Distribution of filipin-sterol complexes in sperm membranes from hypercholesterolaemic rabbits

The distribution of membrane filipin-sterol complexes (FSC) was examined ultrastructurally in cauda epididymal sperm from normal and hypercholesterolaemic rabbits. Membrane FSC were quantitatively analysed on replicas of filipin-treated cells. We determined a significant difference in FSC concentration in the plasma membrane of the acrosome region (PMAR) of hypercholesterolaemic animals compared to normal rabbits. Hypercholesterolaemic animals had 0.56 +/- 0.05 FSC complex per micron 2 (enriched Cholesterol diet: Diet 2) in the marginal segment of PMAR; 0.62 +/- 0.05 FSC complex per micron 2 (enriched Cholesterol and fish oil diet: Diet 3) and only 0.28 +/- 0.01 FSC complex per micron 2 for normal animals (Control Diet 1). In the principal (anterior) segment we found 0.54 +/- 0.10 FSC complex per micron 2 (Diet 2), 0.56 +/- 0.03 FSC complex per micron 2 (Diet 3) and 0.30 +/- 0.04 FSC complex per micron 2 (Control Diet 1). We also counted 0.47 +/- 0.1 FSC complex per micron 2 in the equatorial segment of PMAR for Diet 2, 0.27 +/- 0.05 and 0.28 +/- 0.04 FSC complex per micron 2 in Diet 1 and Diet 3 respectively. Diet 4 (fish oil) did not differ from the control. An increase in the Cholesterol (Chol) level in biological membranes or a difference in the Chol membrane domains could cause a variation in the membrane rigidity that could modify the sperm membrane fusion capacity and functionality. The results presented in this paper are in agreement and could explain the decrease in the kinetic of the sperm acrosome reaction that we have observed in experimentally hypercholesterolaemic rabbits (Díaz-Fontdevila & Bustos-Obregón, 1992).     

Seminal fibronectin-like antigen and transferrin concentrations in infertile and fertile men

Summary.  Fibronectin like antigen (Fn) and transferrin (Trs) levels were measured in the seminal plasma of 40 fertile and 102 infertile men. The concentrations of both proteins were significantly ( P <0.001) higher in the fertile controls compared to the infertile groups. The levels of Fn and Trs (mean value ± SEM) in the fertile men were 857.9 ± 9.8 μg ml^-1 and 164.0 ± 6.5 μg ml^-1, respectively; in the azoospermic men ( n = 17) 552.7 ± 24.65 μg ml^-1 and 20.7 ± 2.19 μg ml^-1, respectively; in the group of severe oligozoospermia ( n = 35) 568.34 ± 25.7 μg ml^-1 and 31.1 ± 4.18 μg ml^-1, respectively; in the moderate oligozoospermic group ( n = 8) 572.50 ± 47.9 μg ml^-1 and 43.4 ± 15.4 μg ml^-1 respectively, and in the asthenozoospermic group ( n = 26) 512.76 ± 40.4 μg ml^-1 and 47.0 ± 7.9 μg ml^-1, respectively. Of special interest was the finding from a group of 16 normospermic men (partners of couples with unexplained infertility) who showed significantly lower levels of Fn like antigen, 632.5 ± 26.9 μg ml^-1 ( P <0.001) and Trs 41.8 ± 6.94 μg ml^-1 ( P <0.0001) compared to normals. No correlation was found between Fn levels with either Trs or FSH levels or sperm count. In conclusion, our results indicate that male infertility is associated with changes in seminal plasma Fn like antigen concentrations and that it can be possibly used as an index of sperm fertilizing capacity.     

