The cardiotonic bipyridine AWD 122-60 inhibits adenosine triphosphate-sensitive potassium channels of mouse skeletal muscle

Summary The inhibition of ATP-sensitive potassium channels in mouse skeletal muscle by the cardiotonic bipyridine AWD 122-60 was investigated with the patch-clamp technique. In excised patches of the inside-out configuration, internally applied AWD 122-60 (10^–6–10^–3 mol/1) reversibly reduced the open-probability of single ATP-sensitive potassium channels. The agent shortened the periods of channel activity but did not affect the channel conductance. At positive membrane potentials channel inhibition by AWD 122-60 was more pronounced than at negative potentials, the drug concentrations producing 50% channel inhibition were 11 mol/l at + 40 mV and 29 mol/l at –40 mV. The Hill coefficients of the concentration-response curves were in the range between 0.5 and 0.6 for both potentials. milrinone (10^–4 mol/I), had no effects on ATP-sensitive potassium channels in skeletal muscle. potassium channels in heart muscle by AWD 122-60 are discussed. Send offprint requests to B. Neumcke at the above address     

曲美他嗪对冠状动脉介入治疗患者的心脏保护作用

目的 评价曲美他嗪对经皮冠状动脉介入治疗(PCI)患者的心肌保护作用.方法 在国内5家医院入选拟进行介入治疗的稳定性或不稳定性心绞痛患者共101例,随机分为曲美他嗪组(54例)和对照组(47例).曲美他嗪组在术前(5±2)d开始服用曲美他嗪20 mg,3次/d,手术当天至少提前30 min给予60 mg负荷最,术后继续服用4周.对照组给予常规药物治疗.观察术中心绞痛发作及心电图变化情况;检测术前、术后12 h及24 h磷酸肌酸激酶同工酶浓度;观察术前、术后4周的心脏功能变化.结果 曲美他嗪组介入治疗术中心绞痛发生率显著低于对照组,差异有统计学意义(0%比25.5%,P<0.001).术中球囊扩张时曲美他嗪组出现缺血性心电图改变的比例小于对照组(60.8%比78.3%,P<0.05).PCI术后4周曲美他嗪组左室射血分数值高于对照组[(66.6±7.1)%比(63.0±7.7)%,P=0.03].结论 PCI围手术期应用曲美他嗪可以减少术中心绞痛发作,减轻心肌损伤,进一步改善PCI术后的左心功能.     

三七总皂苷、三七皂苷R1、人参皂苷Rb1、人参皂苷Rg1对光化学反应诱导的大鼠肠系膜细静脉血栓的抑制作用——三七主要成分抑制细静脉血栓

目的:三七总皂苷(PNS)、三七皂苷R1(R1)、人参皂苷Rb1(Rb1)、人参皂苷Rg1(Rg1)是三七的主要水溶性成份.含有PNS、R1、Rb1、Rg1的中药复方制剂复方丹参滴丸(CP)能抑制光化学反应诱导的大鼠肠系膜细静脉血栓的形成.但是有关PNS、R1、Rb1、Rg1对血栓形成的在体影响尚不清楚.本研究探讨PNS、R1、Rb1、Rg1对光化学反应(PR)诱导的大鼠肠系膜细静脉血栓形成的抑制作用.方法:将麻醉的雄性SD大鼠(200～250g)的肠系膜展开至观察板上,经大鼠股静脉注入血啉甲醚(HMME,1mg/kg),用倒置荧光显微镜100瓦汞灯作光源经蓝光滤光片照射在选定的大鼠肠系膜细静脉上.在照射开始时,设定显示器的时间为0分,在血栓达到细静脉管径的1/2时停止照射,通过连接在显微镜上的CCD连续观察并记录30min内细静脉血栓出现的时间、血栓到达细静脉直径一半的时间、血栓与照射的血管面积比.一部分大鼠在光化学反应前10min,经颈静脉分别一次性注入PNS、R1、Rb1、Rg1(各10mg/kg.BW)、或阿斯匹林(AsP,200mg/kg.BW)提前60min灌胃.结果:光化学反应组在照射13.67±2.67s后细静脉开始出现血栓,血栓与血管径的面积比迅速增加.PNS、R1、Rb1、Rg1、ASP可以延长由照射开始到血栓出现的时间,减少血栓的面积.结论:PNS、R1、Rb1、Rg1可以抑制光化学反应后细静脉血栓的形成,其效果与AsP近似.     

