Effect of α1-adrenoceptor stimulation with methoxamine and phenylephrine on spontaneously beating rabbit sino-atrial node cells

Effects of methoxamine and phenylephrine on the action potential and the membrane currents in spontaneously beating rabbit sino-atrial node cells were examined by means of a two-microelectrode voltage-clamp technique. Both methoxamine and phenylephrine (10(-4) mol/l) prolonged the cycle length (CL) and the action potential duration (APD), significantly. At concentrations higher than 3 x 10(-4) mol/l, phenylephrine increased the maximum rate of rise of action potential (Vmax) but methoxamine reduced it. Both agents depolarized the maximum diastolic potential (MDP). These changes in the action potential parameters occurred in a concentration-dependent manner. In the presence of phentolamine (10(-5) mol/l), methoxamine (3 x 10(-4) mol/l) did not modify the action potential parameters. Also, phenylephrine did not affect them during exposure to phentolamine (10(-5) mol/l) and pindolol (10(-7) mol/l). In voltage-clamp experiments, at 10(-3) mol/l both methoxamine and phenylephrine slightly increased the slow inward current (Isi), but decreased the time-dependent outward current (Ik). The steady-state activation variable of Ik (p infinity) was unaffected by these agents. The hyperpolarization-activated current (Ih) was suppressed in the presence of methoxamine, but enhanced in the presence of phenylephrine. An additional application of pindolol (10(-7) mol/l) during exposure to phenylephrine (10(-3) mol/l) depressed the action potential amplitude (APA) and Vmax, and prolonged CL slightly. Under the same condition, all the membrane currents (Isi, Ik and Ih) were decreased. In addition, the time courses of decay for Isi were not modified in the absence and the presence of phenylephrine (10(-3) mol/l) and phenylephrine plus pindolol (10(-7) mol/l).(ABSTRACT TRUNCATED AT 250 WORDS)     

Bronchopulmonary effects of phenylephrine and methoxamine in the guinea-pig. Interaction with bronchoconstrictor drugs

The bronchopulmonary effects of phenylephrine (Phe) and methoxamine (Met) were investigated in vitro on isolated guinea-pig tracheas and lung strips and in vivo on pulmonary airway resistance (Raw) in conscious guinea-pigs. Phe, but not Met, relaxed the isolated trachea precontracted with acetylcholine (ACh); this effect was inhibited by propranolol and ascribed to beta-adrenergic stimulation. In the presence of propranolol, both Phe and Met contracted the isolated trachea (-log EC50 were 3.80 +/- 0.37 and 3.04 +/- 0.25 respectively (n = 5] and this effect was competitively antagonized by phentolamine. Phe and Met contracted the isolated lung strips more strongly than the trachea (-log EC50 were 5.14 +/- 0.23 and 4.30 +/- 0.14 respectively (n = 5]. In contrast with the latter, the maximum response was equivalent to that induced by ACh; this effect was also antagonized by phentolamine. In the conscious guinea-pig, Phe (100 and 300 micrograms/kg) and Met (1 and 3 mg/kg) had no effect on Raw but significantly reduced the bronchoconstriction induced by ACh (25 micrograms/kg), histamine (20 micrograms/kg) and serotonin (15 micrograms/kg); this protective effect was unmodified by propranolol (2 mg/kg), yohimbine (1 mg/kg) or piperoxan (0.3 mg/kg) but was significantly inhibited by prazosin (30 micrograms/kg) or AR- C239 (50 micrograms/kg). These results suggest that alpha-adrenergic vasoconstriction with subsequent shrinkage of the bronchial mucosa is responsible for the protective effect of Phe and Met against ACh-induced bronchoconstriction. In isolated lung strips, vasoconstriction would increase tension.     

Alpha-adrenergic agonists inhibit the dipsogenic effect of angiotensin II by their stimulation of atrial natriuretic peptide release

Angiotensin II (ANG-II) and atrial natriuretic peptide (ANP) have opposing actions on water and salt intake and excretion. Within the brain ANP inhibits drinking induced by ANG-II and blocks dehydration-induced drinking known to be caused by release of ANG-II. Alpha-adrenergic agonists are known to release ANP and antagonize ANG II-induced drinking. We examined the hypothesis that alpha agonists block ANG-II-induced drinking by stimulating the release of ANP from ANP-secreting neurons (ANPergic neurons) within the brain that inhibit the effector neurons stimulated by ANG-II to induce drinking. Injection of ANG-II (12.5 ng) into the anteroventral region of the third ventricle (AV3V) at the effective dose to increase water intake increased plasma ANP concentrations (P<0.01) within 5 min. As described before, previous injection of phenylephrine (an alpha(1)-adrenergic agonist) or clonidine (an alpha(2)-adrenergic agonist) into the AV3V region significantly reduced ANG-II-induced water intake. Their injection also induced a significant increase in plasma ANP concentration and in ANP content in the olfactory bulb (OB), AV3V, medial basal hypothalamus (MBH) and median eminence (ME). These results suggest that the inhibitory effect of both alpha-adrenergic agonists on ANG-II-induced water intake can be explained, at least in part, by the increase in ANP content and presumed release from these neural structures. The increased release of ANP from the axons of neurons terminating on the effector neurons of the drinking response by stimulation of ANP receptors would inhibit the stimulatory response evoked by the action of ANG-II on its receptors on these same effector neurons.     

