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R Larsen

Publications and source records attributed to R Larsen.

At least 91 records · Page 5Linked to original sources
PubMed1996

Platelet-activating factor is involved in the regulation of pathological leukocyte adhesion after liver transplantation.

An increased leukocyte adhesion and loss of integrity of endothelial cells is known to be a critical step in the reperfusion period after cold ischemia of transplanted livers. Platelet-activating factor (PAF) is discussed as one of the inflammatory mediators involved in mediating reperfusion injury, e.g., by regulation of leukocyte adhesion. In this study we investigated the effect of a synthetic PAF receptor antagonist, WEB 2086 (Boehringer Ingelheim, FRG), on microcirculation and adhesion of leukocytes to sinusoidal endothelium after liver transplantation in the rat. Livers from SPRD rats (n = 6 per group) were stored for 5 hr in ice-cold UW solution and orthotopically transplanted using the cuff technique. In a randomized and blinded fashion WEB 2086 (1 mg/kg body wt) or placebo was given twice intravenously, at the beginning of the recipient operation and 1 min prior to reperfusion of the liver graft. After in vivo staining of leukocytes with acridine orange, microcirculation and leukocyte-endothelium interaction of transplanted livers and livers from sham-operated animals were investigated 90 min and 5 hr after surgery by means of intravital microscopy. After 90 min of reperfusion, temporary leukocyte adhesion in periportal regions was increased after liver transplantation (22.0 +/- 2.5%; mean +/- SEM) in contrast to the sham group (14.2 +/- 1.8%). Administration of WEB 2086 reduced temporary leukocyte adhesion significantly (11.5 +/- 2.5%; P < 0.05), whereas no significant differences were observed with respect to permanent leukocyte adhesion. Five hours after recipient operation, a significant increase of permanent leukocyte adhesion was observed after transplantation (21.0 +/- 2.6%; P < 0.05) compared to sham-operated animals (12.1 +/- 1.7%). Application of WEB 2086 diminished permanent leukocyte adhesion significantly (12.2 +/- 1.3%; P < 0.05), whereas no differences were noticed between the different groups with respect to temporary leukocyte adhesion at this time. The results indicate that reduction of temporary leukocyte adhesion in the early reperfusion period by administration of PAF receptor antagonist WEB 2086 was followed by a reduction of permanent leukocyte adhesion in the late reperfusion period, e.g., at 5 hr. Thus, it is concluded that PAF is one of the mediators which is involved in the regulation of leukocyte adhesion after liver transplantation.

Animals↗
PubMed1996

Study of the forces of stabilizing complexes between chlorophylls and heterocyclic amine mutagens.

Chlorophyllin (CHL), a water-soluble derivative of chlorophyll, forms molecular complexes with heterocyclic amine mutagens in vitro. In a previous study [Dashwood and Guo (1993): Environ Mol Mutagen, 22:164-171], we observed an inverse correlation between the binding constants of several mutagen-CHL complexes and the antimutagenic potency of CHL in the Salmonella assay. The present investigation utilized molecular mechanics methods of energy minimization and spectrophotometric titration to examine structural features of chlorophylls, chlorins, and porphyrins that might be important for complex formation with heterocyclic amines. The exocyclic amine group of the mutagen aligned consistently with acid groups in CHL, suggesting that H-bond or electrostatic interactions facilitate complex formation. Replacement of the exocyclic amine with a nitro group abrogated this specific orientation and raised the minimized energies of the complexes. No relationship was found between complex strength and the specific positions of amine or methyl groups on the mutagen. However, the presence of methyl groups increased the minimized energies and lowered the binding constants of the complexes, perhaps due to partial disruption of pi-pi interaction by steric effects. All of the compounds examined, including chlorophyll a, required the presence of pi-pi interactions to form stable complexes with the heterocyclic amines. In general, the present results were in agreement with the inhibitory potency of each compound in the Salmonella assay, and they provide further support for the hypothesis that chlorophylls in the diet might act as interceptor molecules of food-borne carcinogens and mutagens.

Amines↗
PubMed1996

Solid-state NMR studies of the prion protein H1 fragment.

