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Biomedical subjects

D O Warner

Publications and source records attributed to D O Warner.

At least 19 recordsLinked to original sources
PubMed1999

Ulnar neuropathy in surgical patients.

BACKGROUND: The goal of this project was to study the frequency and natural history of perioperative ulnar neuropathy. METHODS: A prospective evaluation of ulnar neuropathy in 1,502 adult patients undergoing noncardiac surgical procedures was performed. Patients were assessed with a standard questionnaire and neurologic examination before surgery, daily during hospitalization in the first week after surgery, and by telephone if they were discharged before 1 postoperative week. Patients in whom ulnar neuropathy developed were followed for 2 yr. RESULTS: Ulnar neuropathy developed in seven patients (0.5%; 95% confidence interval, 0.2% to 1.0%). Six of the seven patients were men. Symptoms of ulnar neuropathy began 2-7 days after surgery. Manifestations were mild and confined to sensory deficits in six patients. Symptoms resolved in four patients within 6 weeks. The remaining three patients had residual symptoms 2 yr later. CONCLUSIONS: In this surgical population, ulnar neuropathy was an infrequent complication. It occurred primarily in men who were 50-75 yr old and was not symptomatic until several days after surgery. Gender-dependent differences in the anatomy of the ulnar nerve and related structures at the elbow may serve as risk factors for ulnar neuropathy in patients having surgery.

Aged↗
PubMed1999

Perioperative pulmonary aspiration in infants and children.

BACKGROUND: Pulmonary aspiration of gastric contents during the perioperative period in infants and children may be associated with postoperative mortality or pulmonary morbidity. There has not been a recent determination of the frequency of this event and its outcomes in infants and children. METHODS: The authors prospectively identified all cases of pulmonary aspiration of gastric contents during the perioperative courses of 56,138 consecutive patients younger than 18 yr of age who underwent 63,180 general anesthetics for procedures performed in all surgical specialties from July 1985 through June 1997 at the Mayo Clinic. RESULTS: Pulmonary aspiration occurred in 24 patients (1: 2,632 anesthetics; 0.04%). Children undergoing emergency procedures had a greater frequency of pulmonary aspiration compared to those undergoing elective procedures (1:373 vs. 1:4,544, P < 0.001). Fifteen of the 24 children who aspirated gastric contents did not develop respiratory symptoms within 2 h of aspiration, and none of these 15 developed pulmonary sequelae. Five of these nine children who aspirated and in whom respiratory symptoms developed within 2 h subsequently had pulmonary complications treated with respiratory support (P < 0.003). Three children were treated with mechanical ventilation for more than 48 h, but no child died of sequelae of pulmonary aspiration. CONCLUSIONS: In this study population, the frequency of perioperative pulmonary aspiration in children was quite low. Serious respiratory morbidity was rare, and there were no associated deaths. Infants and children with clinically apparent pulmonary aspiration in whom symptoms did not develop within 2 h did not have respiratory sequelae.

Adolescent↗
PubMed1999

cGMP modulation of Ca2+ sensitivity in airway smooth muscle.

A beta-escin-permeabilized canine tracheal smooth muscle preparation was used to test the hypothesis that cGMP decreases Ca2+ sensitivity in airway smooth muscle primarily by inhibiting the membrane receptor-coupled mechanisms that regulate Ca2+ sensitivity and not by inhibiting Ca2+/calmodulin activation of the contractile proteins. 8-Bromo-cGMP (100 microM) had no effect on the free Ca2+ concentration-response curves generated in the absence of muscarinic receptor stimulation. In the presence of 100 microM ACh plus 10 microM GTP, 8-bromo-cGMP (100 microM) caused a rightward shift of the free Ca2+ concentration-response curve, significantly increasing the EC50 for free Ca2+ from 0.35 +/- 0.03 to 0.75 +/- 0.06 microM; this effect of 8-bromo-cGMP was concentration dependent from 1 to 100 microM. 8-Bromo-cGMP (100 microM) decreased the level of regulatory myosin light chain (rMLC) phosphorylation for a given cytosolic Ca2+ concentration but had no effect on the amount of isometric force produced for a given level of rMLC phosphorylation. These findings suggest that cGMP decreases Ca2+ sensitivity in canine tracheal smooth muscle primarily by inhibiting the membrane receptor-coupled mechanisms that modulate the relationship between cytosolic Ca2+ concentration and rMLC phosphorylation.

Animals↗
PubMed1999

Effect of halothane on intracellular calcium oscillations in porcine tracheal smooth muscle cells.

