Effect of propranolol on ventricular repolarization and refractoriness: Role of beta-blockade versus direct membrane effects

Summary The purpose of this study was to define the role of beta-adrenergic blockade and direct membrane effects in the ability of dl-propranolol to alter ventricular repolarization and refractoriness in the intact heart. The effective refractory period (ERP) and the local Q-T interval were measured at an epicardial site in the left ventricle in 14 open-chest dogs anesthetized with alpha-chloralose. Beta-adrenergic influences were eliminated in seven dogs (group 1) by stellate transection and nadolol (0.5 mg/kg IV), and enhanced in seven dogs (group 2) by stellate transection and stimulation of the left ansae subclavia. Each dog received an initial beta-blocking dose of propranolol (0.5 mg/kg) followed by a second, cumulative dose of 5.0 mg/kg. In group 1 dogs, there was no significant change in either the ERP or local Q-T interval in response to the first dose of propranolol. In group 2 dogs, left stellate stimulation significantly shortened the ERP (20±2 msec) and the local Q-T interval (17±4 msec). The first dose of propranolol prolonged these parameters to values not different from prestimulation control values. There was no change in the H-V interval, QRS complex duration, or diastolic threshold (DT) in either group after the initial propranolol dose. The second dose of propranolol significantly shortened the ERP (5±1 msec) and the local Q-T interval (11±2 msec) in both groups. This dose also significantly increased the DT, H-V interval, and QRS complex duration. In three additional nadolol-treated dogs, a single 5 mg/kg dose of propranolol shifted the entire strength-interval curve 4 to 7 msec earlier into electrical diastole. The data indicate that a beta-blocking dose of propranolol prolongs repolarization and refractoriness only when adrenergic input is elevated. In the absence of beta-adrenergic influences, high doses of propranolol shorten repolarization and refractoriness. This latter effect may be due to a direct membrane effect of the drug.     

Effect of propranolol on the activity of neutral,alkaline and acidic proteases in rat myocardium after aortic stenosis

Summary The aim of the study was to investigate the effect of propranolol upon the activity of proteases in rat myocardium subjected to aortic stenosis.In acute heart hypertrophy induced by aortic stenosis, the activity of all three proteases in the myocardium does not change significantly. Propranolol in the concentration of 10^–6 to 2×10^–4 M inhibited proteolytic activity dependent on neutral proteases.The degree of inhibition increased simultaneously with increasing concentrations of propranolol.Propranolol in a low concentration (10^–6–10^–5 M) also inhibited proteolytic activity dependent on alkalinc and acidic proteases, but in higher concentration (10^–4–2×10^–4 M) stimulated proteolytic activity of these enzymes 2–3 times.     

Combination of flecainide and propranolol for congenital junctional ectopic tachycardia

Congenital junctional ectopic tachycardia is a rare tachyarrhythmia with high mortality. A pharmacological approach in early infancy is regarded as the first‐line therapeutic option. Pharmacologically, amiodarone alone or in combination with other drugs is the most commonly reported effective agent for congenital junctional ectopic tachycardia, but it has many adverse effects. Here we report the case of a 40‐day‐old infant. The clinical course suggests that combined oral flecainide and propranolol is an effective alternative therapy for early infants. Esophageal lead electrocardiography may give a clear diagnosis of junctional ectopic tachycardia.     

Intragastric nicotine protects against 40% ethanol-induced gastric mucosal injury despite pretreatment with propranolol orN-ethylmaleimide in rats

We tested the hypotheses that the protective effect of intragastric nicotine against ethanol-induced gastric mucosal injury is dependent on propranolol- orN-ethylmaleimide-sensitive mechanisms. Propranolol was administered in doses (2 and 20 mg/kg) that provided dose-related blockade of -adrenoceptors (significant decreases in heart rate).N-Ethylmaleimide was administered in doses that previously had been shown to increase gastric vascular permeability (10 mg/kg) or inhibit gastric mucosal sulfhydryl compounds (50 mg/kg). At 0.5 hr after these or control subcutaneous pretreatments, the rats received intragastric nicotine (4 mg/kg) or vehicle. One hour later 40% ethanol was given intragastrically. The gastric corpus mucosal lesions were recorded by polaroid photographs after another hour, and their areas measured unbiasedly by computerized image analysis. The results showed thatN-ethylmaleimide, but not propranolol, aggravated ethanol-induced gastric mucosal injury. The protective effect of intragastric nicotine was not modified by either pretreatment. We conclude that the mechanism mediating intragastric nicotine protection against 40% ethanol-induced gastric mucosal injury is independent of propranolol- orN-ethylmaleimide-sensitive mechanisms.Supported by Veterans Administration Medical Research Funds, and in part by research grants (0162-01, 02 and 0291-01) from the Smokeless Tobacco Research Council, Inc., and by funds (1RT 80) provided by the Cigarette and Tobacco Surtax Fund of the State of California through the Tobacco-Related Disease Research Program of the University of California to FWL. Dr. Endoh is a recipient of the University of California Tobacco-Related Disease Research Program Research Fellowship Award (FT 37).     

