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PubMed2002

Effects of oxygen and glucose deprivation on the expression and distribution of neuronal and inducible nitric oxide synthases and on protein nitration in rat cerebral cortex.

Changes in the nitric oxide (NO) system of the rat cerebral cortex were investigated by immunohistochemistry, immunoblotting, NO synthase (NOS) activity assay, and magnetic resonance imaging (MRI) in an experimental model of global cerebral ischemia and reperfusion. Brains were perfused transcardially with an oxygenated plasma substitute and subjected to 30 minutes of oxygen and glucose deprivation, followed by reperfusion for up to 12 hours with oxygenated medium containing glucose. A sham group was perfused without oxygen or glucose deprivation, and a further group was treated with the NOS inhibitor N(omega)-nitro-L-arginine methyl ester (L-NAME) before and during perfusion. Global ischemia led to cerebrocortical injury as shown by diffusion MRI. This was accompanied by increasing morphologic changes in the large type I interneurons expressing neuronal NOS (nNOS) and the appearance of nNOS immunoreactivity in small type II neurons. The nNOS-immunoreactive band and calcium-dependent NOS activity showed an initial increase, followed by a fall after 6 hours of reperfusion. Inducible NOS immunoreactivity appeared in neurons, especially pyramidal cells of layers IV-V, after 4 hours of reperfusion, with corresponding changes on immunoblotting and in calcium-independent NOS activity. Immunoreactive protein nitrotyrosine, present in the nuclear area of neurons in nonperfused controls and sham-perfused animals, showed changes in intensity and distribution, appearing in the neuronal processes during the reperfusion period. Prior and concurrent L-NAME administration blocked the changes on diffusion MRI and attenuated the morphologic changes, suggesting that NO and consequent peroxynitrite formation during ischemia-reperfusion contributes to cerebral injury.

Animals↗
PubMed1990

Single, total paracentesis for tense ascites: sequential hemodynamic changes and right atrial size.

Hemodynamic changes induced by a single, total paracentesis were evaluated in 21 patients with tense ascites from whom 4 to 16 L of ascites were drained over 2 to 8 hr with no serious complications. At 60 min, compared to baseline, there was an increase in cardiac output (7.7 +/- 0.5 to 8.5 +/- 0.6 L/min, p less than 0.02) and a tendency for right atrial pressure to decrease (9.3 +/- 0.8 to 7.50 +/- 0.8 mm Hg, NS), with no change in pulmonary capillary wedge pressure (10.9 +/- 0.9 to 10.7 +/- 0.9 mm Hg). Between 3 and 12 hr later, there was a drop in right atrial pressure, pulmonary capillary wedge pressure and cardiac output to 5.6 +/- 0.6 (p less than 0.02), 7.2 +/- 0.8 mm Hg (p less than 0.002) and 7.2 +/- 0.6 L/min (NS) respectively, indicative of the development of relative hypovolemia and suggesting that therapeutic plasma expansion is appropriate at this time. Two-dimensional echocardiography before paracentesis (n = 8) showed a reduction in the right to left atrium area ratio as compared with values in patients with minimal ascites (0.54 +/- 0.04 vs 0.82 +/- 0.02, p less than 0.0001). This technique may help in identifying patients with right atrial compression caused by tense ascites.

Adult↗
PubMed1988

Myocardial oxygen tensions during ischaemia in fluorocarbon diluted pigs.

