Pituitary-adrenocortical axis, serum serotonin and biochemical response after halothane or isoflurane anaesthesia in rabbits

To document the changes in serum serotonin, adrenocorticotrophic hormone (ACTH), corticosterone levels and select biochemical parameters in response to inhalant anaesthesia, 20 New Zealand White (NZW) rabbits were assigned to two treatment groups: halothane and isoflurane. Induction of anaesthesia was achieved using a face mask (3.5% halothane and 4.5% isoflurane in oxygen) followed by endotracheal intubation and maintenance of anaesthesia for 30 min (1.5% halothane and 2.5% isoflurane in oxygen). Blood samples were obtained before anaesthetic induction, and at 1, 10, 30, 60, 120 min and 24, 48 and 72 h after endotracheal intubation. Serum serotonin and corticosterone levels were measured by competitive enzyme immunoassay, ACTH by radioimmunoassay. Serum glucose, alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), blood urea nitrogen (BUN) and creatinine levels were measured using an automated analyser. Significant increases in serum ACTH and corticosterone levels occurred after halothane administration while serum serotonin levels did not change. An increase in serum corticosterone and serotonin levels occurred in the isoflurane group but no changes in ACTH concentrations were detected. Administration of halothane significantly increased serum glucose, ALT, AST, BUN and creatinine levels. After isoflurane administration, there was a significant increase in serum glucose, AST, BUN and creatinine levels. Based on these results, halothane stimulates the hypothalamic-pituitary-adrenal axis to a greater extent than isoflurane, but isoflurane increases serum serotonin levels. Both anaesthetic agents alter select biochemical parameters. These results should be taken into account when blood samples are evaluated in treated isoflurane or halothane anaesthetized rabbits.     

Cardiopulmonary, hemocytologic and biochemical effects of xylazine in goats

Intramuscular administration of xylazine at the rate of 0.22 mg/kg body weight caused a significant reduction in respiratory rates. Mean arterial blood pressure and rectal temperature were not altered. Preadministration of atropine did not affect the depth and pattern of respiration; however, the heart rate increased. A significant reduction in pH and arterial oxygen tension and an increase in carbon dioxide tension was observed after xylazine and xylazine following atropine treatment. Hemocytologic changes included a decrease in total erythrocytes, leukocytes, hematocrit and hemoglobin concentration and a rise in neutrophils with relative decrease in lymphocytes. Biochemical changes included a slight rise in potassium and a decrease in sodium concentration. Glucose level was significantly increased at maximum depth of sedation. The changes in hemocytologic and biochemical parameters returned to near preadministration level in 24-72 hours. No alteration was observed in the electrocardiogram. Xylazine was well tolerated, and the sedation was rapid in onset and lasted for about 30 minutes. The recovery was uneventful.     

Comparative effects of halothane, isoflurane, sevoflurane and desflurane on the electroencephalogram of the rat

Inhalant anaesthetic agents are commonly used in studies investigating the electroencephalographic (EEG) effects of noxious stimuli in animals. Halothane causes less EEG depression than isoflurane, however, the EEG effects of halothane, isoflurane, sevoflurane and desflurane have not been compared in the same model. This study aimed to compare the EEG effects of these inhalational agents in the rat. Forty male Sprague-Dawley rats were assigned to four groups and anaesthetized with halothane, isoflurane, sevoflurane or desflurane. EEG was recorded from the left and right somatosensory cortices for 5 min at three different multiples of minimal alveolar concentration (MAC) (1.25, 1.5 and 1.75). Median, 95% spectral edge frequency and total power were derived and a single mean value for each was calculated for the first 60 s of each recording period. When the raw EEG contained burst suppression (BS), the BS ratio (BSR) over 60 s was calculated. No BS was found in EEG recorded from the halothane group at any concentration. BS was present at all concentrations with the other anaesthetic agents. BS was almost complete at all concentrations of isoflurane, whereas BSR increased significantly with increasing concentrations of sevoflurane and desflurane. No significant differences were found between the BSR due to the 1.75 MAC multiple of isoflurane, sevoflurane or desflurane. Halothane causes significantly less depression of cortical activity than the newer inhalant agents at equivalent multiples of MAC. These data support the hypothesis that halothane has a fundamentally different mechanism of action than the other inhalant agents.     