The influence of sperm/zona pellucida collision rates on zona binding

Summary. The satisfying success rates reported with intra-cytoplasmic sperm injection (ICSI) urged clinicians and scientists to re-address the emphasis in the management of the male factor patient towards gamete manipulation in order to circumvent the underlying problem causing fertilization failure. We have designed a study to (i) calculate the collision rate of a sperm population with the human zona pellucida, using a mathematical hypothesis and (ii) use the calculated collision rate to evaluate subsequent zona binding results obtained under hemizona assay conditions. Microdroplets were used to co-incubate sperm and human oocytes in order to evaluate zona binding. Using microvolumes, the track followed by sperm, as well as the maximum distance travelled were employed to calculate the collision rate of sperm and zona pellucida. The sperm concentrations of swim up samples were adjusted to 4 × 10⁶ and 0.8 × 10⁶ sperm ml⁻¹. Five separate droplets each of 20 μl containing 4 × 10⁶ sperm ml⁻¹ (80000 motile sperm) and 200 μl containing 0.8 × 10⁶ sperm ml⁻¹ (160000 motile sperm), respectively, were prepared. Both volumes were incubated for 18 h at 37°C. The mean (±SD) number of spermatozoa tightly bound to hemizona, incubated in 20 μl and 200 μl sperm droplets, was 2444±612 and 548±315, respectively ( P = 0.0001). The results can be used as a guideline to calculate the optimum insemination concentration needed for a specific sperm population to ensure the maximum collision rates with the oocyte.     

Effects of Prostaglandin F2α on Sperm Count, Sperm Motility and Fertilizing Capacity in the Male Rabbit

Prostaglandin F_2α (PGF_2α) incorporated in Silastic-PVP tubes 2 cm long and one end sealed induced temporary sterility when placed intrascrotally in fertile male rabbits. A significant reduction in sperm number per ejaculate, testicular weight and the number of epididymal sperm accompanied the incidence of sterility which occurred 2–5 weeks after starting the treatment and persisted for 6–10 weeks. During the experimental period, no significant deviation in libido or ejaculate volume compared to sham controls was observed. Prostaglandin F_2α might have a local effect on the testis and epididymis, causing disintegration and depletion of the sperm reserve resulting in temporary sterility.     

Lack of effect of flumazenil on the reversal of propofol anaesthesia

Propofol, like the benzodiazepines, activates the GABA_A receptor-chloride ionophore complex; they potentiate one another. Since neither pharmacodynamic nor pharmacokinetic data concerning drug interaction between flumazenil and propofol is available, and especially considering the relationship of binding sites, flumazenil, the antagonist of benzodiazepines, was investigated to determine its effect upon recovery from propofol anaesthesia. Forty women receiving dilatation and curettage procedures were included in this double-blind test. After 50 μg fentanyl, propofol 2 mg · kg^-1 was injected for induction and followed by infusion at the rate of 15 mg · kg^-1 · hr^-1. After the operation, patients were given normal saline (Group A) or flumazenil 10 μg · kg^-1 (Group B) randomly.
Recovery time in Group A was 15.2±5.1 min and Group B 15.8±4.8 min. Propofol concentrations at the end of infusion were 4.17±1.33 μg ·ml^-1 (Group A) and 4.03±1.45 μg · ml^-1 (Group B); these then declined to 1.22±0.17 μg · ml^-1 (Group A) and 1.18±0.15 μg · ml^-1 (Group B) when patients were able to open their eyes on command. No significant differences were found between the groups based on propofol concentrations and recovery time, nor did haemodynamic changes differ between them after administration of reversal agents. It was concluded that flumazenil 10 μg · ml^-1 does not influence recovery from propofol anaesthesia.     