Previous work by the authors has shown that, following ligation of the left anterior descending coronary artery (LAD), myocardial oxygen tension (PmO2) in expected areas of maximal ischaemia is maintained at the expense of ischaemic border zones of the infarct area. Post-ischaemic haemodilution with the fluorocarbon containing plasma substitute Fluosol-DA 20% (FDA) could significantly improve PmO2 and pre-ischaemic haemodilution can delay myocardial ischaemia. We now present an analysis of the pattern of PmO2 changes to be seen when myocardial ischaemia is induced following prior haemodilution with FDA. Two groups of juvenile Yorkshire pigs were anaesthetised with intraperitoneal thiopentone, intubated and ventilated with halothane, nitrous oxide and oxygen. After placement of cardiovascular monitoring lines, a thoracotomy was performed. The pericardium was opened and 4 steel-protected gold microelectrodes were placed in the terminal supply area of the LAD in such a way that 2 electrodes were in the area of myocardial ischaema to be produced. One group of pigs were bled (20 ml/kg) and the loss was replaced with equal volumes of FDA. The animals were ventilated with halothane and oxygen and the terminal LAD was ligated. Electrode outputs were recorded on a flat bed recorder and analysed. LAD occlusion in the control animals resulted in similar changes in PmO2 to those described above.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1975

On the regulation of the renal response blood volume expansion by vascular parameters in the rat.

The dynamic patterns of body fluid volume distribution, of cardiovascular variables and of renal water, sodium and potassium excretion were studied in the anaesthetized rat following acute, iso-oncotic blood volume expansion. The increased renal excretion following expansion was soon reversed and its pattern to termination was not correlated with changes in pulse and mean arterial pressure, in plasma electrolyte concentration or in haematocrit. At the end of the renal response the change in extracellular fluid volume was not usually corrected, the blood volume was always well above its control value and the interstitial fluid was below its control value. In all cases the temporal pattern and the termination of the renal response corresponded closely with the temporal pattern and the return to the control value of the central venous mean and pulse pressure. The findings of thse experiments are not consistent with the view that any of the measured body fluid volumes directly and always determine renal excretion. It is proposed that in response to an acute blood volume expansion an animal may initially regulate neither its blood volume nor its extracellular fluid volume but rather a factor which is reflected in or related to the central venous pressure.

Animals↗
PubMed1981

The pharmacokinetics of the intravenous steroid anesthetic alphaxalone in the isolated perfused rat lung.

We have examined four mathematical systems modeling the transit of the steroid anesthetic alphaxalone (3 alpha-hydroxy-5 alpha-pregnane-11,20-dione) through the lung. Using the isolated rat lung perfused with a plasma substitute containing 14C-alphaxalone and 3H-dextran, we have obtained results that are incompatible with models involving (a) anatomical variations in the microcirculation, (b) high solubility, or (c) specific binding. We develop a stochastic model of a physical process analogous to the sequence of events that takes place in a chromatography column. This model closely fits the experimental data and predicts a peak effluent concentration of alphaxalone that may occur after washout with several exclusion volumes. It represents a delay with the pulmonary compartment that may explain a difference in induction times observed between various intravenous anesthetic agents.

Anesthetics↗
PubMed1980

Binding of native and denatured collagen to immunoglobulins and cold insoluble globulin in serum of patients undergoing orthopedic surgery.

Native and denatured 125-I-collagen were reacted with sera from 366 patients undergoing orthopedic surgery. Complexes consisting of native or denatured collagen and immunoglobulins or of denatured collagen and cold insoluble globulin were precipitated with secondary antibodies to either immunoglobulins or CIG. Only approximately 10% of the patients' sera bound more than 5 ng native collagen/10 microliter serum. Binding of denatured collagen to immunoglobulins occurred more frequently and in larger amounts. Binding of denatured collagen to CIG was determined in some of the sera and found to occur in all of them and in substantial amounts. Some of the subjects developed pathergic reactions upon subsequent infusion of a gelatin based plasma substitute. There was no correlation between the severity of such adverse reactions and any of the parameters measured. Therefore, the observed clinical reactions are not likely to be caused by true immunological mechanisms.

Binding Sites, Antibody↗
PubMed1995

Mechanisms of postoperative prolonged plasma volume expansion with low molecular weight hydroxethy starch (HES 200/0.62, 6%).