The effect of halothane on intracellular Ca2+ concentration ([Ca2+]i) regulation in porcine tracheal smooth muscle cells was examined with real-time confocal microscopy. Both 1 and 2 minimum alveolar concentration (MAC) halothane increased basal [Ca2+]i when Ca2+ influx and efflux were blocked, suggesting increased sarcoplasmic reticulum (SR) Ca2+ leak and/or decreased reuptake. In beta-escin-permeabilized cells, heparin inhibition of inositol 1,4, 5-trisphosphate-receptor channels blunted the halothane-induced increase in [Ca2+]i. Both 1 and 2 MAC halothane decreased the frequency and amplitude of ACh-induced [Ca2+]i oscillations (which represent SR Ca2+ release through ryanodine-receptor channels), abolishing oscillations in approximately 20% of tracheal smooth muscle cells at 2 MAC. When Ca2+ influx and efflux were blocked, halothane increased the baseline and decreased the frequency and amplitude of [Ca2+]i oscillations, inhibiting oscillations in approximately 70% of cells at 2 MAC. The fall time of [Ca2+]i oscillations and the rate of fall of the [Ca2+]i response to caffeine were both increased by halothane. These results suggest that halothane abolishes agonist-induced [Ca2+]i oscillations by 1) depleting SR Ca2+ via increased Ca2+ leak through inositol 1,4, 5-trisphosphate-receptor channels, 2) decreasing Ca2+ release through ryanodine-receptor channels, and 3) inhibiting reuptake.

Acetylcholine↗
PubMed1998

The role of cGMP in the relaxation to nitric oxide donors in airway smooth muscle.

The aim of this study was to determine the effect of the soluble guanylyl cyclase inhibitors methylene blue and LY83583 (6-anilino-5,8-quinolinedione) on relaxation and increases in intracellular guanosine 3',5'-cyclic monophosphate (cGMP) concentration ([cGMP]i) induced by sodium nitroprusside, 3-morpholinosydnonimine (SIN-1) and diethylamine-nitric oxide (NO) in porcine tracheal smooth muscle in vitro. We measured (1) the effect of NO donors on isometric force and [cGMP]i and (2) the ability of methylene blue and LY83583 to antagonize these effects. In muscle strips contracted with carbachol (0.1-0.3 microM), both sodium nitroprusside and diethylamine-NO caused relaxation and an increase in [cGMP]i. By contrast, SIN-1 caused a relaxation which was not associated with a concomitant increase in [cGMP]i. Methylene blue (10 microM) and LY83583 (10 microM) completely blocked the increase in [cGMP]i induced by sodium nitroprusside and diethylamine-NO; however substantial relaxation remained. It is concluded that in porcine airway smooth muscle, (1) relaxation induced by some NO donors may occur without a concomitant increase in [cGMP]i; and (2) whereas relaxation induced by some NO donors may be associated with increases in [cGMP]i, the relaxation is not completely dependent upon it.

Aminoquinolines↗
PubMed1998

Changing transfusion practices in hip and knee arthroplasty.

BACKGROUND: This study was designed to examine changes in perioperative transfusion practices after the introduction of autologous blood conservation strategies into routine clinical practice. STUDY DESIGN AND METHODS: The existing medical records of all patients undergoing total hip or knee arthroplasty at Mayo Clinic in Rochester, MN, who resided in Olmsted County, were reviewed over three periods: 1981-82 (232 procedures), 1987-88 (269 procedures), and 1993-94 (398 procedures). RESULTS: The proportion of patients receiving any perioperative red cell (RBC) units significantly decreased (from 85% in 1981-82 to 65% in 1993-94). The timing of transfusion also changed; the proportion of RBC units transfused in the preoperative or intraoperative periods decreased from 68 percent in 1981-82 to 38 percent in 1993-94, with the balance of RBC units transfused in the postoperative period. Although the number of RBC units utilized per procedure in the intraoperative period significantly decreased, the number of RBC units transfused in the postoperative period significantly increased (from 0.6 +/- 1.0 to 1.1 +/- 1.4 units per procedure in 1981-82 and 1993-94, respectively, p < 0.05). CONCLUSION: Although blood conservation strategies have been successful in reducing RBC transfusion intraoperatively, avoidance of intraoperative transfusion may in some cases postpone, rather than prevent, transfusion.

Aged↗
PubMed1998

The effect of nitrous oxide on chest wall function in humans and dogs.

