Heparinization in aortic surgery

A prospective study was conducted on 35 patients (25 males and 10 females) undergoing elective reconstructive aortic surgery to examine the heparin activity after a bolus dose of sodium heparin (100 U/kg) given five minutes prior to aortic cross clamping. Recording of heparin activity were made 15 minutes later, on release of the aortic clamp, at abdominal wound closure and hourly thereafter until minimal activity was reached. In 10 patients, protamine was used to reverse anticoagulation. These results were related to clinical parameters of age, renal function, plasma cholesterol, blood pressure, position of the aortic clamp and blood loss. High peak levels of heparin activity were more likely in patients with impaired renal function or high plasma cholesterol concentrations. Heparin activity was prolonged at therapeutic levels in patients with renal impairment, and in this group of patients the use of protamine was significantly increased as was the requirement for blood replacement.     

Effect of Chronic Alcohol Feeding on Hepatic Iron Status and Ferritin Uptake by Rat Hepatocytes

Alcohol abuse is known to cause disturbances to iron homeostasis in man and is associated with elevated serum ferritin levels. We have previously shown that ethanol metabolism in the rat hepatocyte is associated with an immediate reduction in ferritin uptake by this cell. In this study we have examined the effect of pair-feeding the Lieber-DeCarli liquid alcohol diet on ferritin uptake by rat hepatocytes. Rat liver ferritin was radiolabeled with ⁵⁹Fe in vivo and isolated by conventional techniques. Rats were pair-fed the Lieber-DeCarli liquid alcoholic diet for 4–6 weeks. Hepatocytes, isolated from their livers by collagenase perfusion, were incubated with [⁵⁹Fe]ferritin in L-15 medium at 37°C and 4° to measure ferritin uptake and binding. The in vitro effect of ethanol on these hepatocytes was also studied. Ferritin and iron parameters were measured in the sera and hepatocytes of these animals and a comparable group of normal chowfed rats. The rate of ferritin uptake by hepatocytes from alcohol-fed rats was significantly faster than that of their pair-fed controls (0.743 ± 0.061 vs. 0.540 ± 0.042 ng/min/10⁶ cells, p < 0.05). However, the rats on Lieber-DeCarli control diet exhibited a lower hepatocyte ferritin uptake rate than chow-fed animals (79.3 ± 8.1% of the control values, p < 0.01). In vitro incubation of cells in 100 mm ethanol resulted in less inhibition of ferritin uptake by hepatocytes from alcoholic rats than from their pair-fed controls (11 ± 7.1% inhibition vs. 43.6 ± 10.7% for controls, p < 0.05). Receptor-mediated binding of ferritin to hepatocytes showed a 61% increase in saturable binding capacity for alcoholic rats (15,820 ± 4950 molecules/cell vs. 9798 ± 3622, p= 0.05). The presence of ethanol in the medium did not affect ferritin binding significantly. Although there was no significant difference in the serum iron values between all three groups, transferrin concentrations were markedly elevated in the alcohol-fed rats, resulting in a much lower transferrin iron saturation than for the control animals. Because the corresponding serum values for the diet controls were intermediate between those for the alcohol-fed rats and the chow-fed animals, these findings may reflect dietary restriction by the liquid diet, which is exacerbated by the addition of alcohol. These findings suggest that there is increased iron uptake by the hepatocyte following chronic alcohol administration, which may be due to the increased ferritin receptors. This is supported by the observation that this alcohol treatment also causes a depletion of serum ferritin. However, the decreased iron content in the alcohol-fed rats indicate that this may be due to a response to changes in iron homeostasis by the hepatocyte and/or redistribution in the body.     

