Differential response of arteries and vein grafts to blood flow reduction

BACKGROUND: Because the relative efficacy of antiarrhythmic agents on halothane-epinephrine arrhythmias has not been well characterized, this study was undertaken to comparatively evaluate the antiarrhythmic action of Na(+)-, K(+)- and Ca(2+)-channel blockers on epinephrine-induced ventricular arrhythmias during halothane anesthesia in rats. METHODS: Rats were anesthetized at random with either halothane (1.5%), isoflurane (2.0%), or pentobarbital (50 mg/kg intraperitoneally), and the lungs were mechanically ventilated with oxygen. The rats were studied in three consecutive protocols. Protocol I determined the arrhythmogenic thresholds of epinephrine during the three types of anesthesia in 33 rats. Protocol II determined the arrhythmogenic thresholds of epinephrine during halothane anesthesia in 64 rats receiving saline (control) or one of five antiarrhythmic agents. Protocol III measured the duration of epinephrine-induced arrhythmias during halothane anesthesia in 42 rats receiving saline (control) or one of five antiarrhythmic agents. RESULTS: In protocol I, the arrhythmogenic doses of epinephrine during halothane, isoflurane, or pentobarbital anesthesia were 1.7 +/- 3.2, 11.1 +/- 0.6, and 39.0 +/- 3.9 micrograms/kg, respectively, and the corresponding plasma concentrations were 4.3 +/- 0.8, 103.7 +/- 9.2, and 246.7 +/- 28.9 ng/ml, respectively. In protocol II, the arrhythmogenic doses were similar in rats receiving saline and in those receiving lidocaine. The arrhythmogenic doses in rats receiving verapamil, flecainide (Na(+)- and K(+)-channel blocker), E-4031 (K(+)-channel blocker), or amiodarone(K(+)-channel blocker with Na(+)-, Ca(2+)-, and beta-blocking activity) increased significantly, i.e., 4.2, 4.2, 5.5, and 31.7 times control (P < 0.01). In protocol III, lidocaine had no effect on the duration of arrhythmias. Flecainide, E-4031, and verapamil markedly reduced the duration of arrhythmias induced by epinephrine, 8 micrograms/kg intravenously (P < 0.01), whereas only amiodarone markedly reduced the duration of arrhythmias induced by epinephrine, 16 micrograms/kg intravenously (P < 0.01). CONCLUSIONS: It was concluded that agents with K(+)-channel blocking properties were the most effective in preventing halothane-epinephrine arrhythmias in rats.     

Isolation of a non-sedimenting membrane fraction from the water soluble fraction of bovine lens

A membrane fraction was isolated from the water soluble fraction of bovine lens by increasing the density of the water soluble fraction with KBr and subjecting it to overnight centrifugation at 100000 g. We have called this fraction, which floats to the top of the mixture upon centrifugation, the non-sedimenting membrane fraction (NSMF). Electron microscopy of the NSMF revealed that it is composed of the expected membrane structures of unit membrane, fiber junction and cytoskeleton. Significantly less of the total membrane of the NSMF was devoted to fiber junction (22.8%) than in the sedimenting membrane fraction (SMF) (41.1%) prepared by sucrose density centrifugation of the water insoluble fraction. The NSMF accounted for about 7-12% of the total bovine lens membrane, and preliminary experiments demonstrated that a similar fraction could be isolated from the water soluble fraction of lenses from rats, rabbits, chickens and humans. The NSMF contained about 0.9 mg total lipid per mg total membrane protein, which was significantly greater than the value obtained for the SMF (0.5 mg total lipid per mg total membrane protein). The greater relative amount of total lipid in the NSMF was due to a significantly greater relative amount of phospholipid in the NSMF which was further reflected by the observation that the cholesterol: phospholipid molar ration of the NSMF (0.58) was significantly less than that of the SMF (0.88). Thus the relative lipid composition of the NSMF was significantly different than that of the SMF. Although the phospholipid content of the NSMF was greater than that of the SMF, the compositions of the phospholipids in the two membrane fractions were similar. The NSMF possessed essentially the same polypeptides (both extrinsic and intrinsic) which were found in the SMF. The NSMF was found to be distributed throughout the lens in a proportionate manner. We conclude that the NSMF may account for most of the lipid which remains in the water soluble fraction of the normal bovine lens after sedimentation of the water insoluble fraction. This membrane fraction substantially differs from the SMF in terms of structure and relative lipid composition. We speculate that the NSMF may represent a specialised domain of the fiber cell plasma membrane which has been previously unrecognized.     

