bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ketamine Stereoselectively Affects Vasorelaxation Mediated by ATP-sensitive K+Channels in the Rat Aorta
Authors: Dojo Mayuko , Kinoshita Hiroyuki , Iranami Hiroshi , Nakahata Katsutoshi , Kimoto Yoshiki , Hatano Yoshio 
Published: November 2003

Background
The effect of ketamine on vasodilation mediated by adenosine triphosphate (ATP)-sensitive K(+) channels has not been studied. The present study was designed to determine whether ketamine might stereoselectively affect vasorelaxation induced by an ATP-sensitive K(+) channel opener in the isolated rat aorta.

Methods
Rings of the rat aorta with or without endothelium were suspended for isometric force recording. During contraction to phenylephrine (3 x 10(-7) M), vasorelaxation in response to an ATP-sensitive K(+) channel opener levcromakalim (10(-8) to 10(-5) M) or a nitric oxide donor sodium nitroprusside (10(-10) to 10(-5) M) was obtained. Glibenclamide (10(-5) M), S(+) ketamine (10(-4) M), or ketamine racemate (10(-5) to 10(-4) M) was applied 15 min before addition of phenylephrine.

Results
Vasorelaxation induced by levcromakalim was completely abolished by an ATP-sensitive K(+) channel antagonist glibenclamide (10(-5) M) in the aorta with or without endothelium. Ketamine racemate (3 x 10(-5) to 10(-4) M) significantly inhibited this vasorelaxation in a concentration-dependent fashion, whereas S(+) ketamine did not affect the relaxation. However, the highest concentration of ketamine racemate and S(+) ketamine used in the present study did not alter vasorelaxation in response to sodium nitroprusside in the aorta without endothelium.

Conclusion
In the isolated rat aorta, clinically relevant concentrations of ketamine racemate can inhibit relaxation induced by an ATP-sensitive K(+) channel opener, whereas S(+) ketamine did not produce any inhibitory effect on this vasorelaxation. These results suggest that ketamine stereoselectively alters vasodilation ATP-sensitive K(+) channels in the conduit artery.
Myeloperoxidase-associated Tyrosine Nitration after Intratracheal Administration of Lipopolysaccharide in Rats
Authors: Hataishi Ryuji , Kobayashi Hirosuke , Takahashi Yuko , Hirano Seishiro , Zapol Warren M. , Jones Rosemary C. 
Published: November 2003

Background
Previous studies have shown that lipopolysaccharide-induced inflammation in the lung results in tyrosine nitration. The objective of this study was to evaluate the contribution of myeloperoxidase and peroxynitrite pathway to the tyrosine nitration in lipopolysaccharide-administered lungs of rats that were otherwise untreated or leukocyte-depleted by cyclophosphamide or received inhaled nitric oxide (NO).

Methods
The authors analyzed the immunoreactivity of inducible nitric oxide synthase (iNOS), nitrotyrosine (a product of the myeloperoxidase or peroxynitrite pathway), and chlorotyrosine (a byproduct of the myeloperoxidase pathway) by use of specific antibodies. The number of neutrophils in bronchoalveolar lavage fluid (BALF) and levels of myeloperoxidase activity in lung homogenates were also measured.

Results
Lipopolysaccharide enhanced the immunoreactivity of iNOS, nitrotyrosine, and chlorotyrosine in alveolar wall cells, alveolar macrophages, and neutrophils. Leukocyte depletion by cyclophosphamide and inhibition of leukocyte accumulation in the lungs by NO inhalation did not eliminate the increase in iNOS immunoreactivity in alveolar macrophages after lipopolysaccharide treatment, but nitrotyrosine and chlorotyrosine were not produced in these cells. Tyrosine nitration in response to lipopolysaccharide was associated with increases in neutrophil count in BALF and in myeloperoxidase activity in lung homogenates, whereas NO inhalation suppressed the neutrophil count in BALF and reduced tyrosine nitration and chlorination.

