Hookah Smoking, Carbon Monoxide, and Coronary Endothelial Function

吸烟、一氧化碳和冠状动脉内皮功能

• 批准号: 9318088
• 负责人: Ronald G Victor
• 金额: $ 27.66万
• 依托单位: CEDARS-SINAI MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-05-01 至 2019-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9318088
• 关键词: Acute; Age; Age-Years; Antioxidants; Ascorbic Acid; Attention; Biological Markers; Blood Pressure; Blood Vessels; Blood flow; Breathing; Carbon; Carbon Monoxide; Carrying Capacities; Charcoal; Chronic; Cigar; Cigarette; Cigarette Smoker; Coal; Contrast echocardiography procedure; Coronary; Coronary Arteriosclerosis; Coupled; Cyclic GMP; Data; Development; Electronic cigarette; Endothelium; Epidemic; Gases; Goals; Half-Life; Heart Rate; Hemoglobin; Impairment; Intravenous; Isometric Exercise; Label; Left; Left Ventricular Dysfunction; Lipids; Masks; Measures; Mediating; Microcirculation; Microspheres; Myocardial; Nicotine; Nitric Oxide; Oxidants; Perfusion; Plasma; Public Policy; Recruitment Activity; Regulation; Research; Smoke; Smoker; Smoking; Source; Stimulus; Tars; Testing; Tobacco; Ursidae Family; Vascular Smooth Muscle; Vasodilation; Vasodilator Agents; Ventricular; Work; World Health Organization; brachial artery; cigarette smoking; combustion product; comparative; endothelial dysfunction; evidence base; hookah; indexing; inhibitor/antagonist; innovation; middle age; nanoparticle; novel; perfusion imaging; pipe smoking; programs; response; shear stress; tadalafil

ABSTRACT Hookah (water pipe) smoking is a new global epidemic. The World Health Organization wants to prohibit all claims that hookah is less harmful than cigarettes and wants hookah products to bear the same warning labels as cigarettes. But there is little scientific evidence to substantiate this proposal. Hookah tobacco is heated with burning charcoal. So, the smoke contains “tar” and nicotine plus charcoal combustion products including carbon monoxide (CO) and proatherogenic oxidants. With hookah, the CO boost decreases hemoglobin (Hb) O2-carrying capacity, which will decrease myocardial O2 delivery unless offset by increased myocardial blood flow (MBF). The goal of this revised R21 application is to test the novel hypothesis that: In young healthy hookah smokers, CO—a key charcoal combustion product in hookah smoke—acutely enhances nitric oxide (NO)/cGMP-mediated endothelial-dependent vasodilation in the coronary microcirculation, thereby masking acute tobacco-induced impairment. We further hypothesize that in long-term middle-aged hookah smokers: a) the coronary endothelium has become too dysfunctional to respond acutely to CO in hookah smoke, thereby unmasking acute tobacco-induced impairment in endothelial-dependent vasodilation; and b) the impaired microvascular perfusion plus reduced HbO2 carrying capacity from COHb plus increased myocardial work causes an O2 supply/demand imbalance causing subtle ischemic LV dysfunction detected by LV wall strain. Coronary endothelial function will be measured as the increase in myocardial blood flow (MBF) induced by isometric handgrip (increased systolic blood pressure and heart rate and thus shear stress). The MBF will be measured by perfusion imaging using quantitative myocardial contrast echocardiography. The handgrip- induced increase in MBF will be measured in younger and older hookah smokers before and after smoking charcoal-heated or electrically-heated hookah tobacco, and, for comparison, in age-matched cigarette smokers before and after smoking two cigarettes. Sixty subjects will be recruited to determine: 1) the acute effect of hookah smoking on coronary endothelial function in healthy young smokers 21-25 years of age; 2) the acute effect of inhaled CO gas alone (to mimic the safe hookah-induced CO boost of 25 ppm) on coronary endothelial function in the young hookah smokers; and, 3) the acute effect of hookah smoking on coronary endothelial function and left ventricular wall strain in long-term middle-aged smokers 35-49 years of age. The anticipated results of the proposed R21 stand to provide a novel mechanistic understanding of how hookah smoking impacts myocardial blood flow regulation, and, in so doing, inform new evidence-based public policy on hookah regulation.

抽象的 吸水烟（水烟）是一种新的全球流行病。世界卫生组织希望禁止一切 声称水烟比香烟危害小，并希望水烟产品贴有相同的警告标签 作为香烟。但几乎没有科学证据来证实这一提议。水烟烟草被加热 燃烧的木炭。因此，烟雾中含有“焦油”和尼古丁以及木炭燃烧产物，包括 一氧化碳 (CO) 和促动脉粥样硬化氧化剂。使用水烟时，二氧化碳的增加会降低血红蛋白 (Hb) 携氧能力，会减少心肌 O2 输送，除非被心肌血液增加所抵消 流量（MBF）。修订后的 R21 应用程序的目标是测试以下新假设： 水烟吸烟者，一氧化碳（水烟烟雾中的关键木炭燃烧产物）可显着增强一氧化氮 (NO)/cGMP 介导的冠状微循环内皮依赖性血管舒张，从而掩盖 急性烟草引起的损害。我们进一步假设，在长期吸水烟的中年人中：a) 冠状动脉内皮功能失调，无法对水烟烟雾中的二氧化碳做出敏锐的反应，因此 揭示烟草引起的急性内皮依赖性血管舒张损伤； b) 受损者 微血管灌注加上 COHb 带来的 HbO2 承载能力降低加上心肌做功增加 导致氧气供需不平衡，导致左心室壁应变检测到的轻微缺血性左心功能障碍。 冠状动脉内皮功能将通过以下因素引起的心肌血流量（MBF）增加来测量 等长握力（增加收缩压和心率，从而增加剪切应力）。 MBF 将是 使用定量心肌造影超声心动图通过灌注成像进行测量。手柄—— 将在年轻和年长的水烟吸烟者吸烟前后测量MBF的诱导增加 木炭加热或电加热的水烟烟草，以及作为比较的年龄匹配的吸烟者 吸两支烟之前和之后。将招募 60 名受试者来确定：1） 吸水烟对 21-25 岁健康年轻吸烟者冠状动脉内皮功能的影响； 2）急性的 单独吸入 CO 气体（模仿安全的水烟引起的 25 ppm CO 升高）对冠状动脉的影响 年轻水烟吸烟者的内皮功能； 3) 吸水烟对冠状动脉的急性影响 35-49岁长期中年吸烟者的内皮功能和左心室壁应变。这 拟议的 R21 的预期结果将为水烟如何产生新的机制提供新的理解 吸烟影响心肌血流调节，并以此为新的基于证据的公共政策提供信息 关于水烟的监管。