bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of Intrathecal Neostigmine, Bupivacaine, and Their Combination on Sympathetic Nerve Activity in Rats
Authors: Pan Hui-Lin , Song Ho-Kyung , Eisenach James C. 
Published: November 2003

Background
Intrathecal injection of local anesthetic agents is associated frequently with hypotension. Conversely, intrathecal administration of neostigmine increases blood pressure by enhancing the accumulation of acetylcholine in the spinal cord. The current study examined directly the interaction of intrathecal injection of bupivacaine and neostigmine on splanchnic sympathetic efferent nerve activity.

Methods
Experiments were performed in rats with intrathecal catheters implanted for the long-term. Rats were anesthetized with ketamine (40 mg/kg, intramuscularly) and alpha-chloralose (60 mg/kg, intraperitoneally). The skin incision sites were infiltrated with 1% lidocaine. Sympathetic efferent activity was recorded from the left greater splanchnic nerve. Sympathetic nerve activity was measured continuously before and after intrathecal injection of saline, 430 nmol (140 microg) of bupivacaine, 25 nmol (7.6 microg) of neostigmine, and a combination of bupivacaine and neostigmine all in volumes of 5 microl. Each group consisted of six animals.

Results
Compared with baseline nerve activity, intrathecal injection of neostigmine increased splanchnic sympathetic nerve activity significantly by (mean +/- SEM) 112 +/- 29% after an onset latency of 6.8 +/- 0.9 min. In contrast, bupivacaine decreased splanchnic nerve activity significantly (-65 +/- 13%) after a latency of 3.3 +/- 0.5 min after intrathecal administration. Similar to the effect of saline, intrathecal coadministration of bupivacaine and neostigmine did not alter the splanchnic sympathetic nerve activity significantly.

Conclusions
The current study provides electrophysiologic evidence that intrathecal injection of neostigmine increases whereas bupivacaine decreases sympathetic nerve activity. Further, addition of neostigmine effectively counteracts the inhibitory effect of spinal bupivacaine on the sympathetic nerve activity.
Effects of Intrathecally Administered Lamotrigine, a Glutamate Release Inhibitor, on Short- and Long-term Models of Hyperalgesia in Rats
Authors: Klamt Jyrson G. 
Published: November 2003

Background
Lamotrigine is a sodium channel blocker that inhibits the neuronal release of glutamate. Systemic administration of lamotrigine induces analgesia in short- and long-term models of hyperalgesia in rats. Considering the key role of N-methyl-D-aspartate receptors in the sensitization of dorsal horn neurons that leads to hyperalgesia, the author hypothesizes that intrathecally injected lamotrigine would be effective in reducing the hyperalgesia.

Methods
Short-term hyperalgesia was induced by unilateral intraplantar injection of prostaglandin E2. Long-term hyperalgesia was produced by treating rats with streptozotocin, which causes diabetic neuropathy and, in a different group of animals, by loose ligation of the sciatic nerve (chronic constriction injury). Hyperalgesia was assessed by measuring withdrawal reaction time after paw pressure, and analgesia was measured by the thermal tail-flick test.

Results
In the short-term model, intrathecally administered lamotrigine (12.5, 25.0, and 100.0 microg) produced a dose-dependent increase in the reaction time of the hyperalgesic paw. The highest dose that completely restored the reaction time to control levels (26-29 s) from the hyperalgesic levels (12-15 s) did not affect the reaction time of the normal contralateral paw. In the tail-flick test, a consistent effect could be observed only with doses of 200 microg, which caused transient motor impairment of the hind paws. In the long-term models of hyperalgesia, intrathecally administered lamotrigine produced a dose-dependent and long-lasting (24-48 h) antihyperalgesic effect.

Conclusions
Intrathecally administered lamotrigine produced a spinal, dose-dependent, and long-lasting antihyperalgesic effect in short- and long-term neuropathic models of hyperalgesia.
The Sensitivity and Specificity of the Caffeine-Halothane Contracture Test
Authors: Allen Gregory C. , Larach Marilyn Green , Kunselman Allen R. 
Published: November 2003

Background
The caffeine-halothane contracture test (CHCT) is the only recognized laboratory test to diagnose malignant hyperthermia (MH). The authors report the results of their analysis of pooled data from the North American Malignant Hyperthermia Registry database to determine the sensitivity and specificity of the CHCT.

