Volatile Anesthetics Halothane Research Articles

Effects of the volatile anesthetic halothane on fertilization and early development in the sea urchin Lytechinus variegatus: Evidence that abnormal development is due to polyspermy

The volatile anesthetic halothane, when present at fertilization, dose-dependently increases the incidence of abnormally developing sea urchin embryos at the first cell division. Microscopic examinations of eggs stained with aceto-orcein or the DNA fluorochrome bisbenzimide and direct observations on isolated sperm aster complexes show that halothane induces polyspermy (multiple sperm entry) when present at fertilization. Experimental evidence suggests that anesthetic-induced polyspermy involves impairment of both the fast (electrically mediated) and slow (morphological) blocks to multiple sperm entry. These observations clearly show that relatively brief exposures to halothane at fertilization cause polyspermy and that this effect is almost certainly responsible for the ensuing abnormal development observed at the first cell division.

Induction of the Acrosome Reaction in Sea Urchin Spermatozoa by the Volatile Anesthetic Halothane1

The volatile anesthetic halothane rapidly and dose-dependently induces the acrosome reaction in sperm of the sea urchin Lytechinus variegatus. The reaction occurs equally well in artificial sea water containing 10 mM Ca2+ and in low (less than 100 microM)-Ca2+ media. The anesthetic-induced acrosome reaction can be prevented by pretreating sperm with EGTA, lanthanum, or procaine. In contrast, the Ca2+ channel blockers D-600, verapamil, diltiazem, and nitrendipene do not prevent the reaction. Acrosomal processes induced by halothane are ultrastructurally identical to those induced by egg jelly, the natural inducer of the acrosome reaction. These results suggest that Ca2+ in low quantity is required for the anesthetic-induced acrosome reaction and may be derived from internal sources. Enflurane, isoflurane, and methoxyflurane also induce the acrosome reaction, indicating that volatile anesthetics may be useful in studying ion changes accompanying sperm activation.

Reversible inhibition of protein synthesis in lung by halothane.

Alterations in the synthesis and degradation of proteins were investigated in intact lungs exposed to the volatile anaesthetic halothane. In rat lungs perfused in situ with Krebs-Henseleit bicarbonate buffer containing 4.5% (w/v) bovine serum albumin, 5.6 mM-glucose, plasma concentrations of 19 amino acids and 690 microM-[U-14C]-phenylalanine and equilibrated with O2/N2/CO2 (4:15:1), protein synthesis, calculated based on the specific radioactivity of aminoacyl-tRNA, was inhibited by halothane. The anaesthetic did not affect degradation of lung proteins. The inhibition of protein synthesis was rapid in onset, dose-dependent, and quickly reversible. It did not appear to be associated with overall energy depletion, with non-specific changes in cellular permeability, or with decreased availability of amino acids as substrates for protein synthesis.

Further studies on dividing sea urchin eggs exposed to the volatile anesthetic halothane

Mitotic apparatus (MA)-isolation techniques and SDS-gel quantitation show that halothane, a widely used volatile anesthetic, inhibits the growth of the mitotic apparatus of echinoderm eggs in vivo, but has no detectable effect on the amount of actin associated with the cell cortex. These studies confirm and extend long standing observations on anesthetic-treated echinoderm eggs and support the hypothesis that anesthetics indirectly prevent cleavage by inhibiting the growth of mitotic asters.

Structural changes in dividing sea-urchin eggs induced by the volatile anaesthetic halothane.

Fertilized Lytechinus eggs exposed to the volatile anaesthetic halothane before metaphase do not undergo cytoplasmic cleavage. This effect has been correlated with the failure of the contractile ring to assemble. Comparative studies on mitotic apparatuses isolated from control and halothane-treated cells show that halothane significantly impairs both spindle and aster growth as early as metaphase. When transferred to control solutions, halothane-treated cells initiate furrowing activity in association with either the first or second mitotic division, depending on the duration of the exposure to anaesthetic and the concentration employed. In contrast to these effects, halothane has no effect on any aspect of the cleavage process if applied later than metaphase. In this case, furrows develop even in the presence of halothane, deepen progressively, and complete cell division. These observations confirm and extend previous studies on echinoderm eggs exposed to volatile anaesthetics, and support the view that anaesthetic agents indirectly prevent cell cleavage by inhibiting the growth of mitotic apparatus.