Conformational changes in the prion protein (PrP) seem to be responsible for prion diseases. We have used conformation-dependent chemical-shift measurements and rotational-resonance distance measurements to analyze the conformation of solid-state peptides lacking long-range order, corresponding to a region of PrP designated H1. This region is predicted to undergo a transformation of secondary structure in generating the infectious form of the protein. Solid-state NMR spectra of specifically 13C-enriched samples of H1, residues 109-122 (MKHMAGAAAAGAVV) of Syrian hamster PrP, have been acquired under cross-polarization and magic-angle spinning conditions. Samples lyophilized from 50% acetonitrile/50% water show chemical shifts characteristic of a beta-sheet conformation in the region corresponding to residues 112-121, whereas samples lyophilized from hexafluoroisopropanol display shifts indicative of alpha-helical secondary structure in the region corresponding to residues 113-117. Complete conversion to the helical conformation was not observed and conversion from alpha-helix back to beta-sheet, as inferred from the solid-state NMR spectra, occurred when samples were exposed to water. Rotational-resonance experiments were performed on seven doubly 13C-labeled H1 samples dried from water. Measured distances suggest that the peptide is in an extended, possibly beta-strand, conformation. These results are consistent with the experimental observation that PrP can exist in different conformational states and with structural predictions based on biological data and theoretical modeling that suggest that H1 may play a key role in the conformational transition involved in the development of prion diseases.

Amino Acid Sequence↗
PubMed1996

The influence of resuscitation on hemodynamics and oxygen radical-induced reperfusion injury after arterialized liver transplantation in the rat.

Extended hemodynamic monitoring during arterialized rat liver transplantation procedure and the effects of resuscitation with albumin, starch-desferrioxamine-conjugated hydroxyethyl starch (HES-DFO), or hydroxyethyl starch (HES) on hemodynamics are presented. Livers from SPRD rats were stored for 20 hr in ice-cold UW solution and were orthotopically transplanted with reconstruction of the hepatic artery under hemodynamical monitoring applying invasive measurement of mean arterial blood pressure (MAP) and cardiac output (CO). Comparable amounts of albumin, HES-DFO, and HES were given in a randomized and blinded fashion after transplantation. Ringer's solution was given additionally when blood pressure was below 65 mmHg. Fifteen, 60, and 90 min after surgical procedure blood samples were taken to determine acid base status, blood gases, and blood cell count. Oxygen radical-induced reperfusion injury was determined by thiobarbituric acid reactive substances (TBARS) in serum and total glutathione in liver tissue 90 min after surgery. During the anhepatic period CO was reduced to 20% of baseline and MAP to 40 mmHg. In all groups, declamping led to a transient recovery of hemodynamic situation, whereas during further reperfusion, CO and MAP were significantly reduced in the HES- and HES-DFO-treated group in contrast to the group receiving albumin. Animals of the HES group required significantly more Ringer's solution to maintain blood pressure (2.6 +/- 0.9 ml; 4 of 6 animals needed additional resuscitation) than animals given albumin (0.4 +/- 0.3 ml, P < 0.05, 2/9 needed further supplementation) or HES-DFO (1.2 +/- 0.5 ml; 5/10 required additional resuscitation), respectively. Animals treated with HES or HES-DFO failed to restore base excess and serum lactate in contrast to resuscitation with albumin. However, TBARS was mitigated by resuscitation with HES-DFO compared to albumin and HES, whereas no significant differences were observed in respect to tissue glutathione of transplanted livers. In conclusion the model described allows intensive monitoring of hemodynamic parameters and metabolic status during arterialized rat liver transplantation procedure. Moreover, the results indicate that resuscitation with albumin could maintain central hemodynamics and restore homeostasis during the early reperfusion period after transplantation in contrast to resuscitation with HES or HES-DFO, respectively. Although resuscitation with HES-DFO resulted in mitigation of lipid peroxides determined by TBARS, no significant improvement of hemodynamics and homeostasis could be observed during reperfusion as it can be observed with albumin.

Animals↗
PubMed1996

[Desflurane and isoflurane. A comparison of recovery and circulatory parameters in surgical interventions].