Cadmium, lead, selenium, and zinc in semen of occupationally unexposed men

Summary. Concentrations of cadmium, lead, selenium, and zinc were determined in semen and seminal plasma of 22 volunteers by atomic absorption spectrometry. Additionally conventional semen parameters and, by means of computer videomicrography, motion parameters of spermatozoa were evaluated. Concentrations of Cd, Pb, and Zn determined in semen were not significantly different from those measured in seminal plasma. However, selenium levels were significantly higher in semen (53.8 ± 22.9 μg 1⁻¹) than in seminal plasma (40.4 ± 15.5 μg 1⁻¹, P <0.01). The investigated semen samples on average contained low levels of Cd (0.4 ± 0.23 μg 1⁻¹) and Pb (9.8 ± 6.5 μg 1⁻¹). Studies on the intra-individual variability revealed the following average coefficients of variation (%) for element concentrations: Pb (70), Cd (53), Se (27), and Zn (23); and for semen parameters: total sperm count (46), sperm concentration (37), motility (22), ejaculate volume (21), linearity (19), linear velocity (11), curvilinear velocity (10), and percentage of normally formed sperm (9). Significant positive correlations were detected between semen selenium levels and sperm concentration ( r =0.51, P <0.05), and percentage of normally formed sperm ( r =0.46, P <0.05), respectively. Sperm motility ( r =0.53, P <0.02), linear ( r = 0.76, P <0.001) and curvilinear velocity ( r = 0.64, P < 0.002) were significantly correlated with semen cadmium levels.     

Potency and maintenance requirement of atracurium and vecuronium given alone or together

A synergism exists between some competitive muscle relaxants. However, maintenance requirement of a combination of muscle relaxants has been evaluated only in paediatric patients. We studied 45 elective adult surgical patients (ASA I-II) during propofol-alfentanyl-N₂O-O₂-anaesthesia. The first 30 patients were randomized to receive either atracurium or vecuronium to create individual dose-response curves for these muscle relaxants. ED₉₅-values for atracurium and vecuronium were 260±9 and 59±3 μg · kg^-1, respectively (mean±s.e.mean). Requirements of atracurium and vecuronium to maintain an 85–95% neuromuscular blockade were 301 and 83 μg kg^-1 h^-1, respectively. An additional 15 patients received a combination of atracurium and vecuronium (cAV) in an equipotent dose ratio. An ED₉₅ of a cAV was 94± 7 μg · kg^-1 of atracurium together with 21±2 μg · kg^-1 of vecuronium, or 72±6% of one ED₉₅ dose of a parent agent. Potentiation was significant ( P =0.0001). A maintenance requirement of a cAV was 120 μg kg^-1 h^-1 of atracurium together with 27 μg kg^-1 h^-1 of vecuronium. Thus, a significant potentiation was maintained also during the course of anaesthesia. A cAV had an effect like one intermediate-acting agent. If a cAV is used instead of using atracurium or vecuronium alone, the maximal reduction of drug consumption would be approximately 30%.     

L- carnitine in idiopathic asthenozoospermia: a multicenter study

Summary. The aim of the study described here was to evaluate any possible effect of L-carnitine on spermatozoal motility in a group of patients with unexplained asthenozoospermia in four different infertility centres. One hundred patients received 3 g d⁻¹ of oral L-carnitine for 4 months. Sperm parameters were studied before, during and after this treatment. Motility was also studied by means of a computer-assisted sperm analysis.
The results of the study indicate that L-carnitine is able to increase spermatozoal motility, both in a quantitative and in a qualitative manner (per cent motile spermatozoa increased from 26.9±1.1% to 37.7 ± 1.1% [ P < 0.001]; per cent spermatozoa with rapid linear progression increased from 10.8 ± 0.6% to 18.0 ± 0.9% [ P < 0.001]; mean velocity increased from 28.4 ± 0.6 μm s⁻¹ to 32.5 ± 0.8 μm s⁻¹ [ P < 0.001]; linearity index increased from 3.7 ± 0.1 to 4.1±0.1 [ P < 0.001], especially in the subgroup of patients with poor rapid linear progression of spermatozoa (per cent of motile spermatozoa increased from 19.3± 1.9% to 40.9± 1.4% [ P < 0.001], and per cent of spermatozoa with rapid linear progression increased from 3.1±0.4% to 20.3±1.6% [ P < 0.001]) An increase in spermatozoal output was also observed (total number of ejaculated spermatozoa increased from 142.4 ± 10.3 10⁶ to 163.3 ± 11.0 × 10⁶ [ P < 0.001]). The authors conclude that oral administration of L-carnitine may improve sperm quality at least in patients with idiopathic asthenozoospermia.     