Conclusions
These findings suggest that myeloperoxidase pathway has a role in tyrosine nitration in the lungs of lipopolysaccharide-treated rats, and that NO inhalation during early phase of inflammation does not increase but rather decreases tyrosine nitration and chlorination, possibly by reducing neutrophil sequestration.
Cost-efficacy of Rofecoxib versus Acetaminophen for Preventing Pain after Ambulatory Surgery
Authors: Issioui Tijani , Klein Kevin W. , White Paul F. , Watcha Mehernoor F. , Skrivanek Gary D. , Jones Stephanie B. , Hu Jie , Marple Bradley F. , Ing Caleb 
Published: November 2003

Background
Nonsteroidal antiinflammatory drugs are commonly administered as part of a multimodal regimen for pain management in the ambulatory setting. This randomized, double-blinded, placebo-controlled study was designed to compare the analgesic effect of oral rofecoxib, a cyclooxygenase-2 inhibitor, and acetaminophen when administered alone or in combination prior to outpatient otolaryngologic surgery.

Methods
A total of 143 healthy outpatients undergoing elective otolaryngologic surgery were assigned to one of four study groups: group 1 = control (500 mg vitamin C); group 2 = 2 g acetaminophen; group 3 = 50 mg rofecoxib; or group 4 = 2 g acetaminophen and 50 mg rofecoxib. The first oral dose of the study medication was taken 15-45 min before surgery, and a second dose of the same medication was administered on the morning after surgery. Recovery times, side effects, and the need for rescue analgesics were recorded. Follow-up evaluations were performed at 24 and 48 h after surgery to assess postdischarge pain, analgesic requirements, nausea, and patient satisfaction with their postoperative pain management and quality of recovery. Peak pain scores and the need for rescue analgesic medication were used as the endpoints for estimating efficacy of the study drugs, while cost to achieve complete satisfaction with analgesia was used in the cost-effectiveness analysis.

Results
Premedication with rofecoxib (50 mg) was significantly more effective than either placebo or acetaminophen (2 g) in reducing the peak postoperative pain, the need for analgesic medication, and improving the quality of recovery and patient satisfaction. Moreover, the addition of acetaminophen failed to improve its analgesic efficacy. An expenditure for rofecoxib of 16.76 US dollars (95% confidence interval, 7.89 to 21.03 US dollars) and 30.24 US dollars (95% confidence interval, 5.25 to 54.20 US dollars) would obtain complete satisfaction with pain control in one additional patient who would not have been satisfied if placebo or acetaminophen, respectively, had been administered prior to surgery.

Conclusions
Rofecoxib, 50 mg administered orally, decreased postoperative pain and the need for analgesic rescue medication after otolaryngologic surgery. The addition of 2 g oral acetaminophen failed to improve its analgesic efficacy.
Dose Response of Intrathecal Adenosine in Experimental Pain and Allodynia
Authors: Eisenach James C. , Curry Regina , Hood David D. 
Published: November 2003

Background
Intrathecal adenosine reduces areas of mechanical hypersensitivity and provides analgesia in patients with neuropathic pain. Adenosine also causes side effects, yet its dose response for either efficacy or side effects has not been examined in double blind studies. We studied two doses of intrathecal adenosine in humans with experimental hypersensitivity and the ability of the adenosine receptor antagonist, aminophylline, to reverse adenosine's effects.

Methods
Following Internal Review Board approval and written informed consent, 35 volunteers were studied. Five volunteers were studied to confirm the stability of a new method of inducing hypersensitivity with capsaicin. The remaining 30 volunteers received, in a randomized, double-blind manner, saline, or adenosine, 0.5 or 2.0 mg, by intrathecal injection 40 min after areas of allodynia and hyperalgesia were established from capsaicin. Two hr later, volunteers were randomized to receive intravenous saline or aminophylline, 5 mg/kg.