UNLABELLED: The purpose of this study was to determine the effects of nitrous oxide (N2O) on the chest wall of anesthetized humans and dogs. Six human subjects and six mongrel dogs were studied during 1 minimum alveolar anesthetic concentration halothane anesthesia before and during the substitution of 70% N2O for 70% N2 in the inspired gas mixture. On a separate occasion, measurements also were made in pentobarbital-anesthetized dogs. Respiratory muscle activity was measured using electromyographic (EMG) electrodes. Chest wall configuration was determined by using fast three-dimensional computed tomography in dogs and by using respiratory impedance plethysmography in humans. N2O consistently decreased inspiratory ribcage displacement, a decrease attributable in dogs to decreased inspiratory activation of parasternal intercostal muscles; parasternal intercostal activity was not present in anesthetized humans. The decrease in ribcage motion decreased the tidal volume in humans, but not in dogs, because displacement of the diaphragm was better preserved in dogs, in association with changes in diaphragm EMG activation. N2O significantly increased phasic expiratory muscle activity in halothane-anesthetized humans and pentobarbital-anesthetized dogs. Thus, as has been demonstrated for other anesthetics, the actions of N2O are caused by alterations in the distribution and timing of neural drive to the respiratory muscles, rather than by a global depression of respiratory motoneuron drive. IMPLICATIONS: In this study, we examined the effects of nitrous oxide on breathing in halothane-anesthetized dogs and humans. Nitrous oxide affected breathing by changing the distribution and timing of neural drive to the respiratory muscles in a species-dependent manner, rather than by causing a global depression of their activity.

Animals↗
PubMed1998

Drug-specific effects of volatile anesthetics on Ca2+ sensitization in airway smooth muscle.

UNLABELLED: Halothane directly relaxes airway smooth muscle, partly by decreasing the Ca2+ sensitivity during membrane receptor stimulation. The effects of other volatile anesthetics on Ca2+ sensitivity are unclear. In the current study, we compared the ability of halothane, sevoflurane, and isoflurane to inhibit increases in Ca2+ sensitivity during muscarinic receptor stimulation. Beta-escin-permeabilized canine tracheal smooth muscle strips were used. Anesthetics were applied during contractions induced by 3 microM acetylcholine and 10 microM guanosine 5'-triphosphate at a constant cytosolic Ca2+ concentration of 0.3 microM. Effects were evaluated as a percent relaxation from initial force corrected for time. Halothane significantly decreased force at both low (0.76 minimum alveolar anesthetic concentration [MAC]) and high (1.8 MAC) concentrations in a concentration-dependent manner. Sevoflurane also decreased force, significantly so at a high concentration (1.7 MAC). Isoflurane did not significantly affect force even at a high concentration (1.7 MAC). Halothane's relaxing effect was significantly greater than that of the other two anesthetics at each corresponding MAC concentration. Among these three volatile anesthetics compared at equipotent anesthetic concentrations, halothane was the most potent in reducing Ca2+ sensitivity during muscarinic receptor stimulation in canine tracheal smooth muscle. This may contribute to halothane's greater relaxing effect compared with isoflurane at the same MAC concentrations in intact airway smooth muscle. IMPLICATIONS: In this study, we showed that three volatile anesthetics (halothane, sevoflurane, and isoflurane) compared at equipotent anesthetic concentrations differed in their ability to inhibit Ca2+ sensitivity during muscarinic receptor stimulation in airway smooth muscle. The potency order was halothane > sevoflurane > or = isoflurane.

Acetylcholine↗
PubMed1998

Halothane attenuates calcium sensitization in airway smooth muscle by inhibiting G-proteins.