Effect of succinylcholine on subsequently administered mivacurium in children

The interaction between mivacurium and succinylcholine when mivacurium was administered during the early recovery from succinylcholine block was studied in 30 children 2-12 years of age anaesthetized with propofolalfentanil-N₂O-O₂. Neuromuscular response was monitored by adductor pollicis EMG. Fifteen patients received 200 μg. kg^-1 of mivacurium (Group M), and another fifteen received 1500 μg. kg^-1 of succinylcholine followed by 200 μg. kg^-1 of mivacurium when the first EMG response recovered to 5% of calibration value (Group SchM). Plasma cholinesterase (pChE) activity was normal in each patient. The recovery times following mivacurium did not differ between the two groups. Times required for recovery of the first EMG response from 25 to 75% of full EMG recovery were 3.6±1.0 (mean±SD) and 4.0±0.7 min for the Groups M and SchM, respectively. The time from administration of mivacurium to the recovery of train-of-four ratio 0.70 was 13.2±3.3 min for the Group M and 13.6±3.1 min for the Group SchM (NS). Thus, in patients with normal pChE activity preceding administration of succinylcholine did not influence the recovery of neuromuscular function from subsequent mivacurium.     

Motility initiation of quiescent spermatozoa from rat caudal epididymis: effects of pH, viscosity, osmolality and inhibitors

Non-motile spermatozoa freshly extruded from the rat caudal epididymis can be initiated to full motility immediately after diluting with 0.9% NaCl. The motility initiation was dependent on the pH, viscosity and osmolality of the diluent. Diluent with pH 4 to 8 could optimally initiate the motility. Osmolality of most diluents suitable for the initiation was between 130 to 600 mOsm/kg. The motility initiation was inhibited by Hg²⁺ > Cu²⁺ > Cd²⁺, chlorpromazine, Triton X-100 and SDS. The following compounds showed essentially no inhibitory effect: EGTA, chlortetracycline, calcein, ruthenium red, phloridzin, myo-inositol and carnitine. The findings suggested that spermatozoa were kept in quiescence in the cauda epididymis not by the pH, osmolality, viscosity, myo-inositol, carnitine, Ca²⁺ or K⁺ of the caudal epididymal fluid. It was also suggested that motility initiation did not involve Ca²⁺. calmodulin and transport of Ca²⁺ or glucose across sperm membrane.     

Gonadal and Extragonadal Sperm Reserves of the Brazilian Nelore Zebu (Bos indicus)

Summary: Gonadal and extragonadal sperm reserves were estimated through hemocytometric method in six Nelore zebu bulls, aging 4–6 years, with normal spermatogenesis, and kept at sexual rest. Gonadal sperm reserve was estimated to be 47.8 ± 5.8 times 10⁶ sperm cells/g testis parenchyma and 9.8 ± 1.7 times 10⁹ sperm cells/testis. Using a time divisor of 4.94 days the daily sperm production was estimated to be 10.0 ± 0.9 times 10⁶ sperm cells/g testis parenchyma/day and 2.0 ± 0.3 times 10⁹ sperm cells/testis/day. Epididymal sperm reserve amounted 11.9 ± 1.6 times 10⁹ spermatozoa/organ, distributed as follows: 35.3 ± 3.6% in the head, 16.9 ± 1.7% in the body and 47.7 ± 3.7% in the tail.
Zusammenfassung: Gonadale und extragonadale Spermareserven des brasilianischen Nelore-Zebu (Bos indicus)
Bei sechs Nelore-Zebubullen im Alter von vier bis sechs Jahren mit normaler Spermatogenese und unter sexueller Karenz wurden mit einer haemocytometrischen Methode die gonadalen und extragonadalen Spermareserven bestimmt. Für die gonadale Spermareserve wurden Werte von 47.8 ± 5.8 times 10⁶ Spermatozoen/g Hodenparenchym und 9.8 ± 1.7 times 10⁹ Spermatozoen/Hoden gefunden. Unter Benutzung eines Zeitdivisors von 4.94 Tagen berechnet sich die tägliche Spermaproduktion zu 10.0 ± 0.9 times 10⁶ Spermatozoen/g Hodenparenchym/Tag und 2.0 ± 0.3 times 10⁹ Spermatozoen/Hoden/Tag. Die Spermareserve im Nebenhoden betrug 11.9 ± 1.6 times 10⁹ Spermatozoen/Nebenhoden in folgender Verteilung: 35.3 ± 3.6% im Nebenhodenkopf, 16.9 ± 1.7% im Nebenhodenkörper und 47.7 ± 3.7% im Nebenhodenschwanz.     