OBJECTIVE: To define the mechanisms of the stable and prolonged post-operative plasma volume expansion observed with Hydroxyethyl Starches (HES) and to determine whether a partial intravascular hydrolysis of large molecules contribute to reinforce the colloid-osmotic effect. DESIGN: Prospective, pharmacologic study using single dose of drug. SETTING: University-based, post-anesthesia care unit. PATIENTS: The protocol was performed during the post-operative period, in 10 patients after stable recovery from general anesthesia for carotid endarterectomy. INTERVENTIONS: HES 200/0.62 (500 ml) was infused over 30 min. Standard hemodynamic and biological variables, HES concentration and colloid osmotic pressure were obtained at each measurement. Plasma volume was calculated using 51Cr-labelled RBCs. Patterns of changes in number average molecular weight (MWn) and weight average MW (MWw) were measured using gel permeation chromatography. Measurements were obtained at control, end of infusion, 1 h, 3 h, 6 h and 24 h after infusion. MEASUREMENTS AND MAIN RESULTS: Plasma volume increased by 693 ml (+21%) after the infusion of HES and remained constant over 24 h. HES concentration progressively decreased to reach a value of 35% of the peak at 24 h. MWn and MWw, initially decreased when compared with the dose solution and changed little in the 24 h study period. Diuresis significantly decreased at 3 h up to 24 h. Plasma albumin decreased after infusion and then progressively increased to reach a significantly higher value at 24 h than after infusion. CONCLUSION: Initial plasma volume expansion and decrease in HES concentration agree with previously-published data. Maintenance of plasma volume expansion over 24 h was not related to a partial intravascular hydrolysis. Low elimination rate of HES, extravascular mobilization of albumin and post-operative renal adaptations were possibly the 3 main mechanisms to explain a prolonged plasma volume expansion with HES 200/0.62, 6%.

Aged↗
PubMed1988

Prediction of risk for pseudoallergic reactions and histamine release in patients undergoing anaesthesia and surgery: a computer-aided model using independence-Bayes.

A computer-aided model for the prediction of pseudoallergic reactions was developed using prospective data collected from 581 patients in a controlled clinical trial examining pseudoallergic reactions to the plasma substitute Haemaccel (outdated formulation). The multivariate analysis of 22 proposed risk factors was performed using Bayes theorem. This enabled the accurate prediction of 86% of the patients who had a systemic reaction. The clinical use of such system would enable a selection of patients to receive the effective prophylactic measure of pretreatment with H1 plus H2-receptor antagonists.

Anesthesia↗
PubMed1997

[Economic aspects of modern inhalation anesthetics with sevoflurane as an example].

The economic impact of the new German health care laws requires an awareness of cost-effectiveness when using newer drugs. The main goal in patient care, i.e., effective treatment, must be achieved by the rational use of restricted resources at a maximum degree of effectiveness. Economic aspects of the new inhalational anaesthetics such as sevoflurane are discussed in this article. The cost of inhalational anaesthetic agents accounts for up to 5% of all the running expenses of an anaesthesia department. The consumption and cost of an inhalational agent depend on fresh gas flow, vapour setting, and duration of anaesthesia. Comparing the cost for 1 MAC-h of anaesthesia, desflurane is more expensive at current market prices than sevoflurane and isoflurane. However, at low or minimal fresh gas flows, the price for one MAC-h is almost the same for these volatile anaesthetics. Total intravenous anaesthesia using propofol is even more expensive, partly due to wastage, i.e., opened ampoules with a remainder of propofol that has to be discarded after each case. When choosing an anaesthetic agent, the price of 1 ml liquid anaesthetic is an important factor. However, the overall cost-effectiveness analysis must balance the cost of the agent with its pharmacodynamic advantages such as more rapid recovery from anaesthesia. Furthermore, the indirect costs of side effects have to be taken into account. For example, nausea and vomiting lead to a prolonged stay in the recovery room after anaesthesia for outpatient surgery, which in turn incurs additional costs for antiemetic drugs and the extra time for nursing care. Therefore, a lower incidence of nausea and vomiting and a more rapid recovery from anaesthesia leading to earlier discharge from the recovery room may compensate for the higher price. Volatile agents account for up to 1% of the total intraoperative costs. In analysing the costs of 1 h of anaesthesia, other products such as plasma substitutes and blood products account for a much higher proportion than anaesthetic agents, and reductions or increases in costs pertaining to these products have a bigger impact on overall costs than do volatile anaesthetics. We conclude that volatile anaesthetics account for only a minor portion of the anaesthesia department budget and the cost of anaesthesia delivery. The higher market price of the new agents may be compensated for by the economic impact of fewer side effects and a shorter post-anaesthesia stay in the hospital. In analysing data for sevoflurane, this agent may be cost-effective, for example, for outpatient anaesthesia.