Influence of hepatic innervation on renal glomerular filtration rate

Electrical stimulation of perivascular portal nerves leads to rapid, transient increase of renal glomerular filtration rate (GFR) and of urinary flow rate ( ). In contrast, perivascular stimulation at the vena cava inferior does not significantly alter GFR and . Spinal transfection at the thoracocervical junction does not significantly modify the effect of periportal nerve stimulation. Infusion of the -adrenergic agonist phenylephrine (20 nmol/min) into the superior mesenteric vein increases GFR and , whereas infusion of identical amounts of phenylephrine (20 nmol/min) into the jugular vein does not significantly alter GFR or . The observations indicate that -adrenergic innervation of the liver modifies renal function.     

Autonomic modulation of the U wave during phenylephrine and esmolol infusions

The etiology of U waves on the electrocardiogram is uncertain. We previously found that U waves could be amplified by isoproterenol infusion. Whether other autonomic interventions modify U-wave amplitude is unknown. Twenty-five healthy subjects underwent graded infusions of esmolol and phenylephrine. Heart rate, T-wave amplitude, U-wave amplitude, and QT and QU intervals were measured using interactive computerized electrocardiogram software. Heart rate decreased with both interventions ( P < .001), though to a greater degree with phenylephrine. U-wave amplitude increased by 16.3% during phenylephrine ( P < .001) but decreased by 14.5% during esmolol ( P < .001). The change in U-wave amplitude was strongly dose-dependent for both phenylephrine ( P < .001) and esmolol ( P < .001). T-wave amplitude increased with phenylephrine (597-692 microV, P < .001) but decreased with esmolol (632-568 microV, P < .001). QT and QU intervals increased with both interventions ( P < .001). We conclude that sympathetic and parasympathetic activities are important determinants of U-wave timing and amplitude.     

Safety of bolus-dose phenylephrine for hypotensive emergency department patients

Introduction

Bolus-dose phenylephrine (BDPE) is routinely used to treat hypotension in the operating room. BDPE's fast onset of action and ability to be administered peripherally have prompted calls for its use in the Emergency Department (ED). There are few published data on the safety of BDPE use in the ED. Primary concerns include BDPE's potential to cause dangerous hypertension or reflex bradycardia. We hypothesize that BDPE is a safe short-term vasopressor choice for hypotensive ED patients.

去氧肾上腺素维持腰-硬联合麻醉下剖宫产术中血液循环稳定的观察

目的：观察用微量泵持续静脉推注去氧肾上腺素对腰-硬联合麻醉下剖宫产术中血液循环稳定的影响。方法：选择100例择期剖宫产产妇,随机分为F组（在鞘内注局麻药即刻以25-100μg/min静脉泵入去氧肾上腺素维持循环稳定）和M组（根据血压下降程度,静注麻黄碱5 mg）。记录麻醉后多时点的血压,心率,恶心、呕吐发生情况,失血量,输液量,新生儿生后Apgar评分情况,胎儿娩出即刻脐静脉血血气分析指标。结果：F组各时点观察指标均优于M组（P〈0.05）,与麻醉前比较差异无统计学意义（P〉0.05）;M组各时点血压与麻醉前比较差异有统计学意义（P〈0.05）,心率在麻醉后5 min时减慢（P〈0.05）;F组脐静脉血气pH值、BE值均高于M组（P〈0.05）,PaCO2低于M组（P〈0.05）;F组恶心、呕吐率低于M组（P〈0.05）。结论：以25-100μg/min静脉泵入去氧肾上腺素,更能稳定腰-硬联合麻醉下剖宫产术中产妇的血液循环。     

