Effects of adrenergic blockade on serum potassium changes in response to acute insulin-induced hypoglycemia in nondiabetic humans.

OBJECTIVE: To determine the possible role of adrenergic mechanisms in mediating the fall in serum potassium concentration after intravenous injection of insulin. RESEARCH DESIGN AND METHODS: Eighteen nondiabetic male volunteers, divided into three groups of six subjects, comprised the study. Hypoglycemia was induced by a bolus of short-acting insulin (0.15 U/kg body wt). Six subjects were studied in control conditions, six during alpha-adrenergic blockade with phentolamine, and six during beta-adrenergic blockade with propranolol. RESULTS: In the control group, there was an immediate fall in serum potassium from 4.0 +/- 0.1 to 3.6 +/- 0.1 mM at baseline + 15 min. After the onset of acute hypoglycemia, potassium decreased further in the control group, reaching a lowest concentration of 3.3 +/- 0.1 mM. In the propranolol group, the late decrease in potassium was inhibited, and there were no further changes in serum potassium. During alpha-blockade, there was an exaggerated fall to 2.6 +/- 0.1 mM at 30 min after the onset of hypoglycemia. CONCLUSIONS: The later fall in serum potassium, which occurs after the onset of hypoglycemia, is probably mediated by stimulation of beta-adrenoreceptors, whereas coincidental stimulation of alpha-adrenoreceptors opposes this fall in potassium and may prevent the development of severe hypokalemia in response to acute hypoglycemia.     

亚低温对急性肺损伤大鼠肺泡表面活性蛋白A含量的影响

目的 探讨亚低温对内毒素脂多糖(LPS)诱导急性肺损伤(ALI)大鼠肺泡表面活性蛋白A(SP-A)含量的影响.方法 按随机数字表法将40只雄性Wistar大鼠分组.采用气管内滴入LPS制备ALI动物模型;对照组气管内只滴人生理盐水.模型组和对照组分别于术后1 h和8 h处死8只大鼠;亚低温组于滴入LPS 1 h后将体温降低并维持在32.5～33.0℃,8 h后处死8只大鼠.各组分别于术前及术后1 h、8 h测定动脉血气,并计算氧合指数(PaO2/FiO2);采用酶联免疫吸附法检测支气管肺泡灌洗液(BALF)中SP-A含量;光镜下观察肺组织形态结构的变化.结果 气管内滴入LPS 1 h后,大鼠PaO2/FiO2均达到ALI的诊断标准.与对照1 h组比较,模型1 h组BALF中SP-A含量(μg/L)明显降低(53.27±1.95比74.81±6.55,P＜0.01);模型8 h组和亚低温8 h组SP-A含量(4.35±2.76和51.36±2.33)均较对照8 h组(70.81±5.01)明显降低,但亚低温8 h组SP-A含量较模型8 h组明显增高(均P＜0.01).光镜下观察,对照1 h和8 h组肺泡结构基本正常;模型8 h组肺组织炎症反应最重;模型1 h组和亚低温8 h组肺组织炎症反应较模型8 h组有所减轻.结论 亚低温能延缓内毒素诱导的ALI大鼠早期肺泡内SP-A含量下降的程度,在一定程度上可减轻肺损伤.