Anesthesia Department, Hospital↗
PubMed2002

Hydroxyethyl starch and modified fluid gelatin maintain plasma volume in a porcine model of septic shock with capillary leakage.

OBJECTIVE: To compare the effects of different volume replacement therapies on maintenance of plasma volume in septic shock and capillary leakage syndrome. DESIGN AND SETTING: Prospective randomized, controlled animal laboratory study in a university animal laboratory. MEASUREMENTS AND RESULTS: Twenty-five fasted, anaesthetized, mechanically ventilated and multi-catheterized pigs (20.8+/-1.8 kg) received 1 g/kg body weight faeces into abdominal cavity to induce sepsis and were observed over 8 h. Five animals each received volume replacement therapy with modified fluid gelatin 4% or 8% (MFG4%, MFG8%), 6% HES 200/0.5, or Ringer's solution and were compared to controls receiving 6% HES 200/0.5. Infusion rate was titrated to maintain a central venous pressure of 12 mmHg. Plasma volume was determined using (51)Cr-labelled erythrocytes and standard formulae. Albumin escape rate was calculated using technetium (99m)Tc-labelled albumin. Colloid osmotic pressure, systemic haemodynamics and oxygenation were obtained before and 4 and 8 h after induction of sepsis. Plasma volume was reduced in the Ringer's solution group (-46%) but was maintained in HES (+/-0%), MFG4% (+4%), MFG8% (+23%) groups. Albumin escape rate increased in HES (+52%), MFG4% (+47%), MFG8% (+54%) and the Ringer's solution group (+41%) compared to controls. CONCLUSION: In this porcine septic shock model with concomitant capillary leakage syndrome, confirmed by an increased albumin escape rate, the artificial colloids HES, MFG4%, and MFG8% maintained plasma volume and colloid osmotic pressure. These results suggest the intravascular persistency of artificial colloids in the presence of albumin leakage. An editorial regarding this article can be found in the same issue (http://dx.doi.org/10.1007/s00134-002-1283-9)

Albumins↗
PubMed2004

Volume expansion of albumin, gelatin, hydroxyethyl starch, saline and erythrocytes after haemorrhage in the rat.

OBJECTIVE: To compare the colloids 5% albumin, 4% gelatin and 6% hydroxyethyl starch (HES) 130/0.4 with each other and with saline, regarding their plasma-expanding effects after haemorrhage; these were also compared with the intravascular volume-expanding effect of re-transfusion with erythrocytes. DESIGN: Controlled, prospective, randomised laboratory study. SETTING: University research laboratory. SUBJECTS: Thirty-five adult rats. INTERVENTIONS: Plasma volume was determined (I(125) albumin tracer technique) after haemorrhage of 20 ml/kg and 3 h after a bolus infusion of 20 ml/kg of each of the colloids or 80 ml/kg of saline, or 6.7 ml/kg of erythrocytes diluted in 9 ml/kg of saline. Blood pressure, haematocrit (Hct), blood gases and physiological parameters were measured. MEASUREMENTS AND RESULTS: Plasma volume after haemorrhage was 29.6+/-2.6 ml/kg (n=35). With the bolus infusion, plasma volume increased by 21.1+/-3.6 ml/kg in the albumin group (n=7), by 13.1+/-2.9 ml/kg in the gelatin group (n=7), by 13.8+/-2.2 ml/kg in the HES group (n=7), by 16.0+/-2.4 ml/kg in the saline group (n=7) and by 6.9+/-2.3 ml/kg in the erythrocyte group (n=7) 3 h after the infusion. In the latter group, there was a total increase in intravascular volume of 13.6+/-2.5 ml/kg including the erythrocyte volume. Arterial pressure was better preserved in the albumin and erythrocyte groups than in the other groups. CONCLUSION: Albumin 5% was a more effective plasma volume expander than gelatin and HES. Saline, with a four times larger volume, and erythrocytes in about 1/3 of the volume had a similar volume-expanding effect to gelatin and HES.