静脉预注去氧肾上腺素联合持续泵注对无痛胃肠镜检查患者血流动力学影响的随机对照研究

目的 探讨无痛胃肠镜检查前预防性静脉注射去氧肾上腺素联合持续泵注对检查过程中患者血流动力学的影响。方法 采用前瞻性随机对照研究方法,选取2019年12月10~31日在首都医科大学附属北京友谊医院接受无痛胃肠镜检查的患者72例,利用SPSS的随机数生成器将患者随机分为去氧肾上腺素组(P组)和对照组(C组),每组各36例。P组患者在麻醉诱导给药后,立即缓慢静脉注射去氧肾上腺素50μg,同时开始静脉持续泵注去氧肾上腺素,起始剂量为30μg/min,检查过程中酌情增减泵注速度,以维持平均动脉压(MAP)波动于基础值20%以内,检查结束时停止泵注;C组患者常规给药。比较两组患者检查前、诱导给药后即刻,检查开始3 min、5 min、10 min、15 min、20 min及检查结束时的血流动力学参数(包括收缩压、舒张压、MAP和心率)、脉搏血氧饱和度、检查时间、苏醒时间、麻醉药物及血管活性药等用量和不良反应。结果 因操作方式改变,P组剔除1例。与C组(n=36)相比,P组(n=35)患者在诱导给药后,低血压的发生率较低(2. 9%vs. 36. 1%),差异具有统计学意义(P <0. 001);P组患者的MAP在诱导给药后即刻[(92±13) mmHg vs.(82±13) mmHg,P=0. 030],检查开始3 min[(87±12) mmHg vs.(77±11) mmHg,P=0. 006]、5 min[(84±11) mm Hg vs.(77±9) mm Hg,P=0. 002]、10 min[(89±8) mm Hg vs.(77±9) mm Hg,P <0. 001]、15 min[(90±9) mm Hg vs.(77±9) mm Hg,P=0. 001]、20 min[(88±8) mm Hg vs.(81±10) mm Hg,P=0. 001]、检查结束[(89±9) mm Hg vs.(84±12) mm Hg,P=0. 001]较高,但P组心动过缓(心率<50次/min)的发生率也较高(14. 3%vs. 0),差异具有统计学意义(P=0. 019);C组患者的麻黄碱用量高于P组[0(0,6) mg vs. 0(0,0) mg],差异具有统计学意义(P=0. 004)。但两组患者的脉搏血氧饱和度、胃肠镜检查时间[(20. 9±5. 8) min vs.(21. 3±6. 1) min,P=0. 752]、苏醒时间[0(0,0) min vs. 0(0,0) min,P=0. 921]、麻醉药及阿托品[0(0,0) mg vs. 0(0,0) mg,P=0. 921]等用药相比,差异无统计学意义(P> 0. 05)。结论 在无痛胃肠镜检查前,预防性静脉注射去氧肾上腺素联合持续泵注,可明显减少检查期间低血压的发生率,维持血流动力学稳定,但需警惕心动过缓的发生,必要时静注阿托品处理。     

甲基莲心碱对兔离体脑基底动脉收缩的影响

为了研究甲基莲心碱对兔离体脑基底动脉收缩的影响及与血管内皮的关系 ,采用离体家兔脑基底动脉环实验方法 ,以苯肾上腺素为兔脑基底动脉环的预收缩剂 ,测定血管张力变化 ,观察甲基莲心碱对血管收缩张力的影响 ;测定血管内皮完整组和去血管内皮组的张力变化 ,观察甲基莲心碱对血管收缩张力的影响是否为血管内皮依赖性的作用。结果发现 :甲基莲心碱抑制苯肾上腺素引起的兔脑基底动脉环收缩的作用与生理盐水对照组比较差异显著 (P <0 .0 0 1 ) ;甲基莲心碱对内皮完整组和对去内皮组血管环的最大舒张百分值分别为 38.4 %± 9.1 %和33.4 %± 1 1 .5 % ,差异无显著性统计学意义 (P >0 .0 5 )。提示甲基莲心碱能抗苯肾上腺素诱导的兔离体脑基底动脉收缩 ,其扩血管的作用主要是其直接松弛血管平滑肌所致     

苯肾上腺素预输注防治老年人脊麻后低血压的临床研究

目的 评估预防性输注苯肾上腺素用于防治老年人脊麻后低血压的疗效和安全性。方法 将2017年1月~4月在本院行骨科下肢手术且年龄超过60岁的52例患者,随机分为P组和C组,每组26例。两组患者均使用0.5%布比卡因2 ml进行腰麻,P组在腰麻注药后立即静脉给予苯肾上腺素（100 μg/ml）1 ml/min,C组给予生理盐水1 ml/min。观察两组患者的术中MAP、每例患者低血压、高血压、心动过缓的发作次数,发作低血压、高血压、心动过缓的患者数,初次低血压的发作时刻,术中最低和最高MAP,苯肾上腺素和液体的总使用量,术后6 h、24 h、48 h发生心电图改变的患者数以及肌钙蛋白增加的患者数。结果 P组MAP高于C组,初次低血压的发作时刻大于C组,差异有统计学意义（P＜0.05）。P组每例患者低血压的发作次数少于C组,差异有统计学意义（P＜0.05）。两组患者发生低血压的患者数、术中最低和最低MAP比较,差异无统计学意义（P＞0.05）。P组患者的无低血压发作的累计比例高于C组,差异有统计学意义（P＜0.05）。两组患者术中发生高血压和心动过缓例数、每例患者高血压和心动过缓的发作次数、术中液体总使用量比较,差异无统计学意义（P＞0.05）。P组的苯肾上腺素总使用量高于C组（P＜0.05）。两组患者在术后6 h、24 h均未发生心电图异常改变情况。P组患者在术后48 h内未发生心电图异常改变情况,C组有2例患者（7.69%）在术后48 h发生了心电图异常改变,两组差异无统计学意义（P＞0.05）。C组患者在术后6 h、24 h、48 h发生肌钙蛋白定量升高的患者数均高于P组,但差异无统计学意义（P＞0.05）。结论 预防性输注苯肾上腺素可有效防治老年人脊麻后低血压,减少低血压发作次数,延迟低血压发作时间,提高手术麻醉的安全性。