholesterol deposit.
But in the usual artery where surface tension is intact, Ellis’s law places the cholesterol component of blood in immediate apposition to the mechanically damaged endothelial lining of the artery. This allows cholesterol to traverse the intercellular cement substance, where depolymerisation renders it permeable (15) and ‘sticky’ (16). Adhesion of platelets is facilitated (10) for thrombus formation, and lipid can penetrate the arterial intima. There, by physicochemical binding to the depolymerised intimal ground substance (16) cholesterol is securely and diffusely deposited as a sheet. Glue is depolymerised collagen. Thus an atherosclerotic plaque is formed. The law of mass action ensures that the higher the level of blood cholesterol, the greater the atherogenic propensity.
Conclusion #2: To form an atherosclerotic plaque, cholesterol must have access to the ground substance of the arterial intima. This is prevented by turbulence in coarctation, homogenizing the blood so that Ellis’ law is broken and cholesterol is diverted away from the arterial endothelium. For atherogenesis the artery must first be injured and have its ground substance depolymerised to form a substrate to which cholesterol can bind. Under usual circumstances this damage is the mechanical stress imposed upon the artery’s wall by the blood pressure. The damage first induces depolymerisation of the interendothelial cement, increasing its permeability to cholesterol. Then physicochemical binding holds the cholesterol to the ‘sticky’ to intimal ground substance, to form an atherosclerotic plaque. In summary, for atherogenesis, the artery must first be damaged by mechanical stress, cholesterol must be available and be able to traverse the endothelium, and finally bind to the ‘sticky’ depolymerised ground substance of the arterial intima. Any interruption in this chain of events will prevent atherosclerosis, arrest its progress, and restore the artery to normal if the process has not yet gone on to scar and hyalinization.
The influence of lowered surface tension upon vessel radius.
Unlike turbulence in coarctation which locally totally disrupts surface tension, there are circumstances where surface tension of the blood is somewhat lower than normal, (e.g. in hyperlipidemia); a generalized, moderate persistent effect throughout the entire circulation results. This would cause a modest increase in hydrostatic blood pressure throughout, and shift the equilibrium in Laplace’s law. With ‘P’ elevated, ‘T’ would increase a little, and cause ‘R’ to slightly increase. The net result promotes atherosclerosis. Figs 2 (a) and (b) demonstrate arteriographically, the surface tension manifestations in the femoral arteries of two patients that illustrate this point.
Artery (2a) shows atherosclerosis in its usual appearance by arteriography. At variable intervals there are plaques, mechanically distributed (7). Normal appearing artery intervenes between them. The vessel radius varies from 2.5 to 3 mm.
Case (2b) is of a 56 year old male with angina pectoris, diabetes and xanthoma tuberosum. His atherosclerosis is quite different from the usual. It is not focal with intervening intervals of normal appearing artery. A generalized process is going on. The disturbance of cholesterol metabolism in xanthoma tuberosum is inborn and lifelong; his artery resembles the aorta of a cholesterol-fed rabbit. Its radius is about double that in 2a. The local mechanical effects of bifurcations and other local mechanical factors, are seen, but are partially buried by the generalized mechanical factor of hyperlipidemia-induced dilatation and mild hypertension. Normal artery intervening between plaques is obscured.
Conclusion #3: If the surface tension of blood is decreased (as in hyperlipidemia), arteries dilate moderately. This is because even a minor generalized decrease in surface tension affects the entire circulation and upsets the equilibrium of the components of Laplace’s law. This modest increase in ‘P’ is reflected in an increase in ‘R’, and the arterial load ‘T’ increases proportionately, contributing to atherogenesis.
The influence of the nature of the arterial wall.
Hydrostatic pressure within arteries closes the heart valves preventing diastolic back flow. This systolic pressure distends the larger arteries so that they briefly store potential energy and maintain flow while the heart rests between beats. In diastole the arteries recoil, propelling the blood onwards, but at the lower pressure of disatole. The recoil of elastic tissue is passive, while the smooth muscle recoil of diastolic pressure is reflex and subject to humoral influences. Smooth muscle, with its metabolic and nervous limitations, is inferior to elastic tissue in the economy of sustaining the load imposed upon arteries. In practice, elastic arteries are less vulnerable to atherosclerosis than are arteries with a predominantly smooth muscular media (7). In disease of elastic collagen, congenital or acquired, (e.g. homocystinuria, pseudoxanthoma elasticum, Ehler’s Danlos syndrome, syphilitic aortitis), the importance of elastic tissue is clinically manifested.
