G(s) protein dysfunction in allergen-challenged human isolated passively sensitized bronchi.

We studied the intracellular mechanisms of allergen-induced beta(2)-adrenoceptor dysfunction in human isolated passively sensitized bronchi. Sensitization was obtained by overnight incubation of bronchial rings with serum containing a high specific IgE level to Dermatophagoides but a low total IgE level. Allergen challenge was done by incubation with a Dermatophagoides mix. The G(s) protein stimulant cholera toxin (2 microg/ml) displaced the carbachol (CCh) concentration-response curves of control and sensitized but not of challenged rings to the right. Cholera toxin (10 microg/ml) displaced the concentration-response curves to CCh of control, sensitized, and challenged rings to the right, but this effect was less in challenged rings. The effects of the G(i) protein inhibitor pertussis toxin (250 ng/ml or 1 microg/ml) on salbutamol concentration-relaxation curves did not differ significantly between challenged and sensitized rings. The adenylyl cyclase activator forskolin and the Ca(2+)-activated K(+)-channel opener NS-1619 relaxed CCh-contracted bronchial rings without significant differences between control, sensitized, and challenged rings. Neither G(i) nor G(s) alpha-subunit expression differed between control, sensitized, and challenged tissues. We conclude that G(s) protein dysfunction may be a mechanism of allergen-induced beta(2)-adrenoceptor dysfunction in human isolated passively sensitized bronchi.

Do pipecuronium and rocuronium affect human bronchial smooth muscle?

BACKGROUND: Muscle relaxants affect nicotinic and muscarinic receptors. Interaction of muscle relaxants with muscarinic receptors of human airways has been studied incompletely. METHODS: The effects of pipecuronium bromide (long-acting, nondepolarizing) and rocuronium bromide (intermediate-acting, nondepolarizing) on prejunctional and postjunctional muscarinic receptors were studied in 96 isolated human bronchial rings from 12 patients. Contractile isometric responses to electric field stimulation of pilocarpine-stimulated and nonstimulated M2 muscarinic receptors were compared before and after incubation with the two muscle relaxants. The effect on postjunctional muscarinic receptors was studied by comparing acetylcholine concentration-response curves before and after incubation with the two muscle relaxants. RESULTS: Pipecuronium bromide, but not rocuronium bromide, inhibited pilocarpine-stimulated prejunctional M2 muscarinic receptors. Neither pipecuronium bromide nor rocuronium bromide had significant inhibitory effects on nonstimulated M2 muscarinic receptors and on postjunctional M3 muscarinic receptors. CONCLUSIONS: The inhibitory effect of pipecuronium bromide on pilocarpine-stimulated prejunctional M2 muscarinic receptors occurred at clinical concentrations.

Anti-inflammatory agents and allergen-induced beta2-receptor dysfunction in isolated human bronchi.

Antigen challenge causes beta2-adrenoceptor dysfunction in sensitized human bronchi (Am. J. Respir. Crit. Care Med. 1997;155:1230-1234). This study investigated whether the dysfunction can be prevented by anti-inflammatory agents. Human bronchial rings (2 to 4 mm) from surgery were passively sensitized to house dust mite and challenged (1) with allergen only, (2) with allergen plus indomethacin (10(-)5 M), (3) with allergen plus nedocromil sodium (10(-)7 M to 10(-)5 M), (4) with allergen plus the H1-receptor antagonist cetirizine (10(-)7 M to 10(-)5 M), and (5) with allergen plus the peptido-leukotriene receptor antagonist iralukast (10(-)7 M to 10(-)5 M). Rings were first contracted with 10(-)6 M carbachol and then relaxed with salbutamol (10(-)9 M to 10(-)4 M). The concentration-relaxation curve to salbutamol was shifted significantly to the right in the rings challenged with allergen only compared with control rings. In the rings challenged with allergen plus nedocromil sodium (10(-)6 M and 10(-)5 M) or iralukast (10(-)6 M and 10(-)5 M) the concentration-relaxation curves to salbutamol were significantly shifted to the left compared with rings challenged in saline alone, suggesting a protective effect against beta2-adrenoceptor dysfunction. Neither allergen plus cetirizine nor allergen plus indomethacin shifted significantly the concentration-relaxation curves to salbutamol compared with rings challenged in saline alone. We conclude that the release of peptido-leukotrienes may play a significant role in causing the allergen-induced beta2-receptor dysfunction in passively sensitized human bronchi.

