bluuebunny/crossref_metadata_2025_split huggingface dataset:
NOS Inhibitors Decrease Hypoxia-induced ATP Reductions in Respiring Cerebrocortical Slices
Authors: Litt Lawrence , Espanol Maryceline T. , Hasegawa Koh , Chang Lee-Hong , Gregory George A. , James Thomas L. , Beal Flint M. , Chan Pak H. 
Published: November 2003

Background
Excess neuronal nitric oxide (NO) production might cause adenosine triphosphate loss and cellular damage in hypoxic brain parenchyma. 31P nuclear magnetic resonance spectroscopy was used to study hypoxic intracellular responses in perfused respiring cerebrocortical slices, in which NO scavenging by hemoglobin is absent, during NO synthase blockade and NO augmentation.

Methods
Adenosine triphosphate concentrations were monitored at 4.7 Tesla in respiring slices before, during, and after 60 min of hypoxia (oxygen tension < 5 mmHg). Slices were not treated or were pretreated with 27 microM L-nitroarginine methyl ester (L-NAME), 27 microM 7-nitroindozole (7-NI), or 27 microM L-nitroarginine. Nitrotyrosine:tyrosine ratios of slice extracts were measured using high-performance liquid chromatography. Cresyl violet-stained sections (2 microm) from random slices were examined histologically.

Results
After 60 min of hypoxia, adenosine triphosphate decreased to < or = 3, < or = 3, 65 +/- 6, and 25 +/- 4% of control in slices that were untreated or treated with L-nitroarginine, L-NAME, and 7-NI, respectively. After 120 min of hyperoxic recovery, adenosine triphosphate levels returned to control values in slices pretreated with L-NAME and 7-NI, but to only 30% of control in untreated or L-nitroarginine-treated slices. Nitric oxide donors administered during posthypoxic recovery partially antagonized the adenosine triphosphate recovery found with L-NAME and 7-NI. Nitric oxide synthase activity in slice homogenates, assayed via conversion of L-arginine to citrulline, was < or = 2% of control after all inhibitory treatments. The nitrotyrosine:tyrosine ratio increased by 52% in slices treated with 7-NI and by 200-300% in all other groups. Pretreatment with L-NAME and 7-NI reduced histologic evidence of cell swelling.

Conclusion
Neuronal NO is associated with rapid adenosine triphosphate reductions and peroxynitrite formation in acutely hypoxic cerebrocortical slices.
Brain Injury after Cerebral Arterial Air Embolism in the Rabbit as Determined by Triphenyltetrazolium Staining
Authors: Hindman Bradley J. , Dexter Franklin , Subieta Alberto , Smith Tom , Cutkomp Johann 
Published: November 2003

Background
Microscopic cerebral arterial air embolism (CAAE) occurs commonly during cardiac surgery and causes acute and chronic nonfocal neurologic dysfunction. Nevertheless, most neuroimaging studies do not detect brain injury after cardiac surgery. Using a rabbit model, the authors hypothesized they could detect and quantitate severe brain injury and infarction 24 h after microscopic CAAE using the vital stain triphenyltetrazolium chloride.

Methods
Experiments were conducted in methohexital anesthetized New Zealand white rabbits. Surgical shams (n = 5) underwent surgery but had no neurologic insult. Positive controls (n = 3) received 200 microl/kg of intracarotid air. Other animals were randomized to receive either 50 microl/kg intracarotid air, which produces microscopic CAAE (n = 18), or 300 microl intracarotid saline (control, n = 18). Outcomes included somatosensory evoked potential amplitude at 90 min, neurologic impairment score at 4 and 24 h (0 [normal] to 99 [coma]), and percentage of nonstaining brain at 24 h using color-discrimination image analysis. Severely injured or infarcted brain does not stain with triphenyltetrazolium chloride.

Results
Surgical shams had little neurologic impairment and a small amount of nonstaining brain at 24 h (5.2 +/- 2.4%; mean +/- SD). Positive controls had profound neurologic impairment and large amounts of nonstaining brain (40-97%). Ninety-minute somatosensory evoked potential amplitude was less in animals receiving 50 microl/kg air versus saline: 38 +/- 28% versus 102 +/- 32%, respectively, P < 1 x 10(-7). Neurologic impairment scores were greater in animals receiving 50 microl/kg air versus saline: at 4 h, 43 +/- 16 versus 23 +/- 9, P < 1 x 10(-7); at 24 h, 24 +/- 12 versus 15 +/- 8, P = 0.013. Nevertheless, there was no difference between 50 microl/kg air and saline in nonstaining brain: 5.5 +/- 2.9% versus 6.8 +/- 5.4%, P = 0.83.

Conclusions
Neurologic injury after CAAE is dose-dependent. Although microscopic CAAE causes somatosensory evoked potential abnormalities and neurologic dysfunction, severe cerebral injury or infarction is not present at 24 h. The author's findings are consistent with clinical imaging studies that suggest microscopic CAAE causes neurologic dysfunction even though overt infarction is absent.
The Influence of Age on Propofol Pharmacodynamics
Authors: Schnider Thomas W. , Minto Charles F. , Shafer Steven L. , Gambus Pedro L. , Andresen Corina , Goodale David B. , Youngs Elizabeth J. 
Published: November 2003

Background
The authors studied the influence of age on the pharmacodynamics of propofol, including characterization of the relation between plasma concentration and the time course of drug effect.