BACKGROUND: Halothane directly relaxes airway smooth muscle partly by decreasing the Ca2+ sensitivity. In smooth muscle, receptor stimulation is thought to increase Ca2+ sensitivity via a cascade of heterotrimeric and small monomeric guanine nucleotide-binding proteins (G-proteins). Whether this model is applicable in the airway and where halothane acts in this pathway were investigated. METHODS: A beta-escin-permeabilized canine tracheal smooth muscle preparation was used. Exoenzyme C3 of Clostridium botulinum, which inactivates Rho monomeric G-proteins, was used to evaluate the involvement of this protein in the Ca2+ sensitization pathway. The effects of halothane on different stimulants acting at different levels of signal transduction were compared: acetylcholine on the muscarinic receptor, aluminum fluoride (AIF4-) on heterotrimeric G-proteins, and guanosine 5'-O-(3-thiotriphosphate) (GTPgammaS) on all G-proteins. RESULTS: Exoenzyme C3 equally attenuated acetylcholine- and AIF4--induced Ca2+ sensitization, suggesting that these pathways are both mediated by Rho. Halothane applied before stimulation equally attenuated acetylcholine- and AIF4--induced Ca2+ sensitization. However, when added after Ca2+ sensitization was established, the effect of halothane was greater during Ca2+ sensitization induced by acetylcholine compared with AIF4-, which, along with the previous result, suggests that halothane may interfere with dissociation of heterotrimeric G-proteins. Halothane applied during GTPgammaS-induced Ca2+ sensitization had no significant effect on force, suggesting that halothane has no effect downstream from monomeric G-proteins. CONCLUSION: Halothane inhibits increases in Ca2+ sensitivity of canine tracheal smooth muscle primarily by interfering with the activation of heterotrimeric G-proteins, probably by inhibiting their dissociation.

ADP Ribose Transferases↗
PubMed1998

Outcomes of anesthesia and surgery in people 100 years of age and older.

OBJECTIVE: To assess the outcomes of anesthesia and surgery for men and women 100 years of age and older. DESIGN: Retrospective cohort study in the 20-year time period from 1975 to 1994, with follow-up through 1995. SETTING: Mayo-affiliated hospitals and Olmsted Community Hospital, Rochester, Minnesota. PARTICIPANTS: All men and women 100 years of age and older who underwent surgery at a participating hospital. MEASUREMENTS: Forty-eight-hour and 30-day perioperative morbidity and mortality; long-term survival. RESULTS: Thirty-one men and women aged 100 to 107 years underwent 42 procedures. One major complication (3%) within 48 hours was observed. The 48-hour, 30-day, and 1-year mortality rates were 0%, 16.1%, and 35.5%, respectively. When compared with survival rates for age-, gender-, and calendar year of birth-matched peers from the general population, the survival rate for centenarians who underwent surgery and anesthesia was comparable to the rate expected. CONCLUSION: These data suggest that people 100 years of age and older who have operable diseases or injuries should not be denied surgical interventions because of perceived risks associated with their advanced age.

Age Factors↗
PubMed1998

Effect of phorbol esters on Ca2+ sensitivity and myosin light-chain phosphorylation in airway smooth muscle.

We studied in beta-escin-permeabilized canine tracheal smooth muscle (CTSM) the effect of the protein kinase C (PKC) agonist phorbol 12,13-dibutyrate (PDBu) on isometric force at a constant submaximal Ca2+ concentration (i.e., the effect on Ca2+ sensitivity) and regulatory myosin light-chain (rMLC) phosphorylation. PDBu increased Ca2+ sensitivity, an increase associated with a concentration-dependent, sustained increase in rMLC phosphorylation. PDBu altered the relationship between rMLC phosphorylation and isometric force such that the increase in isometric force was less than that expected for the increase in rMLC phosphorylation observed. The effect of four PKC inhibitors [calphostin C, chelerythrine chloride, a pseudosubstrate inhibitor for PKC, PKC peptide-(19-31) (PSSI), and staurosporine] on PDBu-induced Ca2+ sensitization as well as the effect of calphostin C and PSSI on rMLC phosphorylation were determined. Whereas none of these compounds prevented or reversed the PDBu-induced increase in Ca2+ sensitivity, the PDBu-induced increase in rMLC phosphorylation was inhibited. We conclude that PDBu increases rMLC phosphorylation by activation of PKC but that the associated PDBu-induced increases in Ca2+ sensitivity are mediated by mechanisms other than activation of PKC in permeabilized airway smooth muscle.

Animals↗
PubMed1998

cGMP-independent mechanism of airway smooth muscle relaxation induced by S-nitrosoglutathione.

This study tested the hypothesis that the NO donor S-nitrosoglutathione (GSNO) relaxes canine tracheal smooth muscle (CTSM) in part by a cGMP-independent process that involves reversible oxidation of intracellular thiols. GSNO caused a concentration-dependent relaxation in ACh-contracted strips (EC50 approximately 1.2 microM) accompanied by a concentration-dependent increase in cytosolic cGMP concentration ([cGMP]i). The soluble guanylate cyclase inhibitor methylene blue prevented the increase in [cGMP]i induced by 1 and 10 microM GSNO, but isometric force decreased by 10 +/- 4 and 55 +/- 3%, respectively. After recovery of [cGMP]i to baseline, GSNO-induced relaxation persisted during continuous ACh stimulation. Dithiothreitol caused a rapid recovery of isometric force to values similar to those obtained with ACh alone in these strips. We conclude that GSNO relaxes CTSM contracted by ACh in part by oxidation of intracellular protein thiols.