Methods
The MH Clinical Grading Scale was used to identify 32 case subjects who were "almost certain" to be MH susceptible based on clinical criteria alone. Their CHCT results were compared with those of a group of 120 control subjects considered to be at low risk for MH. Diagnostic thresholds of the CHCT were adjusted, and its component tests were combined to generate receiver operating characteristic curves. The maximal Youden index for each component test was chosen as the diagnostic threshold indicative of MH susceptibility.

Results
The highest sensitivity (97%; 95% CI, 84-100%) was achieved with a two-component test with thresholds of > or = 0.5 g contracture for 3% halothane, > or = 0.3 g contracture at 2 mM caffeine, or both, considered positive for MH. The test specificity was 78% (95% CI, 69-85%). The addition of other CHCT component tests did not improve CHCT sensitivity or specificity.

Conclusion
The CHCT achieves high sensitivity and acceptable specificity as a clinical laboratory diagnostic test when it is performed according to published standards. However, it cannot be used as a screening test because of the low prevalence of MH in the general population.
The Response to Repeated Nitric Oxide Inhalation Is Inconsistent in Patients with Acute Respiratory Distress Syndrome
Authors: Treggiari-Venzi Miriam , Ricou Bara , Romand Jacques-Andre , Suter Peter M. 
Published: November 2003

Background
Nitric oxide (NO) is administered frequently in patients with acute respiratory distress syndrome (ARDS) and pulmonary hypertension. The efficacy of this therapy over several days is not well known. The authors first determined the consistency of the response to repeated administration of NO and then the baseline variables that were associated with improvement in patients with severe ARDS.

Methods
In a prospective trial, 32 mechanically ventilated patients with severe ARDS received 10 parts per million NO by inhalation. In 22 of these patients, its effect was tested repeatedly (up to four times) in several days. Improvement was defined as an increase >10% in the ratio of pressure of oxygen in arterial blood (P(aO2)) to the inspiratory pressure of oxygen (FIO2) from baseline. Patients showing such an improvement were maintained on NO inhalation.

Results
Twelve of the 22 patients (54%) showed a clinically significant and reproducible increase in the P(aO2)/FIO2 ratio with NO, from 74 +/- 30 mmHg (mean +/- SD) to 95 +/- 41 mmHg (P < 0.001). In three patients (14%), P(aO2) did not improve, even with multiple exposures. In seven patients (32%), an inconsistent response was seen on different days. Mean pulmonary artery pressure decreased for the entire group from 34 +/- 10 mmHg to 29 +/- 9 mmHg (P < 0.01), but this decrease did not correlate with the increase in P(aO2) in individual patients. The baseline P(aO2)/FIO2 ratio and mixed venous oxygenation (P(vO2)) were significantly lower, and the venous admixture was greater in patients showing beneficial effects of NO inhalation on P(aO2).

Conclusions
Repeated NO inhalation caused a consistent improvement in P(aO2) in about one half of these patients with severe ARDS; no significant benefit or inconsistent effects on pulmonary gas exchange were noted in the others. These findings could be related to the complexity of the mechanisms regulating the vasomotor changes in this syndrome. Severe baseline hypoxemia may be associated with a more favorable effect of NO on P(aO2).
A Comparison of the Intubation Conditions between Mivacurium and Rocuronium during Balanced Anesthesia
Authors: Pino Richard M. , Ali Hassan H. , Denman William T. , Barrett Pamela S. , Schwartz Ann 
Published: November 2003

Background
Comparisons of the intubation conditions with mivacurium and rocuronium from previous reports are confounded by the use of varied induction regimens. The authors compared intubation conditions of mivacurium, rocuronium, and a placebo at 90 s and their recovery profiles during anesthesia with nitrous oxide, oxygen, and propofol.

Methods
After induction with midazolam, fentanyl, and propofol in a randomized blinded study, 100 patients received one of the following treatments: 0.25 mg/kg mivacurium in divided doses (0.15 mg/kg followed by 0.1 mg/kg 30 s later); 0.45, 0.6, 0.9, or 1.2 mg/kg rocuronium; or placebo. Evoked thumb adduction was measured throughout. Intubation was attempted 90 s after the initial dose of mivacurium and other treatment doses by a "blinded" physician. Intubating conditions were graded as excellent, good, poor, or not possible. Spontaneous recovery was studied until a 25% initial twitch height was reached. Mean arterial blood pressure and heart rate changes between groups were determined before induction through 6 min after administration of the study drugs.