Results
Topical capsaicin with intermittent heating resulted in stable areas of allodynia and hyperalgesia. Intrathecal adenosine, but not saline, reduced areas of allodynia and hyperalgesia from capsaicin, with no differences between doses. Side effects occurred in 1, 2, and 6 volunteers receiving saline, 0.5 mg and 2.0 mg adenosine, respectively. Aminophylline failed to reverse adenosine's effects.

Conclusions
There is no difference in efficacy to experimental hypersensitivity between the largest approved dose of intrathecal adenosine and a dose 25% this size, but side effects are more common with the larger dose. Failure of aminophylline to reverse adenosine's effects could reflect inadequate concentrations at receptors in the spinal cord after intravenous injection.
PACU Bypass after Outpatient Knee Surgery Is Associated with Fewer Unplanned Hospital Admissions but More Phase II Nursing Interventions
Authors: Williams Brian A. , Kentor Michael L. , Williams John P. , Vogt Molly T. , DaPos Stacey V. , Harner Christopher D. , Fu Freddie H. 
Published: November 2003

Background
The authors recently proposed a recovery scoring system for outpatients receiving regional anesthesia (RA) or general anesthesia (GA). This scoring system was designed to allow qualifying patients to be directly routed to the phase II (step-down) recovery unit instead of the traditional postanesthesia care unit (PACU). We report PACU bypass rates using these criteria, and the extent to which PACU bypass was associated with (1) required nursing interventions in the step-down recovery unit, and (2) successful same-day discharge.

Methods
Day-of-surgery outcomes were studied for 894 outpatients undergoing outpatient sports medicine surgery on the lower extremity. We determined PACU-bypass rates, nursing interventions in the step-down recovery unit for common symptoms, and unplanned hospital admissions. Using logistic regression, we analyzed step-down nursing interventions based on PACU requirement versus PACU bypass, and anesthesia techniques used (GA vs. not, peripheral nerve blocks vs. not).

Results
Eighty-seven percent (778/894) of all patients bypassed PACU. Of PACU-bypass patients, 241/778 (31%) required step-down nursing interventions. Of patients requiring PACU, only 19/116 (16%) required additional interventions in step-down (P < 0.001). PACU-bypass patients were almost three times more likely (odds ratio 2.9,P < 0.001) to require at least one nursing intervention in the step-down unit, when compared with patients requiring PACU. Fewer unplanned admissions were required by patients who bypassed PACU (odds ratio = 0.3,P = 0.007).

Conclusions
For outpatient lower extremity surgery, applying our PACU-bypass criteria led to an 87% PACU bypass rate with no reportable adverse events.
Synchronous Rhythmical Vasomotion in the Human Cutaneous Microvasculature during Nonpulsatile Cardiopulmonary Bypass
Authors: Podgoreanu Mihai V. , Stout Robert G. , El-Moalem Habib E. , Silverman David G. 
Published: November 2003

Background
The origin, control mechanisms, and functional significance of oscillations in microvascular flow are incompletely understood. Although the traditional belief has been that only low-frequency oscillations (0.04-0.10 Hz) can originate at the microvascular level, recent evidence in healthy volunteers has suggested that high-frequency oscillations (> 0.10 Hz) also may have a microvascular origin (as opposed to being mechanically transmitted respiratory-induced variations in stroke volume). The current study determined if such oscillations would emerge in the absence of cardiac and respiratory activity during nonpulsatile cardiopulmonary bypass (NP-CPB).

Methods
Forehead and finger laser Doppler flow, arterial pressure, and core temperature were simultaneously recorded in eight patients during NP-CPB. Analyses included time- domain indices, frequency-domain indices (auto power spectral density), and a measure of regularity (approximate entropy) for standardized time segments.

