Catalase prevents increased lung vascular permeability during air emboli in unanesthetized sheep

Abstract

We studied the effects of bovine catalase on increased lung vascular permeability to fluid and protein during air emboli in unanesthetized sheep. Pulmonary arterial and left atrial pressures, cardiac output, lung lymph flow, lymph and plasma protein concentrations, arterial PO2, and numbers of arterial leukocytes were measured in paired experiments in which each sheep served as its own control. We found an increase in protein-rich lung lymph flow during embolization in untreated sheep, indicating an increase in microvascular permeability. When sheep were pretreated with intraperitoneal injections of catalase (50 mg/kg divided over the 24 h before air infusion), vascular pressures, arterial PO2, and leukocyte counts were not different from when the sheep were untreated, but the expected increases in transvascular fluid and protein flow during emboli were significantly attenuated (by approximately 50%). This effect required catalase enzyme activity, as demonstrated by the failure of enzymatically inactivated catalase (by reaction in vitro with aminotriazole in the presence of H2O2) or catalase vehicle (0.1% thymol in water) to affect the lung lymph response to air emboli. We conclude that H2O2 plays a role in the pathogenesis of the acute lung injury caused by intravenous air infusions into unanesthetized sheep. Because both catalase and superoxide dismutase have protected sheep lungs from air emboli-induced increased vascular permeability, a possible specific cause of microvascular barrier injury could be hydroxyl radicals formed from reactions between H2O2 and superoxide anion.

Pulmonary function one and four years after a deep saturation dive.

“…Th ese findings are consistent with the development of an emphysematou s lesion. Venous ga s mi croemboli generated during decompression are common, e ve n in the absence of clinical de compression sickness (18), and can induce pulmonary inflammatory lesion s and gas exchange abno rmalities (19,20). This effect ca n be pot entiated by hyp eroxia since oxygen radi cals are in vol ved in the inflammatory reaction s induced by gas microembolism ( 19) .…”

“…Venous ga s mi croemboli generated during decompression are common, e ve n in the absence of clinical de compression sickness (18), and can induce pulmonary inflammatory lesion s and gas exchange abno rmalities (19,20). This effect ca n be pot entiated by hyp eroxia since oxygen radi cals are in vol ved in the inflammatory reaction s induced by gas microembolism ( 19) . Th e exposure to fact ors such as cumulative hyperoxic exposure, cumulative hyperbaric exposure , time in saturatio n, and tim e in de compression we re all inte rrelated and co rre lated with the maximal pre ssure to which the deep divers were e xpos ed during the ob servation period .…”

Effect of Venous Air Embolization on Pulmonary Microvascular Protein Permeability

“…A study reported by Ohkuda et al demonstrated that pulmonary air embolization leads to increases in pulmonary artery pressure, pulmonary vascular resistance, flow from cannulated pulmonary lymphatic vessels, and pulmonary lymph protein clearance (16). Subsequent reports confirmed these findings (2,8,10,14). These studies concluded that air embolization results in pulmonary vascular injury and increased microvascular permeability characterized by increased flow of protein‐rich pulmonary lymph (2,8,10,14,16).…”

Influence of Hypoxia and Pulmonary Air Embolism on Lung Injury in Perfused Rat Lungs

“…Animal studies have shown increases in the number of pulmonary neutrophils and in the microvascular permeability of the lungs after embolization [22,23]. Leukocytes are effective producers of oxygen radicals, and catalase or superoxide dismutase has been shown to protect the lungs of sheep from exces sive fluid leakage after air embolization [9]. Therefore, reactive oxygen metabolites such as superoxide anions, hydrogen peroxide, and hydroxyl radicals may be respon sible for the acute lung injury caused by air emboli.…”

“…Pulmonary vessels trap air bubbles that gain access through the systemic venous system, prevent ing them from entering the arterial system and producing catastrophic results. This entrapment process can lead to pulmonary hypertension [7] and injury [8][9][10]; the injury of lung vascular tissue is believed to result from increases in both vascular hydrostatic pressure and permeability.…”