Results
There were no important changes or intergroup differences in mean arterial blood pressure and heart rate. Intubation conditions were good or excellent for both mivacurium and rocuronium at the 0.9 mg/kg dose (93%) and at the 1.2 mg/kg dose (100%). Rocuronium at the 0.6 mg/kg dose was excellent in 27% of patients, whereas rocuronium at the 0.45 mg/kg dose had the least number of excellent conditions and the most poor or not possible assessments. Patients given placebo could not be intubated. Times to maximum blockade for 0.9 and 1.2 mg/kg rocuronium were the shortest. The times to 25% recovery for 0.6 mg/kg rocuronium (mean +/- SD = 27 +/- 8.6 min), 0.9 mg/kg (43.1 +/- 10.8), and 1.2 mg/kg (62.3 +/- 17.4 min) were significantly longer than were those for mivacurium (17.4 +/- 6.2 min).

Conclusions
Mivacurium in a 0.25 mg/kg divided dose and rocuronium at 0.9 mg/kg and 1.2 mg/kg provide good or excellent intubation conditions at 90 s in most patients. Rocuronium was faster in onset at the higher doses (0.9 and 1.2 mg/kg) but had more prolonged recovery times to 25% single twitch height.
Recovery of Evoked Potential Amplitude after Cerebral Arterial Air Embolism in the Rabbit
Authors: Hindman Bradley J. , Dexter Franklin , Enomoto Sakae , Subieta Alberto , Smith Tom , Cutkomp Johann 
Published: November 2003

Background
Cerebral arterial air embolism (CAAE) may cause neurologic injury during cardiac surgery. It is not known whether cardiopulmonary bypass (CPB) increases or decreases brain injury from CAAE compared with the normal circulation.

Methods
A model of CAAE was produced by injection of 50 microl/kg air into the internal carotid artery of methohexital-anesthetized New Zealand white rabbits. Somatosensory-evoked potential (SSEP) amplitude was measured serially as a marker of neurologic recovery. In experiment A, saline rather than air was injected to control for surgical manipulation and time in CPB (n = 4) and nonheparinized non-CPB (n = 4) animals. In experiment B, 50 microl/kg air was injected in CPB (n = 11) and nonheparinized non-CPB (n = 11) animals. In experiment C, non-CPB animals (n = 6) were given heparin according to the same protocol as for CPB.

Results
In experiment A, SSEP latencies and amplitudes did not differ between CPB and non-CPB conditions. In experiment B, there was no SSEP recovery 5 min after CAAE in either CPB or non-CPB animals. Thereafter, SSEP recovery was less in CPB animals than in non-CPB animals at 30 min (9 +/- 12% vs. 29 +/- 20%; P = 0.009) and 60 min (18 +/- 15% vs. 39 +/- 22%; P = 0.030) after CAAE. Ninety-minute SSEP recovery did not differ between CPB and non-CPB groups (at 24 +/- 19% vs. 39 +/- 24%, respectively; P = 0.146). In experiment C (heparinized non-CPB), SSEP recovery 5, 30, 60, and 90 min after CAAE was 67 +/- 48%, 72 +/- 47%, 80 +/- 35%, and 77 +/- 35%, respectively.

Conclusions
Somatosensory-evoked potential recovery after CAAE is no better (and is probably worse) during CPB than during normal circulation. The adverse effect of CPB occurs despite heparinization, which, under non-CPB conditions, appears to be protective. Therapies in addition to heparin are needed during CPB to reduce neurologic injury from CAAE.
Stereoselective Effects of Etomidate Optical Isomers on Gamma-aminobutyric Acid Type A Receptors and Animals
Authors: Tomlin Sarah L. , Jenkins Andrew , Lieb William R. , Franks Nicholas P. 
Published: November 2003

Background
The intravenous anesthetic etomidate is optically active and exists in two mirror-image enantiomeric forms. However, although the R(+) isomer is used as a clinical anesthetic, quantitative information on the relative potencies of the R(+) and S(-) isomers is lacking. These data could be used to test the relevance of putative molecular targets.

Methods
The anesthetic concentrations for a half-maximal effect (EC50) needed to induce a loss of righting reflex in tadpoles (Rana temporaria) were determined for both etomidate enantiomers. The effects of the isomers on gamma-aminobutyric acid (GABA)-induced currents in stably transfected mouse fibroblast cells was also investigated using the patch-clamp technique. In addition, the effects of the isomers on a lipid chain-melting phase transition were determined.

Results
The EC50 concentrations for general anesthesia for the R(+) and S(-) isomers were 3.4 +/- 0.1 microM and 57 +/- 1 microM, with slopes of n = 1.9 +/- 0.1 and n = 2.9 +/- 0.2, respectively. The R(+) isomer was also much more effective than the S(-) isomer at potentiating GABA-induced currents, although the degree of stereoselectivity varied with anesthetic concentration. R(+) etomidate potentiated the GABA-induced currents by increasing the apparent affinity of GABA for its receptor. Both isomers were equally effective at disrupting lipid bilayers.

