Carotenoid compound crocetin improves cerebral oxygenation in hemorrhaged rats.

The carotenoid compound crocetin has been shown to increase oxygen diffusivity in vitro. In the present study the effect of crocetin on tissue oxygenation was examined in the cerebral cortex of rats subjected to hemorrhage. Twelve male Sprague-Dawley rats were anesthetized with pentobarbital and ventilation was controlled (PaCO2 = 33 mm Hg). A craniotomy was performed and the animals were hemorrhaged (20% of estimated total blood volume). Six of 12 animals then received a bolus of crocetin (2 U in 0.1 ml saline); the remaining animals received saline (0.1 ml i.v.) only. Values for mean arterial pressure. PO2, PCO2, pH, and hematocrit did not differ in rats that received either saline or crocetin. Tissue oxygen tension (PtO2) was measured at approximately 170 locations in the parietal cerebral cortex of each rat by a platinum-oxygen microelectrode technique. Results were compared by PtO2 frequency histograms. Crocetin as compared with saline treatment resulted in a right shift of the PtO2 frequency distribution and a significant decrease in the frequency of occurrence of low PtO2 values. The average of individual median PtO2 values was significantly greater in crocetin-treated animals as compared with those receiving saline (7.6 +/- 1.7 vs. 3.2 +/- 1.2 mm Hg, respectively). The results suggest that the carotenoid compound crocetin improves tissue oxygenation in the cerebral cortex of hemorrhaged rats.

Oxygen partial pressure distribution within skeletal muscle: indicator of whole body oxygen delivery in patients?

Simultaneously with determination of cardiac output, the distribution of oxygen partial pressure within biceps muscle was measured during and after open heart surgery in 29 patients. During extracorporeal circulation (ECC) mean muscular oxygen partial pressure (MPO2m) decreased from 25 mmHg to 14 mmHg with an increase of MPO2 values below 5 mmHg from 4% to 20%. Sustained decrease of MPO2m (greater than 1h) did not occur after ECC. Before ECC and in the postoperative period, MPO2m was lineary correlated (r = 0.85) to whole body oxygen delivery (Ox. offer) suggesting that local oxygen delivery within biceps muscle was sufficiently indicated only by systemic parameters of oxygen transport which require determination of cardiac output. Particularly with regard to relative changes, MPO2m might be used for estimation of whole body oxygen offer clinically.

Cerebral oxygen tension in rats during deliberate hypotension with sodium nitroprusside, 2-chloroadenosine, or deep isoflurane anesthesia.

Thirty-four male Sprague-Dawley rats were divided into four groups: control animals and those receiving sodium nitroprusside (SNP), 2-chloroadenosine, or a high, inspired concentration of isoflurane to produce deliberate hypotension to a mean arterial blood pressure of 50 mmHg. Ventilation was controlled (FIo2 = 0.3); control animals and those treated with sodium nitroprusside or 2-chloroadenosine breathed isoflurane 1.4 vol%, whereas isoflurane, 3.9 vol%, was required to produce hypotension by deep anesthesia alone. Multiple tissue oxygen tension values (PtO2) were measured at intervals of 10 micron over a distance of 2 mm by advancing an oxygen microelectrode through the parietal cerebral cortex of all animals. The frequency of low tissue PO2 values (less than 10 mmHg) was increased with all forms of deliberate hypotension, but the magnitude of this change (a shift to the left in the frequency histogram) was significantly different among techniques. The shift toward lower PtO2 values during hypotension was least in animals receiving deep isoflurane anesthesia, intermediate in those receiving SNP, and greatest in those treated with 2-chloroadenosine. In rats, areas of the brain appear to be at risk for significant tissue hypoxia during hypotension produced by 2-chloroadenosine.

[Propofol versus midazolam. Long-term sedation in the intensive care unit]. / Propofol versus Midazolam. Langzeitsedierung auf der Intensivstation.

