It is likely that the alveolar macrophage is the key early source of multiple proinflammatory mediators that orchestrate lung ischemia-reperfusion injury. Depleting alveolar macrophages is protective against injury, supporting its central role in oxidant stress-induced cytokine and chemokine release and the subsequent development of lung injury.

In this model of chronic valvular aortic stenosis, both Gorlin and continuity equation valve areas were flow-dependent indices of stenosis severity and demonstrated linear relations with transvalvular volume flow rate. The changes in calculated valve area that occur with changes in transvalvular volume flow should be considered when measures of valve area are used to assess the hemodynamic severity of valvular aortic stenosis.

In addition to its antioxidant properties, the protective effects of simvastatin are likely mediated by modulation of endothelial nitric oxide synthase. The potential to pretreat recipients of lung transplantation with statins to ameliorate reperfusion injury is promising.

Cerebral palsy is a common birth disorder that frequently involves ischemic-type injury to developing white matter (WM). Dead glial cells are a common feature of this injury and here we describe a novel form of acute ischemic cell death in developing WM astrocytes. Ischemia, modeled by the withdrawal of oxygen and glucose, evoked [Ca2+]i increases and cell death in astrocytes in post-natal day 10 (P10) rat optic nerve (RON). Removing extracellular Ca2+ prevented increases in [Ca2+]i but increased the amount of cell death. Astrocytes showed rapid [Na+]i increases during ischemia and cell death was reduced to control levels by substitution of extracellular Na+ or Cl- or by perfusion with bumetanide, a selective Na-K-Cl cotransport (NKCC) blocker. Astrocytes showed marked swelling during ischemia in the absence of extracellular Ca2+, which was blocked by bumetanide. Raising the extracellular osmolarity to limit water uptake reduced ischemic astrocyte death to control levels. Ultrastructural examination showed that post-ischemic astrocytes had lost their processes and frequently were necrotic, effects partially prevented by bumetanide. At this point in development, therefore, NKCC activation in astrocytes during ischemia produces an osmo-regulatory challenge. Astrocytes can subsequently regulate their cell volume in a Ca2+-dependent fashion but this will require ATP hydrolysis and does not protect the cells against acute cell death.

The alveolar macrophage secretes tumor necrosis factor-alpha protein by 15 minutes of reperfusion, which orchestrates the early events that eventually result in lung ischemia-reperfusion injury at 4 hours. Gadolinium pretreatment markedly reduces tumor necrosis factor-alpha elaboration, resulting in significant protection against lung ischemia-reperfusion injury.