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PubMed1990

Long-term effects of developmental halothane exposure on radial arm maze performance in rats.

Chronic exposure of rats to low levels of halothane during development, a treatment which retards synaptogenesis, was found to cause a long-term impairment of choice accuracy in the radial-arm maze. In Expt. 1, the relative importance of dose level and dosing regimen was examined. Dose level seemed the more critical variable for causing impaired choice accuracy. Exposure to 100 parts per million (ppm) of halothane in the air either on an intermittent or continuous schedule from day two of conception until 60 days after birth significantly impaired choice accuracy, whereas exposure to 25 ppm on a continuous schedule did not cause a deficit, even though with this condition the total amount of halothane exposure was about the same as with 100 ppm given intermittently. In Expt. 2, the 100 ppm intermittent exposure regimen was used to examine the relative importance of exposure during early and late developmental periods for producing the cognitive effects of halothane. Groups were divided into those exposed to halothane during gestation and until 30 days after birth (early exposure), those exposed from day 31 until day 90 (late exposure) and those exposed during both early and late periods (combined exposure). Adverse effects on choice accuracy were seen with all 3 types of exposure, but surprisingly, it was the late exposure that caused the most severe effects. These results show that developmental exposure to halothane which impairs synaptogenesis also causes long-lasting cognitive impairment. Halothane exposure can be a useful experimental tool for examining the relationship between synaptic and behavioral development.

Age Factors↗

PubMed1991

Arrhythmias, haemodynamic changes and extent of myocardial damage during coronary ligation in rabbits anaesthetized with halothane, alpha chloralose or pentobarbitone.

We investigated the incidence of ventricular arrhythmias, extent of myocardial infarction and alteration in haemodynamic parameters during 30 minutes of coronary arterial occlusion in rabbits anaesthetized with halothane, alpha chloralose and pentobarbitone. Ventricular tachycardia and fibrillation occurred in 10 of 15 given halothane and in 11 of 15 animals given alpha chloralose while of 15 animals given pentobarbitone, 5 developed tachycardia and 8 had fibrillation. Following ligation, blood pressure promptly fell in each group to 71-76% of control values at 1 minute and remained low throughout the occlusion period. This was most marked in the group receiving halothane which had significantly lower pressures at 30 minutes than those anaesthetized with alpha chloralose or pentobarbitone (P less than 0.01 in each case). Those receiving halothane also recovered less on reperfusion. Heart rate remained stable with pentobarbitone anaesthesia during coronary occlusion and reperfusion, but promptly declined in the first minute of occlusion in the groups given halothane and alpha-chloralose and then remained low throughout occlusion, especially in the group given alpha-chloralose (P less than 0.001 vs pentobarbitone and P less than 0.01 vs halothane). The extent of myocardial damage was measured from nitroblue tetrazolium-stained sections and expressed as a percentage of the zone at risk, which was obtained in five hearts following 90 minutes coronary ligation. Values were 44.0% with pentobarbitone, 54.0% with alpha chloralose (P less than 0.01 vs pentobarbitone) and 62.1% with halothane (P less than 0.001 vs pentobarbitone). Thus, the choice of anaesthetic employed during experimental myocardial ischaemia may have significant effects on the incidence of ventricular tachycardia, haemodynamic changes and extent of necrosis observed.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗

PubMed1985

Plasma and myocardial catecholamine levels in young and aged rats during halothane anesthesia.

Plasma and heart tissue catecholamines were measured in young (4-month) and aged (28-month) Sprague Dawley rats under unanesthetized conditions and following the induction of halothane anesthesia. Arterial blood pressure, blood gases, plasma and heart tissue norepinephrine, epinephrine and dopamine concentrations were measured in separate groups of unanesthetized and halothane anesthetized rats. Young and aged rats were tested under equal anesthetic levels and blood halothane concentrations were measured using gas chromatography. Aged rats required significantly less halothane to maintain anesthesia compared to young animals (7.25 +/- 1.43 vs. 14.91 +/- 0.93 mg/dL, p less than 0.05). Cardiovascular parameters were similar in young vs. aged rats under unanesthetized conditions, but blood pressure decreased significantly more in aged than in young rats during halothane anesthesia (43% vs. 17%, p less than 0.05). Heart tissue catecholamines were not different between young and aged and did not change during halothane anesthesia. Plasma norepinephrine concentrations were consistently elevated in aged vs. young rats under both unanesthetized and anesthetized test conditions, but there was no significant change in these levels from the unanesthetized to the anesthetized state. Results suggest that increased catecholamine levels in aged animals may be necessary to maintain a normal cardiovascular state under unanesthetized conditions and that catecholamines do not increase during the hypotensive state produced by halothane anesthesia in spite of marked hypotension.