Albumins↗
PubMed2006

Plasma volume expansion of 5% albumin, 4% gelatin, 6% HES 130/0.4, and normal saline under increased microvascular permeability in the rat.

OBJECTIVE: To compare the colloids 5% albumin, 4% gelatin, and 6% HES 130/0.4 with one another and with normal saline regarding their plasma expanding effects at increased permeability and to compare the results with those from a previous study at normal permeability. DESIGN AND SETTING: Prospective controlled randomized laboratory study in a university research laboratory. SUBJECTS: 48 adult male Sprague-Dawley rats. INTERVENTIONS: Permeability was increased by an injection of 0.5 ml dextran 70 using the fact that dextran causes anaphylactic reaction in the rat. Plasma volume was determined ((125)I albumin tracer technique) after anesthesia, 1 h after dextran injection (before infusion for 10-15 min of 20 ml/kg bw of each of the colloids or 80 ml/kg saline), and 3 h later. Blood pressure, hematocrit, blood gases, and electrolytes were measured. CVP was measured in four rats. MEASUREMENTS AND RESULTS: Plasma volume was 41.1+/-1.9 ml/kg at baseline (n=9), and 29.1+/-4.1 ml/kg (n=35) 1 h after the dextran injection. Three hours after infusion of the plasma expander plasma volume had increased by 17.1+/-3.4 ml/kg in the albumin group, 7.9+/-3.6 ml/kg in the gelatin group, 7.4+/-4.4 ml/kg in the HES group, and 12.2+/-3.1 ml/kg in the saline group. It was unchanged in a control group given no solution (n=7 for all groups). CONCLUSION: Albumin was a more effective plasma volume expander than gelatin or HES or saline (saline in 4 times larger volume). Gelatin and HES were equally effective. All solutions showed a smaller plasma expanding effect than observed in a previous study with normal permeability.

Albumins↗
PubMed1998

Volume therapy in the critically ill: is there a difference?

OBJECTIVE: There are still several concerns about the extensive and prolonged use of hydroxyethylstarch solution (HES) in critically ill patients. The effects of volume replacement with HES over 5 days on hemodynamics, laboratory data, and organ function were compared with volume therapy using human albumin (HA). DESIGN: Prospective, randomized study. SETTING: Clinical investigations on a surgical intensive care unit (ICU) of a university hospital. PATIENTS: 150 traumatized patients (injury severity score > 15) and 150 postoperative patients with sepsis were analyzed. INTERVENTIONS: Either 10% low-molecular weight HES (HES-trauma, n = 75; HES-sepsis, n = 75) or 20% HA (HA-trauma, n = 75; HA-sepsis, n = 75) was given for 5 days to maintain the pulmonary capillary wedge pressure (PCWP) between 12 and 15 torr. The entire management of therapy of the patients was performed by physicians who were not involved in the study and blinded to the infusion regimen. MEASUREMENTS AND RESULTS: In addition to extensive cardiorespiratory monitoring, several routine laboratory parameters for assessing pulmonary, renal, hepatic, and coagulation function were analyzed from arterial blood samples on the day of admission to the ICU and on the day of sepsis diagnosis, respectively ("baseline" value) and daily over the following 5 days. Mortality during and after the study did not differ significantly between the infusion groups. There were also no differences between the incidence of pulmonary, renal, or hepatic failure in the two subgroups. Mean arterial pressure, heart rate, and PCWP were similar in both subgroups, whereas cardiac index, oxygen delivery index, oxygen consumption index, and the ratio between the partial pressure of oxygen in arterial blood and fractional inspired oxygen were higher in the HES- than in the HA-treated groups. Standard coagulation parameters did not differ, albumin concentration increased significantly in both HA groups, and lactate concentrations decreased only in the HES-sepsis patients (from 2.8 +/- 0.5 to 1.5 +/- 0.4 mg/dl). Volume replacement using albumin was significantly (p < 0.001) more costly than therapy with HES. CONCLUSIONS: Volume therapy with 10% HES for 5 days in the ICU patient showed no disadvantages compared with an infusion regimen using 20% albumin. Volume replacement using HES may even be associated with improved hemodynamics. HES appears to be a valuable and significantly cheaper alternative to albumin--even for prolonged volume therapy in the critically ill patient.