Abstract：

Objective To investigate the effect of hypothermia (HT) on the concentration of surfactant protein A (SP-A) during lipopolysaccharide (LPS) induced acute lung injury (ALI) in rats.Methods Forty male Wistar rats were randomly divided into three groups. The ALI model was reproduced by LPS intratracheal instillation; only saline was instilled intratracheally for control group. Rats in both model group and control group were sacrificed respectively at 1 hour and 8 hours (each n= 8). In HT group the body temperature was lowered to 32. 5 - 33.0 ℃ 1 hour after LPS instillation, and 8 rats were sacrificed st 8 hours. The arterial blood gas was determined in all the groups before and 1 hour and 8 hours after instillation of saline or LPS, and the oxygenation index (PaO2/FiO2) was calculated. The concentration of SP-A in bronchoalveolar lavage fluid (BALF) was determined by enzyme linked immunosorbent assay. The morphological changes in lung tissue of rats were observed under light microscope. Results At 1 hour after intratracheal instillation of LPS, the PaO2/FiO2 of each group reached the diagnostic criterion of ALI.Compared with control 1-hour group, the SP-A (μg/L) in BALF of model 1-hour group was decreased (53. 27±1.95 vs. 74. 81±6. 55, P＜0. 01); the SP-A in model 8-hour group and HT 8-hour group (4.35±2. 76 and 51.36±2. 33) was both obviously decreased compared with control 8-hour group (70. 81±-5. 01,both P＜0. 01). Compared with model 8-hour group, the SP-A of HT 8-hour group was obviously increased (P＜0. 01). Results of light microscopic examination, it was revealed that the alveolar structure of control 1-hour group and control 8-hour group was almost normal. Inflammatory response in lung tissues in model 8-hour group was found to be most serious; compared with model 8-hour group, inflammatory response in lung tissues in model 1-hour group and HT 8-hour group was reduced in certain degree. Conclusion A certain extent of HT may reduce lung injury of early endotoxin-induced ALI rats by delaying lowering of alveolar SP-A levels.     

不同透析液钾离子浓度对透析前血钾及透析中心律失常的影响

目的 探讨2种透析液钾离子浓度（dialysate potassium,KD）对透析前血钾、高钾血症和透析中严重心律失常事件发生率的影响.方法 1个单中心、开放、自身对照试验,以一定标准纳入患者.于2010年5月某周在用KD=2.0mmol/L（简称KD2.0,以下类同）时为所有入组患者查透析前血钾（此时间点定义为0点）,之后调整至KD 2.5,分别于2周、4周、8周和12周查透析前血钾.收集0点前后12周内透析中严重心律失常事件.对比调整KD前后的血钾水平、高钾血症和严重心律失常事件发生率.结果 入组158例患者,2例退出,156例纳入分析.对比KD2.0,使用KD2.5虽然使透析中严重心律失常发生率有所下降,但差异无统计学意义（0.78％比0.47％,P=0.054）.在上调KD 2周后,患者透析前平均血钾、高钾血症及严重高钾血症发生率均显著高于0点,分别为4.78±0.80比4.51±0.79 mmol/L、26.9％比15.4％、9.6％比3.2％,P均＜0.05.加予临床干预10周后,透析前平均血钾仍高于0点,但高钾血症发生率可下降至0点水平.结论 使用KD2.5比KD2.0可使透析中严重心律失常发生率有下降趋势,但可导致透析前高钾血症增多,后者可通过临床干预予以控制.     

Effects of beta-adrenergic receptor blockade on metabolic rate and mixed venous blood temperature during dynamic exercise

Mixed venous blood temperature and energy exchange were measured in sixteen healthy male volunteers at rest and during bicycle exercise of 12 min duration performed before and after intravenous administration of propranolol. The rise in blood temperature induced by exercise was about 30% greater following propranolol. This effect was probably due to a reduction of skin blood flow, which impaired the conditions for heat loss from the blood. The exercise induced rise in total energy exchange was reduced after propranolol by around 20 W. In consequence, the calculated mechanical efficiency increased significantly. Since the respiratory quotient showed no increase but rather the reverse, the observed effect could not be attributed to any transient changes in body oxygen stores. The results thus indicate that propranolol caused a true deceleration of the metabolic rate. This effect might be secondary to inhibition of catecholamine-dependent oxygen consuming metabolic processes in peripheral organs. A possible hypothalamic mechanism, triggered by the blood temperature level, is also discussed.     