In vitro applications of surface tension that can aid understanding of the in vivo.
Obviously the heart is the pump. Less obvious is the relatively inconspicuous pumping action that blood vessel recoil plays in diastole; still less noticeable and usually overlooked, is the restraining role of blood surface tension upon hydrostatic pressure.
A needle, floating on the surface tension of undisturbed water in a beaker, demonstrates the internal force of surface tension exerted against the external force of gravity. Surface tension of blood is a force that restrains the pressure gradient of hydrostatic force originating internally from the heart. Thus while gravity offers a gradient from outside, blood pressure offers its gradient from inside. Surface tension resists both. But a needle will immediately sink in its beaker if turbulence disrupts the surface tension. In the body, turbulence occurs with striking effect under certain pathological circumstances, coarctation being an example. When the blood circulates away from the turbulence, surface tension is restored.
The needle will also sink if a detergent or other agent of low surface tension is added to the water. The resulting surface tension becomes insufficient to counteract gravity. The effect of factors such as hyperlipidemia is to slightly lower, but not eliminate, surface tension throughout the circulation. Apart from turbulence and the effect of ‘wetting agents,’ and a variety of injuries to the vascular endothelium, surface tension, measured in vitro, is also subject to relatively minor changes in other blood ingredients, particularly protein (11).
The perplexing problem of post stenotic dilatation, is not restricted to coarctation of the aorta. Halstead described it almost 100 years ago in the subclavian artery compressed as it crosses the first rib. The phenomenon is commonly seen in arteriograms wherever there is significant stenosis. An example in a branch of the femoral artery is shown in fig 3 in which the stenosis was caused by an atherosclerotic plaque.
Surface tension maintains the cylindrical form of water sprayed from a garden hose. Though no longer contained by the wall of the hose, surface tension alone preserves the cylindrical form of the jet as though passing through, but not touching, an invisible sleeve. The hydrostatic pressure that would disperse the jet as it emerges from the nozzle of the hose, temporarily remains restrained in jet form by the ‘hidden barrier’ of surface tension. Adjusting the nozzle, or directing the hose at a nearby fence, turbulence immediately breaks surface tension, releasing hydrostatic pressure from its restraint and the jet disperses like rain. The unopposed hydrostatic pressure then exerts its independent centrifugal force and immediately loses its cylindrical form. Turbulence has broken surface tension, freeing it of restraint. The analogy may help explain what happens in circumstances of post stenotic dilatation.
The relationship of coarctation to the pathogenesis of atherosclerosis.
The lower half of the body in patients with coarctation of the aorta is protected from the atherosclerosis, although their death is often from cerebral thrombosis, myocardial infarction or other manifestations of atherosclerosis in their upper body (13, 14,7). This is conclusive evidence that the initiating and basic cause of atherosclerosis is mechanical, not a disturbance of cholesterol metabolism.
The whole body, both upper and lower halves, is bathed by the same cholesterol-containing blood often deemed the basic etiological factor in atherogenesis. Coarctation alone refutes this notion. Nor is coarctation the only evidence that causes concern. All the many examples of factors that localize the disease point the finger at mechanical injury (7). Cholesterol must be present for there to be atheroma. Atheroma is the deposit of cholesterol in the ground substance of arteries. Absence of atheroma in the region of turbulence in post stenotic dilatation demonstrates that; but cholesterol must have a substrate capable of binding it to form a plaque. The preparation is ground substance of the arterial intima, depolymerised by mechanical stress. Virchow and Aschoff (15) took the first step in the right direction by drawing attention to this morphological first beginning of atherosclerosis.
The mechanism of collateral circulation to ischemic regions.
Coarctation, impairing circulation to the lower half of the body, is a stimulus to collateral circulation. The flow of blood in the collaterals is increased both by dilatation of the collateral channels and by increasing the pressure within them. Surface tension induces both. The main collateral is the internal mammary artery, embryologically the ventral aorta. As such it is ideally suited to this role. It has the composition of the aorta, with the same mainly elastic tissue media, resistant to atherogenesis (7). It has the advantage of a small calibre, and as Laplace’s law predicts (7), this makes it highly resistant to atherosclerosis. Its value as a collateral is proven by its successful use in by-pass surgery for coronary artery disease. Duff and McMillan (17) wrote, in praise of this artery, ‘We have never seen an internal mammary artery in which atherosclerotic lesions were visible to the naked eye.’