Results
Nonpulsatile cardiopulmonary bypass was associated with the emergence of rhythmical oscillations in laser Doppler flow, with characteristic frequencies for the forehead (0.13 +/- 0.03 Hz) and finger (0.07 +/- 0.02 Hz). Forehead vasomotion became progressively synchronized, with a gain in high-frequency spectral power from 17.5 (minute 1) to 89.1 (minute 40) normalized units, and a decrease in approximate entropy from 1.2 (before NP-CPB) to less than 0.5 (minute 40).

Conclusions
The emergence of forehead microvascular oscillations at greater than 0.10 Hz (characteristic of parasympathetic frequency response), in the absence of cardiac and respiratory variability, demonstrates their peripheral origin and provides insights into parasympathetic vasoregulatory mechanisms. The progressive synchronization of forehead vasomotion during NP-CPB, suggestive of increased coupling among microvascular biologic oscillators, may represent a microcirculatory homeostatic response to systemic depulsation, with potential implications for end-organ perfusion.
The Minimum Alveolar Concentration of Xenon in the Elderly Is Sex-dependent
Authors: Goto Takahisa , Nakata Yoshinori , Morita Shigeho 
Published: November 2003

Background
The minimum alveolar concentration (MAC) of xenon in the elderly has not been determined. Moreover, because xenon inhibits the activity of the N-methyl-D-aspartate receptors, and because N-methyl-D-aspartate receptor antagonists such as ketamine and MK-801 exert sex-dependent actions, we hypothesized that the MAC of xenon would also be sex-dependent.

Methods
Forty-eight patients of both sexes (24 patients of each sex), who were aged 65 yr or older and were undergoing elective laparotomy, were anesthetized with inhalational induction of xenon. Those who demonstrated marked agitation received supplemental propofol intravenously. After tracheal intubation, the end-tidal concentration of xenon was maintained at 45 (women only), 50, 55, 60, 65, 70, or 75% (men only) for at least 15 min before skin incision. These concentrations were randomly allocated to four patients of each sex. Each patient was monitored for the presence or absence of any purposeful bodily movement for 1 min following skin incision. The MAC of xenon was calculated separately for men and women using logistic regression analysis.

Results
The MAC of xenon was 69.3% (95% CI, 63.0-75.6%) for men and 51.1% (44.6-57.6%) for women. The two 95% confidence intervals did not overlap, indicating a statistically significant difference (P < 0.05).

Conclusions
The MAC of xenon in the elderly is higher in men than in women.
Biphasic Effects of Isoflurane on the Cardiac Action Potential
Authors: Suzuki Akihiro , Aizawa Kei , Gassmayr Susanne , Bosnjak Zeljko J. , Kwok Wai-Meng 
Published: November 2003

Background
The mechanism underlying isoflurane modulation of cardiac electrophysiology is not well understood. In the present study, the authors investigated the effects of isoflurane on the cardiac action potential (AP) characteristics. The results were correlated to modulation of the L-type calcium (I(Ca,L)), the delayed-rectifier potassium (I(Kdr)), and the inward-rectifier potassium (I(Kir)) currents.

Methods
Single ventricular myocytes were enzymatically isolated from guinea pig hearts. The current clamp and whole cell voltage clamp configurations of the patch clamp technique were used to monitor the cardiac AP and ionic currents, respectively. A dynamic AP voltage protocol that mimicked changes in membrane potential during an AP was used to monitor the I(Ca,L), I(Kdr) and I(Kir).

Results
Isoflurane produced a concentration-dependent, biphasic effect on the AP duration (APD). At 0.6 mm (1.26 vol%), isoflurane significantly increased APD50 and APD90 by 50.0 +/- 7.6% and 48.9 +/- 7.2%, respectively (P < 0.05; n = 6). At 1.0 mm (2.09 vol%), isoflurane had no significant effect on APD (n = 6). In contrast, at 1.8 mm (3.77 vol%), isoflurane decreased APD50 and APD90 by 38.3 +/- 5.4% and 32.2 +/- 5.5%, respectively (P < 0.05; n = 7). The inhibitory effects of isoflurane on I(Kdr) chord conductance were greater than those on I(Ca,L) (P < 0.05; n = 6/group). Both I(Ca,L) inactivation and I(Kdr) activation kinetics were accelerated by isoflurane. Isoflurane had no significant effects on I(Kir) chord conductance (n = 6).