Acetylcholine↗
PubMed1998

Forearm blood flow responses to handgripping after local neuromuscular blockade.

To test the hypothesis that acetylcholine "spillover" from motor nerves contributes significantly to skeletal muscle vasodilation during exercise, we measured the forearm blood flow responses during attempted handgripping after local paralysis of the forearm with the neuromuscular-blocking drug pipecuronium. This compound blocks postsynaptic nicotinic receptors but has no impact on acetylcholine release from motor nerves. The drug was administered selectively to one forearm by using regional intravenous drug administration techniques in five subjects. Pipecuronium reduced maximum forearm grip strength from 40.0 +/- 3.2 kg before treatment to 0.0 kg after treatment. By contrast, drug administration had no effect on maximum voluntary contraction in the untreated forearm (41.3 +/- 3.3 vs. 41.4 +/- 2.7 kg). During 2 min of attempted maximal contraction of the paralyzed forearm, the forearm blood flow increased from only 3.4 +/- 0.8 to 4.8 +/- 1.2 ml.100 ml-1.min-1 (P < 0.05). Heart rate increased from 63 +/- 3 to 73 +/- 8 beats/min (P > 0.05) during attempted contraction, and only three of five subjects showed obvious increases in heart rate. Mean arterial pressure increased significantly (P < 0.05) from 102 +/- 6 to 109 +/- 9 mmHg during attempted contractions. When these increases in flow are considered in the context of the marked (10-fold or greater) increases in flow seen in contracting forearm skeletal muscle, it appears that acetylcholine spillover from motor nerves has, at most, a minimal impact on the hyperemic responses to contraction in humans.

Adult↗
PubMed1997

Stereospecific effects of ketamine enantiomers on canine tracheal smooth muscle.

1. Ketamine is a potent bronchodilator which relaxes airway smooth muscle (ASM). Clinically, ketamine is used as a 1:1 racemic mixture of enantiomers that differ in their analgesic and anaesthetic effects. The aim of this study was to determine whether there was a difference between the enantiomers in their ability to relax isolated ASM and to explore mechanisms responsible for any observed differences. 2. Canine tracheal smooth muscle strips were loaded with fura-2 and mounted in a photometric system to measure simultaneously force and [Ca2+]i. Calcium influx was estimated by use of a manganese quenching technique. 3. In strips stimulated with 0.1 microM ACh (EC50) R(-)-ketamine (1-100 microM) caused a significantly greater concentration-dependent decrease in force (P<0.0001) and [Ca2+]i than S(+)-ketamine (1-100 microM) (P<0.0005). In contrast, there was no significant difference between the enantiomers in their ability to inhibit calcium influx (45% decrease in influx rate for R(-)-ketamine and 44% for S(+)-ketamine, P =0.782). In strips contracted with 24 mM isotonic KCI (which activates voltage-operated calcium channels), the enantiomers modestly decreased force and [Ca2+]i; there was no significant difference between the enantiomers in their effects on force (P=0.425) or [Ca2+]i (P=0.604). 4. The R(-)-enantiomer of ketamine is a more potent relaxant of ACh-induced ASM contraction than the S(+)-enantiomer. This difference appears to be caused by differential actions on receptor-operated calcium channels.

Acetylcholine↗
PubMed1997

The effects of halothane pretreatment on manganese influx induced by muscarinic stimulation of airway smooth muscle.

We hypothesized that halothane inhibits contraction of canine airway smooth muscle in part by depleting sarcoplasmic reticulum (SR) calcium stores, which affects subsequent force and calcium influx. This hypothesis was tested by using the rate of quenching of fura-2 fluorescence by manganese (Mn2+) as an index of calcium influx. When added 10 min before submaximum muscarinic stimulation (with 0.3 microM acetylcholine [ACh]), halothane (0.60 +/- 0.04 mM [mean +/- SE]) reduced subsequent isometric force and intracellular calcium concentration ([Ca2+]i) measured 10 min after contraction (to 55%) +/- 5% and 69% +/- 4% of control, respectively). The Mn2+ influx measured concurrently was significantly increased by halothane (by 57% +/- 22%). Depletion of SR calcium stores by ACh prior to contraction also increased Mn2+ influx (by 46% +/- 6%) but did not affect developed force or increase [Ca2+]i in response to submaximum muscarinic stimulation. Halothane did not affect [Ca2+]i or Mn2+ influx when added prior to maximum stimulation with 100 microM ACh but significantly reduced developed force. These findings are consistent with the hypothesis that halothane-induced SR depletion prior to contraction stimulates subsequent calcium influx, but they further suggest that halothane-induced SR depletion itself does not contribute significantly to the reduction in contractility produced by halothane in the canine airway smooth muscle.

