艾司洛尔与尼卡地平联合使用对全麻诱导插管时循环的稳定作用

目的：探讨全麻诱导气管皇管时艾司洛尔与尼卡地平联合应用对循环的影响。方法：60例病人随机分成4组,A组为对照组,B组为艾司洛尔组,C组为尼卡地平组,D组为艾司洛尔与尼卡地平联合应用组。气管插管前,B、C组分别给予2mg/kg艾司洛尔、30μg/kg尼卡地平,D组给予1mg/kg艾司洛尔和15μg/kg尼卡地平,观察插管过程中的心率和血压变化。结果：诱导插管后,D组能同时抑制心率和血压的升高,与对照组相差显著（P＜0．01）,B组虽能抑制心率的增快（P＜0．01）,但不能完全控制血压的上升;C组则只抑制血压的升高（P＜0．01）,对心率无作用。结论：在全麻诱导插管时,艾司洛尔1mg/kg和尼卡地平15μg/kg联合应用能有效地抑制插管应激产生的心血管反应,稳定循环,二者联合应用可作为抑制插管反应的有效方法之一。     

Comparison of the potassium channel blocker tedisamil with the beta-adrenoceptor blocker esmolol and the calcium antagonist gallopamil in patients with coronary artery disease

Background: Tedisamil is a new bradycardic agent proven to exert anti-ischemic and antiarrhythmic effects by blockade of the different cardiac and vascular K⁺ currents. Hypothesis: It was the aim of the present study to compare the favorable anti-ischemic effects of tedisamil, with two long established representatives in the treatment of coronary artery disease (CAD), namely, the beta₁ blocker esmolol and the Ca² antagonist gallopamil. Methods: The hemodynamic and neurohumoral effects of the new potassium channel blocker tedisamil, an agent with negative chronotropic and class III antiarrhythmic properties, were compared with the ultra-short-acting beta₁-selective adrenoceptor blocker esmolol and the calcium antagonist gallopamil. A total of 22 patients with angiographically proven CAD and reproducible ST-segment depression in the exercise electrocardiogram was included in two studies with an almost identical design and inclusion criteria. The investigation was carried out using right heart catheterization and bicycle ergometry. A subgroup of 8 patients receiving 0.3 mg/kg body weight tedisamil intravenously (IV) in an open dose-finding study was compared with a group of 14 patients who had received esmolol (IV bolus of 500 μg/kg, maintenance dose 200 μg/kg/min) and gallopamil (initial dose 0.025 mg/kg, maintenance dose 0.0005 mg/kg/h) in a second intraindividual comparison. Results: Tedisamil and esmolol reduced heart rate at rest by 13% (p < 0.001), and 6% (p < 0.05), and at maximum working levels by 8% (p>0.01) and 9% (p>0.05), respectively. Gallopamil increased heart rate at rest by 7% (p < 0.05), with only slight changes occurring during exercise. Corresponding findings for each drug were observed for cardiac output both at rest and during exercise [tedisamil: at rest -10% (NS), max. exercise - 8%; esmolol: at rest -14% (NS), max. exercise -18% (NS); gallopamil: no significant changes]. Compared with tedisamil, stroke volume was reduced by esmolol [at rest and max. workload: -9% (NS)] and gallopamil [rest: -6% (NS), max. exercise: -2% (NS)]. Of the indirect parameters of ventricular function, that is, mean capillary wedge pressure (PCWPm) and right ventricular ejection fraction, only PCWPm demonstrated significant differences between tedisamil and gallopamil (+18% and -6% at rest, + 17% and -21% during exercise, respectively; p>0.001). Compared with gallopamil, both tedisamil and esmolol were superior in their effects on rate-pressure product, myocardial oxygen consumption, and ST-segment depression, whereas plasma lactate concentration was more reduced by tedisamil and gallopamil. Tedisamil led to a fall in norepinephrine levels in particular. Conclusion: Tedisamil and esmolol showed almost equipotent anti-ischemic effects at the doses administered. Tedisamil acts mainly by reductions in heart rate, and esmolol, though to a lesser degree, also by reductions in systolic blood pressure. The mechanism of gallopamil is to reduce afterload and to improve coronary perfusion. At the doses applied, however, it has lower antianginal potency compared with tedisamil and esmolol.     

