Responses of baboons to prolonged hyperoxia: physiology and qualitative pathology

Abstract

Cardiopulmonary responses to prolonged hyperoxia and their relationships to the development of lung pathology have not been fully characterized in primates. In this study, circulatory hemodynamics and pulmonary function, vascular permeability, and leukocyte sequestration were measured in male baboons after 100% O2 exposure and related to ultrastructural changes of lung injury by electron microscopy. Three groups of animals were exposed to 100% O2 in an exposure cage for 40, 66, and 80 h, respectively. A fourth group of animals was exposed in a cage for 80 h and then anesthetized and ventilated with 100% O2 for additional time. These animals were exposed for a total duration of 110 h or until death from the injury. Physiological responses to hyperoxia were characterized by decreases in total lung capacity and inspiratory capacity at 80 and 110 h. A significant increase in pulmonary leukocyte accumulation was noted by 80 h. Extravascular lung water and permeability surface-area product increased at 80 and 110 h. Cardiac output and stroke volume also decreased, and systemic vascular resistance increased after 80 and 110 h of hyperoxia. Histopathological changes were present in the lungs of all but the 40-h exposure group. Animals exposed for 66 h showed endothelial injury and neutrophil accumulation. By 80 h, animals showed endothelial cell destruction, interstitial edema, and type I cell injury. At 110 h, animals showed substantial destruction of endothelial and type I epithelial cells, exposure of alveolar basement membrane, congestion of capillaries, and substantial interstitial edema. The data indicate that histological changes by electron microscopy precede physiological responses to hyperoxic pulmonary injury in baboons by as much as 14 h and that the physiological responses to early hyperoxic injury are relatively insensitive to the pathological injury.

CXCR2 Is Critical to Hyperoxia-Induced Lung Injury

“…High concentrations of oxygen may perpetuate lung injury and result in persistent inflammation indistinguishable from that seen in ARDS (28 -30). Hyperoxia-induced lung injury is characterized by noncardiogenic pulmonary edema, alveolar hyaline membrane formation, type I alveolar epithelial cell injury, type II alveolar epithelial cell hyperplasia, neutrophil infiltration, alveolar hemorrhage, and increased alveolar wall thickness (31,32). As the lung injury progresses, the interstitium becomes infiltrated with leukocytes, FIGURE 7.…”

Genetic basis of murine responses to hyperoxia-induced lung injury

“…This injury is thought to be initiated by the local generation of reactive oxygen species (ROS), and as it evolves, pulmonary structural damage becomes extensive, accompanied by airway inflammation, alveolar and interstitial edema, and reduced lung function (Kapanci and Weibel, 1969;Crapo, 1986). The components of the inflammatory response include increased levels of pro-inflammatory cytokines, such as tumor necrosis factor-alpha (TNF-α), interleukin (IL)-1beta and IL-6 (Johnston et al 1997), and the recruitment of neutrophils to the distal airspaces (Johnston et al 1997;Keeney et al 1995;Fracica et al 1991;Bureau et al 1985). The roles of neutrophils in hyperoxic lung injury remain unclear, but it has been suggested that the neutrophils in the airways release oxidants that contribute to tissue damage (Keeney et al 1995).…”

Endostatin and Vascular Endothelial Cell Growth Factor (VEGF) in Piglet Lungs: Effect of Inhaled Nitric Oxide and Hyperoxia

“…Hyperoxia paradoxically raises lavageable VEGF levels. This latter effect and that on VEGF mRNA level but not protein is abrogated by recovery in reduced There are many pathologic manifestations of hyperoxic lung injury, but widespread endothelial cell damage and necrosis, with resultant high pulmonary microvascular permeability, are of particular importance (1,2). The normal resolution of this vascular damage requires angiogenesis (3).…”