Fig 4(b) shows the internal mammary artery of a patient, age 40, with coarctation of the aorta and B.P. of 165/100, who died of cerebral thrombosis, while his lower limb vessels had no plaques. His collateral internal mammary artery is about four times larger than the usual internal mammary artery shown beside it. As a price for this large radius, it, itself has lost to atherosclerosis more than 50% of its lumen. The smaller artery, Fig 4(a), demonstrates that even though the patient without coarctation was a 70 year old lady with BP of 220/110 dying of cerebral hemorrhage, her internal mammary artery is free of atheroma ‘visible to the naked eye.’
In these two patients, using Laplace’s equation and their actual ‘P’ levels, and actual ‘R’ values which are available to us, the load ‘T’ in the internal mammary artery of the man with coarctation is 3.75 times greater than the load imposed upon the normal appearing artery of the elderly hypertensive lady. The importance of vessel radius and normal elastic tissue is plain. But even the most ideal collateral, (the elastic internal mammary and its small calibre) succumbs to atherosclerosis when exposed from birth to a lifetime of mechanical overload.
But what dilates this internal mammary artery? Obviously a dilated vessel carries more blood (rate of flow directly related to the 4th power of the vessel radius). Dilatation is a major advantage in a collateral, but yet the great radius has compounded the moderate hypertension and produced this large plaque.
The answer to why this collateral is dilated is found by study of the artery’s morphology. In 4(b) the blood-endothelial barrier has been broken a number of times, and attempts to replace it have failed, leaving shreds of endothelium buried here and there in the atherosclerotic plaque. Damage to the blood-endothelial barrier has repeatedly abolished surface tension, locally raising the blood pressure by removing the 65 dynes /cm2 of blood pressure restraint for long enough to cause more injury. The process is repeatedly going on, and in so doing has caused more damage. Attemps have been made to heal but their effects have not prevailed.
Moolten, et al (18) described the phenomenon of disrupting the endothelium in the veins of pithed frogs. Exposing the mesenteric veins they introduced a small air bubble to form a meniscus at the blood-endothelial junction. Over the next few minutes, the meniscus thus formed, changed its angle and then disappeared when the barrier was wetted and lost. Can it be that the arterial damage of ischemia which induces a collateral ucirculation in the first place, damages the blood-endothelial barrier so that the interface between blood and endothelium becomes wetted and surface tension lost? If this is so, the surface tension restraint upon the local hydrostatic pressure would be lost while healing is awaited, meanwhile proving a higher local perfusion pressure to the ischemic area. This higher perfusion pressure not only provides more flow, but operating through Laplace’s equation, is amplified to produce a greater ‘R’ which further increases the flow, unfortunately at the cost of obstructing plaque.
Fig 6 is of two separate femoral arteries with severe occlusive disease. One is almost completely occluded by atherosclerotic plaques. This is not a collateral like 4(b), but the same surface tension mechanism that increased local perfusion in 4(b) is operative here. Several almost concentric fragments of tell-tale former endothelium are randomly strewn along the way. A small lumen is achieved with an intact endothelial lining, but the small calibre has protected it from further atheroma.
The other artery is totally occluded by old thrombus. The endothelium remains intact in its position at the perimeter, and the thrombus is detached in most of the circumference. No fragments of endothelium are present to indicate an attempt to restore a new lumen such as in the artery filled with multiple atheromatous plaques. Instead there is a cluster of capillaries, of which, one near the centre, has recently bled. When thrombosis occurred, the artery was almost free of atherosclerosis, but the damaged depolymerized endothelium with its stickiness trapped blood platelets. In a few minutes, what took perhaps years to happen in the atherosclerotic artery of Fig 6a, totally blocked this vessel.
Conclusion #4: The response to impaired perfusion raises local hydrostatic pressure and tissue perfusion by local impairment of surface tension restraint upon blood pressure. This surface tension effect is induced by ischemia to the blood-endothelial barrier such as Moolten et al (18) described in frogs. If there is also local vasodilatation, this further increases flow. Further evidence for this is provided by the morphological distribution of fragments of endothelium scattered in atheromatous plaques. Thrombosis is a greater threat to perfusion than is atherosclerosis, and may occur unexpectedly whenever the arterial endothelium depolymerises and becomes ‘sticky.’