复方丹参滴丸加蒙诺治疗慢性心力衰竭临床研究

目的观察复方丹参滴丸加蒙诺对慢性心力衰竭(CHF)患者的临床治疗效果。方法78例CHF患者随机分成治疗组和对照组。治疗组给予复方丹参滴丸10粒,每日3次,并加蒙诺(福辛普利)10mg,每日1次;对照组给予蒙诺10mg,每日1次。两组疗程皆为3个月,观察患者临床症状体征、心功能参数及心功能分级情况的变化。结果两组患者治疗后临床症状、体征、心功能参数及心功能分级情况较治疗前有明显改善(P<0.05),治疗组患者的临床症状、体征、心功能参数及心功能分级与对照组比较有显著性差异(P<0.05)。结论中西医结合较单纯西医治疗CHF疗效显著。     

Memantine Prevents Cardiomyocytes Nuclear Size Reduction in the Left Ventricle of Rats Exposed to Cold Stress

OBJECTIVES

Memantine is an N-methyl-d-aspartate (NMDA) glutamate receptor antagonist used to treat Alzheimer’s disease. Previous studies have suggested that receptor blockers act as neuroprotective agents; however, no study has specifically investigated the impact that these drugs have on the heart. We sought to evaluate the effects of memantine on nuclear size reduction in cardiac cells exposed to cold stress.

METHOD

We used male EPM-Wistar rats (n=40) divided into 4 groups: 1) Matched control (CON); 2) Memantine-treated rats (MEM); 3) Rats undergoing induced hypothermia (IH) and 4) Rats undergoing induced hypothermia that were also treated with memantine (IHM). Animals in the MEM and IHM groups were treated by oral gavage administration of 20 mg/kg/day memantine over an eight-day period. Animals in the IH and IHM groups were submitted to 4 hours of hypothermia in a controlled environment with a temperature of − 8°C on the last day of the study.

RESULTS

The MEM group had the largest cardiomyocyte nuclear size (151 ± 3.5 μm³ vs. CON: 142 ± 2.3 μm³; p<0.05), while the IH group had the smallest mean value of nuclear size. The nuclear size of the IHM group was preserved (125 ± 2.9 μm³) compared to the IH group (108 ± 1.7 μm³; p<0.05).

CONCLUSION

Memantine prevented the nuclear size reduction of cardiomyocytes in rats exposed to cold stress.     

F90927: A New Member in the Class of Cardioactive Steroids

F90927 is a newly developed cardioactive drug with a steroid-like structure. It acts directly and agonistically on the cardiac L-type Ca²⁺ channel by shifting its voltage-dependent activation toward more negative potentials. This leads to an increased influx of Ca²⁺ and, therefore, to a stronger contraction; however, no arrhythmias occur. Calcium current stimulation can already be observed at nanomolar concentrations, but higher concentrations of F90927 elevate intracellular Ca²⁺ concentration, causing a reduction of the myocardial compliance and an increased diastolic blood pressure. Vessels also react to F90927 and contract in its presence. Binding of F90927 with the L-type Ca²⁺ channel presumably occurs in the vicinity of the transmembrane domains III and IV of the α₁ subunit. F90927 exhibits no use dependence and interacts with Ca²⁺ channel inhibitors of all three known classes of channel modulators (dihydropyridines, phenylalkylamines, and benzothiazepines), suggesting that it is a member of a new class of Ca²⁺ channel modulators. Due to its adverse effects on blood pressure and vessel contraction, F90927 is not an ideal drug candidate. It has, however, some unique properties, which makes it a promising tool to study the function of the L-type Ca²⁺ channel.     