Effects of inhalation anesthetics halothane, sevoflurane, and isoflurane on human cell lines

Cytotoxic and antiproliferative effects of halothane, isoflurane, and sevoflurane in anesthetic doses on human colon carcinoma (Caco-2), larynx carcinoma (HEp-2), pancreatic carcinoma cells (MIA PaCa-2), poorly differentiated cells from lymph node metastasis of colon carcinoma (SW-620), and normal fibroblasts were investigated. Cells were exposed to anesthetic gas mixture consisting of O(2): N2O (35:60 vol.%), halothane (1.5 vol.%) or isoflurane (2.0 vol.%) or sevoflurane (3.0 vol.%), and CO(2) (5 vol.%), for 2, 4, and 6 h. Cytotoxicity of anesthetics was analyzed by validated tetrazolium dye assay MTT test. All anesthetics expressed cytotoxic effects on treated tumor cells in time and cell line dependent manner. Growth suppression in cells exposed to halothane was enhanced in HEp-2 (to 67.7%), Caco-2 (to 76.3%), and SW620 cells (to 80.9%), and was minimal in normal fibroblasts (to 89.4%). Antiproliferative activity of halothane was measured via radioactive precursors incorporation assay. In Caco-2 cells treated by halothane, decrease in DNA synthesis (52.4%, p=0.001), RNA synthesis (39.2%, p<0.001), and protein synthesis (19.2%, p=0.004) was observed. In HEp-2 cells, DNA and RNA syntheses were decreased to 72.5% and 79.9%, whereas protein synthesis was 14.0% of control (p<0.001). In SW620 cells, protein synthesis after 4 h was 24.4% (p=0.007). A DNA fragmentation was observed in Caco-2 and MIA PaCa-2 cells. Exposition of phosphatidylserine on outer lipid bilayer plasma membrane of tumor cell treated by halothane proved apoptosis as mode of cell death.     

Effects of halothane, isoflurane, sevoflurane and desflurane on contraction of ventricular myocytes from streptozotocin-induced diabetic rats

Various clinically used volatile general anaesthetics (e.g. sevoflurane, halothane, isoflurane and desflurane) have been shown to have significant negative inotropic effects on normal ventricular muscle. However, little is known about their effects in ventricular tissue from diabetic animals. Streptozotocin (STZ)-induced diabetes is known to induce changes in the amplitude and time course of shortening and one report suggests that the inotropic effects of anaesthetics are ameliorated in papillary muscles from diabetic animals. The aim of these studies was to investigate this further in electrically stimulated (1 Hz) ventricular myocytes. Cells were superfused with either normal Tyrode (NT) solution or NT containing anaesthetic (1 mM) for a period of 2 min (at 30-32 degrees C). Myocytes from STZ rats were shown to have a significantly longer time to peak shortening (p > 0.001, n = 50) and the amplitude of shortening tended to be greater but this was not significant (p = 0.13, n = 50). Halothane, isoflurane, desflurane and sevoflurane significantly (p < 0.05) reduced the magnitude of shortening of control cells by 72.5 +/- 3.2%, 46.5 +/- 9.7%, 28.9 +/- 4.3% and 22.8 +/- 5.6%, respectively (n > 11 per group) but their steady-state negative inotropic effect was found to be no different in cells from STZ-treated rats (73.0 +/- 4.8%, 40.7 +/- 4.7%, 25.0 +/- 5.2% and 19.8 +/- 5.2%, respectively, n > 10 per group). Therefore, we conclude that the inotropic effects of volatile anaesthetics were not altered by STZ treatment.     

Effects of halothane,isoflurane, sevoflurane and desflurane on contraction of ventricular myocytes from streptozotocin-induced diabetic rats