运动对糖尿病大鼠血清瘦素水平的影响

目的：探讨运动与血清瘦素水平的关系,观察不同运动量对糖尿病大鼠体质量、血糖、血清胰岛素和血清瘦素的影响。方法：将动物分成6组,分别为正常对照组、正常运动组、糖尿病组、糖尿病小运动量组、糖尿病中运动量组和糖尿病大运动量组。运动组按Ploug方法进行游泳训练。结果：正常运动组大鼠游泳8周后的血清瘦素浓度较运动前显著降低。运动前4个组的糖尿病组大鼠与正常对照组相比,体质量、血清胰岛素和血清瘦素水平显著降低,血糖浓度显著升高。游泳8周后只有糖尿病中运动量组大鼠的每周体质量增加数明显回升,血糖浓度较运动前降低35％,血清胰岛素浓度较运动前升高38％,血清瘦素浓度较运动前升高40％。而糖尿病小运动量组和糖尿病大运动量组大鼠运动8周后的上述指标与运动前相比无显著变化。多元相关回归分析,仅提示糖尿病大鼠血清胰岛素是血清瘦素有意义的影响因素。结论：正常生理状态下运动降低血清瘦素水平是机体为维持自身体质量稳定和能量平衡的一种适应性反应：而在链脲佐菌素（streptozotocin,STZ)糖尿病状态下,瘦素似乎与胰岛素关系更密切,中等强度运动在降低血糖,改善机体对胰岛素敏感性的同时,似乎也改善了对瘦素的敏感性;运动量不足或运动量过大对糖尿病均无明显治疗效果。     

Effects of mild hypothermia on survival and serum cytokines in uncontrolled hemorrhagic shock in rats

Previous studies have suggested benefit of mild hypothermia during hemorrhagic shock (HS). This finding needs additional confirmation and investigation into possible mechanisms. Proinflammatory cytokines are mediators of multiple organ failure following traumatic hemorrhagic shock and resuscitation. We hypothesized that mild hypothermia would improve survival from HS and may affect the pro- and anti-inflammatory cytokine response in a rat model of uncontrolled HS. Under light halothane anesthesia, uncontrolled HS was induced by blood withdrawal of 3 mL/100 g over 15 min followed by tail amputation. Hypotensive (limited) fluid resuscitation (to prevent mean arterial pressure [MAP] from decreasing below 40 mmHg) with blood was started at 30 min and continued to 90 min. After hemostasis and resuscitation with initially shed blood and Ringer's solution, the rats were observed for 72 h. The animals were randomized into two HS groups (n = 10 each): normothermia (38 degrees C +/- 0.5 degrees C) and mild hypothermia (34 degrees C +/- 0.5 degrees C) from HS 30 min until resuscitation time (RT) 60 min; and a sham group (n = 3). Venous blood samples were taken at baseline, RT 60 min, and days 1, 2, and 3. Serum interleukin (IL)-1beta, IL-6, IL-10, and tumor necrosis factor (TNF)-alpha concentrations were quantified by ELISA. Values are expressed as median and interquartile range. Survival time by life table analysis was greater in the hypothermia group (P = 0.04). Survival rates to 72 h were 1 of 10 vs. 6 of 10 in the normothermia vs. hypothermia groups, respectively (P = 0.057). All cytokine concentrations were significantly increased from baseline at RT 60 min in both HS groups, but not in the shams. At RT 60 min, in the normothermia vs. hypothermia groups, respectively, IL-1beta levels were 185 (119-252) vs. 96 (57-135) pg/mL (P = 0.15); IL-6 levels were 2242 (1903-3777) vs. 1746 (585-2480) pg/mL (P = 0.20); TNF-alpha levels were 97 (81-156) vs. 394 (280-406) pg/mL (P= 0.02); and IL-10 levels were 1.7 (0-13.3) vs. 15.8 (1.9-23.0) pg/mL (P = 0.09). IL-10 remained increased until day 3 in the hypothermia group. High IL-1beta levels (>100 pg/mL) at RT 60 min were associated with death before 72 h (odds ratio 66, C.I. 3.5-1255). We conclude that mild hypothermia improves survival time after uncontrolled HS. Uncontrolled HS induces a robust proinflammatory cytokine response. The unexpected increase in TNF-alpha with hypothermia deserves further investigation.     

Effects of beta-adrenergic blockade on verapamil-responsive and verapamil-irresponsive sustained ventricular tachycardias.