Conclusions
These data are consistent with the idea that the GABA(A) receptor plays a central role in the actions of etomidate. Etomidate exerts its effects on the receptor by binding directly to a specific site or sites on the protein and allosterically enhancing the apparent affinity of GABA for its receptor.
Stereoselective Differences in the Vasorelaxing Effects of S(+) and R(-) Ketamine on Rat Isolated Aorta
Authors: Kanellopoulos Adriani , Lenz Gunther , Muhlbauer Bernd 
Published: November 2003

Background
S(+) ketamine, because of its higher anesthetic potency and lower risk of psychotomimetic reactions, has been suggested to be superior to presently available racemic ketamine. The racemate is a direct vasodilator in vivo, and thus the authors investigated the vasorelaxing effects of ketamine enantiomers on rat aorta.

Methods
Rat isolated aortic rings with and without endothelium were contracted with 3 x 10(-7) M norepinephrine. Then 10(-5) to 3 x 10(-3) M S(+), R(-), or racemic ketamine were added cumulatively. Vascular responses to ketamine were further studied in rings pretreated with the nitric oxide synthase inhibitor N(omega)-nitro-L-arginine (NNLA), the adenosine triphosphate-sensitive K+ channel antagonist glibenclamide, and the L-type calcium channel blocking agent D888.

Results
Ketamine enantiomers and the racemate produced concentration-dependent vasorelaxation. The relaxing effect of S(+) ketamine was significantly weaker compared with R(-) ketamine and the racemate reflected by the half-maximum effective concentration (EC50) values of 11.6 x 10(-4), 4.8 x 10(-4), and 6 x 10(-4) M, respectively. Removal of the endothelium and NNLA or glibenclamide pretreatment did not significantly alter the vasorelaxing effect of ketamine. In contrast, D888 pretreatment significantly shifted the concentration-effect curves of both S(+) and R(-) ketamine rightward (EC50 values of 18.9 x 10(-4) and 8.5 x 10(-4) M, respectively), whereas the difference between the isomers was not affected.

Conclusions
Vasorelaxation by ketamine enantiomers is quantitatively stereoselective: The effect of S(+)ketamine is significantly weaker compared with that of the racemate and R(-) ketamine. This stereoselective difference is not due to nitric oxide release, activation of adenosine triphosphate-sensitive potassium channels, or differential inhibition of L-type calcium channels.
Is Calcium a Coronary Vasoconstrictor In Vivo?
Authors: Crystal George J. , Zhou Xiping , Salem Ramez M. 
Published: November 2003

Background
Calcium produces constriction in isolated coronary vessels and in the coronary circulation of isolated hearts, but the importance of this mechanism in vivo remains controversial.

Methods
The left anterior descending coronary arteries of 20 anesthetized dogs whose chests had been opened were perfused at 80 mmHg. Myocardial segmental shortening was measured with ultrasonic crystals and coronary blood flow with a Doppler flow transducer. The coronary arteriovenous oxygen difference was determined and used to calculate myocardial oxygen consumption and the myocardial oxygen extraction ratio. The myocardial oxygen extraction ratio served as an index of effectiveness of metabolic vasodilation. Data were obtained during intracoronary infusions of CaCl2 (5, 10, and 15 mg/min) and compared with those during intracoronary infusions of dobutamine (2.5, 5.0, and 10.0 microg/min).

Results
CaCl2 caused dose-dependent increases in segmental shortening, accompanied by proportional increases in myocardial oxygen consumption. Although CaCl2 also increased coronary blood flow, these increases were less than proportional to those in myocardial oxygen consumption, and therefore the myocardial oxygen extraction ratio increased. Dobutamine caused dose-dependent increases in segmental shortening and myocardial oxygen consumption that were similar in magnitude to those caused by CaCl2. In contrast to CaCl2, however, the accompanying increases in coronary blood flow were proportional to the increases in myocardial oxygen consumption, with the result that the myocardial oxygen extraction ratio remained constant.

Conclusions
Calcium has a coronary vasoconstricting effect and a positive inotropic effect in vivo. This vasoconstricting effect impairs coupling of coronary blood flow to the augmented myocardial oxygen demand by metabolic vascular control mechanisms. Dobutamine is an inotropic agent with no apparent direct action on coronary resistance vessels in vivo.
Benzodiazepines Differentially Inhibit Phenylephrine-induced Calcium Oscillations in Pulmonary Artery Smooth Muscle Cells
Authors: Hong Sung Jin , Damron Derek S. , Murray Paul A. 
Published: November 2003

Background
Modulation of intracellular free calcium is a critical determinant of vasomotor tone. The authors investigated the effects of three benzodiazepines on alpha-adrenergic-induced oscillations in intracellular free calcium in individual pulmonary artery smooth muscle cells.