OBJECTIVES: The new volatile anaesthetic desflurane is characterized by very low blood-gas and tissue-blood partition coefficients, so that rapid induction of anaesthesia and shorter recovery times can be expected. The aim of this investigation was to compare the effects of desflurane and isoflurane on haemodynamics and recovery time when used as part of a balanced anaesthesia technique for elective surgery. METHODS: Fifty patients (18 years and older, ASA status I-III) scheduled for elective surgery (no laparoscopies) of at least 60 min duration were included in this open, randomised, phase-III clinical trial. After oral premedication with midazolam 7.5 mg 45 min before transfer to theatre, anaesthesia was induced with fentanyl 0.1 mg and thiopental 5 mg/kg; succinylcholine or vecuronium facilitated intubation. Desflurane and isoflurane, respectively, were used for maintenance of anaesthesia, both in 50% N2O, with the inspired concentration adapted to the degree of stimulation. All patients were ventilated in a semi-closed system; muscle relaxation was achieved with vecuronium. The electrocardiogram, heart rate (HR), and direct arterial blood pressure (BP) were recorded continuously and anaesthetic gas detection was performed by an infrared absorption technique. With termination of surgery the volatile anaesthetic was discontinued and the following emergence times recorded: spontaneous ventilation (VT > 300 ml), extubation, eye opening, correctly answering the date of birth, arrival in and possible discharge from the post-anaesthesia care unit (PACU). RESULTS: In all, 49 patients were studied at random (desflurane n = 24, isoflurane n = 25). Data of demographics and anaesthetic technique were comparable in both groups (Tables 2 and 3). Anaesthetic elimination (expressed as FA/FAO) was significantly more rapid in the desflurane group 3 min after termination of anaesthesia (Fig. 1). Comparing the emergence times, there was no significant difference between desflurane and isoflurane: in both groups patients opened their eyes 12 min (median time) after termination of the operation (Table 4). Haemodynamics (HR, systolic and diastolic BP) were comparable at intubation, skin incision, end of surgery, extubation, and in the PACU (Fig. 2a, b). In 2 patients a rapid increase in the inspired concentration of desflurane during induction of anaesthesia produced a profound sympathoadrenergic reaction with an excessive increase in BP and HR. Similar reactions in other patients did not occur when the inspired concentration of desflurance was slowly increased. CONCLUSIONS: Despite the physicochemical properties of the new agent, emergence times were similar for desflurane and isoflurane in our study. These results, which are in contrast to those of some other authors, are most probably due to the study design, which included the use of premedicants (midazolam) and a low dose of fentanyl. The reported sympatho-adrenergic reactions after rapid changes in the inspired concentration of desflurane during induction of anaesthesia have been observed by others as well. It seems that this initial cardiovascular stimulation can be avoided by slow increases in desflurane concentration. In summary, desflurane compares to isoflurane in balanced anaesthesia for general surgical procedures with regard to haemodynamics, while the time to awakening is not necessarely reduced.

Adolescent↗
PubMed1996

High energy phosphates and direct calorimetry as predictive parameters for metabolic recovery of the rat liver following ischemia.

BACKGROUND AND METHODS: Alteration of the hepatocellular function following ischemic damage may play a crucial role in the limited recovery after reperfusion. In spite of numerous efforts, finding a simple technique for predicting recovery of the liver after ischemic damage is still an unresolved problem. During ischemic storage of isolated rat livers at 25 degrees C tissue concentrations of high energy phosphates and lactate were determined photometrically and interstitial pH was measured by glass electrodes. In comparison, the metabolic rate was measured continuously by direct calorimetry. In a second series of experiments these results were compared with functional recovery after ischemia and reperfusion. Following ischemic storage at 25 degrees C for 60, 120 or 240 min, the isolated livers were reperfused for 30 min in a non-recirculating system with a constant flow rate. During reperfusion functional recovery, as assessed by oxygen consumption and bile flow, was determined. At the end of reperfusion tissue samples were taken for biochemical analysis of adenine nucleotides. Furthermore, morphologic integrity was determined by electron microscopy. RESULTS: Whereas the ATP concentration drops within 60 min of ischemia to 6.9% of the control value without further significant change, the continuously measured metabolic rate as assessed by direct calorimetry decreases in an exponential manner. Accordingly, a better correlation of hepatocellular secretory function and calorimetrically measured heat output (r2 = 0.85; P < 0.001) was observed than with high energy phosphates (r2 = 0.56; P < 0.001). CONCLUSIONS: These data suggest that if the metabolism of the ischemic rat liver falls below a critical level, recovery is incomplete or impossible. Therefore, assessment of the global metabolic rate by direct calorimetry seems not only to be a very good predictor of recovery after ischemic damage but also a good tool in the laboratory for studies concerning the sequelae of ischemic metabolism and for improvement of tissue protection.

