Modulation of Decompression Sickness Risk in Pigs

1. * * * 10 7/16 9/10 10 16 10 9/10 4/10 Introduction In H2 biochemical decompression, a small but significant portion of the inert gas load in a diver’s tissues is removed by biochemical processes inside the diver during a H2 dive. This gas removal supplements the gas loss by diffusion during decompression, thereby reducing the risk of decompression sickness (DCS). The biochemical machinery is provided by intestinal microbes that metabolize H2 to methane. Rats receiving intestinal injections of methanogenic microbes had a 50% lower risk of DCS than untreated rats (Am. J. Physiol. 275:R677-R682, 1998). Pigs treated with these microbes also had a 50% lower risk of DCS from a chosen compression and decompression sequence in H2 (J. Appl. Physiol., in press 2001). We wanted to determine if we could increase the H2 scrubbing by the intestinal microbes by increasing perfusion of the intestines. Failing to identify a drug that would selectively increase gut perfusion, we treated pigs with caffeine to elevate cardiac output in general. The effect this had on DCS risk was paradoxical. Modulation of Decompression Sickness Risk in Pigs by Caffeine Administration during H2 Biochemical Decompression S.R. Kayar, A. Fahlman, W.C. Lin and W.B. Whitman Naval Medical Research Center, Silver Spring, MD 20910 and University of Georgia, Athens, GA 30602 Results Materials and Methods Animals: - Yorkshire pigs (Sus scrofa), castrated or uncastrated males, n = 46, body mass range 17 - 24 kg. Treatments: - Caffeine (5 mg/kg) by mouth. - Cultures of Methanobrevibacter smithii (200-2200 mol CH4/min activity in 12-116 ml volumes) surgically injected into large intestine. Dive Simulation: - H2 dive simulated in a dry hyperbaric chamber (5660 L volume). - Chamber initially pressurized with He to 11 bar (to dilute O2). - Chamber flushed with H2 at constant total pressure to 60 -75% H2. - Chamber pressurized with H2 to 24 bar for 3 h. - Final chamber [H2] = 84 - 93%; PO2 = 0.3 - 0.5 bar. - Decompression rate 0.9 bar/min to 11 bar. - Observation for DCS at 11 bar for 1 hour. - Euthanized in chamber on confirmation of DCS or at end of hour. (1 bar = 0.99 atm = 33 feet of sea water = 10 m sea water) Measurements: - Chamber gases analyzed by gas chromatography for H2, O2, He, N2, CH4. - Chamber CH4 output concentration (ppm) used as index of CH4 release rate by pigs (mol CH4/min). - DCS diagnosed as pigs walked on treadmill in chamber; symptoms of severe DCS include difficulty walking, falling, inability to stand, seizures. • Methane release rate was significantly higher in pigs with vs. without caffeine, and without microbial treatments.  Increasing cardiac output with caffeine increased intestinal perfusion and H2 supply to native intestinal microbes. • Methane release rate was significantly higher in microbe-treated vs. untreated pigs, if neither had caffeine.  Increasing H2-metabolizing microbial content of the intestine elevated H2 removal rate. • In microbe-treated pigs, methane release rate was not different with vs. without caffeine.  Combining microbial treatments and caffeine failed to elevate methane release rate further. Higher cardiac output without increased intestinal H2 elimination suggests greater tissue H2 load. • DCS incidence was significantly lower in pigs with vs. without caffeine and without microbial treatments.  Elevating intestinal H2 removal by increasing H2 delivery to native microbes decreased DCS risk. • DCS incidence was significantly lower in microbe-treated vs. untreated pigs, if neither had caffeine. Elevating intestinal H2 removal by increasing H2-metabolizing microbial content decreased DCS risk. • In microbe-treated pigs, DCS incidence was significantly higher in animals with vs. without caffeine. Combining microbial treatments and caffeine failed to lower DCS risk further.Higher DCS incidence in caffeine plus microbe-treated group suggests greater tissue H2 load. Conclusions • Increasing cardiac output with caffeine led to higher activity of H2-metabolizing microbes in the native intestinal flora of pigs; this reduced DCS risk by reducing the tissue H2 load. • Increasing microbial activity by injecting microbes in the absence of caffeine reduced DCS risk. • Increasing cardiac output with caffeine did not increase H2 elimination by microbes injected into the intestine; consequently, tissue H2 load was probably elevated following a H2 dive, and DCS risk increased. • We need to learn more about cardiac output, intestinal perfusion and inert gas fluxes before we can extend biochemical decompression to human divers. Sample DiveThis pig released increasing amounts of methane throughout the exposure to hyperbaric H2. Effects of caffeine at 1 atm Animals treated with caffeine had O2 consumption rates elevated by ~20% for over 3 h (means  1 SD; † P < 0.05 different from initial. Contact information: S.R. Kayar: kayars@nmrc.navy.mil W.B. Whitman: whitman@arches.uga.edu A. Fahlman: afahlman@maties.sun.ac.za W.C. Lin: wclin@arches.uga.edu