Influence of epinephrine on alcohol dehydrogenase activity in rat hepatocyte culture

The effects of epinephrine on alcohol dehydrogenase activity and on rates of ethanol elimination were determined in rat hepatocyte culture. Continuous exposure of the hepatocytes to epinephrine (10 microM) in combination with dexamethasone (0.1 microM) enhanced alcohol dehydrogenase activity on days 4-7 of culture, whereas neither hormone alone had an effect. The increased alcohol dehydrogenase activity was associated with an increased rate of ethanol elimination. Acute addition of 10 microM epinephrine to hepatocytes maintained in culture with 0.1 microM dexamethasone did not change alcohol dehydrogenase activity, but resulted in an immediate marked, but transitory, increase in ethanol elimination within the first 5 min after the addition of the hormone. Prazosin, an alpha 1-adrenergic blocker, and antimycin, an inhibitor of mitochondrial respiration, were powerful inhibitors of the transient increase in ethanol elimination, whereas 4-methylpyrazole was only partially inhibitory. These observations indicate that epinephrine has a chronic effect in increasing alcohol dehydrogenase activity and ethanol elimination and, also, an acute transient effect of increasing ethanol elimination which is not limited by alcohol dehydrogenase activity.     

Second-generation antidepressants

The host of newly developed antidepressant drugs offer important clinical advantages to some patients, although their promises of improved therapeutic efficacy and reduced adverse effects compared with conventional treatments are not fully realized. Increased biochemical specificity and unique mechanistic or clinical profiles render these compounds valuable in research into the pathophysiology of affective disorders and mode of action of antidepressant agents.     

Subcellular fractionation of bovine ganglion stellatum: co-storage of noradrenaline, Met-enkephalin and neuropeptide Y in large 'dense-cored' vesicles

The subcellular localization of noradrenaline, Met-enkephalin and neuropeptide Y was studied in homogenates of bovine ganglion stellatum. After differential centrifugation most of the noradrenaline (70%) was found soluble, while both neuropeptide Y and Met-enkephalin were sedimented for more than 65%. However, the 3 substances co-sedimented mainly in the microsomal fraction. The microsomal fraction was further analyzed by differential and equilibrium density gradient centrifugation. In both types of gradient, Met-enkephalin and neuropeptide Y were found in the more dense region of the gradient, coinciding with the main peak of noradrenaline. In this fraction, the molar ratio of Met-enkephalin to noradrenaline was 1:95. The corresponding molar ratio for neuropeptide Y to noradrenaline was 1:253. These results indicate that neuropeptide Y and Met-enkephalin are stored with noradrenaline in 'heavy' or large 'dense cored' vesicles in the cell bodies of sympathetic neurons of bovine ganglion stellatum. We present here for the first time biochemical evidence for the co-localization of neuropeptides and a classical transmitter in a neuronal cell body.     

Myocardial hydroxyproline and mechanical response to prolonged pressure loading followed by unloading in the cat.

To determine the myocardial response to prolonged pressure-loading and unloading, kittens weighing 0.8-1.2 kg underwent pulmonary artery banding, which initially elevated right ventricular (RV) systolic pressure by 10-15 mm Hg. 52 and 76 wk later; RV weight/body weight had increased by approximately 80%. Total RV hydroxyproline had increased significantly, whereas hydroxyproline concentration was unchanged from that of nonbanded animals of comparable age. In isometrically contracting RV papillary muscles, peak active force was significantly less at 76 wk (3.3 +/- 0.8 [SD] g/mm2 than at 52 wk (5.1 +/- 0.8 g/mm2) or in nonbanded animals (4.8 +/- 0.8 g/mm2). Velocity of muscle shortening at comparable loads was unchanged after 52 wk but was significantly less after 76 wk. In nonstimulated, slowly stretched muscles, passive stiffness constants, alpha and beta, derived from delta = alpha(e beta epsilon - 1), where delta is instantaneous stress and epsilon is Lagrangian strain, were unchanged by banding. The band was removed after 52 wk in additional animals that were studied 24 wk later. In those animals with normal RV pressures at death, hypertrophy had regressed and hydroxyproline concentration was comparable to that of nonbanded and banded animals; Active and passive mechanical function remained normal. In this model, changes in hydroxyproline parallel changes in muscle mass, and passive stiffness remains normal during development and regression of hypertrophy. Removal of the pressure load after prolonged hypertrophy prevents or retards the late development of myocardial dysfunction.