Correlation between neutral alpha-glucosidase activity and sperm DNA fragmentation

To evaluate the association between neutral α-glucosidase (NAG) activity and sperm DNA fragmentation (DFI), ejaculates from 24 men undergoing evaluation for sperm DNA damage as a part of infertility assessment were analysed. The mean ± SD and range for the semen quality of the 24 ejaculates are as follows: volume (3.1 ± 1.3, 1.8–6.0 ml); sperm concentration (45.6 ± 41.1, 1.3–151.2 × 10⁶ ml⁻¹); sperm motility (52.8 ± 28.8, 1–95%); sperm with fragmented DNA (17.6 ± 15.4, 1.7–56.0%); sperm with immature chromatin (9.6 ± 3.8, 2.5–19.1%); NAG activity (37.9 ± 18.3, 4.4–75.3 mU ml⁻¹). The only sperm parameter significantly correlated with neutral α-glucosidase is the percentage of sperm DFI [correlation coefficient ( r ) = 0.4376, P  = 0.03].     

Quantifying the interaction of vecuronium with enflurane using closed-loop feedback control of vecuronium infusion

The influence of different levels of enflurane anaesthesia on infusion requirements of vecuronium was studied in 40 adult surgical patients. Ninety percent neuromuscular block was maintained by computer controlled infusion of vecuronium. During the first 90 min study period all patients received fentanyl-nitrous oxide-oxygen (2:1) anaesthesia. For the following 90 min the patients were randomly assigned to receive enflurane at different end-tidal concentrations: group I, control, fentanyl-nitrous oxide anaesthesia; group II, enflurane 0.3%-nitrous oxide; group III, enflurane 0.6%-nitrous oxide; group IV, enflurane 0.9%-nitrous oxide. Every patient served as his/her own control and the changes of vecuronium infusion requirements were determined individually. When the administration of enflurane was started, vecuronium infusion requirements decreased progressively until 90 min. In group II the infusion rate lowered from 80±28 to 56±20 μg . kg^-1 . h ^-1, in group III from 61 ±29 to 34±17 μg . kg^-1 . h^-1 and in group IV from 65±20 to 30± 14 μg . kg^-1 . h^-1. In the control group the infusion rate decreased during the three hour study period from 69± 17 (first 90 min period) to 59± 16 μg . kg^-1 . h^-1 (second 90 min period). Enflurane reduces the dose requirements of vecuronium administered by continuous infusion in a dose- and time-dependent manner.     

Secretion of macromolecules by the rat epididymis

Sperm maturation in the rat epididymis is dependent on the secretion of specific proteins by the epididymal epithelium and subsequent interaction of these proteins with spermatozoa. Evidence has shown that fertility and motility development of epididymal spermatozoa may be impaired by interfering the interaction of these proteins with spermatozoa. When the spermatozoa reach the cauda epididymidis, they are fully mature but their longevity is maintained by being stored in a quiescent state in the cauda. The unique ionic medium therein (low Na⁺, low Ca²⁺, high K⁺ and low pH) suppresses sperm motility and hence reserving energy for the vital processes of capacitation and fertilization. During ejaculation, when the spermatozoa are mixed with the copious secretion from the accessory glands they burst into vigorous motility. This results from an influx of sodium coupled to efflux of K⁺ and H⁺ across the mature sperm membrane. In the presence of a peptide secreted by the cauda epididymidis, these ionic events activate the already mature but otherwise inactive spermatozoa to full motility.     

