Concomitant food intake can increase the bioavailability of propranolol by transient inhibition of its presystemic primary conjugation

The influence of concomitant food intake on the bioavailability and presystemic primary conjugation of propranolol (80 mg) was studied in 11 healthy women. Food increased the maximum serum concentration and serum AUC of propranolol (P less than 0.05) and reduced those of conjugated propranolol (P less than 0.05). The mean AUC ratio of conjugated/unchanged propranolol was 13:1 in the fasting state but only about 6:1 in the nonfasting state (P less than 0.001). The time to maximum serum concentration and the t1/2 were not affected by food. There was no influence of food on any kinetic parameter of propranolol or conjugated propranolol when a slow-release formulation was used. We conclude that concomitant food intake can evoke a short-lasting, delivery rate-dependent inhibition of the presystemic primary conjugation of propranolol. This is one, but not the sole, mechanism by which food can enhance propranolol bioavailability.     

体位和压力改变对肝性脑病患者保留灌肠时间的影响

目的探讨体位和压力改变对肝性脑病患者保留灌肠时间的影响.方法对120 例肝性脑病前驱期患者分别采取不同体位和压力进行白醋和中药保留灌肠.结果中药灌肠保留时间明显长于白醋灌肠保留时间;左侧卧位灌肠保留时间明显长于右侧卧位灌肠保留时间;低压力灌肠保留时间明显长于高压力灌肠保留时间.结论中药灌肠采取低压力左侧卧位保留时间最佳.     

造影剂量和注射流率对肝脏CT灌注成像影响的实验研究

目的探讨用斜率法进行肝脏CT灌注成像时造影剂量和注射流率对灌注参数的影响。方法分别用0．5、1ml／kg体重的造影剂量和3、5、7、9ml／s的注射流率对6只犬进行肝脏灌注成像，计算肝动脉灌注量(HAP)、门脉灌注量(PVP)和肝动脉灌注指数(HPI)。结果造影剂量为0．5ml／kg体重时，3ml／s流率与其他流率测得的HAP和PVP有显著性差异(P＜0．05)，HPI随着流率的增加而略有下降；造影剂量为1ml／kg体重时，各种流率下的HAP和HPI均无显著性差异(P＞0．05)，PVP先升高后降低。结论用斜率法进行肝脏灌注成像时，造影剂量和注射流率对灌注参数有所影响。     

Influence of posture on the Valsalva manoeuvre

The objective of the present study was to evaluate the influence of posture on the responses of blood pressure (BP) and heart rate (HR) to the Valsalva manoeuvre (VM). Neurohumoral activation, as well as changes in intravascular and intracardiac volumes and pressures, are well known effects of orthostatic stress. These changes are likely to have significant effects on cardiovascular reflexes, such as the response to the VM. However, the influence of posture on the VM has not been intensively evaluated, except for a few studies involving small sex- and age-selected case series. We therefore investigated the effects of posture on the VM in a larger non-selected group of healthy control subjects. In 19 healthy volunteers (ten female/nine male; age range 20-72 years, mean age 43 years), two reproducible VMs (40 mmHg; 15 s) were performed after 10 min of supine rest, 10 min of sitting and 10 min of standing. HR and BP were monitored continuously. End-diastolic volume, total peripheral resistance and cardiac output were calculated at baseline for each position. We found that assuming an upright position resulted in increases in total peripheral resistance and HR, accompanied by decreases in end-diastolic volume and cardiac output. The fall in BP during early phase II and the BP overshoot during phase IV were clearly more pronounced with increasing orthostatic stress, whereas the rise in BP during late phase II remained unchanged; pulse pressure was more compressed during phase II, but higher during phase IV. The Valsalva ratio was not significantly affected, but baroreflex gain (calculated from early phase II) was significantly decreased in the upright position. While a reduced late phase II was observed on one occasion in each of the lying and sitting positions, three abnormal responses were observed during standing. We conclude that posture has a significant influence on BP responses to the VM, probably resulting from changes in the intrathoracic blood volume. Standing results in a lower rate of 'flat-top' responses, but also seems to reduce the specificity of this test. Sympathetic activation in the upright position seems to blunt baroreflexes, leading to similar HR responses in spite of larger changes in BP.     