Sedative-analgesic treatment of patients on long-term artificial ventilation aims at protection from stress related to their disease or therapy. By stabilising both the patient's vital functions and psychological state this treatment may contribute to therapeutic success. The choice of drugs depends primarily on the nature and course of the underlying disease. Midazolam and propofol are available as hypnotics for short-term sedation during the post-operative period. The purpose of this study was to evaluate the effects of both agents on cardiovascular function, cortisol production, lipometabolism, and the recovery period following 24-h sedation. METHODS. Twenty female patients (mean body weight: 72 kg, mean age: 60 years) were randomly assigned to receive either midazolam or propofol over 24 h following major abdominal surgery. Balanced anaesthesia (halothane/O2/N2O/fentanyl) was administered for the surgical procedure. Assisted ventilation was used in all patients during the post-operative sedation period. Sedation depth was maintained at III-IV on the Ramsey scale. On arrival in the intensive care unit (ICU), an initial i.v. bolus of midazolam 0.1 mg/kg or propofol 1 mg/kg was followed by a continuous infusion (midazolam: 0.1 mg/kg.h; propofol: 2 mg/kg.h). Supplementary boluses of one-half the initial dose were given if required. Post-operative analgesia was achieved with 3 mg intravenous piritramide at 2-h intervals. A 7F Swan-Ganz catheter was inserted in the pulmonary artery and haemodynamic and biochemical parameters were monitored at 4-h intervals over 24 h starting 2 h after arrival in the ICU. Catecholamines were measured by high-pressure lipid chromatography (HPLC), cortisol by radioimmunoassay, midazolam by HPLC and ultraviolet detection, and propofol by HPLC and fluorescence detection. Data were calculated as means. The statistical analysis was performed according to the Mann-Whitney test, and significance was accepted for P less than 0.05. RESULTS. On administration of the propofol bolus at the onset of sedation, a decrease in blood pressure was particularly observed in patients with masked hypovolaemia, however, this decrease was easily controlled by volume administration. Independent of the type of sedation, the haemodynamic parameters remained unchanged throughout the observation period. At all times of measurement the mean heart rate was lower in the propofol group (90/min) when compared with the midazolam group (100/min), however, this difference did not reach significance. There were also no significant differences in cardiac index at all times of measurement, although it increased in both groups within the first 12 h by 0.6 l/min.min2. In both groups this increase was associated with a reduction in peripheral resistance and an increase in rectal temperature. To achieve the desired sedation depth, midazolam was administered at a mean dosage of 0.11 mg/kg.h and propofol at 1.9 mg/kg.h. Catecholamine levels decreased in both groups within the first 8 h: after 8 h of sedation the plasma levels of noradrenaline and adrenaline were 525 and 65 pg/ml, respectively, in the midazolam group and 327 and 51 pg/ml in the propofol group. (ABSTRACT TRUNCATED AT 400 WORDS)

Anesthetic influences on regional hemodynamics in normal and hemorrhaged rats.

Forty-six male Sprague-Dawley rats were divided in five groups: awake animals and those receiving ketamine, halothane, enflurane, or isoflurane anesthesia. Cannulae were inserted into the left femoral artery and vein and the left ventricle. Inspired concentrations of the volatile anesthetics were adjusted to achieve the minimal alveolar concentration (MAC) of each drug. Ketamine, 125 mg . kg-1, was injected intraperitoneally and then infused at a rate of 1 mg . kg-1 . min-1. All animals breathed spontaneously throughout the experiment (FIO2 = 0.3). Following a 2-h stabilization period, 30% of estimated blood volume was withdrawn gradually over 10 min. Immediately before and 20 min after hemorrhage, cardiac output and regional blood flows were measured by the microsphere method (85Sr, 141Ce-labeled 15-microns microspheres, respectively). Arterial blood samples were analyzed for PO2, PCO2, pH, lactate, and pyruvate at these times also. Prior to hemorrhage, cardiac output (CO) values were similar in awake rats and those receiving ketamine or isoflurane, but CO was reduced moderately by enflurane and to a greater extent by halothane. After hemorrhage, CO was greatest in awake animals and those receiving isoflurane, and awake rats tended to have the greatest organ blood flows. Values of lactate/pyruvate and excess lactate were least in awake animals. Overall results suggested that, in terms of cardiac output and regional blood flows, ketamine approximates the awake state most closely in normovolemic animals, whereas isoflurane anesthesia is most like the awake condition after hemorrhage.

