Cardiac metabolism: A technical spectrum of modalities including positron emission tomography,single-photon emission computed tomography,and magnetic resonance spectroscopy

Noninvasive techniques for the assessment of cardiac metabolism are important for the detection of potentially salvageable tissue in jeopardized areas of the myocardium. The correct identification of hibernating and stunned myocardium in patients with severely depressed cardiac function can have vital therapeutic consequences for the patient. Changes in myocardial fatty acid and glucose metabolism during acute and prolonged ischemia can be traced by positron-emitting or gamma-emitting radiopharmaceuticals. Alternatively,³¹P-labeled magnetic resonance spectroscopy can be used for the assessment of high-energy phosphate metabolism. It is not yet clear which modality will emerge as the most useful in the clinical setting. Positron emission tomography (PET) that uses combinations of flow tracers and metabolic tracers offers unique opportunities for quantification and high-resolution static and rapid dynamic studies. Currently, assessment of glucose metabolism with¹⁸F-fluorodeoxyglucose is regarded as the gold standard for myocardial viability and prediction of improvement of impaired contractile function after revascularization. However, preserved oxidative metabolism may be required for potential functional improvement, and therefore assessment of residual oxidative metabolism by¹¹C-labeled acetate PET may prove to be more accurate than¹⁸F-fluorodeoxyglucose PET, which reflects both anaerobic and oxidative metabolism. Moreover, because fatty acids are metabolized only aerobically, they are excellent candidates for the clinical assessment of myocardial viability and prediction of functional improvement after revascularization. Especially derivatives of fatty acids that are not metabolized but accumulate in the myocyte are attractive for myocardial imaging. Examples are¹²³I-beta-methyl-p-iodophenyl pentadecanoic acid and 15-(o-¹²³I-phenyl)-pentadecanoic acid. These tracers can be detected by planar scintigraphy and single-photon emission computed tomography, which are more economical and widely available than PET. In addition, 511 keV collimators have been developed recently, making the detection of positron emitters by planar scintigraphy and single-photon emission computed tomography feasible. The experience with³¹P-labeled magnetic resonance spectroscopy in humans is still limited. With current magnetic resonance spectroscopic techniques, insufficient spatial resolution is achieved for clinical purposes, but the possibility of serial measurements to monitor rapid changes of phosphate-containing molecules in time makes magnetic resonance spectroscopy very valuable for the research of myocardial metabolism.     

Thoracic epidural analgesia in aortocoronary bypass surgery II: effects on the endocrine metabolic response

Thoracic epidural analgesia (TEA) may offer haemodynamic benefits for patients with coronary heart disease going through major surgery. This may – in part – be secondary to an effect on the endocrine and metabolic response to surgery. We therefore investigated the effect of TEA on the endocrine metabolic response to aortocoronary bypass surgery (ACBS).
Thirty male patients (age < 65 years, ejection fraction > 0.5) were randomized into 3 groups; the HF group receiving a high dose fentanyl (55 μg–kg^-1) anaesthesia, the HF + TEA group with the same fentanyl dose + TEA with 10 ml bupivacain 5 mg ml^-1, followed by 4 ml every hour, and the LF + TEA group receiving fentanyl 15 μg kg^-1 + TEA. Adrenalin, noradrenalin, systemic vascular resistance (SVR), glucose, Cortisol, lactate and free fatty acids were followed during the operation and for 20 h postoperatively.
A significant increase in adrenalin, noradrenalin and SVR was found in the HF group whereas this increase was blocked in both epidural groups. An increase in glucose and Cortisol was noticed in all groups, but the increase was delayed in the epidural groups.
Our results suggest that a more effective blockade of the stress response during ACBS is obtained when TEA is added to general anaesthesia than with high dose fentanyl anaesthesia alone.     

Acute toxicity of two pyrethroids,permethrin, and cypermethrin in neonatal and adult rats

The present study aims specifically at obtaining a comparison of the acute toxicity of cypermethrin (CY), a type I pyrethroid, and permethrin (PERM), a type II pyrethroid, administered orally as a single dose to neonatal and adult rats, and at assessing the importance of pyrethroid biotransformation in CY and PERM toxicity through use of drug metabolism inhibitors. Our experiments show that CY is more toxic than PERM to adult and neonatal rats. The sensitivity of neonatal rats both to CY and to PERM toxicity is higher, the younger the animals. CY is much more toxic than PERM in the neonatal rat, compared with the adult. In rats aged 8, 16, and 21 days, pretreatment with piperonil butoxide (PB), a monooxygenase inhibitor, or with tri-o-tolyl phosphate (TOTP), an esterase inhibitor, does not produce significant variations in the lethal effects of CY and PERM. Instead, in the adult rats, a significant increase in CY (X²=5.97;p<0.05) and PERM (X²=4.37;p<0.05) mortality occurred in rats pretreated with esterase inhibitors, whereas no increase in CY and PERM toxicity was found in adult animals pretreated with monooxygenase inhibitor. It was concluded that the higher level of sensitivity of the neonate rat to pyrethroid toxicity is probably due to incomplete development of the enzymes which catalyze the metabolism of pyrethroids in the liver of young animals. It is suggested that ester hydrolysis is an important pyrethroids detoxification reaction in the adult rat.     