Postural changes in respiratory function.

Changes in body position alters the functional residual capacity (FRC). Most anesthetics reduce FRC in the recumbent but not sitting position. Inspired gas distribution in anesthesia-paralyzed subjects whose lungs are mechanically ventilated, is different from that in the awake state in all but the prone position. The function of the diaphragm is altered by postural changes. The pattern of motion of the diaphragm is different during mechanical ventilation than during spontaneous breathing. Also the end-expiratory shape is affected by induction of anesthesia, but this shape change contributes little to the reduction of FRC. The distribution of pulmonary blood flow is determined not only by gravity, but also by an intrinsic non-gravity dependent factor. These two factors can be additive in some positions but opposing in others.

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.

Inhibition of airway constriction by opioids is different down the isolated bovine airway.

BACKGROUND: Opioid agonists attenuate in isolated airways contractile responses to electrical field stimulation (EFS), and this attenuation is mediated by opioid receptors. Differences exist in the density of muscarinic and beta-adrenergic receptors between large and small airways. The authors hypothesized that the density of opioid receptors may also be different down the airway. METHODS: The effects of three selective opioid agonists (mu, kappa, delta) on EFS-induced contractions were compared between isolated bovine sublobar (4- or 5-mm inner diameter) and segmental (2- or 3-mm inner diameter) bronchial rings and between trachealis strips and bronchial rings. RESULTS: D-Ala2-N-MePhe4-Gly-ol5 enkephalin (DAMGO; 10(-5) M), a mu-opioid agonist, attenuated EFS-induced contractions of isolated sublobar and segmental bronchial rings at low stimulating frequencies of 0.5 Hz (P < 0.001), 2 Hz (P < 0.001), and 8 Hz (P < 0.001), but not at 32 Hz (P = 0.071). The inhibitory effect of DAMGO was antagonized by naloxone (10(-5) M) (P = 0.025). The selective kappa-opioid agonist U-50488 H (10(-5) m) attenuated EFS-induced contractions at 32 Hz (P = 0.008) and 8 Hz (P = 0.045), but not at 2-Hz (P = 0.893) or 0.5-Hz (P = 0.145) contractions. The inhibitory effects of 10(-5) M U-50488 H were not antagonized by the highly selective kappa-antagonist 2,2'-[1,1'-biphenyl] 4,4'-diyl-bis [2-hydroxy-4,4-dimethyl]-morpholinium (nor-BNI; 10(-5) M; P = 0.216) or naloxone (10[-5]) M; P = 0.065). The selective delta-agonist D-penicillamine2-D-penicillamine5-enkephalin (DPDPE) (10(-5) M) had no inhibitory effects (P = 0.256). The inhibitory effects of the selective mu-opioid agonist DAMGO were smaller (P < 0.001) and those of U-50488 H larger (P < 0.001) in trachealis strips compared with bronchial rings. CONCLUSIONS: The attenuation of EFS-induced contractions by DAMGO in isolated bovine bronchi was mediated by prejunctional opioid receptors. In contrast, the inhibitory effect of U-50488 H was probably not mediated by opioid receptors in the bronchi.

Maturation of porcine tracheal cholinergic and inhibitory non-adrenergic, non-cholinergic innervation.