Differential Effect of Esmolol on the Fast and Slow AV Nodal Pathways in Patients with AV Nodal Reentrant Tachycardia

Esmolol Effect on AV Nodal Pathways. Introduction: AV nodal reentrant tachycardia (AVNRT) usually involves anterograde conduction over a slowly conducting (“slow”) pathway and retrograde conduction over a rapidly conducting (“fast”) pathway. A variety of drugs, such as beta blockers, digitalis, and calcium channel blockers, have been reported to prolong AV nodal refractoriness in both the anterograde and retrograde limbs of the circuit. However, few data are available that address whether the fast and slow pathways respond in a quantitatively different manner to drugs such as beta-adrenergic antagonists. In addition, it is not known whether the effects of these agents on refractoriness parallel the effects on conduction in the fast and slow pathways. The present study was performed to measure the effect of the intravenous beta-adrenergic agent, esmolol, on refractoriness and conduction in both the fast and slow AV nodal pathways in patients with AVNRT. Methods and Results: Thirteen patients with discontinuous AV nodal conduction properties and typical AVNRT were studied. Anterograde and retrograde AV nodal functional assessment was performed at baseline and following steady-state drug infusion of intravenous esmolol at a dose of 500 μg/kg for 1 minute, 150 /μg/kg per minute for the next 4 minutes, followed by a continuous maintenance infusion of 50 to 100 μg/kg per minute. The anterograde effective refractory period of the fast pathway increased from 381 ± 75 msec at baseline to 453 ± 92 msec during the infusion of esmolol (P = 0.003). The anterograde effective refractory period of the slow pathway was also prolonged by esmolol, from 289 ± 26 msec to 310 ± 17 msec (P = 0.005). However, the absolute magnitude of the change in the anterograde effective refractory period of the fast pathway (+72 ± 59 msec) was significantly greater than the change in anterograde effective refractory period of the slow pathway (+21 ± 16 msec, P = 0.01). The mean retrograde effective refractory period of the fast pathway increased from 276 ± 46 msec to 376 ± 61 msec during esmolol infusion (P = 0.03). Retrograde slow pathway conduction that could not be demonstrated at baseline became manifest in three patients during esmolol infusion. In contrast to the effects of esmolol on refractoriness, the AH interval during anterograde slow pathway conduction prolonged to a far greater extent (+84 msec) than the HA interval associated with retrograde fast pathway conduction (+5 msec, P = 0.04). Conclusion: The beta-adrenergic antagonist, esmolol, has a quantitatively greater effect on anterograde refractoriness of the fast than the slow AV nodal pathway. However, the effects on conduction intervals during AVNRT are greater in the anterograde slow pathway than in the retrograde fast pathway. These observations suggest that the fast and slow pathways may have differential sensitivities to autonomic influences. This difference in the response to beta-adrenergic antagonists may be exploited as a clinically useful method for demonstrating slow pathway conduction in some individuals with AVNRT.     

艾司洛尔对靶控输注异丙酚诱导下喉罩置入反应影响的临床研究

目的将短效β1-受体阻滞剂艾司洛尔加入靶控异丙酚（TCI）诱导并插入喉罩（LMA）,观察艾司洛尔的抗伤害刺激作用。方法50例择期乳腺癌根治术患者,分为对照组与艾司洛尔组,以TCI输注异丙酚效应部位浓度3．0μg/ml,平衡6min后,加入艾司洛尔0．5mg／kg继以0．05mg·kg^-1·min^-1维持,同时静脉注射芬太尼0．25μg/kg,4min后置入LMA（对照组予以等量盐水）记录各时点HR、MAP、脑电双频指数（BIS）及体动情况。结果在置入LMA之后,艾司洛尔组较对照组血流动力学及BIS反应减轻。在对照组,LMA的插入伴随着BIS明显升高（与插入前比较）最大增加△BIS（P〈0．05）;AMAP（P〈0．05）;AHR（P〈0．05）。体动反应（无／有）在艾司洛尔组较轻微（P〈0．05）。艾司洛尔组未观察到心动过缓和低血压,也未发生知晓和回忆事件。结论艾司洛尔0．5mg／kg＋0．05mg·kg^-1·min^-1与靶控异丙酚3．0μg/ml合用,降低了喉罩插入的血流动力学、BIS波动,并减少了体动反应。