To assess effects of beta-adrenergic blockade on ventricular tachycardia (VT) of various mechanisms, electrophysiology studies were performed before and after intravenous infusion of propranolol (0.2 mg/kg) in 33 patients with chronic recurrent VT, who had previously been tested with intravenous verapamil (0.15 mg/kg followed by 0.005 mg/kg/min infusion). In the verapamil-irresponsive group, 10 patients (group IA) had VT that could be initiated by programmed ventricular extrastimulation and terminated by overdrive ventricular pacing, and 11 patients (group IB) had VT that could be provoked by isoproterenol infusion (3-8 micrograms/min) but not by programmed electrical stimulation, and that could not be converted to a sustained sinus rhythm by overdrive ventricular pacing. Notably, in the group IA patients, all 10 patients had structural heart disease (coronary arteriosclerosis or idiopathic cardiomyopathy); beta-adrenergic blockade accelerated the VT rate in one patient but exerted no effects on the VT rate in the remaining 9 patients, and VT remained inducible in all 10 patients. By contrast, in the group IB patients, 7 of the 11 patients had no apparent structural heart disease; beta-adrenergic blockade completely suppressed the VT inducibility during isoproterenol infusion in all 11 patients. There were 12 patients with verapamil-responsive VT (group II). 11 of the 12 patients had no apparent structural heart disease. In these patients, the initiation of VT was related to attaining a critical range of cycle lengths during sinus, atrial-paced or ventricular-paced rhythm; beta-adrenergic blockade could only slow the VT rate without suppressing its inducibility. Of note, 14 of the total 33 patients had exercise provocable VT: two in group IA, five in group IB, and seven in group II. Thus, mechanisms of VT vary among patients, and so do their pharmacologic responses. Although reentry, catecholamine-sensitive automaticity, and triggered activity related to delayed afterdepolarizations are merely speculative, results of this study indicate that beta-adrenergic blockade is only specifically effective in a subset group (group IB) of patients with VT suggestive of catecholamine-sensitive automaticity.     

Antiarrhythmic efficacy of combined I(Ks) and beta-adrenergic receptor blockade

Suppression of malignant ventricular arrhythmias by selective blockade of the cardiac slowly activating delayed rectifier current (I(Ks)) has been demonstrated with the benzodiazepine L-768673 [(R)-2-(2,4-trifluoromethyl-phenyl)-N-[2-oxo-5-phenyl-1-(2,2,2-trifluoro-ethyl)-2,3-dihydro-1H-benzo[e][1,4]diazepin-3-yl]acetamide] in canine models of recent and healed myocardial infarction. The present study extends the initial antiarrhythmic assessment of I(Ks) blockade by demonstrating prevention of ischemic malignant arrhythmias in dogs with recent (8.0 +/- 0.4 days) anterior myocardial infarction with the coadministration of a subeffective dose of L-768673 and a subeffective, minimally beta-adrenergic blocking dose of timolol. Administered individually, neither 0.3 microg/kg i.v. L-768673 nor 1.0 microg/kg i.v. timolol prevented the induction of ventricular tachyarrhythmia (VT) by programmed ventricular stimulation (PVS) or the development of malignant ventricular arrhythmia in response to acute coronary artery thrombosis. In contrast, coadministration of 0.3 microg/kg i.v. L-768673 + 1.0 microg/kg i.v. timolol suppressed the induction of VT by PVS (8/10, 80% rendered noninducible versus 1/10, 10% noninducible in vehicle group; p < 0.01) and prevented the development of acute ischemic lethal arrhythmias (3/10, 30% incidence versus 8/10, 80% incidence in vehicle group; p < 0.05). Concomitant administration of low-dose L-768673 + timolol produced modest increases in QTc and paced QT intervals (4.5 +/- 1.2 and 5.5 +/- 1.4%; both p < 0.01), increases in noninfarct zone relative and effective refractory periods (7.0 +/- 1.7 and 12.3 +/- 3.0%; both p < 0.01), and lesser increases in infarct zone relative and effective refractory periods (5.3 +/- 1.6 and 5.8 +/- 1.4%; both p < 0.01). These findings suggest that concomitant low-dose I(Ks) and beta-adrenergic blockade may constitute a potential pharmacologic strategy for prevention of malignant ischemic ventricular arrhythmias.     