早期营养对IUGR大鼠糖耐量和胰岛素敏感性的远期影响

【目的】了解宫内发育迟缓(IUGR)和生后早期蛋白质营养不良对IUGR大鼠糖耐量和胰岛素敏感指数(ISI)及胰岛素抵抗指数(IRI)的远期影响。【方法】采用被动吸烟法制作IUGR大鼠动物模型,新生正常鼠仔102只和IUGR鼠仔105只随机分为4组:①正常对照组;②IUGR模型组;③正常大鼠低蛋白饮食组(CLP组);④IUGR大鼠低蛋白饮食组(SLP组)。观察各组大鼠在生后4周(幼年期)、12周(成年期)和48周龄(老年期)时糖耐量和胰岛素释放试验变化。【结果】①SLP组大鼠宫内发育迟缓和生后早期蛋白质营养不良其远期葡萄糖-胰岛素代谢功能受损明显,至48周时空腹血糖(5.2±1.4)mmol/L已升高,胰岛素(31. 2±3.4)mU/L水平明显升高,ISI(1.7±0.4)明显下降,IRI(8.7±1.8)明显升高,与正常对照组[(4.5±1.1)mmol/L,(12.9±1.0)mU/L和2.8±0.2,2.3±0.41比较均有显著性差异(P<0.05或P<0.01)。②CLP组大鼠生后早期单纯蛋白质营养不良的远期影响主要表现为糖负荷后胰岛素对血糖升高的应答分泌反应延迟和糖耐量减低。③IUGR模型组大鼠生后即给予正常营养供给,其葡萄糖-胰岛素代谢紊乱的程度减轻,但仍有糖耐量减低。【结论】在宫内和/或生后早期机体发育的关键时期,蛋白质营养不良将对葡萄糖-胰岛素代谢功能产生长期的不良影响,主要表现为糖耐量减     

低剂量激素替代治疗对绝经后妇女骨代谢的影响

目的 探讨低剂量结合型雌激素（ＣＥ）和安宫黄体酮（ＭＰＡ）联合应用对骨代谢的影响，方法３４例绝经后妇女随机分为两组，试验组１７例，ＣＥ０．６２５ｍｇ与ＭＰＡ２ｍｇ隔日口服交替应用，对照组１７例，口服ＣＤ０．６２５ｍｇ／ｄ，每月连续服用２５ｄ，后１０ｄ加用ＭＰＡ４ｍｇ。两组均连续服用４周期，于用药前后分别测定血碱性磷酸酶（ＡＬＰ）及尿Ｃａ／Ｃｒ比值。结果 实验组完成治疗者１６例，对照组完成治疗者１５     

烧伤后红细胞损伤的机制——过氧化脂质、维生素E与溶血的关系

本实验发现大鼠体表面积20％Ⅲ°烧伤后,皮肤内产生了大量丙二醛(MDA),第二天达最高,第七天有第二高峰,血浆和红细胞(RBC)MDA第三天达最高,血浆和RBC维生素E(VE)于伤后第二天后迅速下降,RBC溶血第三天最甚。对皮肤MDA、血浆MDA、RBCMDA、血浆VE、BBC VE、1％H_2O_2溶血进行相关分析后发现在不同时相,有不同的相关关系,但基本遵循烧伤皮肤MDA增加、血浆MDA增加、RBC MDA增加、血浆和RBC VE降低,溶血增加的规律。文中讨论了RBC损伤的机制。     

Almitrine bismesylate disposition in the human digestive tract

Summary The absorption of almitrine from the upper gastrointestinal tract has been evaluated in 6 healthy volunteers by an intubation technique. Almitrine bismesylate dissolved in malic acid was introduced into the stomach after homogenization with a meal containing the marker¹⁴C-polyethylene glycol (PEG) 4000. Unlabeled PEG 4000 was infused into the second part of duodenum throughout the experiment. Samples of the luminal content were collected every 15 min for four hours from the stomach and at the ligament of Treitz. Blood was also collected.Almitrine was neither absorbed from nor metabolized in the stomach. About 37% of the quantity of drug emptied from the stomach was absorbed from the duodenum. Almitrine was detected in plasma 50 min after ingestion of the meal and its plasma concentration-time profile reflected the cumulative gastric emptying rate. The metabolite tetrahydroxy almitrine was found in intestinal samples as soon as unchanged drug was detected in plasma. The intraluminal rate of formation of the metabolite increased with time.The results suggest hepatic metabolism of almitrine followed by rapid excretion of the metabolite in the bile.     

Functional meaning of tryptophan-induced increase of 5-HT metabolism as clarified by in vivo voltammetry

Differential pulse voltammetry with carbon fiber electrodes was used to study serotonin (5-HT) metabolism in freely moving rats. The electrodes implanted in the striatum recorded the extracellular 5-hydroxyindoleacetic acid (5-HIAA) oxidation peak after oral tryptophan (150 mg/kg). This 5-HT precursor did not modify the 5-HIAA peak in any rat tested, but it raised 5-HIAA levels determined in total tissue by a classical biochemical method (HPLC). The administration of 5-hydroxytryptophan (5-HTP) (25 mg/kg i.p.) induced an increase of 5-HIAA detectable both in the extracellular medium by voltammetry and in tissue samples. As previously shown, dorsal raphe electrical stimulation raises extracellular 5-HIAA in the striatum and this effect is enhanced by pretreatment with tryptophan. The results suggest that tryptophan in 'normal' conditions enhances 5-HT metabolism without affecting 5-HT release unless such release is stimulated. 5-HTP increases 5-HT metabolism and release.