Duplessis Christopher A, Fothergill David, Schwaller Derek, Hughes Linda, Gertner Jeffrey
Naval Submarine Medical Research Laboratory, Groton, CT 06349-5900, USA.
Aviat Space Environ Med. 2007 Apr;78(4):430-4.
Nitric oxide (NO) may decrease bubble formation in diving. Statin medications are attractive potential options to increase NO. Statins exhibit a proven safety profile, and possess a myriad of pleiotropic properties improving vascular endothelial function. Additionally, statin-mediated lipid reduction may reduce bubble generation via alterations in plasma surface tension. We investigated the efficacy of atorvastatin as a pharmacological intervention to reduce the risk of bubble formation after diving, a surrogate for decompression sickness (DCS).
There were 16 trained military divers who completed a provacative hyperbaric chamber dive protocol after taking either 80-mg of atorvastatin or placebo for 4 d. Subjects completed the alternate medication regimen no sooner than 2 wk. After each dive, subjects were subjected to precordial trans-thoracic echocardiographic exams via standardized protocols. Bubbles were graded via a non-parametric, ordinal grading system and statistically analyzed via Wilcoxon signed-rank tests.
We found no within subject differences for the maximum bubble grade scores (z = 0.00, p = 1.00, n=16). Low-density lipoprotein (LDL), and total cholesterol (TC) levels decreased significantly (107.6 +/- 26.2 to 79.3 +/- 21.9 mg x dl(-1) and 175 +/- 20.9 to 147 +/- 22.4 mg x dl(-1), respectively) 1-2 wk post statin administration. Age, bioelectrical impedance (BEI), TC, LDL, potassium, and calcium demonstrated positive correlations to placebo bubble grades.
Prophylactic 80-mg atorvastatin administration for 4 d failed to reduce the number of intravascular bubbles observed following a 60-ft, 80-min dry chamber dive despite significant acute reductions in lipid levels. Several hypotheses may explain why statins failed to decrease bubble volume: (1) differential influence of statins on the venous vs. arterial vasculature; (2) failure to elicit an improvement in endothelial function and, therefore, the hypothesized endothelial conditioning in younger patients possessing normal baseline; and (3) the ordinal grading system encompassing a substantial variation in bubble volume (bubbles Scm(-2)).
一氧化氮（NO）可能会减少潜水过程中的气泡形成。他汀类药物是增加NO的有吸引力的潜在选择。他汀类药物具有已证实的安全性，并且具有多种改善血管内皮功能的多效性特性。此外，他汀类药物介导的血脂降低可能通过改变血浆表面张力来减少气泡产生。我们研究了阿托伐他汀作为一种药理学干预措施，以降低潜水后气泡形成风险（减压病（DCS）的替代指标）的疗效。
16名经过训练的军事潜水员在服用80毫克阿托伐他汀或安慰剂4天后，完成了一项高压舱激发潜水方案。受试者在至少2周后完成交替用药方案。每次潜水后，通过标准化方案对受试者进行心前区经胸超声心动图检查。气泡通过非参数有序分级系统进行分级，并通过Wilcoxon符号秩检验进行统计分析。
我们发现受试者内部最大气泡分级分数没有差异（z = 0.00，p = 1.00，n = 16）。他汀类药物给药后1 - 2周，低密度脂蛋白（LDL）和总胆固醇（TC）水平显著降低（分别从107.6 +/- 26.2降至79.3 +/- 21.9毫克/分升和从175 +/- 20.9降至147 +/- 22.4毫克/分升）。年龄、生物电阻抗（BEI）、TC、LDL、钾和钙与安慰剂气泡分级呈正相关。
尽管脂质水平在短期内显著降低，但预防性服用80毫克阿托伐他汀4天未能减少在60英尺、80分钟的干式舱内潜水后观察到的血管内气泡数量。有几个假设可以解释为什么他汀类药物未能减少气泡体积：（1）他汀类药物对静脉与动脉血管系统的不同影响；（2）未能改善内皮功能，因此未能在具有正常基线的年轻患者中产生假设的内皮调节作用；（3）有序分级系统涵盖了气泡体积的大量变化（气泡/平方厘米）。
