Modified Ultrafiltration Attenuates Dilutional Coagulopathy in Pediatric Open Heart Operations

Background. Extreme hemodilution caused by relatively large prime volumes required for cardiopulmonary bypass in infants causes a dilutional coagulopathy, characterized by low concentrations of fibrinogen and other circulating coagulation factors. Modified ultrafiltration results in hemoconcentration and is associated with decreases in postoperative bleeding and transfusion requirements in children. This study was undertaken to quantify the effect of modified ultrafiltration on concentrations of fibrinogen, plasma proteins, and platelets in infants and small children.

Methods. Twenty patients less than 15 kg were studied. Cardiopulmonary bypass circuits were primed with crystalloid solutions. Red blood cells were added during cardiopulmonary bypass for hematocrits less than 15%. Colloid solutions were not administered. Concentrations of fibrinogen, plasma proteins, and platelets, and hematocrit were measured before cardiopulmonary bypass, before modified ultrafiltration, and after modified ultrafiltration.

Results. Modified ultrafiltration was associated with significant (p < 0.001) increases in hematocrit (19% ± 6% to 31% ± 9%), fibrinogen (65 ± 29 to 101 ± 45 mg/dL), and total plasma proteins (2.7 ± 0.3 to 4.9 ± 0.7 g/dL), but no change (p = 0.129) in platelet count.

Conclusions. We conclude that modified ultrafiltration significantly attenuates the dilutional coagulopathy associated with cardiopulmonary bypass in infants.     

Human Aldehyde Dehydrogenase: Kinetic Identification of the Isozyme for Which Biogenic Aldehydes and Acetaldehyde Compete

Michaelis constants and maximal velocities for phenylacetaldehyde (a metabolite of phenylethylamine), 3,4-dihydroxyphenylacetaldehyde (a metabolite of dopamine), 5-hydroxyindole acetaldehyde (a metabolite of serotonin), and 3,4-dihydroxyphenylglycolaldehyde (a metabolite of epinephrine and norepinephrine) have been determined for both cytoplasmic (E1) and mitochondrial (E2) isozymes of human liver aldehyde dehydrogenase (EC 1.2.1.3). Kinetic constants with biogenic aldehydes have never been previously determined for individual homogeneous isozymes of aldehyde dehydrogenase from any species. Mathematical treatment of these constants suggests that competition with acetaldehyde during alcohol metabolism would severely inhibit dehydrogenation of biogenic aldehydes with the mitochondrial and not the cytoplasmic isozyme of human liver aldehyde dehydrogenase.     

Effects of Ethanol on Arachidonic Acid Incorporation Into Lipids of a Plasma Membrane Fraction Isolated from Brain Cerebral Cortex

In the presence of ATP, MgCl2, and CoASH, somal plasma membranes isolated from rat cerebral cortex were active in transferring arachidonic acid to phosphatidylinositols, phosphatidylcholines, and triacylglycerols. Ethanol (350-525 mM) added to the incubation mixture inhibited arachidonic acid incorporation into phospholipids, while it enhanced the incorporation into triacylglycerols. Under these conditions, ethanol was found to react with arachidonic acid to form arachidonoyl ethyl ester. The incorporation of labeled arachidonic acid into glycerolipids as well as the synthesis of ethyl esters required the presence of ATP and CoASH for maximal activity. Nevertheless, each uptake process exhibited a unique pH profile. The esterification of arachidonic acid was not specific for ethanol as other aliphatic alcohols (e.g., propanol and butanol) were also able to react with labeled arachidonic acid to form the respective esters. Somal plasma membranes isolated from mice after chronic ethanol administration showed an increase in arachidonoyl transfer to both phospholipids and triacylglycerols. When these membranes were challenged with ethanol (325 mM), those isolated from the chronic ethanol group showed a greater increase in the labeling of triacylglycerols and ethyl esters than those from controls. Thus, different acyltransferases exhibite different responses to the effects of ethanol in vitro and in vivo.     

Regional specificity of gamma-aminobutyric acid receptor regulation by estradiol

In vitro quantitative autoradiography and the microdissection technique of Palkovitz were used to examine the effects of estradiol-17 beta on GABAA receptors and on glutamic acid decarboxylase in discrete areas of rat brain. Under the conditions examined, estradiol did not affect glutamic acid decarboxylase activity. However, treatment with estradiol decreased GABAA receptor binding in a majority of areas that contain high levels of intracellular estradiol receptors and in a number of areas that contain few or no estradiol receptors. Within one brain area, the ventromedial nucleus of the hypothalamus, the estradiol effect was mapped and found to occur within the estradiol-sensitive ventrolateral portion and the surrounding dendritic plexus. Time- and dose-response relationships were region specific suggesting that estradiol might influence GABAA-receptor binding through multiple mechanisms. Estradiol does not appear to interact directly with GABAA receptors since addition of estradiol to the assay system did not affect binding. Our findings suggest that one way estradiol might affect neuroendocrine and other centrally mediated processes is through effects on GABAA-receptor binding.     

Dose-Additive Inhibition of Intake of Ethanol by Cholecystokinin and Bombesin

Cholecystokinin (CCK) and bombesin (BBS) are neuropeptides of the brain and gut which have been shown to inhibit intake of ethanol. CCK octapeptide and BBS tetradecapeptide were injected intraperitoneally in both single doses and combinations of doses to determine interactions of the two peptides in the control of consumption of ethanol. Water-deprived rats were given access to 5% w/v ethanol for 30 min, followed by a 30-min access to water, daily. One minute before presentation of ethanol, rats were injected with either saline or one of ten peptide solutions (three of CCK alone, three of BBS alone, and four combinations of both). Results from the injections of single peptides were used to determine predicted inhibitions of the peptide combinations, assuming perfect additivity of doses. None of the actual values of inhibition of intake of ethanol by peptide combinations differed significantly from its predicted additive value. Endogenous CCK-like and BBS-like peptides may suppress intake of ethanol by an additive mechanism of inhibition.     

Effect of hemodilution on brain tissue during global ischemia

This study evaluates the effect of blood volume and hematocrit changes on brain tissue during temporary global ischemia. Normal saline was administered intravenously to 55 gerbils to achieve hypo-, normo-, and hypervolemic hemodilution and uniform 30% hematocrit reduction. Each group had unilateral carotid artery ligation and temporary (20 minute) contralateral carotid occlusion. After ten days or death, brains were harvested, preserved in formalin, sectioned in a manner which provided adequate samples of both cortex and hippocampus, and stained with H&E and luxol fast blue. They were then examined and staged microscopically for white and gray matter infarction, edema, and neuronal injury and loss. Histologic studies were performed in a randomized and blinded manner and were classified by one of four categories: normal, minimal, moderate, and severe changes. Three of ten (30%) controls survived ten days but had severe neuronal loss, minimal cerebral edema and a minimal to moderate number of white matter strokes. Survival was best in animals treated with hypovolemic hemodilution (43%). Other rates were: normovolemic (33%), controls (30%), and hypervolemic (8.3%). The degree of brain tissue damage was markedly less in the normovolemic group. In this model, normovolemic hemodilution followed by hypovolemic hemodilution offered the best overall cerebral protection during global ischemia.