The hemodynamic response to isoflurane is altered in genetically hypertensive (SHR), as compared with normotensive (WKY), rats.

The authors compared the hemodynamic effects of isoflurane anesthesia in normotensive (WKY) and genetically hypertensive (SHR) rats. Eighteen male SHR and 18 WKY rats were subdivided into conscious animals and those anesthetized with isoflurane, 1.2 vol% inspired. During brief isoflurane anesthesia, cannulae were placed in the left cardiac ventricle, the femoral artery, and the femoral vein. Central and regional hemodynamics were determined with 85Sr-labeled microspheres (15 +/- 1 micron) using the reference sample technique in both conscious and anesthetized animals. Isoflurane anesthesia caused similar reductions in mean arterial blood pressure (MAP) in all rats. This was due to a significant decrease in systemic vascular resistance in WKY rats, whereas MAP declined due to a significant decrease in cardiac output in SHR rats. In the anesthetized WKY rat, the decrease in total systemic vascular resistance resulted from significant decreases in vascular resistance of the brain and nonrespiratory skeletal muscles. In the anesthetized SHR rat, both decreases (cerebellum, hepatic artery) and increases (GI tract, skin, diaphragm) in regional vascular resistances occurred, resulting in no net change in total systemic vascular resistance. In both SHR and WKY rats, isoflurane redistributed blood flow in favor of the brain at the expense of blood flow to the GI tract, diaphragm, and skin. Blood flows to the liver, GI tract, and skin were significantly less in the anesthetized SHR as compared with WKY rats. It is concluded that isoflurane influences central and regional hemodynamics differently in hypertensive, as compared with normotensive, rats.

[Non-invasive Doppler-ultrasound determination of cardiac output. Results and experiences with the ACCUCOM]. / Nicht-invasive Doppler-Ultraschallmessung des Herzzeitvolumens. Ergebnisse und Erfahrungen mit dem ACCUCOM.

Because of the invasiveness of the method, the determination of cardiac output (CO) by the thermodilution technique is not without a certain risk to the patient. Previous studies have suggested that noninvasive Doppler technology could be used to determine the velocity of blood in the aorta. With knowledge of the diameter of the aorta, CO can be calculated. The newly developed ACCUCOM (Datascope Corp.) measures CO noninvasively by Doppler ultrasound. However, there is not much information as to how the ACCUCOM performs in clinical practice. The present study was designed to compare the determination of CO by the ACCUCOM with that by thermodilution. CO was determined simultaneously in 12 anesthetized patients scheduled for abdominal or orthopedic surgery. There was a significant but not very tight linear correlation (r = 0.82) between ACCUCOM and reference measurements. The ACCUCOM underestimated CO on the average by 32%. In order to analyze the ACCUCOM tracking of relative changes in CO, in 6 out of 12 patients CO was also determined during cardiac stimulation by isoprenaline (0.5-1.0 microgram.min-1) IV. The resulting increase in CO was detected reliably using the ACCUCOM. It was, however, significantly overestimated by the Doppler technique (average increase = 58%) as compared to the reference method (average increase = 42%). These results suggest the possibility of major deviations in determining CO with the ACCUCOM.(ABSTRACT TRUNCATED AT 250 WORDS)

The addition of nitrous oxide to halothane decreases renal and splanchnic flow and increases cerebral blood flow in rats.

Thirteen male Sprague-Dawley rats were anaesthetized with halothane and catheters were placed in the femoral artery and left ventricle. The animals breathed spontaneously through a tracheostomy throughout the investigation. After the surgical preparation, the inspired halothane concentration was maintained at 1.5 vol% (F/O2 = 0.3). After a 30-min stabilization period, strontium-85 radiolabelled microspheres (15 +/- 1 micron) were injected to the left ventricle for determination of cardiac output and regional blood flows. In six rats, nitrous oxide was then substituted for nitrogen in the inspired gas mixture. Ten min thereafter, 141Ce-labelled microspheres were injected and the haemodynamic measurements were repeated in all animals. The administration of the nitrous oxide to halothane-anaesthetized rats resulted in a decrease in cardiac output and decreases in blood flow to kidneys, liver, small bowel and spleen. Cerebral perfusion was increased.