Sperm Storage Capacity of the Indigenous West African Boar

The sperm reserves in the testis and epididymis of pubertal and adult indigenous West African boars were 4.22 and 4.99 times 10⁹ and 1.81 and 1.92 times 10⁹ respectively and were influenced by age and organ weight ( P < 0.05). Although these values were much less than those of exotic boars of about the same age, distribution in weights and sperm content of both indigenous and exotic boars is similar. However, testicular and epididymal sperm reserves were unrelated ( r = 0.19, P > 0.05) indicating that sperm storage capacity was still developing.     

Acute Humoral Rejection of Renal Allografts in CCR5–/– Recipients

Increasing detection of acute humoral rejection (AHR) of renal allografts has generated the need for appropriate animal models to investigate underlying mechanisms. Murine recipients lacking the chemokine receptor CCR5 reject cardiac allografts with marked C3d deposition in the parenchymal capillaries and high serum donor-reactive antibody titers, features consistent with AHR. The rejection of MHC-mismatched renal allografts from A/J (H-2^a) donors by B6.CCR5^–/– (H-2^b) recipients was investigated . A/J renal allografts survived longer than 100 days in wild-type C57BL/6 recipients with normal blood creatinine levels (28 ± 7 μmol/L). All CCR5^–/– recipients rejected renal allografts within 21 days posttransplant (mean 13.3 ± 4 days) with elevated creatinine (90 ± 31 μmol/L). The rejected allografts had neutrophil and macrophage margination and diffuse C3d deposition in peritubular capillaries, interstitial hemorrhage and edema, and glomerular fibrin deposition. Circulating donor-reactive antibody titers were 40-fold higher in B6.CCR5^–/– versus wild-type recipients. Depletion of recipient CD8 T cells did not circumvent rejection of the renal allografts by CCR5-deficient recipients. In contrast, μMT^–/–/CCR5^–/– recipients, incapable of producing antibody, did not reject most renal allografts. Collectively, these results indicate the rapid rejection of renal allografts in CCR5^–/– recipients with many histopathologic features observed during AHR of human renal allografts.     

The duration of action of mivacurium is prolonged if preceded by atracurium or vecuronium

We studied 45 patients (ASA I-II) during propofol-alfentanil-N₂O-O₂ anaesthesia to determine if recovery from neuromuscular block induced by mivacurium is influenced differently by prior injection of atracurium or vecuronium. Neuromuscular function was monitored by adductor pollicis EMG. Patients were randomized to receive two dosesof either mivacurium (150 and 70 μg kg^-1), atracurium (350 and 75 μg kg^-1) or vecuronium (70 and 15 μg kg^-1) followed by a final dose of mivacurium 70 μg kg^-1. The second and third doses of the muscle relaxants were administered at 25–30% recovery of the E₁ (first EMG response in the train-of-four series). Following the final dose of mivacurium, the EMG response recovered to 25 and 95% in 10.4±3.9 and 19.7±5.7 min (mean±SD), respectively, if mivacurium was the only muscle relaxant. Respective times were 100% longer if mivacurium had been preceded by atracurium (23.8 ± 3.3 and 39.8±6.9 mm) or vecuronium (22.6±3.5 and 44.1 ±7.9 min) ( P =0.000l). The 25–75% recovery times in the three groups were 4.9±1.0, 8.7±2.4 and 10.5±2.5 min, respectively ( P =0.0001). Our results indicate that there is no benefit in giving mivacurium at the end of surgery after peroperative use of atracurium or vecuronium.     