Effects of acute cardioselective and non-selective beta-adrenergic blockade on left-ventricular volumes and vascular resistance at rest and during exercise.

The effects of intravenous metoprolol and propranolol on left-ventricular performance were studied by radionuclide cardiography in eight healthy young men at rest and during exercise. At rest, a fall of 7 to 10 mmHg was recorded in systolic blood pressure after both drugs (p less than 0.05). The decrease in cardiac output entirely ascribed to relative bradycardia was 18% after propranolol (p less than 0.01) compared with 6% after metoprolol (p less than 0.05). Left-ventricular volumes did not change at rest. Systemic vascular resistance increased by 14% after metoprolol and by 28% after propranolol (both p less than 0.05). During submaximal bicycle exercise the systolic blood pressure fell by 15 mmHg after both drugs (p less than 0.05). The reduction in exercise heart rate was 17 beats min-1 and 18 beats min-1 (both p less than 0.01), but propranolol reduced cardiac output by 18% (p less than 0.01) compared with 5% (p less than 0.05) after metoprolol, reflecting a reduction in stroke volume induced only by non-selective blockade. A more pronounced left-ventricular end-diastolic dilatation during exercise was allowed by metoprolol and the fall in the exercise ejection fraction was, therefore, smaller after this drug. Concomitantly, the calculated systemic vascular resistance was increased only 6% by metoprolol (p less than 0.05) compared with a 29% increase by propranolol (p less than 0.01). These findings suggest that, at least in healthy subjects, metoprolol is superior to propranolol in the ability to limit adverse cardiovascular changes.     

降低透析液钾离子浓度对血清钾离子清除及透析效率的影响

目的评估不同钾浓度透析液透析过程中血清钾离子清除程度和对尿素氮清除的影响。方法前瞻性、随机对照分析,32例稳定的维持性血液透析患者参与试验,在5周稳定的血液透析间期(使用1.5m2三醋酸纤维膜透析器,透析时间240min,血流量250ml/min,透析液流量500ml/min,无糖透析液,碳酸氢钠浓度为35mmol/L),使用透析液包括0(0K),1(1mmol/LK),和2(2mmol/LK),在每周中间1次透析治疗后收集部分透析液并计算钾离子的清除量MK和尿素氮的清除量MU,计算尿素氮降解率URR和尿素氮清除指数Kt/V。结果 3组患者在透析过程中,血清钾离子浓度持续稳定下降,在180min左右达到一稳定的浓度。0K、1K和2K透析液组分别达到108.5mmol,84.5mmol和60.3mmol(P<0.05),尿素氮的清除量MU不受钾离子的清除量MK的影响(r=0.49),3组患者尿素氮的清除、尿素氮降解率URR和尿素氮清除指数Kt/V均无明显的变化。结论低钾透析液能显著性增加钾离子的清除量,透析钾离子的清除量并不影响尿素氮的清除水平及透析效率。     

中度低温对急性出血坏死性胰腺炎大鼠胰腺损伤的保护作用

目的 观察中度低温对急性出血坏死性胰腺炎(AHNP)大鼠胰腺损伤和死亡率的影响。方法将112只大鼠随机分为假手术组(n=24)、AHNP常温组(n=44)和AHNP低温组(n=44)。以牛磺胆酸钠逆行注射制备大鼠AHNP模型,低温组诱导AHNP后通过体表降温将体温控制在32.0-33.0℃。各组中24只大鼠分别在AHNP诱导后第2和5 h取标本,观察血清淀粉酶、脂肪酶以及胰腺血管通透性变化、病理形态学改变和胰腺组织湿重／干重比值。AHNP常温组和低温组中余20只大鼠将体温控制在预定范围12 h,观察大鼠72 h的生存率。结果 与AHNP常温组比较,低温组AHNP后2、5 h血清淀粉酶和脂肪酶水平、血管渗透指数及AHNP后5 h胰腺组织水肿程度均明显降低(P均<0.05)。AHNP常温组平均生存时间是7.5 h(3.0-18.0 h),而低温组则延长至25.5 h(13.0-72.0 h)。低温组大鼠生存率显著高于常温组(P=0.000 1)。结论 急性胰腺炎应用中度低温可减轻胰腺损伤,延长大鼠生存时间,提示低温有可能作为一项有益的辅助措施用于急性胰腺炎的治疗中。     

