Adventitial Thickening Research Articles

Severe pulmonary hypertension and arterial adventitial changes in newborn calves at 4,300 m.

Some human newborns have a syndrome characterized by irreversible pulmonary hypertension and severe hypoxemia and by medial hypertrophy and adventitial thickening of pulmonary arteries. We considered that newborn calves made severely hypoxic might reproduce features of the human disease. When 2-day-old calves were placed at 4,300 m simulated altitude, pulmonary arterial pressure was increased and could be reversed by 100% O2. However, after 2 wk at 4,300 m, pulmonary arterial pressures were suprasystemic and there was right-to-left shunting probably through the foramen ovale and a patent but restrictive ductus arteriosus. Suprasystemic pulmonary pressure and hypoxemia persisted with 100% O2 breathing. Morphometrical examination of the lung arteries showed a markedly thickened adventitia with cellular proliferation and collagen and elastin deposition. There was increased medial thickness and distal muscularization of the pulmonary arteries associated with decreased luminal diameter. The rapid development of severe pulmonary hypertension and poor responsiveness to O2 was associated with increased arterial wall thickness, particularly involving the adventitia. Thus the pulmonary arterial circulation in these calves, which were placed at high altitude for 2 wk, exhibited features resembling persistent pulmonary hypertension in newborn infants.

梗塞巣における脳細小動脈外膜肥厚

To assess an influence of ischemia on arteriolar walls, a morphometrical study was performed on arterioles in cerebral infarcted areas of various days' duration. The ratio of the summing thickness of media and adventitia to the diameter of the circle formed by internal elastic membrane was microscopically determined with micrometer. 19 cases were divided into 4 groups according to days after stroke.There was a statistically significant increase of the ratio among group A (1-3 days), B (7-11 days) and C (14-25 days). The increase of the ratio was mainly due to adventitial thickening, consisting of fibrosis or hyalinosis. Nearly all arterioles of group D (52-71 days) were destroyed, so the ratio could not be measured.The result suggests that one type of cerebral arteriolosclerosis such as hyalinosis and adventitial fibrosis may be a result, rather than a cause, of ischemia.

Pathology of spinal cord lesions caused by ossification of the posterior longitudinal ligament.

The pathologic changes in the spinal cord of three autopsied cases associated with ossification of the posterior longitudinal ligament ( OPLL ) are reported. Compression of the spinal cord was marked at the level of the intervertebral disc, and the spinal cord was strikingly flattened antero-posteriorly. Intensive damage was seen in the gray matter as compared to the white matter. The white matter showed demyelination and axon loss with status spongiosus, which was more marked in the postero-lateral than in the anterior columns. The most seriously damaged parts of the spinal cord showed tissue necrosis and cavity formation which extended from the central parts of the gray matter to the ventral parts of the posterior columns. Adventitial fibrous thickening of the vein, hyaline degeneration of the walls of the arterioles, and compression of the anterior spinal vein were observed in the damaged regions. It was evident that secondary circulatory disturbance due to the compression produced by the ossification was of significance in the pathogenesis of the spinal cord damage. A tangle of peripheral nerves, ectopic and reactive, with Schwann cell proliferation was present in the posterior median fissure and the postero-lateral columns in one case. The spinal nerve roots that showed marked demyelination and axon loss were damaged by ossification at the places where the anterior nerve roots emerged from the spinal cord and where the roots penetrate the dura. There was ossification of the dura mater in all cases examined.

Influence of hypertension and hypoxemia on arterial biochemistry and morphology in swine

Eleven miniature swine were exposed to a simulated altitude of 5,490 m for 4 weeks and eleven control animals were maintained at the laboratory altitude of 1,524 m to study the effects of hypoxemia and hypertension on the biochemistry and morphology of the arterial wall. In comparison to controls, swine at 5,490 m had normal levels of plasma lipid and systemic arterial pressure, were extremely hypoxemic, and developed severe pulmonary hypertension. Enzyme analyses revealed increased activities of nucleotide pyrophosphatese and lactate dehydrogenase and decreased activity of succinate dehydrogenase in the media of both the hypoxic/normotensive aorta and hypoxic/hypertensive pulmonary artery. Electron microscopy indicated that smooth muscle cells in the mid-media of both vessels contained swollen mitochondria, focal areas of cytoplasmic degeneration, and lipid droplets. While there were no discernible alterations of aortic morphology at the light-microscopic level, the hypoxic/hypertensive pulmonary artery underwent a diffuse intimal, medial, and adventitial thickening. The thickening was characterized by an accumulation of fibrous protein and an increased amount of ground substance. Smooth muscle cells in the inner media of the thickened pulmonary artery contained an increased amount of granular endoplasmic reticulum and a prominent Golgi apparatus. The intima-media levels of cholesterol and free fatty acid were elevated in the hypoxic/hypertensive pulmonary artery, but not in the hypoxic/normotensive aorta. This study demonstrated that 4 weeks of severe hypoxemia in miniature swine elicited measurable changes in the enzymatic activity of the aortic and pulmonary arterial walls. In conjunction with alterations of glycolytic and oxidative enzyme activities that were indicative of decreased oxidative metabolism, ultrastructural changes demonstrated abnormalities of the metabolic machinery. In the absence of additional stresses, the metabolic abnormalities did not lead to the gross accumulation of lipid by the aortic wall within the 4-week period of study. However, when the arterial wall was subjected to the combined stresses of hypoxia and hypertension (as was the hypoxic/hypertensive pulmonary artery), the resulting metabolic and morphologic alterations were sufficiently pathogenetic to elicit vascular lipid accumulation within 4 weeks.