Conclusion
At the lower anesthetic concentration, the prolongation of the APD may be the result of the dominant inhibitory effects of isoflurane on I(Kdr). At the higher concentration, the shortening of the APD may be caused by the inhibitory effects on I (Ca,L) combined with the isoflurane-induced acceleration of I(Ca,L) inactivation kinetics. Because I(Kdr) is significantly inhibited by isoflurane, I(Kir) appears to be the major repolarizing current, which is minimally affected by isoflurane.
Comparison of Predicted Induction Dose with Predetermined Physiologic Characteristics of Patients and With Pharmacokinetic Models Incorporating those Characteristics as Covariates
Authors: Kazama Tomiei , Morita Koji , Ikeda Takehiko , Kurita Tadayoshi , Sato Shigehito 
Published: November 2003

Background
The relationship between patient characteristics and anesthesia induction dose at a high administration rate is unclear. This study was designed to investigate the relation between induction dose and patient characteristics and to compare it to the predicted induction dose using the previously reported pharmacokinetic model.

Methods
Diluted propofol (0.5 mg/ml) dose required to reach loss of consciousness, when infused at an infusion rate per lean body mass (LBM) of 150 mg x kg(-1) x h(-1) (high rate), was determined in 82 patients, ages 10-85 yr. Cardiac output, blood volume, central blood volume (CBV), and hepatic blood flow were measured with indocyanine green pulse spectrophotometry. Stepwise multiple linear regression models were used to investigate the relations between the patient characteristics and induction dose. These were compared with our previously reported parameters at the rate of 40 mg x kg(-1) x h(-1) (low rate) and with predicted induction doses with two previously reported pharmacokinetic models.

Results
Significant factors for predicting the induction dose at a high rate were age, LBM, and CBV. Induction dose with one pharmacokinetic model was 1.5 times that of the measured one and the other was half that of the measured one at a high rate. At a low rate, one pharmacokinetic model provided an accurate induction dose.

Conclusions
The prediction of induction dose from physiologic characteristics of patients provides reasonable accuracy at both high and low administration rates of propofol. A previously reported pharmacokinetic model that incorporated patient characteristics provides the same accurate induction dose at a low rate.
Response Surface Modeling of Remifentanil–Propofol Interaction on Cardiorespiratory Control and Bispectral Index
Authors: Nieuwenhuijs Diederik J.F. , Olofsen Erik , Romberg Raymonda R. , Sarton Elise , Ward Denham , Engbers Frank , Vuyk Jaap , Mooren Rene , Teppema Luc J , Dahan Albert 
Published: November 2003

Background
Since propofol and remifentanil are frequently combined for monitored anesthesia care, we examined the influence of the separate and combined administration of these agents on cardiorespiratory control and bispectral index in humans.

Methods
The effect of steady-state concentrations of remifentanil and propofol was assessed in 22 healthy male volunteer subjects. For each subject, measurements were obtained from experiments using remifentanil alone, propofol alone, and remifentanil plus propofol (measured arterial blood concentration range: propofol studies, 0-2.6 microg/ml; remifentanil studies, 0-2.0 ng/ml). Respiratory experiments consisted of ventilatory responses to three to eight increases in end-tidal Pco2 (Petco2). Invasive blood pressure, heart rate, and bispectral index were monitored concurrently. The nature of interaction was assessed by response surface modeling using a population approach with NONMEM. Values are population estimate plus or minus standard error.