Free L-carnitine in human seminal plasma

It has often been suggested that determination of free L(—)-carnitine in seminal plasma may provide a good indication of epididymal function. However, there has been disagreement regarding the origin of L(—)-carnitine (epididymis and seminal vesicles) and its concentration in human seminal plasma. In this study, free L(—)-carnitine was determined after deproteinization with an enzymatic spectrophotometric method. In 29 semen samples from fathers and with normal spermiograms (semen volume between 2 and 6 ml, sperm count over 20.10⁶/ml, more than 50% motile spermatozoa), the total free L(—)-carnitine in the seminal plasma was 1010 nmoles (SD:±480), in 16 samples from vasectomized men it was 131 nmoles (SD:±77), and in 5 from men with agenesis of the vas deferens and seminal vesicles it was 21 nmoles (SD:±25). These results suggest that free L(—)-carnitine in the seminal fluid is predominantly of epididymal origin. The results of free L(—)-carnitine determinations in split ejaculates and the absence of a correlation between L(—)-carnitine and fructose concentrations in semen from normal subjects indicate that the seminal vesicles make only on minor contribution to L(—)-carnitine in the seminal plasma.     

Neuromuscular interactions between mivacurium and esmolol in rabbits

We compared the dose–response relationship and the neuromuscular blocking effects of mivacurium during infusions of esmolol in 40 anaesthetised rabbits. Train-of-four stimuli were applied every 10 s to the common peroneal nerve and the force of contraction of the tibialis anterior muscle was measured. Plasma cholinesterase activity decreased by 13% after esmolol infusion. The ED₉₅ of mivacurium increased significantly from 29 (4.8) μgkg⁻¹ with placebo to 61 (9.8) μgkg⁻¹ during esmolol 100 μgkg⁻¹.min⁻¹, 49 (8.2) μgkg⁻¹ during esmolol 300 μgkg⁻¹.min⁻¹ and 54 (7.3) μgkg⁻¹ during esmolol 500 μgkg⁻¹.min⁻¹, respectively (p < 0.001). The duration of neuromuscular block with mivacurium 0.16 mgkg⁻¹ was prolonged by 30% with esmolol due to diminished plasma cholinesterase activity (p < 0.05). Heart rate and mean arterial blood pressure decreased by 15% with esmolol (p < 0.05). The results of this study show that, in rabbits, esmolol decreased plasma cholinesterase activity, antagonised the neuromuscular blocking potency of mivacurium and prolonged its neuromuscular blocking effect.     

Effects of Fentanyl on Local Cerebral Blood Flow in the Rat

Fentanyl reduces the cortical cerebral blood flow and metabolic rate for oxygen in rats, though seizure activity occurs in some animals at high doses. However, the effects of fentanyl on blood flow and metabolism in subcortical structures have not been clearly delineated. The present study examines the effects of intravenous fentanyl (100 or 400 μg·kg^-1) on local cerebral blood flow (1-CBF) in paralyzed, mechanically ventilated rats. Rats ventilated with 70% N₂O in 30% O₂ served as controls. Local CBF was measured using ¹⁴C-iodoantipyrine and autoradiography. Blood pressure, Pao₂, Paco₂, pH, and temperature were comparable in all groups. The EEG showed slow wave activity in most animals given 100 μg·kg^-1 fentanyl while seizure activity occurred in all animals given 400 μg·kg^-1 fentanyl. With 100 μg·kg^-1 fentanyl, CBF tended to be depressed in all cortical and subcortical areas, except the peri-aqueductal gray; and with 400 μg·kg^-1 fentanyl, 1-CBF tended to be elevated (compared to 100 μg·kg^-1 fentanyl) in most areas of the brain. The limbic system structures, however, were most affected by 400 μg·kg^-1 fentanyl with statistically significant increases (compared to the 100 μg · kg^-1 group) in 1-CBF of 86% and 67% respectively in the amygdala and septal nucleus. These results confirm that moderately high doses of fentanyl which cause slow wave activity on the EEG also depress 1-CBF in rats; moreover, doses of fentanyl that produce seizure activity produce increases in 1-CBF in most cerebral structures with greatest effects on limbic system 1-CBF.