It is known that both excitatory cholinergic neural activity and nitric oxide (NO) release from inhibitory non-adrenergic, non-cholinergic (iNANC) nerves are important determinants of adult human airway smooth muscle tone. However, the level of cholinergic and iNANC activity in the newborn is unknown. Therefore, isolated trachealis muscle strips were obtained from neonatal, 10-day-old, and adult pigs. To quantify cholinergic nerve activity, isometric contractions were elicited by stimulating the nicotinic receptors of the cholinergic intramural ganglia with dimethyl-phenyl-piperazinium (DMPP). After ganglionic blockade with hexamethonium, the post-ganglionic cholinergic nerves were subjected to electrical field stimulation (EFS). To assess whether DMPP and EFS were also stimulating nitric oxide release from iNANC nerves, the stimulations were repeated after NO-synthase inhibition with 3 x 10(-5) M NG-monomethyl-L-arginine acetate (LNMMA). All responses were expressed as a percentage of maximal response to 10(-4) M acetylcholine. Although no significant age-related differences in the contractile responses to DMPP were demonstrated between the three age groups, the EFS responses were significantly different. At EFS frequencies of 1 and 2 Hz the responses of all three groups were different (P < 0.05, unpaired t-test). At frequencies of 0.125 and 0.5 Hz the contractile responses in the neonatal and 10-day-old groups were less than in the adult animal tissues (P < 0.05, unpaired t-test). At 4 Hz and above, the responses of the 10-day-old and adult groups became greater than the neonatal (P < 0.05, unpaired t-test). LNMMA did not significantly increase the contractile responses to DMPP at any age. Only in the neonatal rat and 10-day-old groups was a significant increase of the EFS frequency responses by LNMMA demonstrated (140.4 +/- 38.2% and 144.2 +/- 41.2%, respectively, at 0.5 Hz, ANOVA, P < 0.001). In conclusion, the DMPP responses suggest that the neonatal porcine cholinergic innervation is mature at birth. This contrasts with a frequency-dependent increase in EFS responses from birth. This may be due in part to a relative increase in iNANC modulation of post-ganglionic cholinergic activity at birth. This mechanism is not responsible for the increase in higher EFS frequency responses with post-natal maturation. Inhibitory iNANC activity may serve a protective role in the newborn, given the reported hyper-responsiveness of airway smooth muscle, small airway caliber, and high chest wall compliance at this age.

Allergen challenge of passively sensitized human bronchi alters M2 and beta2 receptor function.

We investigated whether antigen challenge may alter M2 and beta2 receptor function in isolated passively sensitized human bronchi. Bronchial rings (2-4 mm internal diameter) were obtained from 12 patients. Passive sensitization was induced by serum containing high IgE levels to Dermatophagoides pteronyssinus and Dermatophagoides farinae. Rings from six patients were used to study M2 receptor function by incubating with cumulatively increasing concentrations (10(-8) M to 10(-4) M) of pilocarpine and applying electric field stimulation (EFS) at 24 Hz. The rings from the other six patients were used to study beta2 receptor function by precontracting with carbachol 10(-6) M and adding cumulatively salbutamol (10(-9) M to 10(-4) M). Additional rings from these patients were used to determine whether dysfunction occurred distal to cAMP production by precontracting with carbachol 10(-6) M and adding cumulatively theophylline (10(-9) M to 10(-4) M). The attenuation of EFS-induced force by pilocarpine and the relaxation of carbachol-precontracted rings by salbutamol were less in challenged than in control and sensitized rings. No difference between challenged, sensitized, and control rings was observed with theophylline. We conclude that allergen challenge in passively sensitized isolated human bronchial rings may result in M2 and beta2 receptor dysfunction without involving mechanisms distal to cAMP formation. It appears that products from inflammatory cells recruited from blood are not necessary for this receptor dysfunction.

Postjunctional effect of pinacidil on contractility of isolated bovine trachealis.