Results
A total of 94 responses were obtained at various drug combinations. When given separately, remifentanil and propofol depressed cardiorespiratory variables in a dose-dependent fashion (resting V(i) : 12.6 +/- 3.3% and 27.7 +/- 3.5% depression at 1 microg/ml propofol and 1 ng/ml remifentanil, respectively; V(i) at fixed Petco of 55 mmHg: 44.3 +/- 3.9% and 57.7 +/- 3.5% depression at 1 microg/ml propofol and 1 ng/ml remifentanil, respectively; blood pressure: 9.9 +/- 1.8% and 3.7 +/- 1.1% depression at 1 microg/ml propofol and 1 ng/ml remifentanil, respectively). When given in combination, their effect on respiration was synergistic (greatest synergy observed for resting V(i)). The effects of both drugs on heart rate and blood pressure were modest, with additive interactions when combined. Over the dose range studied, remifentanil had no effect on bispectral index even when combined with propofol (inert interaction).

Conclusions
These data show dose-dependent effects on respiration at relatively low concentrations of propofol and remifentanil. When combined, their effect on respiration is strikingly synergistic, resulting in severe respiratory depression.
Intracranial Pressure and Cerebral Hemodynamic in Patients with Cerebral Tumors
Authors: Petersen Kurt D. , Landsfeldt Uffe , Cold Georg Emil , Petersen Carsten B. , Mau Søren , Hauerberg John , Holst Peter , Olsen Karsten Skovgaard 
Published: November 2003

Background
A critical point during craniotomy is opening of dura, where a high intracranial pressure (ICP) results in swelling of cerebral tissue. Controlled studies concerning ICP, degree of dural tension, and degree of cerebral swelling are therefore warranted.

Methods
In an open-label study, 117 patients with supratentorial cerebral tumors were randomized to propofol-fentanyl (group 1), isoflurane-fentanyl (group 2), or sevoflurane-fentanyl anesthesia (group 3). Normo- to moderate hypocapnia was applied, with a target level of arterial carbon dioxid tension of 30-40 mmHg. Mean arterial blood pressure was stabilized with intravenous ephedrine (2.5-5 mg) if necessary. Subdural ICP, mean arterial blood pressure, cerebral perfusion pressure (CPP), arteriovenous oxygen difference (AVDo2), internal jugular vein oxygen saturation were monitored before and after a 10-min period of hyperventilation, and the carbon dioxide reactivity was calculated. Furthermore, the tension of dura before and during hyperventilation and the degree of cerebral swelling during hyperventilation and after opening of the dura were estimated by the neurosurgeon.

Results
No differences were found between groups with regard to demographics, neuroradiologic examination, positioning of the head, and time to ICP measurement. Before and during hyperventilation, ICP was significantly lower and mean arterial blood pressure and CPP significantly higher in group 1 compared with groups 2 and 3 (P < 0.05). The tension of dura before and during hyperventilation was significantly lower in group 1 compared with group2 (P < 0.05), but not significantly different from group 3. In group 1, cerebral swelling after opening of dura was significantly lower compared with groups 2 and 3 (P < 0.05). Furthermore, AVDo was significantly higher and jugular vein oxygen saturation and carbon dioxide reactivity were significantly lower in group 1 compared with groups 2 and 3 (P < 0.05). No significant differences with regard to ICP, CPP, AVDo, carbon dioxide reactivity, and jugular vein oxygen saturation were found between patients anesthetized with isoflurane and sevoflurane.

Conclusions
The study indicates that before as well as during hyperventilation, subdural ICP and AVDo2 are lower and CPP higher in propofol-anesthetized patients compared with patients anesthetized with isoflurane or sevoflurane. These findings were associated with less tendency for cerebral swelling after opening of dura in the propofol group. The carbon dioxide reactivity in patients anesthetized with isoflurane and sevoflurane was significantly higher than in the propofol group. The differences in subdural ICP between the groups are presumed to be caused by differences in the degree of vasoconstriction elicited by the anesthetic agents, but autoregulatory mechanisms caused by differences in CPP cannot be excluded.