内镜干预联合普萘洛尔治疗食管胃底静脉曲张破裂出血的临床研究

目的评价内镜套扎术和(或)硬化剂注射结合组织胶黏合剂联合普萘洛尔治疗食管胃底静脉曲张破裂出血患者的疗效。方法2017年10月—2019年10月同济大学附属第十人民医院崇明分院收治的食管胃静脉曲张破裂出血(esophagogastric variceal bleeding, EVB)患者共120例,将患者随机分为研究组和对照组,每组60例。两组患者在治疗前的年龄、性别、体质量指数、病因、Child-Pugh评分、静脉曲张严重程度、血液学检查(血红蛋白、C-反应蛋白(C-reactive protein, CRP)、肝酶水平、凝血酶原时间(prothrombin time, PT)、电解质）和影像学检查(静脉曲张直径、门静脉宽度、脾静脉宽度、门静脉流速)等基线资料均一致。研究组给予内镜下套扎术和(或)硬化剂注射结合组织胶黏合剂联合普奈洛尔治疗,而对照组长期口服普奈洛尔,根据最大耐受量调整剂量,术后随访24个月。评价患者的死亡率、再出血率以及实验室指标。结果研究组与对照组死亡率差异无统计学意义(P>0.05);研究组输血量、止血时间和住院日与对照组相比明显减少,差异具有统计学意义(P<0.05);研究组的Child-Pugh评分、PT、血钠水平、炎症指标CRP、静脉曲张直径、门静脉和脾静脉宽度改善较为明显,差异具有统计学意义(P<0.05);血红蛋白、肝酶、血钾水平和门静脉流速在两组间无明显差异(P>0.05);术后18个月和24个月,研究组再出血发生率显著低于对照组,差异具有统计学意义(P<0.05);治疗前Child-Pugh评分、PT、丙氨酸氨基转移酶(alanine aminotransferase, ALT)、天冬氨酸氨基转移酶(aspartate aminotransferase, AST)、血钠水平、静脉曲径直径大小对预后具有重要意义,差异具有统计学意义(P<0.05);Chlid-Pugh评分、PT、血钠水平、静脉曲径直径大小可能是肝硬化静脉曲张预后不良的独立影响因素(OR>1,P<0.05)。结论内镜干预联合普萘洛尔治疗方案用于防治食管胃底静脉曲张再出血的效果确切,安全性较高,值得广泛推广。     

普萘洛尔预防肝硬化初次上消化道出血的meta分析

对普萘洛尔能否预防肝硬化上消化道出血进行系统评价。检索1980年1月至2000年12月期间发表的有关普萘洛尔预防肝硬化初次上消化道出血的随机对照临床试验。按照入选标准，有9项临床试验纳入本研究，由两名作者各自独立地对入选研究中有关试验设计、研究对象的特征、干预措施、研究结果等内容进行摘录，并用RevMan3.1软件进行分析。上消化道出血、死亡及因出血死亡的合并优势比（OR）分别为0.45[95%CI0.34，0.60]、0.73[95%CI0.55，0.96]、0.44[95%CI0.28，0.69]。肝功能越差，预防效果越差；腹水患者的预防效果亦较差。普萘洛尔可以预防肝硬化上消化道出血，并可降低总死亡率以及出血所致的死亡率。肝功能的状况和腹水的有无是影响普萘洛尔的预防效果的重要因素。     