Buchbesprechungen

Ohne Zusammenfassung     

Prophylactic effects of recombinant human superoxide dismutase in neonatal lung injury

To determine if recombinant human Cu-Zn superoxide dismutase (rhSOD) would prevent acute lung injury caused by hyperoxia and barotrauma, 26 newborn piglets were studied. Ten piglets were hyperventilated (arterial PCO2 15-20 Torr) with 100% O2 for 48 h. A second group received identical treatment for 4 h (n = 2) or 48 h (n = 8) but was given 5 mg/kg of rhSOD intratracheally at time 0. Six piglets were normally ventilated (arterial PCO2 40-45 Torr) for 48 h with 21% O2. Pulmonary function and tracheal aspirates were examined at time 0 and at 24 and 48 h, and bronchoalveolar lavage was performed at 48 h. In piglets treated with hyperoxia and hyperventilation, lung compliance decreased 42%, and tracheal aspirates showed an increase in neutrophil chemotactic activity (32%), total cell counts (135%), elastase activity (93%), and albumin concentration (339%) over 48 h (P < 0.05). All variables were significantly lower in rhSOD-treated piglets and comparable to normoxic control values. Surfactant remained active in all groups. Immunohistochemistry demonstrated that at 48 h significant rhSOD was distributed homogeneously in terminal airways. Adding rhSOD to tracheal aspirates of hyperoxic hyperventilated piglets did not alter neutrophil chemotaxis, suggesting that rhSOD protected the lung by reducing the production of chemotactic mediators. Results indicate that acute lung injury caused by 48 h of hyperoxia and hyperventilation is significantly ameliorated by prophylactic intratracheal administration of rhSOD.     

Pronoun resolution without pronouns: some consequences of memory-based text processing

A memory-based processing approach to discourse comprehension emphasizes the rapid deployment of information in memory to facilitate understanding of the text that is currently being read. S. B. Greene, R. J. Gerrig, G. McKoon, and R. Ratcliff (1994) demonstrated that when a text described the reunion of 2 characters who had previously discussed a 3rd character, the accessibility of the 3rd character increased, and the use of an unheralded pronoun (R. J. Gerrig, 1986) to refer to that character was felicitous. In experiments in this article, the authors demonstrate that concepts related to the unheralded pronoun also increase in accessibility and that those concepts form associations in memory with concepts present in the discourse at the time the pronoun is used. The authors also show that the increase in accessibility for the referent of the pronoun, as well as the appropriate long-term memory associations, occurs even in the absence of the pronoun.     

Binding of human single chain urokinase to Chinese Hamster Ovary cells and cloning of hamster u-PAR

In the present study, we assessed oxidative stress in patients with dilated cardiomyopathy of ischemic or idiopathic etiology. For this reason we measured whole blood reduced glutathione, erythrocyte superoxide dismutase, susceptibility of erythrocyte membranes and erythrocytes to peroxidation, and SH content of erythrocyte membranes in 12 patients (8 men and 4 women, ages 31 to 66 years) with idiopathic dilated cardiomyopathy, in 11 patients (8 men and 3 women, ages 32 to 65 years) with ischemic dilated cardiomyopathy, and in 21 healthy volunteers (12 men and 9 women, ages 25 to 67 years). There was no statistically significant difference between the two patient groups for the indicators studied (P >0.05). Blood glutathione, erythrocyte superoxide dismutase, and membrane SH content of both groups of patients was decreased compared with controls (P <0.05), whereas erythrocyte and membrane susceptibility to peroxidation were increased (P <0.05). We conclude that patients with idiopathic or ischemic dilated cardiomyopathy exhibit abnormalities of a range of markers of increased oxidative stress. These abnormalities may contribute to contractile dysfunction, increased incidence of fatal arrhythmias, and sudden death.     