Potassium channel openers hyperpolarize the smooth muscle cell membrane and relax airway smooth muscle. In this study, pre- and postjunctional effects of pinacidil ((+/-) N-cyano-N'-(4-pyridil)-N"-(1,2,2-trimethylpropyl)-guanidine monohydrated), an adenosine triphosphate (ATP)-sensitive K(+)-channel opener, were determined in isolated bovine trachealis. The effects of pinacidil on the frequency-response to electrical field stimulation (EFS), 0.1-32 Hz, and on the concentration response to acetylcholine (ACh), 10(9)-10(-4) M, were compared in muscle strips from six animals. In addition, the effect of pinacidil on the inhibitory nonadrenergic noncholinergic (iNANC) system was evaluated in histamine-contracted muscle strips from another eight animals. Pinacidil (10(-6) or 10(-5) M) shifted both the EFS frequency-response and the ACh concentration-response curves significantly (p < 0.01) to the right. Glibenclamide (10(-7)-10(-5) M) antagonized these responses in a concentration-dependent manner. The inhibitory effects of pinacidil on contractions of the same magnitude induced by EFS or exogenous ACh were not significantly different (p = 0.11), suggesting that pinacidil had only a postjunctional effect. Pinacidil had no effect on iNANC-mediated muscle relaxation. We conclude that pinacidil attenuates the contraction of isolated bovine tracheal smooth muscle by postjunctional mechanisms.

Opioid agonists modulate release of neurotransmitters in bovine trachealis muscle.

BACKGROUND: Stimulation of opioid receptors in the airways can modulate cholinergic neurotransmission and thereby reduce bronchoconstriction. This protecting effect of opioids against bronchoconstriction may be of clinical interest. Inhalation of opioids as a method of analgesia is likely to result in an opioid concentration at airway receptors sufficient to protect against bronchoconstriction; the concentration may be insufficient when opioids are administered by conventional techniques. In addition, new selective opioids may be developed that could more selectively protect the airways against bronchoconstriction. METHODS: The effect of three selective opioid agonists on the contractile response to electric field stimulation (EFS) was studied in isolated muscle strips from four regions of the bovine trachea (upper, or laryngeal; upper middle; lower middle; lower, or carinal). RESULTS: The selective kappa agonist trans-3,4-dichloro-N-methyl-N-(2-1-pyrrolidinyl) cyclohexyl benzene acetamide (U-50488 H) and the selective mu-opioid agonist D-Ala2-N-MePhe4-Gly-ol5-enkephalin (DAMGO) reduced significantly (P < 0.001 and P < 0.001, respectively) the contractile response to EFS. The attenuation of the contractile response by U-50488 H was concentration-dependent (P < 0.0001) and tended to be larger at low stimulating frequencies (P = 0.055). The attenuation of the contractile response by DAMGO was frequency-dependent (P < 0.01). The selective delta-opioid agonist D-penicillamine2-D-penicillamine5-enkephalin had no significant effect on the contractile response to EFS (P = 0.71). There were no significant differences among the four regions of the trachea in their responses to the selective opioid agonists U-50488 H (P = 0.50) and DAMGO (P = 0.44). Neither U-50488 H nor DAMGO altered the contractile response to acetylcholine P > 0.11, P > 0.21, respectively), suggesting that the opioid agonists have a prejunctional effect. The attenuation of the contractile response to EFS by U-50488 H was partially but significantly antagonized by 10(-5) M naloxone (P < 0.01) and by 10(-5) and 10(-6) M of the selective kappa-opioid antagonist 2,2'-[1,1'-biphenyl] 4,4'-diyl- bis [2-hydroxy-4,4-dimethyl-morpholinium] (P < 0.05). Naloxone (10(-5) M) abolished the inhibitory effect of DAMGO, suggesting that opioid receptors are involved in the attenuation of the contractile response to EFS afforded by DAMGO and U-50488 H. CONCLUSIONS: We conclude that prejunctional kappa- and mu-opioid receptors attenuate the contractile response of isolated bovine trachealis muscle to EFS by inhibiting cholinergic neurotransmission. This effect is uniform throughout the trachealis muscle. delta-Opioid receptors are apparently not present in the bovine trachealis muscle. Caution must be used in extrapolating these results to the intact human. In this study little or no inhibitory effect of the opioids was observed at concentrations expected at airway receptor sites when administered by conventional techniques. However, the effect may be large enough to protect against bronchoconstriction when nebulized opioids are administered by inhalation.