Methylprednisolone plus ibuprofen increases mortality in septic rats.

Steroids and cyclooxygenase inhibitors have been advocated as adjunctive treatment for sepsis. We studied the influences of these treatments on the survival of 98 male Sprague-Dawley rats in which sepsis was induced by cecal ligation and puncture. Rats received one of four treatments: sodium chloride (NaCl); methylprednisolone, 30 mg/kg (MP); ibuprofen, 12.5 mg/kg (I); methylprednisolone, 30 mg/kg, plus ibuprofen, 12.5 mg/kg (MP + I). Cumulative survival statistics were determined daily for 14 days thereafter. Survival was not altered by either MP or I when compared to animals receiving NaCl only. However, the combination of MP + I increased mortality from day 2 through day 14. The authors conclude that (1) MP administration alone does not increase mortality in septic rats; therefore, the results do not support the contention that steroid treatment in the absence of antibiotic therapy may be detrimental; (2) the cyclooxygenase inhibitor I does not improve survival in septic rats; and (3) the combined administration of MP and I increases mortality in septic rats and the possibility that this combination might be harmful in septic patients should be considered also.

Dose-dependent effects of bupivacaine on rat muscle arterioles.

The dose-dependent actions of bupivacaine on the microvasculature were evaluated by television microscopy in an in vivo rat cremaster muscle preparation. Animals were anesthetized with chloralose and urethane. Mean arterial pressure was measured via a carotid artery cannula; heart rate was calculated from the phasic pressure trace. The cremaster muscle was suffused with a balanced electrolyte solution that was controlled for temperature, pH, PO2, PCO2, and osmolarity to provide a physiologic environment. Internal diameters of fourth-order arterioles were measured with an electronic vernier displayed on the video monitor. Arteriolar diameters were measured every 30 s during a 10-min control period, a 10-min period of topical application of bupivacaine hydrochloride, and a 30-min recovery period. Bupivacaine 10(-1), 10(0), 10(1), and 10(2) micrograms X ml-1 produced progressive vasoconstriction to 82.7 +/- 2.9%, 75.0 +/- 5.6%, 71.0 +/- 7.0%, and 65.7 +/- 9.4% of control (P less than 0.05 for each), respectively. Bupivacaine, 10(3) and 2.5 X 10(3) micrograms X ml-1, did not alter arteriolar diameters significantly, although there was a tendency for vasodilation. In a second group of animals, arteriolar diameters were measured during intravenous bupivacaine infusion that produced stable plasma concentrations of 2.3 +/- 0.2 micrograms X ml-1. Vasoconstriction of 91.4 +/- 2.2%, of control (P less than 0.01) was observed. These results demonstrate that dose-dependent arteriolar constriction occurs even with blood bupivacaine levels that are at the upper limits of those expected to occur during regional anesthesia.

[Energy and amino acid metabolism in the human brain under Disoprivan anesthesia with various paCO2 values]. / Energie- und Aminosäurenstoffwechsel des menschlichen Gehirns unter Disoprivan und verschiedenen paCO2-Werten.

Propofol like thiopental and etomidate, suppresses cortical electrical activity in a dose-related manner, which leads to a 36% decrease in cerebral oxygen uptake and a 51% decrease in cerebral blood flow after an induction dose of 2 mg/kg followed by a maintenance dose of 0.2 mg/kg per min. In this study, the effects of propofol and varying paCO2 values on cerebral energy and amino acid metabolism were examined. METHODS. Eleven male patients between 49 and 63 years of age who were about to undergo coronary artery bypass surgery were studied. Measurements were performed with the patient awake (I), during steady-state maintenance anesthesia after propofol 2 mg/kg as an induction dose with 0.2 mg/kg per min by infusion with normocapnia (paCO2 39.9 +/- 3.1 mm Hg) (II), during hypocapnia (paCO2 29.9 +/- 2.6 mmHg) (III), and during hypercapnia (paCO2 50.6 +/- 3.3 mmHg) (IV). Cerebral blood flow was measured using the argon wash-in technique. A catheter was advanced into the superior bulb of the right internal jugular vein for measurement of cerebral oxygen, glucose, lactate, and amino acid uptake and release, which were calculated by multiplying the arterial-cerebral venous oxygen and substrate difference by the cerebral blood flow. Lactate/glucose index was calculated from the equation. Formula: see text. where a-vD lactate and a-vD glucose represent the arterial-cerebral venous substrate differences in mmol/l. Cerebral electrical activity was recorded by Fourier analysis of the EEG.(ABSTRACT TRUNCATED AT 250 WORDS)

