Snapir Amir, Posti Jussi, Kentala Erkki, Koskenvuo Juha, Sundell Jan, Tuunanen Helena, Hakala Kristo, Scheinin Harry, Knuuti Juhani, Scheinin Mika
Department of Pharmacology, Drug Development and Therapeutics, University of Turku, Itäinen Pitkäkatu 4B, FI-20520 Turku, Finland.
Anesthesiology. 2006 Nov;105(5):902-10; quiz 1069-70. doi: 10.1097/00000542-200611000-00010.
Dexmedetomidine, a selective alpha2-adrenoceptor agonist, has counteracting effects on the cardiovascular system. It mediates sympatholysis by activating alpha2 adrenoceptors in the central and peripheral nervous system, and vasoconstriction and vasorelaxation by activating postsynaptic alpha2 adrenoceptors in blood vessels. The goal of this study was to determine the effects of therapeutic and high concentrations of dexmedetomidine on myocardial perfusion and cardiac function in healthy subjects.
The authors studied 12 healthy young men. Myocardial blood flow (assessed with positron emission tomography), myocardial function (by echocardiography), and hemodynamic data were collected before and during low (measured mean plasma concentration, 0.5 ng/ml) and high (5 ng/ml) plasma concentrations of dexmedetomidine.
The low concentration of dexmedetomidine reduced myocardial perfusion (mean difference, -27% from baseline [95% confidence interval, -31 to -23%], P < 0.001) in parallel with a reduction in myocardial oxygen demand (estimated by the rate-pressure product (-23% [-28 to -18%], P < 0.001). The high dexmedetomidine plasma concentration did not further attenuate myocardial perfusion (-3% [-12 to +6%] from low dexmedetomidine, P > 0.05; -29% [-39 to -18%] from baseline, P < 0.001) or statistically significantly affect the rate-pressure product (+5% [0 to +10%], P > 0.05). Systolic myocardial function was attenuated by sympatholysis during the low infusion rate and was further attenuated by a combination of the sustained sympatholysis and increased afterload during the high infusion rate.
In healthy subjects, plasma concentrations of dexmedetomidine that significantly exceed the recommended therapeutic level do not seriously attenuate myocardial perfusion below the level that is observed with usual therapeutic concentrations and do not induce evident myocardial ischemia.
右美托咪定是一种选择性α2肾上腺素能受体激动剂，对心血管系统有拮抗作用。它通过激活中枢和外周神经系统中的α2肾上腺素能受体介导交感神经抑制，并通过激活血管中的突触后α2肾上腺素能受体引起血管收缩和血管舒张。本研究的目的是确定治疗浓度和高浓度右美托咪定对健康受试者心肌灌注和心功能的影响。
作者研究了12名健康青年男性。在右美托咪定低血浆浓度（实测平均血浆浓度，0.5 ng/ml）和高血浆浓度（5 ng/ml）之前及期间，收集心肌血流（用正电子发射断层扫描评估）、心肌功能（通过超声心动图）和血流动力学数据。
低浓度右美托咪定使心肌灌注降低（平均差异，较基线降低27%[95%置信区间，-31%至-23%]，P<0.001），同时心肌需氧量降低（通过心率-血压乘积估算降低23%[-28%至-18%]，P<0.001）。高右美托咪定血浆浓度未进一步减弱心肌灌注（较低右美托咪定浓度时降低3%[-12%至+6%]，P>0.05；较基线降低29%[-39%至-18%]，P<0.001），对心率-血压乘积也无统计学显著影响（升高5%[0至+10%]，P>0.05）。低输注速率时，收缩期心肌功能因交感神经抑制而减弱，高输注速率时，持续的交感神经抑制和后负荷增加共同作用使其进一步减弱。
在健康受试者中，显著超过推荐治疗水平的右美托咪定血浆浓度不会使心肌灌注严重减弱至低于通常治疗浓度时观察到的水平，也不会诱发明显的心肌缺血。
