The Adult Respiratory Distress Syndrome (ARDS) is characterized initially by increased permeability of the pulmonary microvasculature. In ARDS there appears to be a potential involvement of leukocytes, platelets, oxygen radicals, prostaglandins, complement activation, and intravascular coagulation and fibrinolysis. The observation of both platelet-fibrin plugs and leukostatic plugs in the lungs of man and experimental animals has focused attention on microemboli, and has led to their use of experimental models of acute lung injury. Although the role of superoxide and other oxygen radicals has been described in oxygen toxicity, their role in the injury due to pulmonary microemboli has received little attention and is the overall objective of the proposed research. The isolated, perfused dog lung label will be the basic experimental preparation. The advantages of this preparation are 1) it is perfused with whole blood with all of its constituents, 2) the weight of the lobe is continuously monitored and specified indices of microvascular permeability (Kf an Pci) can be calculated, and 3) arterial, venous, and airway pressures can be adjusted independently to maintain the lobe in Zone 3. This preparation will also extend the observations regarding the effects of microemboli previously made in intact lung preparations.
The specific aims are 1) to characterize the changes in permeability, vascular pressures, and cellular components of blood following microemboli, 2) to determine the protective effects of oxygen scavengers - superoxide dismutase (SOD), catalase (CAT), dimethylthiourea (DMTU), and dimethylsulfoxide (DMSO), 3) to describe the protective effects of granulocytopenia, 4) to observe the effects of allopurinol pretreatment and to correlate them with tissue levels of xanthine oxidase, and 5) to characterize the direct effects of oxygen radicals on the lung and the protective effects of oxygen scavengers. The lungs will be embolized with air bubbles (less than 1 mm in diameter), glass beads (50, 200, and 500 microns in diameter), and leukocyte aggregates (induced by complement activation) during normoxic and hypoxic conditions. It is anticipated that these studies will provide basic information regarding the role of oxygen radicals and their scavengers in injury due to microemboli as well as the role of oxygen radicals generated by xanthine oxidase in ischemic lung tissue.
| Allison, R C; Kyle, J; Adkins, W K et al. (1990) Effect of ischemia reperfusion or hypoxia reoxygenation on lung vascular permeability and resistance. J Appl Physiol 69:597-603 |
| Allison, R C; Rippe, B; Prasad, V R et al. (1989) Pulmonary vascular permeability and resistance measurements in control and ANTU-injured dog lungs. Am J Physiol 256:H1711-8 |
| Allison, R C; Hernandez, E M; Prasad, V R et al. (1988) Protective effects of O2 radical scavengers and adenosine in PMA-induced lung injury. J Appl Physiol 64:2175-82 |
| Cope, D K; Allison, R C; Parmentier, J L et al. (1986) Measurement of effective pulmonary capillary pressure using the pressure profile after pulmonary artery occlusion. Crit Care Med 14:16-22 |