中度低温对急性胰腺炎大鼠核转录因子-κB表达的影响

目的观察急性出血坏死性胰腺炎（AHNP）后不同时间点胰腺和肺组织中核转录因子-κB（NF-κB）的DNA结合活性动态变化，以及胰腺炎后应用中度低温对NF-κB活性的影响。方法第一部分实验采用牛磺胆酸钠逆行注射造成大鼠AHNP模型。大鼠随机分为正常对照组以及AHNP常温2、5和12h组，用电泳迁移率改变法（EMSA）测定各组大鼠胰腺和肺组织中NF-κB的活性。第二部分实验将大鼠随机分为假手术组、AHNP常温组和低温组，诱导AHNP后2h和5h测定各组胰腺和肺组织中NF-κB的活性。结果急性胰腺炎后大鼠胰腺和肺组织NF-κB活性均持续增强，且各时间点胰腺组织NF-κB活性显著强于肺组织（P均〈0．01）。与AHNP常温组相比，低温组AHNP后2h和5h肺组织NF-κB活性均显著降低（P均〈0．01），而胰腺组织NF-κB活性与常温组差异不明显。结论急性胰腺炎伴有胰腺和肺组织NF-κB活性的显著增强。中度低温对急性胰腺炎后肺组织NF-κB的激活有抑制作用。     

Suppression of ventricular arrhythmias in man by d-propranolol independent of beta-adrenergic receptor blockade.

To investigate the mechanisms of ventricular arrhythmia suppression by propranolol, we determined the antiarrhythmic efficacy of d-propranolol in 10 patients with frequent ventricular ectopic depolarizations (VEDs) and nonsustained ventricular tachycardia. After an initial placebo phase, 40 mg d-propranolol was administered orally every 6 h with dosage increased every 2 d until arrhythmia suppression (greater than or equal to 80% VED reduction), intolerable side effects, or a maximal dosage (1,280 mg/d) was reached. Response was verified by documenting return of arrhythmia during a final placebo phase. Arrhythmia suppression occurred in six patients while two more had partial responses. Effective dosages were 320-1,280 mg/d (mean 920 +/- 360, SD) of d-propranolol with corresponding plasma concentrations of 60-2,280 ng/ml (mean 858 +/- 681). For the entire group, the QTc interval shortened by 4 +/- 4% (P = 0.03). Arrhythmia suppression was accompanied by a reduction in peak heart rate during exercise of 0-29%. To determine whether arrhythmia suppression could be attributed to beta-blockade, racemic propranolol was then administered in dosages producing the same or greater depression of exercise heart rate. In 3/8 patients, arrhythmias were not suppressed by racemic propranolol indicating that d-propranolol was effective via a non-beta-mediated action. By contrast, in 5/8 patients racemic propranolol also suppressed VEDs. We conclude that propranolol suppresses ventricular arrhythmias by both beta- and non-beta-adrenergic receptor-mediated effects.     

饮食干预对老年低钾血症患者血钾浓度的影响

目的探讨饮食干预对老年低钾血症患者血钾浓度的影响。方法采用前瞻性随机对照研究,将40例住院治疗的老年低钾血症患者随机均分为2组,即饮食干预观察组和对照组。对照组行常规治疗和护理,观察组在此基础上加以系统化的饮食干预。采用血生化分析仪检测患者人院当日、入院后第4天、1周、2周的血清钾浓度,采用SPSS13．0统计软件比较组间差异。结果观察组与对照组平均血钾浓度在人院当日及第4天差异无统计学意义,在第1周及第2周观察组高于对照组（P〈0．05）。结论系统化的饮食干预有助于老年低钾血症患者血清钾浓度的恢复。