Various clinically used volatile general anaesthetics (e.g. sevoflurane, halothane, isoflurane and desflurane) have been shown to have significant negative inotropic effects on normal ventricular muscle. However, little is known about their effects in ventricular tissue from diabetic animals. Streptozotocin (STZ)-induced diabetes is known to induce changes in the amplitude and time course of shortening and one report suggests that the inotropic effects of anaesthetics are ameliorated in papillary muscles from diabetic animals. The aim of these studies was to investigate this further in electrically stimulated (1 Hz) ventricular myocytes. Cells were superfused with either normal Tyrode (NT) solution or NT containing anaesthetic (1 mM) for a period of 2 min (at 30–32°C). Myocytes from STZ rats were shown to have a significantly longer time to peak shortening (p > 0.001, n= 50) and the amplitude of shortening tended to be greater but this was not significant (p= 0.13, n= 50). Halothane, isoflurane, desflurane and sevoflurane significantly (p < 0.05) reduced the magnitude of shortening of control cells by 72.5 ± 3.2%, 46.5 ± 9.7%, 28.9 ± 4.3% and 22.8 ± 5.6%, respectively (n > 11 per group) but their steady-state negative inotropic effect was found to be no different in cells from STZ-treated rats (73.0 ± 4.8%, 40.7 ± 4.7%, 25.0 ± 5.2% and 19.8 ± 5.2%, respectively, n > 10 per group). Therefore, we conclude that the inotropic effects of volatile anaesthetics were not altered by STZ treatment. (Mol Cell Biochem 261: 209–215, 2004)     

Estimation of minimum alveolar concentration (MAC) for halothane, enflurane and isoflurane in spontaneously breathing guinea pigs

MAC for halothane, enflurane and isoflurane was determined in guinea pigs (Cavia porcellus) exposed to constant anesthetic concentrations (2.5 hours each) in a flow-through glass chamber. The following values were obtained (N = 8 for each anesthetic): 1.01 +/- 0.03 vol% for halothane, 2.17 +/- 0.04 vol% for enflurane, and 1.15 +/- 0.05 vol% for isoflurane. In guinea pigs, MAC for halothane and enflurane are similar to those reported for other rodents, while MAC for isoflurane is lower. The data indicate that guinea pigs possibly are more susceptible to isoflurane's anesthetic actions than other rodents.     

Normal serum biochemical and hematological parameters in Macaca fascicularis.

The effects of age, sex, pregnancy, were analyzed and data from fasted and fed animals were compared in a population of cynomolgus macaques. No significant sex effects were observed for biochemical values and no changes were found in male hematological parameters in relation to age. Most values of females during pregnancy were within normal ranges. Comparison between fed and fasted animals showed that several biochemical parameters (e.g., ALT, glucose, CPK, LDH) and several hematological parameters (e.g., monocytes, eosinophils, basophils, hemoglobin, MCV, MCHC, and MCH) were affected by food intake.     

Induction of anaesthesia with sevoflurane and isoflurane in the rabbit

The effects of induction of anaesthesia with sevoflurane and isoflurane were studied in rabbits. All rabbits had periods of apnoea (ranging from 30-180 s) during induction which resulted in moderate hypercapnia and acidosis. Arterial pCO2 rose from 4.1 +/- 0.3 kPa to a peak of 7.6 +/- 0.4 kPa (mean +/- SD) (both agents). All animals showed a significant reduction in heart rate (P < 0.05). Heart rate (HR) fell from 226 +/- 33 to a minimum during induction of 57 +/- 32 (sevoflurane) and 199 +/- 41 to 45 +/- 11 (isoflurane). Most animals struggled violently during induction. Use of sevoflurane did not prevent the breath-holding response seen during induction of anaesthesia with other volatile anaesthetics in this species, and the severe apnoea which occurs may represent a significant hazard. The behaviour of the animals indicated that both sevoflurane and isoflurane are aversive, suggesting that this technique should be avoided whenever possible.     

Age-related changes in hematological and serum biochemical values in cats]

Nineteen hematological and serum biochemical values were analyzed for 91 healthy cats of both sexes (aged 1 to 48 months) that were bred and reared in our laboratory. Age-related changes were found for many parameters. Red blood cell counts (RBC), hemoglobin (Hb), hematocrit (Ht), Mean corpuscular constants, GPT, total protein (TP) and albumin (ALB) initially were low but increased then stabilized. White blood cell counts (WBC), alkaline phosphatase (ALP), inorganic phosphorus (Pi), total bilirubin (TBil), total cholesterol (TC), glucose (GLU), and triglyceride (TG) initially were high, but decreased then stabilized. No age-related changes were found for GOT, blood urea nitrogen, or calcium. Of the parameters that changed with age, the mean corpuscular constants, GPT, GLU, and TG became stabilized during the first 3 to 4 months of life, but others (RBC, Hb, Ht, TP, ALB) became stabilized after 9 to 11 months, during which period body weight reached a plateau. Some parameters (WBC, ALP, TG, Pi) showed change up to 18 months of age. These results suggest that cats 9 to 11 months old can be regarded as adults; but for some parameters, cats aged 18 months, or older, are better regarded as adults. Sex-related differences in the values for mean corpuscular volume, mean corpuscular hemoglobin, and WBC that were found after 11 months of age were higher in females. ALB was higher in males.     

