威而鋼無法預防高山病AMS

Wilderness medicine at high altitude: recent developments in the field

Nitrates

體內一氧化氮 NO 生成, 可調節血管收縮狀態, 免疫功能, 血小板凝集, 血糖平衡, 肌肉收縮, 粒線體功能. 目前有證據顯示NO與高度適應有關, 在高度適應過程, NO 生成會增加, 低氧引起的適應反應在西藏人很明顯, 他們血清亞硝酸鹽濃度較高, 代表整體NO合成上升, 吐氣排出的NO也較多. 

Nitric oxide (NO) regulates physiological processes in the human body, including vasodilation, immune function, platelet aggregation, glucose homeostasis, muscle contraction, and mitochondrial function. Emerging evidence suggests that NO also plays an important role in altitude acclimatization. Lowlanders exposed to altitude initially exhibit reduced concentrations of exhaled NO, with the magnitude of this decline associated with susceptibility to altitude illness. With acclimatization, lowlanders demonstrate an increase in NO production. The adaptive response to hypoxia is particularly prominent in Tibetans who have greater plasma nitrite concentrations, indicative of elevated whole-body NO production, and higher exhaled NO relative to lowlanders. This affords them unique physiological advantages that result in a remarkable capacity to cope with the challenges of hypoxia relative to lowlanders. Therefore, given the importance of NO during altitude acclimatization, it is tempting to speculate that interventions increasing NO availability, especially during acute (ie, prior to acclimatization) and chronic altitude exposure (ie, during acclimatization), may be advantageous.

經由飲食增加硝酸鹽攝取, 例如紅菜頭果汁, 可增加NO生成. 食用硝酸鹽可增加血清的 NO 代謝物濃度(硝酸鹽, 亞硝酸鹽). 減少穩定期的氧氣消耗, 改善動脈及組織氧和, 增加運動耐力, 改善急性常壓低氧狀態的表現, 在缺氧狀態使用紅菜頭汁補充硝酸鹽可加快肌肉復原, 恢復最大氧化ATP再合成, 正常氧氣濃度的運動耐力. 

One possible means of eliciting this effect is via dietary nitrate supplementation (ie, nitrate-rich beetroot juice). Nitrate ingestion has been shown to increase plasma concentrations of NO metabolites (nitrate and nitrite), reduce steady-state oxygen consumption, improve arterial and tissue oxygenation, enhance exercise tolerance, and improve performance, during acute normobaric hypoxia. Interestingly, under hypoxic conditions, nitrate supplementation in the form of beetroot juice resulted in faster muscle recovery and restored maximal oxidative ATP resynthesis and exercise tolerance to normoxic values, when compared to placebo. The mechanisms underlying these effects are still under investigation, but may involve improved mitochondrial, and/or muscle contractile efficiency,59 and enhanced tissue blood flow/better matching of oxygen delivery to metabolic rate.

AMS 目前認為是由低氧環境導致的動脈氧氣飽和度下降引起, 因此, 改善攝取硝酸鹽改善動脈氧氣飽和度, 可能會降低 AMS 機率, 但食用紅菜頭汁與不含硝酸鹽的安慰劑比較, 在急性期(兩小時)暴露於低氧 (11%, 相當於 5000公尺海拔), 平均的AMS 分數並無差異, 不過, 安慰劑這組, 6/10 的人診斷為 AMS, 食用紅菜頭汁的人 4/10 診斷為 AMS. 在更長時間暴露, 與更低氧氣狀態, 硝酸鹽可能對於減少 AMS 症狀可能更明顯, 但尚未證實. 

It is the prevailing opinion that AMS is triggered by a fall in arterial oxygen saturation (ie, hypoxemia) subsequent to hypoxic exposure.61 Therefore, improved arterial oxygen saturation with nitrate ingestion may be expected to reduce the incidence of AMS. There was no difference in mean AMS scores between participants consuming nitrate-rich beetroot juice and a nitrate-free placebo during acute (~2 hours) exposure to extreme normobaric hypoxia (FiO2 11%, ~5,000 m). However, six out of ten individuals were diagnosed positive for AMS with placebo ingestion versus only four with the ingestion of nitrate-rich beetroot juice. It is possible that the potential for nitrate to attenuate AMS may become more pronounced during more prolonged (>2 hours) or extreme hypoxic exposure (for example, a high-altitude expedition), though this is yet to be established.

全可利 bosentan 治療肺動脈高壓的藥物; sildenafil 威而鋼

曾有人提出, 使用威而鋼與全可利來治療AMS, 因為這兩樣可延長NO效果. 

威而鋼可降低肺動脈收縮壓 PASP, 改善氧氣供應, 減少常壓低氧狀態及高海拔環境引起的運動耐力下降

這兩類藥物可擴張肺部血管床, 減少低氧性肺血管收縮, 以及肺動脈高壓與高海拔肺水腫 HAPE. 理論上這類藥物可以改善低氧環境下的運動耐力, 也可以改善人體在高海拔運動時的動脈氧氣飽和度, 但是研究發現, 兩類藥物無法改善運動能力, 或降低AMS及HAPE機率 (不過有少數研究說威而鋼可以預防HAPE), 事實上服用威而鋼反而 AMS 機率上升, 可能是因為威而鋼本身的副作用包括頭痛, 而增加了病患的路易斯湖評分 LLS, 因此, 雖然這兩類藥物可以改善動脈氧氣飽和度, 但無法改善功能.

Both sildenafil (a selective phosphodiesterase type 5 [PDE-5] inhibitor) and bosentan (a nonselective endothelin-receptor antagonist) have been mooted as potential treatments for AMS, due to their effect on prolonging the effect of NO. Sildenafil has been demonstrated to reduce PASP, increase oxygen delivery, and minimize the decrease in exercise capacity in both normobaric hypoxia and actual high altitude.62 By dilating the pulmonary vascular bed, these drugs reduce the degree of hypoxic pulmonary vasoconstriction and consequent pulmonary hypertension, and therefore, the risk of HAPE. Theoretically, this could improve exercise tolerance under hypoxic conditions. Indeed, they have been demonstrated to improve arterial oxygen saturations in individuals exercising at altitude. However, trials have failed to demonstrate an improvement in exercise capacity or incidence of AMS and HAPE. In fact, higher rates of AMS were reported in individuals treated with sildenafil, compared to placebo. This may be because headache is a recognized side effect of sildenafil, thus increasing an individual’s LLS. Therefore, although there appears to be an improvement in arterial oxygen saturation with these medications, there does not appear to be a consequent improvement in function.