足部姿态变化对静态姿势稳定控制的即刻作用

背景:既往研究表明异常足部的姿态影响人体姿势控制能力,而足部姿态中立化可改善人体姿势控制能力,但机制不明。目的:观察足部姿态中立化后即刻对健康成人静态站立姿势控制能力的影响。方法:健康成人受试者30名,应用足部姿态指数评价足部姿态。测量小腿后足角评价受试者应用非特制足部矫形垫对其足部姿态的中立化的效果。非特质足部矫形垫采用VAS YLI-HowardDananberTM保健系列足部矫形垫。同时评测受试者改变足部姿态前后静态单腿站立姿势控制能力。静态单腿站立姿势控制能力应用电脑平衡仪(ACTIVE BALANCER EAB-100)测试。结果与结论:应用非特制足垫后,足部姿态较前更趋中立化,差异有显著性意义。但单腿站立姿势控制能力没有显著变化。说明应用非特制足部矫形垫后可使轻度旋前的足部姿态中立化,但没有对姿势控制能力产生即刻影响。虽然足部姿态中立化对静态姿势控制具有远期效果,但其机制不单纯为改善足部力线结构,需要进一步的研究。     

Effect of posture on intracranial pressure and cerebral perfusion pressure in patients with fulminant hepatic and renal failure after acetaminophen self-poisoning

We measured the effect of posture on intracranial pressure (ICP) and cerebral perfusion pressure (CPP) in eight patients admitted with grade 4 hepatic coma due to fulminant hepatic failure complicated by renal failure. Upward head elevation greater than 20 degrees did not consistently reduce ICP; instead, ICP increased in three patients who later died of cerebral edema. CPP was reduced significantly by elevation greater than 20 degrees, falling to less than 50 mm Hg in those patients who subsequently died of cerebral edema. Our study does not support the current practice of nursing patients with hepatic coma, who are at risk of dying from cerebral edema, in head-upright postures greater than 20 degrees.     

Effects of venous pressure and posture on skin capillary perfusion.

BACKGROUND: Various vasoconstriction mechanisms after a change in posture are involved in controlling skin blood flow and capillary transmural pressure to maintain adequate transcapillary exchange. The role of venous orthostatic pressure in the regulation of capillary nutritive perfusion, however, is less clear. DESIGN: We investigated capillary perfusion in 30 healthy subjects using intravital capillary microscopy of the big toenail-fold. Measurements were made in the supine and the sitting positions before and after incremental elevation of venous resistance, and thus the pre- to post-capillary pressure difference, by inflating a cuff around the ankle. RESULTS: On dependency, median capillary density rose (P < 0.0001), whereas red blood cell perfusion decreased (P < 0.0001). Cuff inflation of 30-60 mmHg in the supine position induced similar phenomena. Repeatedly, the same capillaries were found to be recruited after an increase in transmural pressure. CONCLUSIONS: We conclude that post-capillary pressure appears to be an important factor in the regulation of capillary perfusion, because an increase in venous resistance mimics the effects of dependency. The findings in this study support the theory of 'minimum perfusion pressure' for each capillary to be perfused with erythrocytes.     

术后体位改良对改善甲状腺手术体位综合征的影响

目的探讨术后不同体位对甲状腺术后头痛、恶心、呕吐的影响。方法119例甲状腺术后患者按顺序分为对照组62例和观察组57例,对照组术后取去枕平卧位,观察组术后取低枕卧位,比较两组术后头痛、恶心、呕吐的发生率。结果观察组头痛、恶心、呕吐的发生率显著低于对照组（P〈0．5;P〈0．5;P〈0．01）。结论术后体位改良能减少甲状腺手术体位综合征的发生。     

肝硬化门脉高压患者门-腔分流状态对肝脏血流灌注的影响

目的应用肝脏CT血流灌注扫描和多层螺旋CT门静脉造影技术(CTPV),评价肝硬化患者门-腔静脉之间侧支循环的形成情况对肝脏血流灌注的影响。方法对我院101例肝硬化合并门静脉高压患者作CT血流灌注扫描和多层螺旋CT门静脉造影。计算肝血流灌注参数,分析不同类型门-腔静脉侧支循环类型的肝脏血流灌注血流参数改变。结果门静脉-上腔静脉分流组,肝血流量(HBF):(115.2±30.8)ml·100ml-1·min-1;肝动脉血流量(HAF):(29.8±21.1)ml·100ml-1·min-1;肝动脉指数(HPI):0.248±0.142;门静脉血流量(PVF):(85.3±23.6)ml·100ml-1·min-1。脾/胃-肾静脉分流组,HBF:(124.6±36.1)ml·100ml-1·min-1;HAF:46.6/29.1ml·100ml-1·min-1;HPI:0.365±0.175;PVF:(77.9±27.2)ml·100ml-1·min-1。门-腔静脉分流术后组,HBF:(101.9±36.5)ml·100ml-1·min-1;HAF:(46.0±21.4)ml·100ml-1·min-1;HPI:0.449±0.183;PVF:(55.8±22.5)ml·100ml-1·min-1。组间差异具有统计学意义,P<0.05。结论肝功能分级和分流方式两个变量对肝血流灌注有独立影响作用。     

Interaction between oral hydralazine and propranolol. II. Assessment of altered splanchnic blood flow as the determinant of altered presystemic extraction