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Fig 1. The bony wall of the carotid canal encloses the internal carotid artery as it traverses the base of the skull. The artery is totally protected from atherosclerosis by the canal's solid support. The blood that bathes this segment of the arterial tree is the same cholesterol-containing blood that serves the other arteries of the same patient. Hultquist (2) reported 400 examples of this protective effect. He had one exception which he considered 'atypical.' (Was this atypical exception an embolus?)
Fig 2a. A femoral arteriogram in a usual case of atherosclerosis. Note the calibre of the artery and the normal appearing segments of artery that separate one atherosclerotic plaque from another.
Fig 2b. The femoral arteriogram of the patient with xanthoma tuberosum described in the discourse. The magnification is the same as fig 2a, but comparison shows the calibre of the artery is approximately twice as great. Note also that the plaques of atheroma converge without normal artery intervening, demonstrating a generalized process over and above the localized mechanical pathogenesis for the atherosclerosis. The appearance reminds one of the aorta of a cholesterol-fed rabbit.
Fig 2c This femoral artery, is also shown for its increase in calibre. It is from a diabetic patient with hyperlipidemia more severe than in Fig 2b, yet the plaques are usual in their distribution and have segments of normal appearing artery between.
Fig 3 Post-stenotic dilatation found unexpectedly in a branch of a femoral artery. The phenomenon tends to occur wherever stenosis is sufficient to produce enough turbulence to interfere with surface tension at the blood-arterial interface. Though the calibre of this artery seems increased like 2b and 2c, this is not the case. In order to better show this post-stenotic dilatation in a small branch artery, the X-ray picture has been enlarged two fold, giving the impression of a large femoral artery.
Fig 4. The two internal mammary arteries described in this paper. Both are at the same magnification and their calibres may be compared. The smaller artery (a) is from an elderly hypertensive lady dying of cerebral hemorrhage. Note there is almost no significant atheroma despite a BP of 220/110. The sparing from atherosclerosis is attributed to the well preserved aortic-like dense elastic tissue in the arterial media coupled with a small arterial radius. By contrast, the other artery, (b) from a patient of 40 with coarctation, dying of cerebral thrombosis, BP 165/100, is an internal mammary artery of about 4 times the radius, and the lumen is encroached by more than 50% by a large atherosclerotic plaque. Meanwhile the elastic tissue of the arterial media has fragmented and decreased, and shreds of endothelium are buried in the plaque.
(a)
(b)
Fig 5 (a) refers to pre-dilatation and (b) refers to post-dilatation of a femoral artery, showing the peculiar common phenomenon of a distal segment becoming more dilated than the segment proximal to it, simulating an early aneurysm. Note the thinner wall in the dilated portion and the metachromatic staining indicative of smooth muscle damage of its media. In an autopsy study of 304 femoral arteries (8), this phenomenon was found in 45, in spite of some encroachment by atherosclerotic plaque on this larger lumen in 11 of the 45. The site of this dilatation corresponded with the site of maximum vulnerability to femoral atherosclerosis (Hunter’s canal) in the total series. The phenomenon was found in a younger age group, with an average blood pressure of 137.5/74.5, and no significant atherosclerosis had yet developed. Horn and Finklestein (19) noted a similar situation in 3 of 100 coronary circulations. The explanation is unclear, but the point is made that smooth muscle is poor material for withstanding the load imposed upon arteries, and that breakdown of the media, as would be expected, results in dilatation.
(a)
(b)
Fig 6. (a) is a femoral artery almost totally occluded by atheroma with no obvious thrombosis. There are fragments of at least four attempts to establish vascular endothelium for preservation of surface tension at the blood-endothelial junctions, finally achieved surrounding the small remaining lumen. By contrast, (b) is a femoral artery totally blocked by old thrombus. Note the intact endothelium visible around most of the perimeter and there are no loose fragments of endothelium anywhere. No significant recanalization has occurred though there is a cluster of capillaries that have done their best. One of these has recently bled. Unlike atheroma, firmly attached to its base, the thrombus has pulled away from its original moorings but the decreasing calibre as the artery continues distally prevents embolization.