Comparison of the pharmacodynamics of ketamine in the isolated neonatal and adult porcine airway.

Ketamine inhibits contractions of adult airway smooth muscle by actions both within the smooth muscle cell and the vagal intramural ganglia. Its effects in the neonate are unknown, as physiological changes occur after birth in both of these structures. Isolated trachealis muscle strips from neonatal and adult pigs were contracted selectively by stimulation of the vagal intramural ganglia using dimethyl-phenyl-piperazinium (DMPP), the post-ganglionic vagus nerve using electrical field stimulation (EFS) and the smooth muscle cell itself using acetylcholine (ACh) in the presence of tetrodotoxin. The inhibitory effects of clinical concentrations of ketamine at each site were compared both within and between age groups. At both ages, ketamine 10(-4) mol litre-1 abolished (P < or = 0.001) and ketamine 10(-5) mol litre-1 attenuated (P < or = 0.001) the contractile responses to DMPP at the intramural ganglia. The inhibitory effect of ketamine 10(-4) mol litre-1 on ACh responses at the smooth muscle cell was greater in neonatal preparations (P = 0.025). Furthermore, only neonatal EFS and ACh responses were attenuated by ketamine 10(-5) mol litre-1 (P = 0.04 and P = 0.03). Ketamine 10(-4) mol litre-1 attenuated EFS responses in both age groups (P < or = 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Mechanisms of the relaxant action of ketamine on isolated porcine trachealis muscle.

Ketamine is a potent bronchodilator, but its mode of action is unclear. We have studied the effect of ketamine on the peripheral vagus nerve motor pathway of isolated porcine trachealis muscle. Postsynaptic nicotinic cholinergic receptors of the intramural ganglia were stimulated selectively with 1,1-dimethyl-4-phenyl-piperazinium iodide, post-ganglionic nerve fibres with electrical field stimulation (in the presence of hexamethonium) and muscarinic cholinergic receptors with acetylcholine (in the presence of tetrodotoxin). Ketamine 10(-4) mol litre-1 significantly shifted the concentration-response curves of acetylcholine (P < 0.02) and electrical field stimulation (P < 0.001) to the right and abolished the response to 1,1-dimethyl-4-phenyl-piperazinium iodide (P < 0.02). Ketamine also caused a concentration-dependent relaxation of muscle strips precontracted with acetylcholine. This was unaffected by propranolol. Ketamine relaxed muscle strips precontracted with potassium chloride, in the absence and presence of atropine. We conclude that ketamine interacts with the peripheral vagus nerve by decreasing the excitability of the postsynaptic nicotinic receptors of the intramural ganglia, and by affecting the muscarinic receptor, smooth muscle, or both. Beta-2 adrenoceptors are not involved in the mechanism of relaxation.

Epidural anesthesia and intrathoracic blood volume.

To investigate how epidural anesthesia changes intrathoracic gas volume, high epidural anesthesia was administered to five pentobarbital-anesthetized dogs lying supine, and the total intrathoracic volume at end-expiration was measured with a high-speed three-dimensional x-ray scanner. The amount of gas in the lungs at end-expiration [the functional residual capacity (FRC)] was measured with a nitrogen washout technique, and the intrathoracic tissue volume, including the intrathoracic blood volume, was calculated as the difference between intrathoracic volume at end-expiration and FRC. High epidural anesthesia with the local anesthetic etidocaine to a T-1 myotomal level significantly (P < 0.05) increased intrathoracic volume at end-expiration [76 +/- 35 mL (M +/- SD)] by significantly increasing both intrathoracic tissue volume (33 +/- 15 mL) and FRC (43 +/- 26 mL). Increases in intrathoracic tissue volume were probably caused by increases in intrathoracic blood volume. We conclude that increases in FRC caused by epidural anesthesia in anesthetized dogs lying supine may be minimized by a concurrent increase in intrathoracic blood volume. These results suggest that measurements of thoracic gas volume alone may be insufficient to describe chest wall responses to epidural anesthesia.