[The effect of selective decontamination on nosocomial infections, their causative agents and antibiotic resistance in long-term intubated intensive care patients]. / Einfluss der selektiven Dekontamination auf nosokomiale Infektionen, Erregerspektrum und Antibiotikaresistenz bei langzeitbeatmeten Intensivpatienten.

During a 12-month period 45 long-term intubated patients were treated by topical application of non-absorbable antibiotics (tobramycin, polymyxin, amphotericin B) together with an initial short-term intravenous application of an antibiotic with only minimal activity against anaerobic intestinal flora. These patients were compared to 48 patients in the previous 12-month period who had only interventional antibiotic therapy in case of established infections. This selective decontamination of the digestive tract (SDD) reduced the colonisation of the respiratory tract, thus also decreasing incidence of nosocomial pneumonia. There were fewer urinary tract infections, while the incidence of wound infections and septicaemia was influenced to microorganism a lesser degree. The number of gram-negative isolated microorganism was reduced, leading to a shift towards gram-positive organisms, especially S. epidermidis. During the 12-month study period there was no change of antibiotic sensitivity of the isolated microorganisms. Although we encountered no problems associated with multiresistant pathogens, routine microbiological surveillance is strongly recommended to detect changes in antibiotic resistance at an early stage.

Effects of anesthetics on regional hemodynamics in normovolemic and hemorrhaged rats.

Twenty-nine male Sprague-Dawley rats were divided into four groups based on anesthetic exposure, i.e., awake animals and those receiving anesthesia produced by chloralose-urethan, pentobarbital, or by midcollicular brain stem transsection. Before and after hemorrhage (30% of the estimated blood volume), cardiac output (CO) and regional blood flows were measured by the microsphere method. Arterial blood gases and lactate (L) and pyruvate (P) were also determined. CO and regional blood flows were greatest and the L/P ratio was least in awake animals both before and after hemorrhage. In normovolemic rats, the frequency of altered values (as compared with those in awake animals) was similar for all anesthetic techniques, whereas the CO and regional blood flow responses to hemorrhage were altered less frequently in decerebrated animals. Decerebration may be the preferable procedure if the intent is to produce responses in anesthetized animals similar to those in awake rats. If the intent is to study hemodynamics in a specific organ, the selection of an anesthetic technique should be guided by the individual anesthetic effects on that particular tissue.

The influence of naloxone on regional hemodynamics in hemorrhaged rats.

Naloxone increases arterial pressure in hemorrhaged animals, but its effects on organ blood flows are not well established. We measured central and regional hemodynamics immediately before and 25 min or 55 min after hemorrhage in 33 anesthetized rats. Fifteen minutes after the beginning of hemorrhage, animals received either vehicle (n = 17) or naloxone (n = 16), 10 mg/kg, intravenously. At 25 min, animals treated with naloxone had a greater blood flow to the left cerebral hemisphere than those receiving vehicle, but all other measurements were similar. At 55 min, the mean arterial pressure and heart rate were greater in animals treated with naloxone, but blood flow was increased to the spleen only. Vascular resistance values were greater in the gastrointestinal tract and less in the spleen in animals receiving naloxone. The data confirmed that, in anesthetized rats, naloxone increased mean arterial pressure and splenic blood flow and transiently increased cerebral blood flow, but other regional flows and cardiac output were similar to those in rats receiving vehicle only.

Haemodynamic and endocrine effects of deliberate hypotension with magnesium sulphate for cerebral-aneurysm surgery.