Aging↗

PubMed1990

The effects of halothane on the contents of putative transmitter amino acids in whole rat brain.

The effects of halothane on brain amino acid contents were investigated in rat by using a gas chromatography-mass spectrometry system. The contents of glycine and glutamate did not show any consistent changes in 1% or 2% halothane, but increased in 3% or 4% halothane. The levels of gamma-aminobutyric acid were not altered in any concentrations of halothane. The levels of aspartate increased in a dose-dependent manner up to 3% halothane, but returned to the control level in 4% halothane. These findings suggest that halothane brings the alteration of brain amino acid contents by affecting their synthesis and catabolism.

Amino Acids↗

PubMed1987

Effects of Sarcocystis miescheriana infection on carcass weight and meat quality of halothane-tested fattening pigs.

Ten halothane-positive pigs (Group A) and ten halothane-negative pigs (Group C) were each infected per os by 50,000 sporocysts of Sarcocystis miescheriana when they had reached a mean body weight of 36 kg. Twelve halothane-positive pigs (Group B) and ten halothane-negative pigs (Group D) served as non-infected controls. Thirteen weeks p.i. (post infection), the pigs were slaughtered and the carcass weights and the number of cystozoites in several muscles were determined. In addition, 11 parameters of meat quality were measured in Musculus longissimus dorsi (M.l.d.) and Musculus semimembranosus (M.s.): pH and temperature 30 min and 24 h p.m. (post mortem), electrical conductance 45 min, 60 min and 24 h p.m., colour brightness (FOP) and rigor values 30 min and 24 h p.m. Additionally, the AMP, ADP, ATP and lactate contents were determined in samples from the M.l.d. The mean carcass weights of the infected pigs (A: 79.9 +/- 6.9 kg; C: 76.3 +/- 11.6 kg) were lower than those of the pigs of the non-infected groups (B: 85.7 +/- 8.0 kg; D: 87.5 +/- 7.0 kg). The pH values at 24 h p.m. were significantly higher in the M.l.d. of infected pigs than in M.l.d. of non-infected pigs. Electrical conductance in the M.s. at 45 min p.m. was significantly higher in the halothane-negative infected pigs, but at 24 h p.m., the mean values of electrical conductance in the M.s. of the pigs of both infected groups were significantly lower than in the control groups. FOP values at 30 min p.m. were raised in the M.l.d. of the halothane-negative infected pigs, but at 24 h p.m., differences between infected and non-infected pigs could no longer be found. Mean rigor values were higher in the pigs of the infected groups at 24 h p.m., but the difference from the non-infected groups was not statistically significant. AMP was reduced only in the meat of halothane-positive infected pigs, while lactate was reduced in both infected groups. Using conventional methods for the determination of meat quality, the hypothesis of impaired meat quality in Sarcocystis-infected pigs could not be confirmed. The meat quality parameters investigated were, in part, better in infected pigs than in non-infected controls.

Adenosine Diphosphate↗

PubMedDate not supplied

Neurobehavioral toxicology of halothane in rats.