Glucuronidation of N-hydroxy heterocyclic amines by human and rat liver microsomes

The food-borne carcinogenic and mutagenic heterocyclic aromatic amines undergo bioactivation to the corresponding N-hydroxy (OH)-arylamines and the subsequent N-glucuronidation of these metabolites is regarded as an important detoxification reaction. In this study, the rates of glucuronidation for the N-OH derivatives of 2-amino-3-methylimidazo[4,5-f]-quinoline (IQ), 2-amino-1-methyl-6-phenylimidazo[4,5-b]-pyridine (PhIP), 2-amino-6-methyl-dipyrido[1,2-a:3',2'-d]imidazole (Glu-P-1) and 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) by liver microsomal glucuronosyltransferase were compared to that of the proximate human urinary bladder carcinogen, N-OH-aminobiphenyl (N-OH-ABP) and the proximate rat colon carcinogen N-OH-3,2'-dimethyl-4-amino-biphenyl (N-OH-DMABP). Human liver microsomes catalyzed the uridine 5'-diphosphoglucuronic acid (UDPGA)-dependent glucuroidation of N-OH-IQ, N-OH-PhIP, N-OH-Glu-P-1 and N-OH-MeIQx at rates of 59%, 42%, 35% and 27%, respectively, of that measured for N-OH-ABP (11.5 nmol/min/mg). Rat liver microsomes also catalyzed the UDPGA-dependent glucuronidation of N-OH-PhIP, N-OH-Glu-P-1 and N-OH-IQ at rates of 30%, 20% and 10%, respectively of that measured for N-OH-DMABP (11.2 nmol/min/mg); activity towards N-OH-MeIQx was not detected. Two glucuronide(s) of N-OH-PhIP, designated I and II, were separated by HPLC. Conjugate II was found to be chromatographically and spectrally identical with a previously reported major biliary metabolite of PhIP in the rat, while conjugate I was identical with a major urinary metabolite of PhIP in the dog. Hepatic microsomes from rat, dog and human were found to catalyze the formation of both conjugates. The rat preferentially formed conjugate II (I to II ratio of 1:15), while the dog and human formed higher relative amounts of conjugate I (I to II ratio of 2.5:1.0 and 1.3:1.0 respectively). Fast atom bombardment mass spectrometry of conjugates I and II gave the corresponding molecular ions and showed nearly identical primary spectra. However, collision-induced spectra were distinct and were consistent with the identity of conjugates I and II as structural isomers. Moreover, the UV spectrum of conjugate I exhibited a lambda max at 317 nm and was essentially identical to that of N-OH-PhIP, while conjugate II was markedly different with a lambda max of 331 nm. Both conjugates were stable in 0.1 N HCl and were resistant to hydrolysis by rat, dog and human liver microsomal beta-glucuronidases.(ABSTRACT TRUNCATED AT 400 WORDS)     

Activated partial thromboplastin time and outcome after thrombolytic therapy for acute myocardial infarction: results from the GUSTO-I trial

BACKGROUND: Although intravenous heparin is commonly used after thrombolytic therapy, few reports have addressed the relationship between the degree of anticoagulation and clinical outcomes. We examined the activated partial thromboplastin time (aPTT) in 29,656 patients in the Global Utilization of Streptokinase and t-PA for Occluded Coronary Arteries (GUSTO-I) trial and analyzed the relationship between the aPTT and both baseline patient characteristics and clinical outcomes. METHODS AND RESULTS: Intravenous heparin was administered as a 5000-U bolus followed by an initial infusion of 1000 U/h, with dose adjustment to achieve a target aPTT of 60 to 85 seconds. aPTTs were collected 6, 12, and 24 hours after thrombolytic administration. Higher aPTT at 24 hours was strongly related to lower patient weight (P < .00001) as well as older age, female sex, and lack of cigarette smoking (all PT< .0001). At 12 hours, the aPTT associated with the lowest 30-day mortality, stroke, and bleeding rates was 50 to 70 seconds. There was an unexpected direct relationship between the aPTT and the risk of subsequent reinfarction. There was a clustering of reinfarction in the first 10 hours after discontinuation of intravenous heparin. CONCLUSIONS: Although the relationship between aPTT and clinical outcome was confounded to some degree by the influence of baseline prognostic characteristics, aPTTs higher than 70 seconds were found to be associated with higher likelihood of mortality, stroke, bleeding, and reinfarction. These findings suggest that until proven otherwise, we should consider the aPTT range of 50 to 70 seconds as optimal with intravenous heparin after thrombolytic therapy.