Adenine Nucleotides↗
PubMed1996

Cardiovascular effects of desflurane and isoflurane in patients with coronary artery disease.

BACKGROUND: Anaesthesia in patients with ischaemic heart disease may cause adverse haemodynamic reactions. This investigation compares the cardiovascular effects of equipotent concentrations of desflurane and isoflurane in 30 patients (ASA III) with coronary artery disease before surgical stimulation. METHODS: After standardised induction of anaesthesia with etomidate, fentanyl and pancuronium and tracheal intubation patients randomly received either desflurane (group I, n = 15) or isoflurane (group II, n = 15) in slowly increasing concentrations. ST-segment analysis and haemodynamic measurements were performed at 0.25, 0.5, 0.75 and 1.0 MAC of desflurane or isoflurane. RESULTS: Cardiac index did not change significantly in the two groups during the administration of the inhalational anaesthetics. Desflurane and isoflurane both caused a dose-dependent significant decrease of mean arterial blood pressure (group I: -16%; group II: -18%). As with isoflurane, the decrease of mean arterial pressure produced by desflurane primarily resulted from a decrease in systemic vascular resistance (group I: -26%, group II: -21%). Central venous pressure was not affected by the two volatile anaesthetics. Pulmonary artery pressure and pulmonary capillary wedge pressure remained unchanged during the administration of isoflurane, but in contrast both parameters significantly increased in patients receiving desflurane (PAP 24%, PCWP 40%). ST-segment analysis provided no signs of myocardial ischaemia. CONCLUSION: The results of this study demonstrate that in patients with coronary artery disease the haemodynamic effects of equipotent concentrations of desflurane and isoflurane are similar except for a significant increase in PAP and PCWP caused by desflurane. Therefore, desflurane should be administered with great caution if it is used as an alternative anaesthetic in patients with ischaemic heart disease.

Adult↗
PubMed1996

Multicenter evaluation of broth microdilution method for susceptibility testing of Cryptococcus neoformans against fluconazole.

We have developed a microdilution method for measuring the susceptibility of Cryptococcus neoformans to fluconazole. The present study evaluated the interlaboratory agreement of the results for the microdilution method obtained at three different sites and compared this method with the National Committee for Clinical Laboratory Standards M27-P reference method. Excellent interlaboratory agreement among the results obtained at the three sites was achieved with this method (83 and 96% agreement within 1 and 2 log2 dilutions, respectively). An overall agreement of 90% between the microdilution method and the M27-P method was observed, demonstrating the comparability of the two methods. However, there are inherent problems with the M27-P method in relation to measuring C. neoformans susceptibility, including suboptimal growth of the organism in RPMI 1640, a longer incubation period, and a narrow range of MICs. On the basis of these data, the microdilution method tested in this study is recommended for inclusion in the National Committee for Laboratory Standards method for testing the antifungal susceptibility of C. neoformans.

AIDS-Related Opportunistic Infections↗
PubMed1996

Evidence for a functional link between stress response and vascular control in hepatic portal circulation.

Heme oxygenase (HO)-derived carbon monoxide (CO) may contribute to vascular control through elevation of guanosine 3',5'-cyclic monophosphate. In the present study, we investigated the functional significance of expression of the isoenzyme HO-1 (heat-shock protein 32) in liver after hemorrhage/resuscitation (H/R) in rats anesthetized with pentobarbital sodium. An increase of mRNA levels for HO-1 was observed at 3 h after resuscitation, followed by induction of the protein at 6 h in pericentral hepatocytes and sinusoidal lining cells. Concomitantly, lower portal resistance was observed in H/R (0.33 +/- 0.060 mmHg.ml-1.min) compared with control rats (0.47 +/- 0.035 mmHg.ml-1.min). Blockade of the HO-CO pathway by tin protoporphyrin-IX (SnPP-IX) led to a transient increase in portal pressure with no effect on portal low in controls, whereas an increase in pressure and a decrease in flow contributed to the sustained increase in portal resistance after H/R. These results indicate that HO contributes to maintenance of hepatic perfusion in vivo under stressful conditions, suggesting a functional link between stress response and vascular control in portal circulation.

Animals↗
PubMed1995

N-acetylcysteine failed to improve early microcirculatory alterations of the rat liver after transplantation.