Halothane, a commonly used general anesthetic, is considered to be relatively safe for that purpose. Chronic exposure, however, has been found to cause long-lasting damage to neural structure and impairment of behavioral function. In rats, behavioral alterations are particularly evident after developmental exposure, but they can also be seen with adult exposure, especially when halothane is given during the period of neural regrowth following a brain lesion. The pattern of neural damage includes retarded synaptogenesis, impaired dendritic branching and disruption of organelle structure. The behavioral syndrome includes learning impairment, decreased exploratory behavior and decreased nociceptive reactivity. In general, the neural pathology is more pronounced and more easily discernible than the behavioral effects. Neural damage, particularly to the hippocampus, can be clearly seen at points when behavioral impairments have not been found. This demonstrates that in some cases changes in neural structure can be more sensitive indicators of toxic damage than behavioral dysfunction. Halothane exposure has proved to be quite useful as an experimental tool in the study of neural and behavioral recovery after brain lesions. For example, after unilateral entorhinal cortical lesions, behavioral recovery and reactive synaptogenesis occur contemporaneously. It has not been demonstrated whether the behavioral recovery is due to this reinnervation. Postlesion halothane exposure almost completely suppresses reactive synaptogenesis, however, behavioral recovery of T-maze alternation behavior occurs in the halothane-treated rats as well as in controls. This suggests that recovery of spatial performance after such a lesion is not due to recovery of innervation in the dentate, but to some other process such as other neural systems taking over the functions lost with the brain lesion. The studies reviewed highlight the dangers of halothane exposure, especially during development or when recovering from brain injury. They also provide a good case study for comparing the relative sensitivity of morphological and behavioral measures in toxicology and point to the potential use of halothane as an experimental tool for examining the relationships between neural structure and behavioral function.

Animals↗

PubMed1992

Effects of halothane and isoflurane on transient renal dysfunction associated with infrarenal aortic cross-clamping.

Aortic cross-clamping for reconstructive aortic surgery is associated with impairment of renal function. Halothane or isoflurane was used to assess the influence of volatile anesthesia on renal hemodynamics during aortic surgery. Nineteen patients with normal preoperative creatinine clearances who were scheduled for reconstructive aortic surgery were randomly divided into two groups: halothane group (n = 9) and isoflurane group (n = 10). Induction of anesthesia consisted of midazolam, fentanyl, and pancuronium. Anesthesia was maintained with fentanyl and halothane or isoflurane in nitrous oxide and oxygen (50/50). Systemic hemodynamics were similar in both groups throughout surgery. Before aortic cross-clamping, effective renal plasma flow (ERPF) (131I-hippuran clearance) and glomerular filtration rate (GFR) (99Tc-DTPA clearance) were significantly lower in the halothane group (118.4 +/- 25.6 and 19.7 +/- 5.2 mL/min, respectively) than in the isoflurane group (253.4 +/- 51.5 and 44.9 +/- 8.4 mL/min) (P less than 0.05 for both). During cross-clamping, the renal variables were not markedly affected in either group and remained higher in the isoflurane-anesthetized patients (232.9 +/- 47.1 and 49.5 +/- 1.2 mL/min for ERPF and GFR, respectively) than in the halothane-anesthetized patients (132.4 +/- 31.6 and 14.8 +/- 3.7 mL/min, respectively) (P less than 0.05). After aortic unclamping, ERPF increased markedly in both groups (467.8 +/- 122 and 362.5 +/- 57.7 mL/min in the halothane and isoflurane groups, respectively), as did GFR (74.8 +/- 22 and 71.8 +/- 13.1 mL/min, respectively). These results suggest that anesthesia with halothane is associated with transient renal vasoconstriction during abdominal surgery. In contrast, aortic cross-clamping during isoflurane anesthesia was not associated with renal hemodynamic impairment.

Adult↗

PubMed2007

A minimal stress model for the assessment of electroacupuncture analgesia in rats under halothane.

The use of anesthetics in acupuncture analgesia is controversial. We evaluate a steady-state light anesthesia model to test whether minimal stress manipulation and reliable measurement of analgesia could be simultaneously achieved during electroacupuncture (EA) in animals. A series of experiments were performed. Firstly, EA compliance and tail-flick latencies (TFL) were compared in rats under 0.1%, 0.3%, 0.5%, 0.7%, or 1.1% halothane for 120min. Under 0.5% halothane, TFL were then measured in groups receiving EA at intensity of 3, 10 or 20 volt (V), 1 or 2mg/kg morphine, 20V EA plus naloxone, or control. Subsequently, the effect of EA on formalin-induced hyperalgesia was tested and c-fos expression in the spinal dorsal horn was analyzed. Rats exhibited profound irritable behaviors and highly variable TFL under 0.1% or 0.3% halothane, as well as a time-dependent increase of TFL under 0.7% or 1.1% halothane. TFL remained constant at 0.5% halothane, and needle insertion and electrical stimulation were well tolerated. Under 0.5% halothane, EA increased TFL and suppressed formalin-induced hyperalgesia in an intensity-dependent and naloxone-reversible manner. EA of 20V prolonged TFL by 74%, suppressed formalin-induced hyperalgesia by 32.6% and decreased c-fos expression by 29.7% at the superficial and deep dorsal horn with statistically significant difference. In conclusion, 0.5% halothane provides a steady-state anesthetic level which enables the humane application of EA stimulus with the least interference on analgesic assessment. This condition serves as a minimal stress EA model in animals devoid of stress-induced analgesia while maintaining physiological and biochemical response in the experiment.