Halothane alters cytosolic calcium transient in tracheal smooth muscle.

Halothane is a potent bronchodilator that attenuates vagally mediated constriction of canine airways, in part by a direct action on the smooth muscle cell. In tracheal smooth muscle, acetylcholine (ACh) produces a transient peak increase in cytosolic ionized calcium concentration ([Ca2+]i), which declines to a sustained plateau concentration that is higher than that of the unstimulated muscle, and a sustained increase in force. The transient peak [Ca2+]i is caused primarily by Ca2+ release from the sarcoplasmic reticulum (SR), whereas the plateau [Ca2+]i is caused primarily by influx of extracellular Ca2+ across the plasma membrane. This study was conducted to investigate the effects of halothane on the 1) transient peak [Ca2+]i during force development (i.e., developed force) and 2) plateau [Ca2+]i during force maintenance (i.e., sustained force) induced by ACh in isolated strips of canine tracheal smooth muscle. Changes in [Ca2+]i were measured with the photoprotein, aequorin. In muscle strips contracted after incubation with 1.1 (n = 5) or 1.5 (n = 5) minimum alveolar concentration (MAC) halothane, halothane significantly attenuated the transient peak aequorin luminescence (AL) and developed force and significantly prolonged the time necessary to reach peak AL and developed force; these effects were not dose dependent. In muscle strips (n = 3) contracted with ACh, addition of halothane caused a reduction in sustained force but no decrease in plateau AL.(ABSTRACT TRUNCATED AT 250 WORDS)

Factors influencing the direct actions of volatile anesthetics on airway smooth muscle.

BACKGROUND: The authors hypothesized that the ability of volatile anesthetics to relax airway smooth muscle (AWSM) depends on: 1) the agonist used to produce muscle contraction, 2) the preexisting level of contraction, and 3) the volatile anesthetic used. METHODS: To test the first hypothesis, isolated strips of canine trachealis muscle were precontracted with acetylcholine (ACh), McN-A-343 (McN, another muscarinic agonist), 5-hydroxytryptamine (5HT, a different receptor agonist), or potassium chloride (KCl, which induces contraction by cell depolarization) to 50% of maximal force, then exposed to halothane (0.2-1.6 MAC). To test the second and third hypotheses, other strips were precontracted to 25, 50, 75, and 100% of maximal force with ACh, or to 10, 30, or 50% of maximal force with KCl, and were then exposed to halothane or isoflurane (0.2-1.6 MAC). RESULTS: For AWSM contracted to 50% of maximal force, the amount of relaxation produced by halothane depended on the agonist used to elicit contraction in the following manner: 5HT = McN > ACh; the muscles contracted with KCL did not relax. For ACh-induced contractions, the absolute amount of relaxation produced by halothane did not depend on the level of precontraction. In muscles contracted with KCl, the volatile anesthetics caused significant relaxation only in muscles contracted to 10% of maximal force. Overall, halothane had a significantly greater relaxing effect as compared with isoflurane during ACh-mediated contractions; the effects of the two agents did not differ significantly during KCl-mediated contractions. CONCLUSIONS: When canine AWSM tone is increased by contractile agonists in vitro, the absolute amount of relaxation produced by halothane depends on the agonist used to elicit contraction, but not the degree of precontraction. In addition, there are small but significant differences between the effects of halothane and isoflurane on ACh-mediated contractions.

Brainstem glioma: I. Pathology, clinical features, and therapy.

Gliomas that arise in the brain stem have been associated with a poor prognosis. Diagnostic neuroimaging readily identifies the tumor as it extends between normal brainstem structures. Histologic sampling of tumor with stereotactic methods is notoriously unreliable in establishing a definitive prognosis. Clinical trials that incorporate high-dose chemotherapy, autologous bone marrow rescue, and irradiation hold promise of better tumor control by overcoming the inaccessibility of the central nervous system to standard doses of chemotherapy. We review the pathology, clinical features, neuroimaging features, and current therapeutic concepts relative to brainstem glioma. The pediatric neurologist has a pivotal role in identifying and monitoring children with this malignancy.