普萘洛尔治疗新疆地区婴幼儿血管瘤的临床疗效观察

目的:研究普萘洛尔治疗新疆地区婴幼儿血管瘤的临床疗效。方法:选择2012年3月~2014年3月于新疆医科大学第一附属医院颌面肿瘤外科接受口服普萘洛尔治疗的血管瘤患儿42例,年龄1~14个月,服药剂量:小于3个月的患儿口服剂量为0.5mg/kg/天;3~6个月的患儿口服剂量为1mg/kg/天;大于6个月的患儿口服剂量为2mg/kg/天。2次/日、饭后30min服药,两次给药间隔6~8h。连续服用1年,服药后1个月、3个月、6个月、9个月、12个月复诊,动态评估患儿瘤体大小、质地、颜色及不良反应,并对出现的不良反应积极处理。以Achauer疗效评定法及服药前后彩色多普勒B超检查结果进行临床疗效评估。结果:42例患儿服药观察12个月后,疗效I级(差)3例,II级(中)16例,III级(好)13例,IV级(优)10例;所有患者均无严重并发症;不同性别、民族、瘤体部位与血管瘤分型治疗效果之间无统计学差异(P0.05);42例患者治疗前PSV(46.47±26.87)与治疗后PSV(17.67±8.05)之间有统计学差异(P0.05);42例患者治疗前RI指数(0.54±0.12)与治疗后RI指数(0.82±0.15)之间有统计学差异(P0.05)。结论:口服普萘洛尔治疗婴幼儿血管瘤作用显著且不良反应轻。     

Propranolol inhibits angiogenesis via down-regulating the expression of vascular endothelial growth factor in hemangioma derived stem cell

Background: Oral propranolol (PRN) has recently been shown to be highly effective for infantile hemangiomas (IHs), and is currently recommended as the first-line treatment of complicated IHs. However, the therapeutic mechanism(s) still remain unclear. Methods: In this study, we tested hemangioma-derived stem cells for expression of vascular endothelial growth factor (VEGF) in vitro and studied the inhibition of VEGF expression. We used PCR, Elisa, Western blotting and immunohistochemistry in vivo and in vitro trial. Results: The study demonstrated that application of PRN at a “normal” concentration equivalent to plasma concentration did not inhibit proliferation or promote apoptosis of hemangioma derived stem cells (HemSCs) isolated from IH patients. PRN suppressed expression of vascular endothelial growth factor (VEGF) and basic Fibroblast Growth Factor (bFGF) in HemSCs in vitro. Morphological, histological and immunohistological improvement were observed in vivo using murine IH model in which HemSCs pre-treated with PRN were implanted into BALB/c-nu mice. In the pre-treated HemSC grafts, mean micro-vessel density (MVD) significantly decreased and protein levels of VEGF markedly decreased, while bFGF was still detectable. Conclusions: The results suggested PRN inhibited angiogenesis via down-regulating the expression of vascular endothelial growth factor in hemangioma derived stem cell. These findings provide critical insight into the potential mechanisms of PRN action on IH.     

口服普萘洛尔联合聚桂醇局部注射治疗婴幼儿血管瘤的疗效评价

目的：评价普萘洛尔联合局部注射聚桂醇治疗婴幼儿血管瘤的临床疗效。 方法：收集2014-2018年我科就诊的婴幼儿血管瘤患者,分为口服普萘洛尔组和口服普萘洛尔联合聚桂醇局部注射治疗组,随访观察12个月。结果：共治疗婴幼儿血管瘤患者43例,其中口服普萘洛尔组21例,口服普萘洛尔联合聚桂醇局部注射治疗组22例。全部患儿随访观察12个月,瘤体均有不同程度缩小、颜色变浅。口服普萘洛尔组治疗时间(148±32)天,治愈率为61.9%;联合治疗组治疗时间为(62±24)天,治愈率为95.45%,两者间差异均有统计学意义（Ps＜0.05）。43例患儿中有4例在服口服普萘洛尔1小时后出现心率减慢,经观察3 h后自行恢复正常,35例患儿血糖轻微降低,降低幅度≤0.2 mmol/L,未给予特殊处理。22例联合聚桂醇局部注射治疗患儿,7例注射局部有少量渗血。结论：口服普萘洛尔联合局部注射聚桂醇治疗婴幼儿血管瘤较单用普萘洛尔治疗疗程缩短,临床疗效更佳。