Acupuncture Analgesia↗

PubMed2006

In vivo versus in vitro comparison of swine cardiac performance: induction of cardiodepression with halothane.

An in situ versus in vitro comparison of relative dose-dependent effects of halothane on cardiac performance was investigated, including ventricular systolic/diastolic function. Such comparative studies may be of interest to individuals working on heart failure models, cardiac device testing, or xenotransplantation. Normal swine (n=9) received halothane at levels of 0.25, 0.5 and 1 MAC (minimum alveolar concentration) for 30 min each. Parameters assessed included: 1) heart rate; 2) arterial blood pressure; 3) pulmonary artery, central venous, left and right ventricular pressures; 4) cardiac output; 5) end-expiratory CO(2) and halothane levels; 6) cardiac temperature; and 7) arterial blood gases. Hearts were removed using standard cardioplegic procedures and reperfused in four-chamber working mode (n=8); again the effects of increasing halothane concentrations on cardiac performance were analyzed. When comparing biventricular depressive effects (negative inotropic, negative lusitropic) of halothane in vivo and in vitro, there were distinct quantitative differences. The negative lusitropic effects were less pronounced in vitro; this was especially true for the right ventricle. Yet, in vitro, halothane at all doses induced more pronounced decreases in left heart output compared to the right. The large mammalian isolated four-chamber working heart model allows for novel assessment of pharmacodynamics and/or evaluation of cardiac devices under a range of hemodynamic performances. Halothane, a cardiodepressive agent, induced direct myocardial depressive effects in vitro similar to those recorded in vivo; hence additional systemic effects are considered to play a minor role in ultimate performances, e.g., compensatory responses due to autonomic controls.

Anesthetics, Inhalation↗

PubMed1999

Effects of halothane on renal hemodynamics and interstitial nitric oxide in rabbits.

The effects of halothane on renal hemodynamics and the nitric oxide (NO)-guanylate cyclase signaling pathway were examined in anesthetized rabbits using a renal microdialysis method. Halothane (0.5 and 2 vol%) caused dose-dependent decreases in blood pressure, renal blood flow and the renal interstitial concentrations of guanosine 3',5'-cyclic monophosphate (cGMP) or nitrate (NO2)/nitrite (NO3). Sodium nitroprusside (20 microg kg(-1) min(-1), i.v.) under the inhalation of halothane (2 vol%) increased the renal interstitial concentration of cGMP. L-Arginine (priming dose, 300 mg kg(-1) 10 min(-1); sustaining dose, 50 mg kg(-1) min(-1), i.v.) did not reverse halothane-induced reductions of cGMP and NO2/NO3. These findings demonstrate that halothane caused a renal vasoconstriction and inhibited the NO-guanylate cyclase signaling pathway in the kidney. Moreover, it is possible that the renal hemodynamic responses to halothane might have been induced, in part, through this inhibition. Finally, it can be assumed that halothane did not interfere with the activation process of guanylate cyclase by NO.

Anesthetics, Inhalation↗

PubMed2003

Facilitatory action of halothane at subanesthetic concentrations on glutamatergic excitatory synaptic transmission in the CA1 area of adult rat hippocampus.

Whole-cell recordings were made from pyramidal cells visually identified in the CA1 field of adult rat hippocampal slices, and the effects of subanesthetic concentrations of halothane on excitatory postsynaptic currents mediated by non-N-methyl-D-aspartate subtype glutamate receptors were investigated. Halothane concentrations were measured by gas chromatography. At concentrations of 0.2 mM and 0.6 mM, halothane reversibly decreased the amplitude of excitatory postsynaptic currents (EPSCs) evoked by electrical stimulation of Schaffer collateral fibers, and the decrease was accompanied by enhanced paired-pulse facilitation, consistent with the previously reported presynaptic site of halothane's inhibitory action. By contrast, at lower concentrations (0.02 mM and 0.05 mM), halothane increased the amplitude of EPSCs without any appreciable changes in paired-pulse facilitation. Moreover, the frequency of miniature EPSCs arising spontaneously in the presence of tetrodotoxin (mEPSCs) was increased by subanesthetic halothane, but the amplitude of the mEPSCs did not change significantly. These observations suggest that at subanesthetic concentrations halothane postsynaptically enhances glutamatergic excitatory synaptic transmission. This may provide a vital clue to elucidation of the neural mechanisms of the nociceptive reflex enhancement and excitatory state that occur at light levels of anesthesia.