Normal serum biochemical and hematological values of the Sulawesi macaques

Sulawesi macaque (SM) species are currently of interest to primatologists for genetic and behavioral studies world wide. However, there are no published reference hematological and serum biochemical profile values for several of the seven SM species. Twenty-five clinically healthy, outdoor housed, ketamine sedated Macaca tonkeana and Macaca maurus were serially sampled (two to four times) over a 16-month period (N = 68). Normal ranges were defined to include two standard deviations and 2.5–97.5 percentile. Significant differences in single sample date comparisons (P < 0.05) of species (serum Ca, MCHC), age (BUN, BUN/creatinine, alkaline phosphatase, phosphorus), gender (total protein, RBC, hemoglobin, HCT) and pregnancy (phosphorus and neutrophil count) groups were found. This normative data facilitates clinical evaluation of SM species and allows comparison to other macaque species.     

Comparison of isoflurane and sevoflurane for anesthesia in beaver

We compared the hemodynamic and respiratory effects, recovery time, and cost of two gas inhalants (isoflurane and sevoflurane) for anesthetic induction and maintenance of beaver (Castor canadensis) during surgery to implant radio transmitters in the peritoneal cavity. Heart rate, respiratory rate, relative hemoglobin saturation with oxygen (SpO2), and body temperature were measured every 5 min for the first 45 min, and arterial blood gas was measured once, 25 min into the anesthetic procedure. Induction for either agent was smooth and rapid. Heart rate and respiratory rate both decreased during the procedure though neither was lower than baseline values reported in the literature for beaver. Relative hemoglobin saturation with oxygen, body temperature, and blood gas variables did not differ between each anesthetic regime. Both inhalants caused slight respiratory acidosis. Recovery time from anesthesia was highly variable (1-178 min) but did not differ statistically between drugs. Sevoflurane costs ($22.30/60 min) were much higher than isoflurane costs ($3.50/60 min). We recommend isoflurane or sevoflurane for anesthetic induction and maintenance of beaver because of the lack of physiologic differences.     

Effects of primaquine on serum biochemical and hematological parameters in anesthetized Macaca fascicularis

Primaquine phosphate treatment (0.5 mg/kg/day, per os [p.o.], 14 days) significantly increased values for serum sodium, potassium, and uric acid, while calcium levels were decreased in male Macaca fascicularis. Serum values returned to baseline (pretreatment) levels by 30 days following primaquine treatment.     

The effects of ketamine anesthesia on hematological and serum biochemical values in female cynomolgus monkeys (Macaca fascicularis)

The effects of ketamine anesthesia (15 mg/kg body weight) on hematological and serum biochemical values were examined in six female cynomolgus monkeys (Macaca fascicularis) who were born in the wild. As control, another six female cynomolgus monkeys of the same origin were injected with physiological saline. The white blood cell count, total protein concentration, albumin concentration and calcium concentration decreased after the injection of ketamine, whereas the red blood cell count, hematocrit value, hemoglobin concentration, total cholesterol concentration, free cholesterol concentration, triglyceride concentration, transaminase activities (GOT, GPT) and alkaline phosphatase activity were not affected. A transient increase of the serum glucose level was observed within 10 minutes after ketamine injection. The relationship between these effects of ketamine anesthesia and serum cortisol levels measured by radioimmunoassay was discussed.     

Normal serum biochemical, hematological, and EKG parameters in anesthetized adult male Macaca fascicularis and Macaca arctoides

Selected serum enzymes, cholesterol, triglycerides, glucose, uric acid, protein, albumin, bilirubin, BUN, hematology, and electrocardiograms (EKG) were obtained from adult male cynomolgus (Macaca fascicularis) and adult male stumptailed (Macaca arctoides) macaques. Serum alkaline phosphatase, uric acid, albumin, bilirubin, mean corpuscular hemoglobin (MCH), mean corpuscular volume (MCV) and monocytes were significantly lower in the cynomogus monkeys. This relationship was reversed for serum levels of triglycerides, phosphorus, red blood cell counts and lymphocytes. EKG analysis revealed significantly increased PR interval and QRS wave duration in the cynomolgus species. However, there were no differences in heart rate. Right axis deviation was common in both species.     

