Ischemia (derived from the Greek ischein, to restrain, plus haima, blood) is defined as “local tissue anemia due to obstruction of the inflow of arterial blood” (1). Anoxia means the absence of oxygen. It has become common to equate ischemia with tissue anoxia. However, although the two conditions commonly coexist, anoxia does not always accompany ischemia, and ischemia has pathophysiological consequences in addition to anoxia. An example of the former is ischemia in the lung, in which continued ventilation provides normal oxygenation to lung cells in the absence of arterial blood flow. (The tissue oxygen [O2] supply might actually increase, because O2 is no longer transported away by the blood.) Nevertheless, anoxia is the major manifestation of ischemia in organs supplied by the systemic circulation. The consequences of ischemia unrelated to anoxia result from loss of the normal endothelial mechanical stimulation – shear stress. These effects have been described only recently. This chapter focuses primarily on events in the pulmonary circulation associated with alterations of endothelial function due to loss of shear stress with ischemia; these events represent altered mechanotransduction.

LUNG PERFUSION

The lung is perfused by the pulmonary artery, which carries the entire output of the right cardiac ventricle. Because the output of the left and right cardiac ventricles should be equal, perfusion to the lung is equal to the blood flow through the rest of the body. Furthermore, essentially the entire systemic blood flow returns through the venous system to the right side of the heart and thence to the lungs. As a consequence, the lung is a very vascular organ that accounts for approximately 30% of the vascular endothelial cells (ECs) of the body.