Anesthetics, Inhalation↗

PubMed1998

Effects of halothane and methoxyflurane on regional brain and spinal cord substance P-like and beta-endorphin-like immunoreactivities in the rat.

Effects of acute exposure (2 hr) to either 1.5% halothane or 0.5% methoxyflurane were investigated in the Sprague Dawley rat. Pituitary (PIT) and central nervous system (CNS) substance P (SP)-like and beta-endorphin (beta-end)-like immunoreactivities were evaluated immediately after anesthetic exposure (2 h), after righting reflex (4 h) or 24 hr postexposure (24 h). Only halothane significantly reduced SP-like immunoreactivity in olfactory bulbs in both the 2-h and 4-h groups. Halothane elevated SP-like immunoreactivity of hippocampus at all three time periods, and in the hypothalamus at 2 h. Both anesthetics significantly depleted thalamic concentrations of SP-like immunoreactivity. Methoxyflurane anesthesia resulted in a drastic decrease in SP-like immunoreactivity in PIT at all three time periods periods, while halothane elevated PIT concentrations of this peptide at 4 h. Both anesthetics significantly decreased beta-end-like immunoreactivity in the olfactory bulbs and thalami at 2, 4, and 24 h. However, halothane alone significantly elevated beta-end-like immunoreactivity in the spinal cord at 24 h. Halothane significantly elevated PIT beta-end-like immunoreactivity at 2 and 24 h, while methoxyflurane significantly lowered it in the 4-h group, but elevated the levels of the same in the 24-h group. Brain stem beta-end immunoreactivity were significantly reduced at 2 h by both anesthetics, and at 4 h by methoxyflurane. Results indicate that halothane and methoxyflurane may differ significantly in their actions on SP and beta-end secreting neurons in the CNS.

Analysis of Variance↗

PubMed2003

Trifluoroacetylated adducts in spermatozoa, testes, liver and plasma and CYP2E1 induction in rats after subchronic inhalatory exposure to halothane.

The induction of cytochrome P450 (CYP) 2E1 in testes and liver and the presence of trifluoroacetylated (TFA) adducts in spermatozoa, testes, liver and plasma were investigated in rats subchronically exposed by inhalation to halothane (15 ppm/4 h/day/5 days/week/9 weeks). After halothane exposure, p-nitrophenol hydroxylase (p-NPH) activity increased 3.2-fold and CYP2E1 apo-protein content 7-fold in testes, whereas in liver, p-NPH increased 2.3-fold and CYP2E1 apoprotein content 1.4-fold. These results suggest a differential inductive effect of halothane on CYP2E1 in these tissues. Moreover, TFA adducts were present in microsomes of testis and liver and in plasma of halothane-treated rats. The immunoblot analysis of testicular microsomes showed two intense TFA protein bands of 63 and 59 kDa, whereas in liver three intense bands of 100, 76 and 63 kDa were observed. Bands of similar molecular weights to those observed in liver were detected in the plasma of halothane-treated animals. In addition, TFA adducts were detected by immunofluorescence in spermatozoa, probably in the acrosome and/or perinuclear theca region, and in the distal tail of spermatozoa. The increase in CYP2E1 apoprotein and p-NPH activity observed in testis and liver microsomes suggests that halothane induces its own biotransformation both hepatically and extrahepatically and in addition, that the nature of the TFA adducts will depend on the proteins present in each tissue. Also, the presence of TFA adducts in spermatozoa may result from the activation of halothane in the reproductive tract. The detailed mechanism of TFA adduct formation and its consequences on the spermatozoa function remain to be fully clarified.

Administration, Inhalation↗

PubMed2003

Effects of intraperitoneally injected selenium and vitamin E in rats anesthetized with halothane.