The application of radical scavengers reduces reperfusion injury of liver grafts despite the natural occurrence of cellular defense mechanisms enabling the cell to tolerate moderate oxidant stress without further cell damage. The glutathione peroxidase mechanism of the liver serves to reduce hydroxyl radical-induced lipid peroxidation by releasing reduced glutathione from intracellular stores. There is evidence that the application of cysteine-providing amino acids for glutathione synthesis could maintain or even increase liver glutathione. Therefore, the purpose of this study was to evaluate the effect of N-acetylcysteine (NAC) on oxidative stress-induced reperfusion injury after liver transplantation. This was done by applying intravital microscopy. Livers from female Sprague-Dawley rats weighing 220-260 g were stored for 20 h in University of Wisconsin (UW) solution and transplanted orthotopically using the cuff technique. Donors were given 150 mg/kg body weight NAC i.v. or placebo in a blind, random fashion 6 h prior to harvesting, followed by two injections of 50 mg/kg body weight, 4 and 2 h before explantation. In additional experimental groups, recipients were given a bolus of 83 mg/kg body weight NAC or placebo at the beginning of the recipient operations, 1 min prior to reperfusion, and 60 min after surgery. Ninety minutes after transplantation, intravital microscopy was applied and five liver lobules were recorded for 30 s after injection of acridine orange, a fluorescent leukocyte marker. Sinusoidal perfusion, sinusoidal width, and leukocyte adhesion, as well as reduced and oxidized glutathione, were determined in all livers.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcysteine↗
PubMed1995

[Three isoflurane preparations from various manufacturers. A comparison of isoflurane concentrations in fresh gas after vaporization with a Drager vaporizer type 19.3].

OBJECTIVES: The purpose of this study was to check the precision of the Dräger vaporizer model 19.3 when filled with three different preparations of isoflurane. METHODS: Six Dräger vaporizers model 19.3 calibrated with forene were filled with forene (Abbott), isoflurane (Lilly) and isoflurane (Pharmacia); gas output was measured by infrared absorption (Irina, Dräger) at vaporizer settings of 0.2, 0.4, 0.6, 0.8, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0 and 5.0 vol%, starting with a fresh gas flow of 2 1/min followed by 4, 6 and 12 1/min. Thus each of the three isoflurane preparations was checked in six different vaporizers and with four different fresh gas flows. RESULTS: Within the concentration range used in clinical practice there was no significant difference in the delivery of the three isoflurane preparations. Each of the six vaporizers produced a controllable and predictable concentration of the three preparations. CONCLUSION: Vaporizers of Dräger type 19.n calibrated with forene deliver the same predictable concentration of the volatile anaesthetic when filled with isoflurane from Lilly or isoflurane from Pharmacia instead of forene and may be used without impairment in patient safety. In addition, no specific calibration with one of the new isoflurane preparations is required.

Calibration↗
PubMed1995

[Controlled hypotension].

Induced hypotension is defined as a reduction in mean arterial blood pressure to 50-60 mm Hg in normotensive subjects. The aim of induced hypotension is to decrease intraoperative blood loss, decrease the need for blood transfusions and improve operating conditions. Most studies indicate that induced hypotension can decrease intraoperative blood loss by 50% in many surgical procedures; however, some studies report that blood loss is not significantly reduced. Current methods of induced hypotension are based on the use of rapid and short-acting vasodilators as primary agents (nitroprusside, nitroglycerine, urapidil), supplemented by volatile anesthetics (isoflurane) and/or beta-blockers (esmolol) to improve effect, reduce dosage and prevent side effects (reflex tachycardia, tachyphylaxis, rebound hypertension). Proper positioning of the patient and controlled ventilation aid in reducing blood loss. Major risks of induced hypotension are a reduction in blood flow (i.e. ischaemia) of vital organs (brain, myocardium) and elevation of intracranial pressure in neurosurgical patients. Thus, major contraindications of induced hypotension are severe coronary artery disease, hypertension combined with arteriosclerosis of cerebral vessels and increased intracranial pressure in patients with cerebral disease. Complications are rare in otherwise healthy patients, but may be higher in elderly patients and those with underlying organ dysfunction. Therefore, careful assessment and selection of patients, together with consideration of the potential complications, appropriate choice of drugs and invasive beat-by-beat monitoring, are essential for the safe practice of induced hypotension.

Anesthesia↗