Deliberate hypotension is widely used during cerebral-artery aneurysm surgery to facilitate clipping and to prevent rupture. A large number of drugs are commonly employed to achieve hypotension, but all have their specific drawbacks. We investigated the effects of magnesium-sulphate-induced hypotension on haemodynamics, as well as on plasma catecholamine and renin concentrations in 11 patients undergoing cerebral-aneurysm surgery. Magnesium sulphate lowered blood pressure by reducing systemic vascular resistance. There was no reflex tachycardia or rebound hypertension, and cardiac output was not decreased. Plasma renin activity increased during hypotension but the inhibitory effects of magnesium on angiotensin converting enzyme prevented angiotensin-II-associated hypertension. Plasma catecholamine concentrations increased moderately during hypotension. Renal perfusion was not impaired since diuresis remained constant or even improved during and after hypotension. Magnesium sulphate in high doses has major drawbacks, however, among which are enhanced neuromuscular blockade and delayed return of consciousness. Although the haemodynamic effects of magnesium sulphate during hypotension appear to be beneficial, these side-effects might limits its usefulness, particularly in neurosurgery. More research must be conducted before magnesium sulphate can be considered a routine method.

Improved haemorheology associated with a reduction in plasma fibrinogen and LDL in patients being treated by heparin-induced extracorporeal LDL precipitation (HELP).

Heparin-induced Extracorporeal LDL-Precipitation (HELP) is an effective procedure for the elimination of both plasma LDL and fibrinogen. In 10 adult patients with severe type II hyperlipoproteinemia, a single HELP treatment of 3 1 plasma led to an acute decrease in the average plasma viscosity (PV) from 1.30 to 1.1 mPas. At the same time, an even more marked decrease in the mean erythrocyte aggregation rate from a pathological value of 7.9% to a value of 3.7% (normal range less than 5%) was observed. Long-term studies on five patients demonstrated a lasting improvement in these two haemorheological variables. The acute rheological changes were also accompanied by an improvement in polarographically determined muscle oxygen tension. Mean oxygen tension values measured in both the m.biceps brachii and the m.tibialis anterior in five patients before and after a single HELP treatment increased from 30 +/- 4 to 37 +/- 7 mmHg and from 27 +/- 2 to 31 +/- 3 mmHg respectively. These results may provide an explanation for the rapid improvement in patients' clinical symptoms such as angina pectoris and in stress electrocardiogram which have been observed during HELP therapy.

Treatment of polycythemia vera by isovolemic large-volume erythrocytapheresis.

Excess red blood cells (RBC) in patients with polycythemia vera (PV) are usually removed by repeated phlebotomy. In order to improve the efficacy of this treatment, we used isovolemic large-volume erythrocytapheresis (EA) by a cell separator. A retrospective analysis of our experience with 69 PV patients (206 EA procedures) is reported. EA induced a rapid, well-tolerated, and long-lasting reduction of Hct, Hb, and RBC counts, as well as an immediate disappearance or reduction of clinical symptoms of PV, while tissue oxygen tension - as measured in 8 patients - increased. Hct was reduced by EA from 56.8% +/- 5.6% to 41.9% +/- 6.6%, Hb from 17.5 +/- 2.3 to 12.7 +/- 2.4 g%, RBC counts from 7.4 +/- 0.9 to 5.4 +/- 0.9 x 10(6)/mm3. The mean volume of the apherisate was 1410 +/- 418 ml, (mean Hct 79.7% +/- 9.3%), and the actual RBC volume removed 1113 +/- 367 ml. The isovolemic procedure was well tolerated and the acceptance by patients seemed to be better than with repeated phlebotomy. In 21 patients whose Hct values (Hct before and after EA 58% +/- 5.7% and 41.5% +/- 4.9%) were regularly followed after EA the mean period with Hct less than 50% after a single EA procedure was 6.1 +/- 4.1 months (median, 6); in 14 out of these 21 patients a Hct of less than 43% after EA was reached and their mean period with Hct less than 50% after EA was 7.6 +/- 4.0 months (median, 7.5). For three patients this period was 11, 13, and 15 months, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)