Influence of changes in gravity on the response of lung and vascular cells to ischemia/reperfusion in vitro.

Gravity and other physical forces (e.g., shear stress or mechanical stretch) will affect organ and cellular function, e.g., blood flow distribution, gas exchange, alveolar size and mechanical stresses within the lung. Microgravity produced marked alterations in lung blood flow and ventilation distribution while hypergravity exaggerated the regional differences in lung structure and function. Microgravity was found to decrease the metabolic activity in cardiac cells, WI-38 embryonic lung cells, and human lymphocytes. These studies show that changes in gravity will affect several aspects of organ and cellular function and produce major changes in blood flow and tissue/organ perfusion. However, these past studies have not addressed whether ischemia-reperfusion injury will be exacerbated or, ameliorated by changes in the gravity environment, e.g., space flight. Currently, nothing is known about how gravity will affect the susceptibility of different lung and vascular cells to this type of injury. Ischemia injury is the underlying cause of many clinical disorders with high morbidity and mortality. The subsequent reperfusion (reoxygenation) further compounds the initial ischemic stress. Understanding the possible exacerbation of transient ischemia under the stress of space flight or an increase in gravity is critical. We conducted studies that examined whether alterations in gravity affect the susceptibility of cells to ischemia-reperfusion injury, using an in vitro anoxia-reoxygenation model.