Plasminogen activator inhibitor protein is a biomarker of decompression stress in rats

AIMS: To determine whether the presence of intravascular gas bubbles after diving alters the concentration of plasminogen activator inhibitor (PAI-1) protein in blood plasma. METHODS: Fifty-six female Sprague-Dawley rats were compressed to 700 kPa breathing air for 50 minutes followed by a 50 kPa min-1 linear decompression to surface. Gas bubble grade in the pulmonary artery was measured by Doppler ultrasound at discrete time points for the first hour after decompression. Blood samples were collected from the abdominal aorta, and total PAI-1 protein in plasma from all surviving animals and 9 additional non-diving controls was measured by ELISA with a polyclonal rabbit anti-rat PAI-1 antibody. The animals were divided into groups according to bubble grade at 60 minutes and multiple comparison analysis between groups was done by ANOVA with Bonferroni corrections using the SPSS analytical software. RESULTS: There was a significant rise in the level of PAI-1 protein in plasma at high bubble grades, grade 4-5, compared to animals with no detectable bubbles, grade 0 (p=0.002) or untreated controls (p=0.006). Differences between groups with lower bubble grades were not statistically significant, but a trend of increasing PAI-1 with increasing bubble grade is apparent. CONCLUSIONS: Elevation of PAI-1 is involved in early response to hypoxia, and the presence of high amounts of PAI-1 is used as a biomarker for risk in several diseases. Functionally, PAI-1 is a major physiological inhibitor of blood clot degradation and has been shown to act cardioprotectively, possibly by guarding the integrity of the cardiac vascular barrier. Our results show that increasing amounts of gas bubbles in vascular tissues after decompression correlate with increased concentration of PAI-1 in blood plasma, indicating the triggering of a hypoxic response by the presence of gas bubbles. Keywords: biomarker, rats, hyperbaric air, decompression, intravascular gas bubbles, Doppler ultrasound, plasminogen activator inhibitor (PAI-1), plasma, hypoxia