Methods
Pulmonary artery smooth muscle cells were cultured from explants of canine intrapulmonary artery. Fura-2-loaded pulmonary artery smooth muscle cells were continuously superfused with phenylephrine (10 microM) at 37 degrees C on the stage of an inverted fluorescence microscope. Intracellular free calcium was measured using a dual wavelength spectrofluorometer. After establishment of steady-state intracellular free calcium oscillations induced by phenylephrine, lorazepam, diazepam, or midazolam was added to the superfusate. The amplitude and frequency of the intracellular free calcium oscillations were compared before and after addition of each agent.

Results
Resting mean +/- SEM values of intracellular free calcium were 68 +/- 8 nM. Phenylephrine stimulated dose-dependent oscillations in intracellular free calcium, which reached a peak concentration of 676 +/- 35 nM and a frequency of 1.08 +/- 0.1 transients/min. Addition of lorazepam (1 microM) inhibited (P < 0.05) the amplitude (591 +/- 32 nM) but not the frequency (0.97 +/- 0.1 transients/min) of the oscillations. Conversely, diazepam (1 microM) decreased (P < 0.05) the frequency (0.79 +/- 0.1 transients/min) but not the amplitude (663 +/- 37 nM) of the oscillations. These effects were dose-dependent. In contrast, midazolam (1-30 microM) had no effect on the amplitude or frequency of intracellular free calcium oscillations. At concentrations higher than 100 microM, however, all three benzodiazepines inhibited both the amplitude and frequency of the intracellular free calcium oscillations.

Conclusion
Lorazepam and diazepam but not midazolam exerted differential inhibitory effects on phenylephrine-induced intracellular free calcium oscillations. Benzodiazepines may alter the pulmonary vascular response to sympathetic alpha-adrenoreceptor activation by direct inhibition of intracellular free calcium signaling in pulmonary artery smooth muscle cells.
Meperidine and Alfentanil Do Not Reduce the Gain or Maximum Intensity of Shivering
Authors: Ikeda Takehiko , Sessler Daniel I. , Tayefeh Farzin , Negishi Chiharu , Turakhia Minang , Marder Danielle , Bjorksten Andrew R. , Larson Merlin D. 
Published: November 2003

Background
Thermoregulatory shivering can be characterized by its threshold (triggering core temperature), gain (incremental intensity increase with further core temperature deviation), and maximum intensity. Meperidine (a combined mu- and kappa-agonist) treats shivering better than equianalgesic doses of pure mu-opioid agonists. Meperidine's special antishivering action is mediated, at least in part, by a disproportionate decrease in the shivering threshold. That is, meperidine decreases the shivering threshold twice as much as the vasoconstriction threshold, whereas alfentanil (a pure mu-agonist) decreases the vasoconstriction and shivering thresholds comparably. However, reductions in the gain or maximum shivering intensity might also contribute to the clinical efficacy of meperidine. Accordingly, we tested the hypothesis that meperidine reduces the gain and maximum intensity of shivering much more than alfentanil does.

Methods
Ten volunteers were each studied on three separate days: (1) control (no drug); (2) a target total plasma meperidine concentration of 1.2 microg/ml; and (3) a target plasma alfentanil concentration of 0.2 microg/ml. Skin temperatures were maintained near 31 degrees C, and core temperatures were decreased by central-venous infusion of cold lactated Ringer's solution until maximum shivering intensity was observed. Shivering was evaluated using oxygen consumption and electromyography. A sustained increase in oxygen consumption identified the shivering threshold. The gain of shivering was calculated as the slope of the oxygen consumption versus core temperature regression, and as the slope of electromyographic intensity versus core temperature regression.

Results
Meperidine and alfentanil administration significantly decreased the shivering thresholds. However, neither meperidine nor alfentanil reduced the gain of shivering, as determined by either oxygen consumption or electromyography. Opioid administration also failed to significantly decrease the maximum intensity of shivering.

Conclusions
The authors could not confirm the hypothesis that meperidine reduces the gain or maximum intensity of shivering more than alfentanil does. These results suggest that meperidine's special antishivering effect is primarily mediated by a disproportionate reduction in the shivering threshold.