Halothane, commonly used for anesthetizing humans and animals, is one of the most important volatile anesthetics and may cause the formation of free radicals during its biotransformation. Free radicals may lead to degeneration of liver cells. Vitamin E and glutathione peroxidase (GSH-Px) containing selenium are two natural antioxidants, and these may protect the cellular lipid and lipoproteins against oxidative damage caused by free radicals. Therefore, the purposes of the present study were to investigate the probable protective effects of intraperitoneally administered Se and vitamin E on liver enzymes and to determine some other hematological parameters in the halothane anesthesia of rats. All rats were randomly divided into five groups. The first group was used as a control, and physiological saline (0.9%) was intraperitoneally injected into these animals as a placebo. The second group was used as an anesthesia control group and was only anesthetized with halothane for two hours. The third group received intraperitoneally administered Se (Na2SeO3, 0.3 mg/200 g body weight), the fourth group vitamin E (dl-alpha-tocopheryl acetate, 100 mg/kg body weight), and the fifth group a Se plus vitamin E combination (Na2SeO3, 0.3 mg/200 g body weight + dl-alpha-tocopheryl acetate, 100 mg/kg body weight). The activities of aspartate aminotransferase, alanine aminotransferase and alkaline phosphatase, triglycerides, erythrocyte counts, the packet-cell volume, hemoglobin concentrations and neutrophyle rates significantly increased (p < 0.05 to p < 0.01) after halothane anesthesia and returned to near control levels after Se, vitamin E and Se plus vitamin E injections. The values of cholesterol, total protein, white blood cell counts and lymphocyte rates significantly decreased (p < 0.05 to p < 0.01) in the anesthesia control group. However, the levels of albumin, total bilirubin, creatinine, the mean corpuscular volume, the mean corpuscular hemoglobin, and the mean corpuscular hemoglobin concentration were not statistically influenced. In conclusion, we have determined that halothane anesthesia affected some liver enzymes and some other biochemical and hematological parameters. Se, vitamin E and their combination may prevent the increase of liver enzymes after halothane anesthesia. Based upon these results, Se and vitamin E may play an important role in the indication of hepatic cellular injury produced by halothane.

Alanine Transaminase↗

PubMed1987

Effects of halothane on dipalmitoylphosphatidylcholine liposomes: a Raman spectroscopic study.

Raman spectroscopy has been used to monitor the concentration of halothane (1-bromo-1-chloro-2,2,2-trifluoroethane) in 20% aqueous dispersions of dipalmitoylphosphatidylcholine (DPPC) as well as to follow changes in the acyl chain order within the hydrocarbon interior of the liposomes. Temperature profiles for the gel to liquid-crystalline phase transitions for the liposomes were constructed from changes in peak height intensity ratios in the C-H stretching mode and C-C stretching mode regions. Halothane present at the clinical level produces a change of -0.5 degrees C in the phase transition temperature. A limiting transition temperature of about 21 degrees C and saturation of the gel phase occur when the molar ratio of halothane to DPPC reaches about 1.25. At molar ratios above 2.1, the liquid-crystalline phase is also saturated with halothane. Calculations of the distribution of halothane between the various phases in the system are presented and used to interpret literature data as well as the present experiments. Ideal solution theory accounts rather well for the depression in the transition temperature over most of the mole ratio range, an outcome which implies that halothane is excluded from the hydrocarbon interior but not the head-group region in the gel phase. The role of halothane in the head-group region is discussed.

1,2-Dipalmitoylphosphatidylcholine↗

PubMed1997

UDP-glucose:glycoprotein glucosyltransferase associates with endoplasmic reticulum chaperones and its activity is decreased in vivo by the inhalation anesthetic halothane.

