INTRODUCTION: Disabled submarine (DISSUB) survivors may face elevated CO₂ levels and inert gas saturation, putting them at risk for CO₂ toxicity and decompression sickness (DCS). Propranolol was shown to reduce CO₂ production in an experimental DISSUB model in humans but its effects on DCS in a DISSUB rescue scenario are unknown. A 100% oxygen prebreathe (OPB) reduces DCS incidence and severity and is incorporated into some DISSUB rescue protocols. We used a swine model of DISSUB rescue to study the effect of propranolol on DCS incidence and mortality with and without an OPB.METHODS: In Experiment 1, male Yorkshire Swine (70 kg) were pressurized to 2.8 ATA for 22 h. Propranolol 1.0 mg · kg⁻¹ (IV) was administered at 21.25 h. At 22 h, the animal was rapidly decompressed and observed for DCS type, onset time, and mortality. Experimental animals (N = 21; 69 ± 4.1 kg), PROP_1.0, were compared to PROP_1.0-OPB₄₅ (N = 8; 69 ± 2.8 kg) with the same dive profile, except for a 45 min OPB prior to decompression. In Experiment 2, the same methodology was used with the following changes: swine pressurized to 2.8 ATA for 28 h; experimental group (N = 25; 67 ± 3.3 kg), PROP_{0.5 bis}, propranolol 0.5 mg · kg⁻¹ bis (twice) (IV) was administered at 22 h and 26 h. Control animals (N = 25; 67 ± 3.9 kg) received normal saline.RESULTS: OPB reduced mortality in PROP_1.0-OBP₄₅ compared to PROP_1.0 (0% vs. 71%). PROP_0.5 bis had increased mortality compared to CONTROL (60-% vs. 4%).DISCUSSION: Administration of beta blockers prior to saturation decompression appears to increase DCS and worsen mortality in a swine model; however, their effects in bounce diving remain unknown.Forbes AS, Regis DP, HallAA, Mahon RT, Cronin WA. Propranolol effects on decompression sickness in a simulated DISSUB rescue in swine. Aerosp Med Hum Perform. 2017; 88(4):385–391.