Fagan S C, Rahill A A, Balakrishnan G, Ewing J R, Branch C A, Brown G G
College of Pharmacy and Allied Health Professions, Wayne State University, Detroit, MI 48202, USA.
J Toxicol Environ Health. 1995 Jun;45(2):221-9. doi: 10.1080/15287399509531990.
Nuclear magnetic resonance (NMR) imaging shows promise in the measurement of human cerebral blood flow (CBF) in that nonradioactive indicators may be used. Our earlier investigations with trifluoromethane (FC-23) gas have shown that this compound can be used to safely and effectively measure CBF in anesthetized animal models. In this Phase I dose-escalation study we set out to determine the maximal tolerated concentration (MTC) of FC-23 in normal healthy male volunteers and to assess its feasibility as an NMR indicator. Five subjects were exposed in a blinded fashion to escalating concentrations of FC-23 between 10% and 60%, randomly interleaved with exposures to both room air and 40% nitrous oxide. On each study day, the subjects breathed the test gas for eight pulses of 3 min each with 2-min clearance periods between the pulses. The subjects underwent intensive physiologic and neurobehavioral monitoring throughout the study period. The first subject experienced an anesthetic response to 60% FC-23, and the second subject experienced "discomfort" and requested discontinuation at the initiation of 40% FC-23. The MTC was subsequently determined to be 30% FC-23 (all subjects tolerated the gas), although a small (37.6 vs. 40.5) but statistically significant retention of carbon dioxide was found (p = .003). When one subject received 30% FC-23 during an NMR imaging study, a pronounced anesthetic effect with intolerable hyperacusis was demonstrated. Human studies of FC-23 have been discontinued in our laboratory.
核磁共振（NMR）成像在测量人体脑血流量（CBF）方面显示出前景，因为可以使用非放射性指示剂。我们早期对三氟甲烷（FC - 23）气体的研究表明，该化合物可用于在麻醉动物模型中安全有效地测量CBF。在这项I期剂量递增研究中，我们着手确定正常健康男性志愿者中FC - 23的最大耐受浓度（MTC），并评估其作为NMR指示剂的可行性。五名受试者以盲法暴露于浓度在10%至60%之间递增的FC - 23中，随机穿插暴露于室内空气和40%氧化亚氮中。在每个研究日，受试者每次呼吸测试气体3分钟，共八个脉冲，脉冲之间有2分钟的间隙期。在整个研究期间，受试者接受了强化的生理和神经行为监测。第一名受试者对60%的FC - 23产生了麻醉反应，第二名受试者在开始吸入40%的FC - 23时感到“不适”并要求停止。随后确定MTC为30%的FC - 23（所有受试者都耐受该气体），尽管发现二氧化碳有少量（37.6对40.5）但具有统计学意义的潴留（p = 0.003）。当一名受试者在NMR成像研究中接受30%的FC - 23时，表现出明显的麻醉效果和无法忍受的听觉过敏。我们实验室已停止对FC - 23的人体研究。
