Experimentally, the changes caused by the toxins above noted are proliferations of cells in the intima and subintimal tissues, and a breaking up of the internal elastic laminæ into several parallel layers which stretch themselves among the proliferating cells. The diphtheria toxin, on the contrary, produces a lesion more like that caused by adrenalin. All pathologists are not agreed as to whether the experimental lesions produced by blood pressure raising drugs are similar to the arteriosclerotic changes in the arteries of man.
Some of the work on rabbits has been discredited for the reason that arteriosclerosis appears spontaneously in about fifteen per cent of all laboratory rabbits. Furthermore, comparatively young rabbits have been found with arteriosclerosis. O. Loeb, however, denies this. He has examined in the course of eight years 483 healthy rabbits and never found arterial changes. The spontaneous lesions can not be distinguished histologically from those due to adrenalin. They differ macroscopically in that the lesion is usually limited to a few foci near the origin of the aorta.
Lesions produced by the drugs enumerated above represent one type of experimental arteriosclerosis. More interesting and important are the experiments which seem to show that high tension alone is capable of producing lesions in arteries which in all respects correspond to Adami's strain hypertrophy and overstrain theory. It has been shown that when a portion of vein is placed under conditions of high arterial pressure, as in a transplantation of a portion of vein into a carotid artery, the vein undergoes marked connective tissue hypertrophy which includes all the coats. This is evidently strain hypertrophy. Again, it has been demonstrated that by suspending a previously healthy rabbit by the hind legs for three minutes daily over a period of three to four months, there results hypertrophy of the heart with thinning and dilatation of the arch and the upper part of the thoracic aorta. No change was found in the abdominal aorta. The carotids, however, were larger than normal and they showed typical intimal sclerosis with connective tissue thickening.
Neither I nor others have been able to confirm this experiment, so it is very doubtful whether mechanical pressure alone can produce true arteriosclerosis. Some evidence is adduced to bear on this point, however, in the fact that sclerosis of the pulmonary artery follows often upon mitral stenosis. Yet we do not know but that factors other than pressure alone produce the arteriosclerotic change in such cases, so we are forced back on our conclusion expressed above; viz., that experiments on animals fail to sustain the purely mechanical origin of arteriosclerosis.
The changes in the intima constitute the effort on the part of nature to repair a defect in the vessel wall which is to compensate for the weakened media and the widened lumen. This applies only to true arteriosclerosis, not to the condition produced experimentally by the toxin of the typhoid bacillus, for example.
When an artery loses its elasticity and begins to have connective tissue deposited in its walls, the pressure of the blood stretches the vessel which is now no longer capable of retracting when the pulse wave has passed, and, in consequence, the artery is actually lengthened. This necessarily causes a tortuosity of the vessel which can be easily seen in such arteries as the temporals, brachials, radials, and other arteries near the surface of the skin.
The exact mechanism of increase of blood pressure is not satisfactorily explained. The smaller arteries all over the body are supplied with vasoconstrictor and vasodilator nerve fibers from the sympathetic nervous system. Normally when an organ is actively functionating the vessels are widely dilated and the flow of blood is rapid. Among the many factors which influence blood pressure and blood supply must be reckoned the psychic.
We know that normally there is a certain resistance offered to the propulsion of blood through the arteries by the contraction of the heart. This tonus is essential to the maintenance of an equalized circulation. The muscular arterioles throughout the body by their tonus serve to keep up the normal blood pressure and to distribute the blood evenly to the various organs. Contraction of a large area of arterioles increases the blood pressure and, strangely enough, the arteries respond to increased arterial pressure, not by dilatation, but by contraction. It would appear that rise of blood pressure tends to throw increased work upon the musculature of the arterioles. This may be sufficient only to cause them to hypertrophy, but further strain may easily lead to exhaustion and to dilatation. "As a result strain hypertrophy of the intima shows itself with thickening, and it may also be of the adventitia, resulting in chronic periarteritis. And now with continued degeneration of the medial muscle in those muscular arteries, fibrosis of the media may also show itself. I would thus regard muscular hypertrophy of the arteries and fibrosis of the different coats as different stages in one and the same process. Whether these peripheral changes are the more marked, or the central, depends upon the relative resisting power of the elastic and muscular arteries of the individual respectively." (Adami.)
