Possible Therapeutic Applications of AT for Microcirculatory Disturbances

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As described earlier, intravenous administration of AT reduced pulmonary vascular injury and hypotension because of its anti-inflammatory activity in rats given endotoxin, suggesting that AT supplementation might be useful for treatment of acute respiratory distress syndrome and shock associated with sepsis. Administration of AT was also effective in the treatment of ischemia-reperfusion-induced liver and kidney injuries and stress-induced gastric mucosal injury in rats based on its capacity to promote endothelial production of PGI2, suggesting that AT might be useful for treatment of various organ failures associated with circulatory shock.

Ischemia-reperfusion-induced spinal cord injury is an important pathologic mechanism for the development of paraplegia after operations on the descending thoracic and thoracoabdominal aorta due to interruption of the intercostal and lumbar arteries feeding the spinal cord. Intravenous administration of AT significantly improved motor disturbances by inhibiting reduction of the number of motor neurons in rats subjected to transient spinal cord ischemia [10]. Since both local inflammatory responses and spinal cord microinfarction were significantly reduced through increases in spinal cord tissue levels of PGI2 in animals treated with AT, both anti-inflammatory and anticoagulant activities of AT might be critical for the therapeutic effect of AT. These observations strongly suggested that AT might be a useful neuroprotective agent for prevention of spinal cord injury after surgery to repair aortic aneurysms. These possibilities should be examined in the clinical setting in the near future.

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