General Anesthesia for Morbidly Obese Patients???An Examination of Postoperative Outcomes

Specific postoperative outcomes were assessed in 67 morbidly obese subjects who received general anesthesia for gastric stapling. Each patient was randomly assigned to receive N2O:O2 combined with fentanyl (n = 20), enflurane (n = 24), or halothane (n = 23). Time from last skin stitch until the patient opened eyes on command was significantly less for the fentanyl group (3.0 +/- 0.7 min) than for the enflurane group (13.2 +/- 1.9 min) or the halothane group (17.4 +/- 2.9 min) with P less than 0.05. However, no significant differences in time from last skin stitch to extubation were noted among the fentanyl (16.2 +/- 7.4 min), enflurane (15.2 +/- 1.6 min), and halothane (21.6 +/- 5.8 min) groups (P greater than 0.05). Recovery room (RR) admission temperatures were similar for the three groups: fentanyl, 36.1 +/- 0.1 degrees C; enflurane, 35.7 +/- 0.2 degrees C; and halothane, 36.0 +/- 0.1 degrees C (P greater than 0.05). Total RR time was not significantly different: fentanyl, 108 +/- 6 min, enflurane, 118 +/- 4 min; and halothane, 112 +/- 10 min (P greater than 0.05). In addition, no difference in RR and 24-hour postoperative narcotic (meperidine) requirements was demonstrated among the anesthetic groups. These data suggest that increased lipid solubility of volatile anesthetics (halothane or enflurane) produces neither delayed awakening nor prolonged recovery time in morbidly obese subjects. Considering the early (24 hour) postoperative outcomes studied, there is little to commend one general anesthetic technique over another in the obese subset of the population.

Effects of halothane on protein synthesis and degradation in rabbit pulmonary macrophages.

The effects of exposure to the volatile anesthetic halothane on the synthesis and degradation of rabbit pulmonary macrophage proteins were investigated. Protein synthesis was inhibited rapidly and reversibly when macrophages were exposed to halothane. The magnitude of the inhibition was dependent upon the dose of anesthetic and upon the composition of the medium. The effect of halothane was not associated with increased cell death or with depletion of cellular ATP. Halothane exposure did not affect the ability of the cells to degrade either endogenous proteins or exogenous bovine serum albumin. These results suggested that halothane exposure favored protein catabolism in pulmonary alveolar macrophages though an inhibition of protein synthesis with no change in protein degradation.

Halothane effect on cAMP generation and hydrolysis in rat brain

The volatile anesthetic halothane increased the rate of cAMP generation and decreased the rate of cAMP hydrolysis in rat cerebral cortex and cerebellum. The effect of halothane on the enzymes was reflected in a two-fold rise in cAMP content of cerebral cortical tissue exposed to the anesthetic at 3 vol% for 15 and 30 min. The action of halothane on adenylate cyclase is calcium-independent and different from the action of guanine nucleotides, sodium fluoride and specific transmitters. The V max of the enzyme is higher in the presence of the anesthetic. It is suggested that halothane, through conformational changes of the enzyme, renders more catalytic sites operative.

Inhibition of sperm motility by the volatile anesthetic halothane

The inhalational anesthetic halothane reversibly inhibits the motility of sea urchin sperm dose-dependently at concentrations up to 5 mM. Experiments with Triton X-100 extracted, trypsinized axonemes showed that halothane has no effect on the rate of axonemal disintegration in the presence of ATP. These results suggest that halothane inhibits flagellar activity by acting at a site other than the dynein ATPase component of the flagellum.

Macrotubules induced by halothane: in vitro assembly.

The formation of macrotubules by the volatile anaesthetic halothane was investigated in vitro using microtubule-enriched fractions of crayfish nerve cords. Sequential studies showed that macrotubules assemble from helical ribbons of 18-20 laterally associated microtubule protofilaments which fold upon themselves to form intact macrotubules averaging 48 nm in diameter. The initial rate of macrotubule assembly is dependent on the concentration of halothane employed and is stimulated by calcium. Glycerol pretreatment blocked macrotubule formation by halothane and caused preformed macrotubules to reassemble rapidly into typical microtubules. These experiments show that microtubules and macrotubules require different conditions for assembly and support the contention that macrotubule formation by halothane is due to a direct interaction between the anaesthetic molecule and the microtubule subunit.

The inhibition of flagellar regeneration in Chlamydomonas reinhardii by inhalational anesthetic halothane

The volatile anesthetic halothane was shown to be an effective and fully reversible inhibitor of flagellar regeneration in Chlamydomonas reinhardii. The concentration at which halothane inhibited regeneration (2 mM), flagellar length and motility was normal. At 10 mM halothane, the flagella of control cultures shortened considerably and most cells ceased swimming; most cells did not recover from exposure to 10 mM halothane. Lastly, data is presented which shows that flagella increase in length when cells are placed in H 2O but not when left in growth medium.