Cemented versus noncemented total hip arthroplasty--embolism, hemodynamics, and intrapulmonary shunting.

Bone cement implantation syndrome is characterized by hypotension, hypoxemia, cardiac arrhythmias, cardiac arrest, or any combination of these complications. It may result from venous embolization that occurs in conjunction with intramedullary hypertension in the femur during insertion of the prosthesis in patients undergoing cemented total hip arthroplasty (THA). Intramedullary hypertension does not occur in patients undergoing noncemented THA. In this study, we sought to compare embolization between patients undergoing cemented and noncemented THA and to determine whether this state resulted in cardiorespiratory deterioration. In this prospective investigation of 35 patients undergoing elective THA, we used transesophageal echocardiography and invasive hemodynamic monitoring, and in 12 of them, we monitored distribution of pulmonary ventilation and perfusion intraoperatively. Embolization was significantly greater after insertion of the prosthesis in patients undergoing cemented than in those undergoing noncemented THA. Cemented THA was also associated with decreased cardiac output and increased pulmonary artery pressure and pulmonary vascular resistance. Increases in ventilation-perfusion mismatching, however, could not be demonstrated 30 minutes after insertion of the femoral prosthesis. Intraoperative monitoring for embolism may help physicians assess patients in whom cardiorespiratory function deteriorates during THA.

Electrical activation of expiratory muscles increases with time in pentobarbital-anesthetized dogs.

Although the pentobarbital-anesthetized dog is often used as a model in studies of respiratory muscle activity during spontaneous breathing, there is no information regarding the stability of the pattern of breathing of this model over time. The electromyograms of several inspiratory and expiratory muscle groups were measured in six dogs over a 4-h period by use of chronically implanted electrodes. Anesthesia was induced with pentobarbital sodium (25 mg/kg iv), with supplemental doses to maintain constant plasma pentobarbital concentrations. Phasic electrical activity increased over time in the triangularis sterni, transversus abdominis, and external oblique muscles (expiratory muscles). The electrical activity of the costal diaphragm, crural diaphragm, and parasternal intercostal muscles (inspiratory muscles) was unchanged. These changes in electrical activity occurred despite stable plasma levels of pentobarbital and arterial PCO2. They were associated with changes in chest wall motion and an increased tidal volume with unchanged breathing frequency. We conclude that expiratory muscle groups are selectively activated with time in pentobarbital-anesthetized dogs lying supine. Therefore the duration of anesthesia is an important variable in studies using this model.

Gas exchange in dogs in the prone and supine positions.

To determine the cause of the difference in gas exchange between the prone and supine postures in dogs, gas exchange was assessed by the multiple inert gas elimination technique (MIGET) and distribution of pulmonary blood flow was determined using radioactively labeled microspheres in seven anesthetized paralyzed dogs. Each animal was studied in the prone and supine positions in random order while tidal volume and respiratory frequency were kept constant with mechanical ventilation. Mean arterial PO2 was significantly lower (P less than 0.01) in the supine [96 +/- 10 (SD) Torr] than in the prone (107 +/- 6 Torr) position, whereas arterial PCO2 was constant (38 Torr). The distribution of blood flow (Q) vs. ventilation-to-perfusion ratio obtained from MIGET was significantly wider (P less than 0.01) in the supine [ln SD(Q) = 0.75 +/- 0.26] than in the prone position [ln SD (Q) = 0.34 +/- 0.05]. Right-to-left pulmonary shunting was not significantly altered. The distribution of microspheres was more heterogeneous in the supine than in the prone position. The larger heterogeneity was due in part to dorsal-to-ventral gradients in Q in the supine position that were not present in the prone position (P less than 0.01). The decreased efficiency of oxygenation in the supine posture is caused by an increased ventilation-to-perfusion mismatch that accompanies an increase in the heterogeneity of Q distribution.