Adult↗
PubMed1991

Impaired response of atrial natriuretic factor to blood volume expansion in acute right ventricular infarction.

To assess the role of atrial natriuretic factor (ANF) in right ventricular (RV) infarction, 30 patients with inferior wall acute myocardial infarction (15 with RV involvement) and normal left heart filling pressures were studied 39 +/- 12 hours after the onset of symptoms. Serial measurements of cardiac output, right atrial, pulmonary artery and pulmonary wedge pressures, as well as plasma ANF, plasma renin activity, plasma aldosterone and vasopressin were obtained before and 30 minutes after acute volume expansion to raise wedge pressure greater than or equal to 20 mm Hg. Baseline mean right atrial pressure and plasma ANF levels were greater in patients with than without RV infarction (8 +/- 3 vs 5 +/- 2 mm Hg; p less than 0.0001, and 4.6 +/- 2.9 vs 2.7 +/- 1.5 fmol/ml; p less than 0.05, respectively). There were no differences in other baseline hemodynamic or humoral parameters between both groups. After volume expansion, pulmonary wedge pressure was similar in both groups, but right atrial pressure increased to higher levels in patients with RV infarction (19 +/- 2 vs 14 +/- 2 mm Hg; p less than 0.0001). Despite this greater stimulus for ANF secretion, the increase in plasma ANF was less pronounced in patients with RV infarction (63 +/- 81 vs 455 +/- 417%; p less than 0.002), especially among those with paroxysmal supraventricular tachyarrhythmias. Thus, despite higher baseline plasma levels of ANF, response to volume loading is markedly attenuated in patients with RV infarction complicating an inferior wall acute myocardial infarction.

Adult↗
PubMed1986

Erythrocyte sedimentation rate during steady state and painful crisis in sickle cell anemia.

To define its diagnostic utility in sickle crisis, the erythrocyte sedimentation rates of oxygenated blood were studied in patients with sickle cell anemia and healthy normal subjects using the Guest-Westergren method. A normal range for sedimentation rate as a function of hematocrit was established in 22 normal subjects. Twenty-seven asymptomatic patients with sickle cell anemia had abnormally low sedimentation rates in relation to their hematocrits. Those low sedimentation rates were not increased by substituting plasma from healthy control subjects, which suggests that the low sedimentation rate was a cell-related phenomenon. Sedimentation rates measured in 28 patients with sickle cell anemia at the end of uncomplicated painful crisis increased to levels appropriate for their degree of anemia. In patients with sickle crisis and medical complications, the sedimentation rates were even higher. At the end of an uncomplicated painful crisis, the mean plasma fibrinogen level was significantly higher than at the onset (p less than 0.005). When red cells from patients with sickle cell anemia at the end of crisis were suspended in normal plasma from control subjects, the sedimentation rates remained high. It is concluded that the erythrocyte sedimentation rate of asymptomatic patients with sickle cell anemia is abnormally low due to cellular factors, and the increase during painful crisis is due primarily to red cell changes, modified by plasma factors.

Adult↗