Coadministration of p.o. hydralazine and d-propranolol or dl-propranolol in six conscious dogs caused a significant increase in peak plasma concentration and area under the p.o. plasma concentration-time curve of propranolol (P less than .01, P less than .01, peak plasma concentration; P less than .01 and P less than .05, area under the plasma concentration-time curve; d-propranolol and dl-propranolol, respectively). Coadministration of p.o. hydralazine with p.o. dl-propranolol resulted in a small trend toward an increase in systemic clearance of i.v. dl-[3H]propranolol; however, this did not reach statistical significance (P less than .2, P less than .1, d-propranolol and dl-propranolol, respectively). When a mixture of d-propranolol and 14C-labeled dl-propranolol was administered into the jejunum of seven anesthetised dogs, the absorption into portal vein of the 14C-labeled dl-propranolol paralleled closely that of d-propranolol both in terms of time to peak and absorption as measured by a percentage of total area under the plasma concentration-time curve at an arbitrary time (10 min) postdose. Assessment of hepatic extraction (E) showed similar close parallels (d-propranolol, E = 0.85 +/- 0.02; dl-[14C]propranolol, E = 0.86 +/- 0.03: mean +/- S.E.M., n = 5, P less than .70). Hepatic extraction of propranolol and blood flow in mesenteric artery and hepatic artery were measured in 23 anesthetised dogs given a constant infusion of d-propranolol into portal vein (11 micrograms/kg/min), made up to 6 control and 17 hydralazine-treated dogs.(ABSTRACT TRUNCATED AT 250 WORDS)     

A positive inotropic effect of propranolol on the canine myocardium: a presynaptic effect.

Administration of propranolol directly into the anterior descending branch of the left coronary artery (LAD) resulted in a localized increase in myocardial contractile force in the area of the left ventricle perfused by the LAD. The onset of the positive inotropic response occurred within 30 seconds after drug administration with a duration of action of approximately 8 minutes and was associated with a significant increase in the coronary sinus/arterial ratio of norepinephrine. Contractile force in an area of the left ventricle perfused by the circumflex artery decreased concomitantly with the characteristic negative chronotropic action of propranolol. Pretreatment with reserpine abolished the positive inotropic effect of propranolol while ganglionic blockade with hexamethonium failed to alter the character of the response. Imipramine pretreatment not only blocked the positive inotropic effect of propranolol but resulted in an exaggerated negative inotropic effect in both areas of the left ventricle along with a significant fall in systemic arterial blood pressure. The data demonstrate that propranolol can evoke the release of norepinephrine from cardiac adrenergic nerve endings and raise the possibility that propranolol may be taken up by the amine uptake system.     

Influence of debrisoquin phenotype on the inducibility of propranolol metabolism

The effects of rifampin (600 mg) once daily for 22 days on the total and fractional metabolic clearances of propranolol were determined in a group of six genetically extensive (EM) and six poor metabolizers (PM) of debrisoquin. The impaired ability of PMs to metabolize propranolol to the ring-oxidized metabolite 4-hydroxypropranolol was confirmed. The total oral clearance of propranolol increased about fourfold in both phenotypes from 219.2 +/- 52.8 to 976.7 L/hr in the EMs and from 75.0 +/- 12.6 to 289.8 +/- 78.2 L/hr in the PMs. The extent of induction of glucuronidation was similar in the two groups. 4-Hydroxylation was induced in both phenotypes but the increase was fifteenfold greater in EMs than in PMs. This would imply that the cytochrome P-450 determined by the debrisoquin allele or some coinherited 4-hydroxylase(s) was induced to a greater extent in EMs than PMs.     

活跃期体位干预对分娩的影响

目的 探讨在产程活跃期对胎头浮动初产妇实施体位干预,提出恰当的处理方法,以取得良好的分娩结局.方法 选择2007年12月-2008年6月住院经阴道分娩的初产妇200例,随机分为观察组和对照组各100例,观察组在待产过程中采用体位干预,对照组取平卧位或侧卧位直至宫口开全,不予体位指导.分析比较2组产后出血、分娩结局、羊水及新生儿Apgar评分情况.结果 观察组的第一、第二产程时间、顺产率及剖宫产率、产后出血、新生儿窒息率等结果均显著优于对照组,而2组新生儿体质量及阴道助产率比较无显著差异.结论 产程活跃期胎头浮动孕妇实施体位干预,可加速胎先露下降,缩短产程,促进自然分娩,降低剖宫产率,减少母儿并发症,从而改善分娩结局.     

The effect of propranolol on catecholamine clearance

Normal subjects given propranolol increased their plasma t1/2 for infused isoproterenol from 2.68 to 6.25 minutes. Propranolol increased plasma norepinephrine (NE) levels only slightly. Propranolol increased the t1/2 of isoproterenol but not that of NE in men with autonomic nervous system degeneration. This suggests that propranolol acts on nonneuronal uptake-2 processes, rather than on uptake-1 mechanisms. alpha-Blockers slow uptake-1 and beta-blockers slow uptake-2 processes. When 27 subjects exercised, those who attained the highest plasma levels of the alpha- and beta-receptor agonist NE also had the briefest apparent t1/2 for NE. Adrenergic receptor blocking drugs slow catecholamine clearance. NE may stimulate its own clearance.