Endothelial Cell Disruption Research Articles

MICROCIRCULATORY CHANGES IN THE LUNG OF THE HYPOXIC AND HYPOVOLEMIC PUPPY AN ELECTRON MICROSCOPE STUDY

The effect of systemic hypoxemia and hypovolemia on pulmonary fine structure was studied and compared in 12 Labrador puppies 6 days to 3 weeks old. Central venous and arterial pressures were monitored and arterial pH, PCO2 and PO2 recorded serially. In 4 puppies lung biopsies were taken after a two hour period of breathing 7% oxygen. Four other puppies were made hypovolemic by acute hemorrhage of 50% of the calculated blood volume and lung biopsies taken after one hour. Four control puppies were maintained under anesthesia for two hours, breathing an atmosphere of 20% oxygen before lung biopsies were taken. Both hypoxemia and hypovolemia resulted in similar pulmonary ultrastructural changes. These changes which occurred more frequently in areas where the air spaces and blood vessels were expanded, were characterized by aggregation of platelets and leucocytes in the vascular space, focal endothelial cell disruption, interstitial edema and type I epithelial cell discontinuities with exudation of plasma into the alveolar air spaces.

Microcirculatory changes in the lung of the hypoxic and hypovolemic puppy: an electron microscope study.

The effect of systemic hypoxemia and hypovolemia on pulmonary fine structure was studied and compared in 12 Labrador puppies 6 days to 3 weeks old. Central venous and arterial pressures were monitored and arterial pH, PCO2 and PO2 recorded serially. In 4 puppies lung biopsies were taken after a two hour period of breathing 7% oxygen. Four other puppies were made hypovolemic by acute hemorrhage of 50% of the calculated blood volume and lung biopsies taken after one hour. Four control puppies were maintained under anesthesia for two hours, breathing an atmosphere of 20% oxygen before lung biopsies were taken. Both hypoxemia and hypovolemia resulted in similar pulmonary ultrastructural changes. These changes which occurred more frequently in areas where the air spaces and blood vessels were expanded, were characterized by aggregation of platelets and leucocytes in the vascular space, focal endothelial cell disruption, interstitial edema and type I epithelial cell discontinuities with exudation of plasma into the alveolar air spaces.

Pathogenesis of gangrene following intra-arterial injection of drugs: a new hypothesis.

We have demonstrated the toxicity of diazepam and the safety of ketamine hydrochloride following intra-arterial injection in an anaesthetized animal model. The pathogenesis of gangrene following intra-arterial injection of drugs is unclear. Clinical reports and this experiment suggest that it only follows injection of highly membrane-soluble drugs. Early swelling and disruption of capillary endothelial cells were demonstrated after intra-arterial injection of diazepam and thiopentone. We believe that a theory of pathogenesis based on this finding is consistent not only with our experimental findings, but with known in vitro effects of membrane soluble drugs on cell membranes and the clinical features following intra-arterial injections in both human subjects and in animals.

Microcirculatory changes in the gastrointestinal tract of the hypoxic puppy: An electron microscope study

Hypoxia and hypovolemia result in similar ultrastructural changes. These changes are characterized by aggregation of platelets and leukocytes in the vascular space, focal endothelial cell disruption, and appearance of increased amounts of perivascular edema, and loss of ultrastructural organization of the mucosal cell. These changes appear to relate to variations in blood flow to the mucosa of different areas of the bowel and to follow the distribution observed for necrotizing enterocolitis in the human infant.

The ultrastructure of human organ-cultured cornea. I. Endothelium.

Human corneal endothelial cells maintained ultrastructural integrity after organ culture storage at 37 C for 10 to 21 days. Those organ-cultured corneas with postmortem times less than 12 hours had a complete layer of ultrastructurally intact endothelial cells of normal thickness and diameter. When postmortem times were longer than 24 hours, there was a complete layer of ultrastructurally intact endothelial cells that were large in diameter and thin. Control fellow corneas in moist chamber storage at 4 C demonstrated endothelial cell disruption proportional in area and severity to postmortem time duration. This implies that a dynamic process of endothelial repair, presumably by enlargement of remaining viable cells, occurs in organ culture.

Microcirculation in Psoriatic Skin

Our previous electron microscopic studies on psoriatic skin demonstrated thin-walled vessels that resembled lymphatics but which contained erythrocytes and had prominent endothelial cell gaps. Gap formation was also found in venous capillaries and postcapillary venules. Reconstruction techniques and further studies with light and electron microscopy have now shown that the thin vessels are lymphatic. The best explanation for the abundance of erythrocytes in their channels is a clearing of the interstitium of red cells escaping from leaking capillaries and venules. Lymphatic capillaries are very numerous and dilated in the lesions and normal skin of psoriatic patients. They are rare and only minimally dilated in control specimens. The superficial lymphatic plexus begins as blind channels in the papillae that link up with one another to form a network in the papillary dermis. Valves are present at most points where lymphatic capillaries join one another. Lymphatic capillaries closed at both ends and unattached to the surrounding plexus are found in psoriatic skin and may be a lymphatic reserve. The blood vessel gaps develop at intercellular junctions and their profiles are identical to those produced by the local injection of histamine. However, distortion of the endothelial cell nuclear membrane which accompanies histamine-induced gaps in animals could not be found in psoriatic vessels, nor could it be produced in normal individuals injected intradermally with histamine. The blood vessel gaps were easily found in psoriatic skin and were very uncommon in control specimens. The gaps may represent an inherent weakness in psoriatic vessels or a histamine-type response to unidentified stimuli in psoriasis.

Electron Microscopic Studies of the Microcirculation in Psoriasis

The microcirculation in the lesions of pustular psoriasis of von Zumbusch and psoriasis vulgaris were studied by light and electron microscopy. A consistent finding in the dermal papillae and upper third of the dermis was the presence of thin walled vessels. They had endothelial cell junctional gaps a poorly developed basal lamina, an absence of pericytes, and they contained red blood cells. The uninvolved skin of these patients showed identical findings, but less often. Less frequently, endothelial cell gaps were also seen in the post-capillary venules in the dermal papillse of psoriatic lesions. None of the control specimens showed these vascular findings in these locations. The presence of endothelial cell gaps implicates a role of the chemical mediators of inflammation in psoriasis. The thin walled vessels could either represent the arterial capillary segment of the microcirculation which is abnormally permeable because of the gaps or else lymphatic capillaries which are clearing the interstitial space of blood cells and serum. The abnormally permeable vessels in this instance could be the post-capillary venules. The nature of the thin walled vessels is currently under study.