Circadian Study of Decompression Sickness Symptoms and Response-Associated Variables in Rats

Abstract

In order to study circadian rhythms and decompression sickness (DCS), we determined: 1) the baseline circadian time structure in noncompressed rats of potential response variables to compression/decompression (C/D), and 2) whether rats subjected to C/D display a circadian time-dependent difference in inflammatory response intensity and biological tolerance. Subgroups of male rats, standardized to a 12 h light/12 h dark schedule, were evaluated every 4 h over 24 h after they were either compressed to 683 kPa (group E) or remained at sea level (group C). During 60 min recovery, evaluation included gross DCS symptoms and pulmonary edema in all E rats, and cell counts, nitric oxide, protein, thromboxane B(2,) and leukotriene E(4) levels in survivors. Chi-square, ANOVA, and 24 h cosinor analyses were used to test for time-of-day effects. C/D exposures near the end of dark/activity or during light/resting were generally better tolerated, with lowest signs of DCS symptoms and lowest responses by most of the variables monitored. More deaths were observed in the first half of the dark/activity span. Of the 16 subsets of inflammatory-associated variables, overall increases were observed in 13 and decreases in 2. Significant or borderline significant circadian time effects were found in 14 variables in group C, 12 variables in group E, and 13 variables in response (E%C). Thus, nearly all baseline indices of DCS demonstrated circadian time-dependencies in the sea-level exposed control rats (group C), and nearly all were modified by the circadian time of C/D. Such time-of-day effects of DCS are potentially relevant to the operational concerns of occupations involving decompression exposures and the investigation of prevention and treatment intervention strategies of DCS.

A New Measure of Decompression Sickness in the Rat

“…In one study a weighted severity score was given according to the number of animals and perceived “severity” of the signs [34]. Objective measures have been proposed such as a walking assessment in a rotating cylindrical cage [18, 25, 33, 35, 36], bubble grades [27, 37, 38], platelet counts [27], nitric oxide [39], bronchoalveolar and/or pleural fluids [39], inflammatory mediators (thromboxane B 2 and leukotriene E 4 ) [39], interleukin-6 [30], whole blood and differential cell counts [39], neutrophils [39], EGR-1/ B -actin ratio in the lung [20], time to lose equilibrium following ether anesthesia [40], lactic dehydrogenase (LDH), and creatine phosphokinase (CPK) plasma activity [29]. Only rarely have objective measures been correlated with subjective observer agreement.…”

Hypobaric Impact on Clinical Tolerance and 24-h Patterns in Iron Metabolism Markers and Plasma Proteins in Men

“…Moreover, the exposures were done only during one span of the 24 h, the daytime. Thus, it is possible the results of this study might have been somehow different if the hypobaric hypoxic exposures were carried out at different circadian spans of time, as found recently in an animal study of circadian rhythms in the response to decompression (Butler et al, 2010). Moreover, the effect of the hypobaric exposures was only assessed over one 24-h span, as opposed to several consecutive 24-h spans; therefore, a possible masking effect of the hypoxia on the expression of the studied rhythms cannot be excluded.…”

“…Although these variables are known to play a key role in the responses to chronic hypobaric hypoxia (Richalet, 1984;Richalet et al, 1994), very little is known about the short-term effects of mild hypoxia, especially involving repeated-measures protocols. Only recently have animal circadian rhythm studies involving rapid pressure variation and decompression sickness been conducted (Butler et al, 2010). Thus, we proposed a circadian study to help improve knowledge in these settings and also to help identify correlations between clinical symptoms observed during long flights and potential circadian alterations of iron biological markers.…”