terbal cardiotonic pills prevent gut ischemia／reperfusion-induced hepatic microvascular dysfunction in rats fed ethanol chronically

AIM: Cardiotonic Pill (CP), an oral herbal medicine that includes Danshen (Salviae Miltiorrhizae), Panax notoginseny and Dyroblanops aromatica gaettn, has been clinically used for vascular diseases such as occlusive vasculitis, coronary diseases, atherosclerosis, and cerebral infarction. The main component, Salviae Miltiorrhizae, has been reported to prevent cerebral and intestinal reperfusion injury. However, little is known about the effect of CP on hepatic microcirculation. Thus, this study aimed to determine whether CP could affect hepatic microvascular dysfunction elicited by gut ischemia/ reperfusion (I/R) in rats fed ethanol chronically. METHODS: Male Wistar rats were pair-fed with a liquid diet containing ethanol or isocaloric control diet for 6 wk. After laparotomy, one lobe of the liver was examined through an inverted intravital microscope. The rats were exposed to 30 min of gut ischemia followed by 60 min of reperfusion. Rhodamine-6G-labeled leukocytes in the sinusoids were observed 90 min after the onset of superior mesenteric artery occlusion. Plasma tumor necrosis factor (TNF)-α and endotoxin levels were measured 1 h after the onset of reperfusion. Plasma alanine aminotransferase (ALT) activities were measured 6 h after the onset of reperfusion. In another set of experiments, CP (0.8 g/kg, intragastrically) was administered 1 and 24 h before the onset of ischemia. RESULTS: In control rats, gut I/R elicited increases in the number of stationary leukocytes, and plasma TNF-α and endotoxin levels and plasma ALT activities. These changes were mitigated by pretreatment with CP. In ethanol-fed rats, the gut I/R-induced increases in the number of stationary leukocytes, plasma endotoxin levels and ALT activities were enhanced. Pretreatment with CP attenuated the enhancement of gut I/R-induced responses by chronic ethanol consumption. CONCLUSION: These results suggest that CP prevents the gut I/R-induced hepatic microvascular dysfunction and hepatocellular injury. A reduction of inflammatory responses such as TNF-α production via reduction of blood endotoxin levels appears to be involved in the mechanisms. Chronic ethanol consumption enhances gut I/R-induced hepatic microvascular and hepatocellular injury. CP also attenuates an enhancement of gut I/R-induced responses by chronic ethanol consumption via the reduction of blood endotoxin levels.     

Reduction of myocardial cross-bridge turnover rate in presence of EMD 53998, a novel Ca2+-sensitizing agent

We have studied the effect of EMD 53998 (5-(1-(3, 4-dimethoxybenzoyl)-1,2,3,4-tetrahydrochinolin-6-yl)-6-methyl-3, 6-dihydro-2H-1,3,4-thiadiazin-2-one) on cross-bridge turnover rate at varying Ca²⁺ concentrations. Cross-bridge cycling rate was estimated both by adenosine triphosphatase measurements and determination of mechanical characteristics of constantly activated fibres, which is assumed to reflect cross-bridge kinetics. The results indicate that the turnover rate of myocardial cross-bridges was reduced in the presence of EMD 53998 at low Ca²⁺ concentrations (pCa6.25), but not at higher Ca²⁺ concentrations (pCa5.85).     

Improvement by denopamine (TA-064) of pentobarbital-induced cardiac failure in the dog heart-lung preparation

Summary The efficacy of denopamine, an orally active ₁-adrenoceptor agonist, in improving cardiac failure was assessed in dog heart-lung preparations. Cardiac functions depressed by pentobarbital (118±28 mg; mean value ± SD) such that cardiac output and maximum rate of rise of left ventricular pressure (LV dP/dt max) had been reduced by about 35% and 26% of the respective controls were improved by denopamine (10–300 µg) in a dose-dependent manner. With 100 µg denopamine, almost complete restoration of cardiac performance was attained, associated with a slight increase in heart rate. No arrhythmias were induced by these doses of denopamine. The results warrant clinical trials of denopamine in the treatment of cardiac failure.