Halothane causes an idiosyncratic hepatitis that is thought to result, in part, from immune reactions against one or more lumenal endoplasmic reticulum (ER) proteins that have been covalently modified by the trifluoroacetyl chloride metabolite of halothane. In this study, we have identified a 170 kDa protein target of halothane in the liver of rats. The 170 kDa protein was first detected when proteins in lysates of hepatocytes from halothane-treated rats were immunoprecipitated with antisera against several resident ER proteins. This 170 kDa protein was found to be associated with other protein targets of halothane, including protein disulfide isomerase, a protein disulfide isomerase isoform, a 59 kDa carboxylesterase, and 78 kDa glucose-regulated protein. Immunoblotting with antiserum directed against the trifluoroacetylated hapten indicated that the 170 kDa protein was trifluoroacetylated. Based upon its subcellular localization, molecular mass, N-terminal amino acid sequence, and antigenicity, the trifluoroacetylated 170 kDa protein was identified as UDP-glucose:glycoprotein glucosyltransferase (UGGT), a lumenal ER protein that is thought to have a role in the folding of N-linked glycoproteins. Moreover, treatment of rats with halothane caused a 44% decrease in the activity of liver microsomal UGGT, and at least 36% of the change in the activity of the enzyme could be due to a decrease in the level of the protein. The results suggest that the function of UGGT in folding of N-linked glycoproteins may be affected by other resident ER proteins or xenobiotics such as halothane.

Anesthetics, Inhalation↗

PubMed1998

Postcardioplegic myocardial recovery: effects of halothane, nifedipine, HOE 694, and quinacrine.

Halothane has been shown to be a powerful myocardial protectant during normothermic cardioplegic arrest and subsequent reperfusion. In view of its multiple effects on cellular Ca2+ movements and the role of this ion in ischemia-reperfusion injury, the questions of whether halothane is capable of maximally protecting the heart or whether combination therapy of halothane with other Ca2+ blocking agents may be more effective arose. Therefore, the effects of combination therapy with halothane and a calcium antagonist (nifedipine), or a Na+/H+ inhibitor (HOE 694), or a Na+/Ca2+ inhibitor (quinacrine) on postcardioplegic functional recovery were evaluated. The isolated perfused rat heart subjected to 45 minutes normothermic cardiac arrest was used as an experimental model. Dose-response curves were performed for each drug. Using the optimal dosage for each drug, the following results were obtained: (1) Nifedipine (10(-7) M; administered retrogradely 10 minutes before and after cardioplegia) and halothane (1.5% administered during cardioplegia), when administered separately, improved functional recovery. Combination therapy did not further improve protection. (2) HOE 694 (10(-7) M) or quinacrine (10(-9) M) improved post-cardioplegic functional recovery when added for 2 minutes at the onset of reperfusion. Simultaneous administration of HOE 694 and 1.5% halothane was the only combination that yielded additive protection. (3) Quinacrine, a phospholipase and Na+/Ca2+ exchanger inhibitor, appeared to be the most powerful drug used. In summary, the results obtained indicate that interventions aimed at preventing intracellular Ca2+ overload improve recovery after cardioplegic arrest. The beneficial effects of halothane could be further improved by HOE 694.

Analysis of Variance↗

PubMed2001

Interactions of halothane with isoproterenol and epinephrine on canine epicardial conduction velocity at normal and elevated potassium levels.

BACKGROUND: Halothane is known to potentiate catecholamine-induced depression of conduction velocity in Purkinje fibers but not endocardial muscle fibers. The purpose of this study was to examine the interactions of halothane with epinephrine and isoproterenol on canine epicardial conduction velocity at moderately elevated extracellular potassium concentration ([K]0). METHODS: Epicardial muscle strips (10x10x2 mm) were superfused with Tyrode's solution containing 4 or 8 mM [K]0 in the presence of 5 microM epinephrine or 1 microM isoproterenol with or without 0.8 mM halothane. Conduction velocity in the longitudinal and transverse directions relative to epicardial fiber orientation was recorded during alternate stimulation in each direction. RESULTS: In the presence of halothane, a change from 4 to 8 mM [K]0 decreased (P< or =0.05) longitudinal and transverse conduction velocities by 26% and 21%, respectively. Isoproterenol alone at 4 and 8 mM [K]0 depressed (P<0.05) both longitudinal and transverse conduction velocities. However, the depression of longitudinal conduction velocity by isoproterenol at 4 mM [K]0 was attenuated by halothane. Epinephrine with or without halothane depressed (P<0.05) both longitudinal and transverse conduction velocities at 8 but not at 4 mM [K]0. CONCLUSION: The results do not support a synergistic interaction between halothane and epinephrine on myocardial conduction but do demonstrate depression of conduction by epinephrine at 8 mM [K+]0, a potassium ion concentration comparable to those reported following epinephrine infusions.

Adrenergic beta-Agonists↗