Impact of lactation stage on milk composition and blood biochemical and hematological parameters of dairy Baladi goats

The objective of this study was to elucidate the impact of lactation stage on milk composition, hematological and biochemical parameters of dairy Baladi goats under Egyptian conditions. Forty-eight Baladi goats (32.8 ± 2.9 kg of BW) were enrolled in the current study. The lactation period has been divided into three stages; early (DIM less than 80 days), Mid (DIM 80–140 days), and Late (DIM over 140 days). Baladi goats had decreased daily-MY at a rate of 18.4% and 31.9% at mid and late stages of lactation, compared with early stage, respectively (p = 0.001). Furthermore, lactose% decreased significantly with progress of lactation (p = 0.017). Total solids%, however, decreased significantly at early stage of lactation in comparison with mid and late stages (p = 0.022). On the contrary, no significant differences were found in protein, fat and SNF percentages at different stages of lactation (p = 0.836, 0.625 and 0.281, respectively). Serum glucose and total protein were significantly reduced at late stage of lactation in comparison with early and mid stages (p = 0.001 and 0.001, respectively). On the contrary, no significant differences were found for erythrocytes count, hemoglobin, serum cholesterol, catalase and triiodothyronine at different stages of lactation. There were high and positive correlations between daily-MY and serum total protein (r = 0.87, P < 0.01) and triiodothyronine (r = 0.41, P < 0.01). However, negative estimates were reported between daily-MY and triglycerides (r = ?0.55, P < 0.01) and cholesterol (r = ?0.33, P < 0.05). Our results indicate that dairy Baladi goats produce milk with relatively stable protein, fat and solid not fat (SNF) contents at the different stages of lactation, encouraging the continuous utilization of their milk in processing. Also, dairy Baladi goats seem able to maintain the most vital biochemical parameters.     

Characterization of progesterone profile,physiological responses,milk composition and blood biochemical and hematological indices at the early stage of lactation in goats

The aim of this research was to describe the progesterone profile, physiological response, milk composition, and blood chemistry at the early stage (DIM 30-90 days) of lactation (E₁:30-50; E₂:50-70; E₃:70-90 days) in Baladi goats under Egyptian conditions. The serum progesterone level was significantly reduced with the progress of the early lactation period to reach the least concentration (0.24 ng/ml) at the E₃ stage of lactation (P=0.001). The daily milk yield was significantly increased with the progress of the lactation to reach the peak at the E₂ stage of lactation (P=0.015). The percentage of milk fat was significantly decreased with the progress of the early lactation period (P=0.032). However, the percentages of total solids and SNF were significantly increased in E₂ and E₃ stages when compared with the E₁ stage (P=0.001 and 0.018, respectively). The serum glucose and total antioxidant capacity were considerably reduced with the progress of the lactation period (P=0.047 and 0.039, respectively). In conclusion, Baladi goats showed a decreased serum progesterone level with the progress of the early lactation period and produce milk with a relatively stable protein and lactose contents. Furthermore, Baladi does able to maintain the stability of most blood biochemical parameters during such period.     

Abeta peptide interactions with isoflurane, propofol, thiopental and combined thiopental with halothane: a NMR study

Abeta peptide is the major component of senile plaques (SP) which accumulates in AD (Alzheimer's disease) brain. Reports from different laboratories indicate that anesthetics interact with Abeta peptide and induce Abeta oligomerization. The molecular mechanism of Abeta peptide interactions with these anesthetics was not determined. We report molecular details for the interactions of uniformly (15)N labeled Abeta40 with different anesthetics using 2D nuclear magnetic resonance (NMR) experiments. At high concentrations both isoflurane and propofol perturb critical amino acid residues (G29, A30 and I31) of Abeta peptide located in the hinge region leading to Abeta oligomerization. In contrast, these three specific residues do not interact with thiopental and subsequently no Abeta oligomerization was observed. However, studies with combined anesthetics (thiopental and halothane), showed perturbation of these residues (G29, A30 and I31) and subsequently Abeta oligomerization was found. Perturbation of these specific Abeta residues (G29, A30 and I31) by different anesthetics could play an important role to induce Abeta oligomerization.