Acetylcholine↗
PubMed1997

Calcium concentration-dependent mechanisms through which ketamine relaxes canine airway smooth muscle.

BACKGROUND: Ketamine is a potent bronchodilator that, in clinically used concentrations, relaxes airway smooth muscle in part by a direct effect. This study explored the role of calcium concentration (Ca2+) in this relaxation. METHODS: Canine trachea smooth muscle strips were loaded with the fluorescent probe fura-2 and mounted in a spectro-photometric system to measure force and intracellular calcium concentration ([Ca2+]i) simultaneously. Calcium influx was estimated using a manganese quenching technique. Cyclic nucleotides in the airway smooth muscle strips were measured by radioimmunoassay. RESULTS: In smooth muscle strips stimulated with submaximal (0.1 microM) and maximal (10 microM) concentrations of acetylcholine, ketamine caused a concentration-dependent decrease in force and [Ca2+]i. The sensitivity of the force response to ketamine significantly decreased as the intensity of muscarinic receptor stimulation increased; the median effective concentration for relaxation induced by ketamine was 59 microM and 850 microM for tissue contracted by 0.1 microM or 10 microM acetylcholine, respectively (P < 0.05). In contrast, the sensitivity of the [Ca2+]i response did not depend on the intensity of muscarinic receptor stimulation. Ketamine at 1 mM significantly inhibited calcium influx. Ketamine did not significantly increase cyclic nucleotide concentrations. CONCLUSIONS: Ketamine-induced relaxation of canine airway smooth muscle is associated with a decrease in [Ca2+]i and calcium influx, effects that are not mediated by an increase in cyclic nucleotides; and the sensitivity of the force response to ketamine decreases as the level of preexisting muscle tone increases, an effect that is not explained by differential effects on [Ca2+]i.

Anesthetics, Dissociative↗
PubMed1997

Halothane attenuation of calcium sensitivity in airway smooth muscle. Mechanisms of action during muscarinic receptor stimulation.

BACKGROUND: In airway smooth muscle, muscarinic receptor stimulation is thought to increase calcium (Ca2+) sensitivity via a guanosine 5'-triphosphate (GTP)-binding protein/protein kinase C (PKC)-mediated mechanism. This study treated the hypothesis that halothane reduces Ca2+ sensitivity during muscarinic receptor stimulation by inhibiting these second messenger pathways. METHODS: A beta-escin permeabilized canine tracheal smooth muscle preparation was used in which the cytosolic Ca2+ concentration ([Ca2+]i) is controlled and the GTP-binding protein/ PKC pathways remain intact and can be activated. The muscarinic receptor was activated with acetylcholine plus GTP; the GTP-binding proteins were directly activated with a nonhydrolyzable form of GTP, guanosine 5'-O-(3-thiotriphosphate; GTP gamma S); and PKC was directly activated with the PKC agonist phorbol 12,13-dibutyrate (PDBu). RESULTS: Free Ca2+ caused a concentration-dependent increase in force. Acetylcholine plus GTP significantly decreased the median effective concentration for free Ca2+ from 0.52 +/- 0.06 microM to 0.21 +/- 0.02 microM, demonstrating an increase in Ca2+ sensitivity. Halothane (0.99 +/- 0.04 mM, equivalent to approximately 4 minimum alveolar concentration in dogs) significantly attenuated this increase in Ca2+ sensitivity induced by acetylcholine plus GTP, increasing the median effective concentration for free Ca2+ from 0.21 +/- 0.02 microM to 0.31 +/- 0.03 microM. However, halothane did not affect the increases in Ca2+ sensitivity induced by GTP gamma S or PDBu. CONCLUSIONS: Halothane had no effect on increased Ca2+ sensitivity caused by direct activation of GTP-binding proteins with GTP gamma S or PKC with PDBu, suggesting that halothane attenuates acetylcholine-induced Ca2+ sensitization via a mechanism independent of these pathways in beta-escin-permeabilized canine tracheal smooth muscle.

Anesthetics, Inhalation↗