Methods
The authors evaluated healthy volunteers aged 25-81 yr. A bolus dose (2 mg/kg or 1 mg/kg in persons older than 65 yr) and an infusion (25, 50, 100, or 200 microg x kg(-1) x min(-1)) of the older or the new (containing EDTA) formulation of propofol were given on each of two different study days. The propofol concentration was determined in frequent arterial samples. The electroencephalogram (EEG) was used to measure drug effect. A statistical technique called semilinear canonical correlation was used to select components of the EEG power spectrum that correlated optimally with the effect-site concentration. The effect-site concentration was related to drug effect with a biphasic pharmacodynamic model. The plasma effect-site equilibration rate constant was estimated parametrically. Estimates of this rate constant were validated by comparing the predicted time of peak effect with the time of peak EEG effect. The probability of being asleep, as a function of age, was determined from steady state concentrations after 60 min of propofol infusion.

Results
Twenty-four volunteers completed the study. Three parameters of the biphasic pharmacodynamic model were correlated linearly with age. The plasma effect-site equilibration rate constant was 0.456 min(-1). The predicted time to peak effect after bolus injection ranging was 1.7 min. The time to peak effect assessed visually was 1.6 min (range, 1-2.4 min). The steady state observations showed increasing sensitivity to propofol in elderly patients, with C50 values for loss of consciousness of 2.35, 1.8, and 1.25 microg/ml in volunteers who were 25, 50, and 75 yr old, respectively.

Conclusions
Semilinear canonical correlation defined a new measure of propofol effect on the EEG, the canonical univariate parameter for propofol. Using this parameter, propofol plasma effect-site equilibration is faster than previously reported. This fast onset was confirmed by inspection of the EEG data. Elderly patients are more sensitive to the hypnotic and EEG effects of propofol than are younger persons.
Augmentation of the Rocuronium-induced Neuromuscular Block by the Acutely Administered Phenytoin
Authors: Spacek Anna , Nickl Stephan , Neiger Franz X. , Nigrovic Vladimir , Ullrich Odo-Winfried , Weindlmayr-Goettel Marta , Schwall Barbara , Taeger Kai , Kress Hans Georg 
Published: November 2003

Background
The effects of an acute administration of phenytoin on the magnitude of the rocuronium-induced neuromuscular block were evaluated.

Methods
Twenty patients (classified as American Society of Anesthesiologists physical status I or II) scheduled for craniotomy were studied: 15 received phenytoin during operation (10 mg/kg), and the others served as controls. Anesthesia was induced with thiopental and fentanyl and maintained with nitrous oxide (65%) in oxygen and end-tidal isoflurane (1%). The ulnar nerve was stimulated supramaximally and the evoked electromyography was recorded using a neuromuscular transmission monitor. Continuous infusion of rocuronium maintained the neuromuscular block with first twitch (T1) between 10 and 15% for 45 min before the start of an infusion of either phenytoin or NaCl 0.9%. Twitch recordings continued for 60 min thereafter. Arterial blood samples were collected at the predefined time points (four measurements before and four after the start of the infusion) to determine the concentrations of phenytoin and rocuronium and the percentage of rocuronium bound to plasma proteins.

Results
The first twitch produced by an infusion of rocuronium remained constant during the 15 min before and the 60 min after the start of the saline infusion. After the phenytoin infusion, the twitch decreased progressively, but the plasma concentrations and the protein-bound fraction of rocuronium did not change.

Conclusion
Phenytoin acutely augments the neuromuscular block produced by rocuronium without altering its plasma concentration or its binding to plasma proteins.
L-Arginine Infusion Dilates Coronary Vasculature in Patients Undergoing Coronary Bypass Surgery
Authors: Wallace Arthur W. , Ratcliffe Mark B. , Galindez Daniel , Kong James S. 
Published: November 2003

Background
Nitric oxide-dependent factors (serotonin, activated platelets, acetylcholine) cause vasodilation in normal coronary arteries but vasoconstrict atherosclerotic vessels. This experiment tested the hypothesis that intravenous systemic infusions of L-arginine, a precursor for nitric oxide production, dilate the coronary vascular bed of patients undergoing coronary artery bypass graft surgery.

Methods
Twenty patients scheduled for coronary artery bypass graft surgery surgery were studied in a prospective, blinded, randomized clinical trial. Saphenous vein graft blood flow was measured with a transit time flow probe, and coronary vascular resistance was calculated. After weaning from bypass, patients were given a venous infusion (placebo or 10% arginine hydrochloride [30 g]) over 15 min. Arterial blood samples for the determination of L-arginine and L-citrulline levels were drawn before, 10 min after starting infusion, and 10 min after end of infusion.

Results
The placebo group experienced an increase in mean arterial pressure and coronary vascular resistance and a decrease in graft blood flow. Patients in the L-arginine group maintained their baseline values. Mean arterial pressure (L-arginine, 88+/-17 to 92+/-13 mmHg vs. placebo, 80+/-12 to 92+/-9 mmHg, P = 0.021), coronary vascular resistance (L-arginine, 97,000+/-60,000 to 99,600+/-51,000 dynes x s x cm(-5) vs. placebo, 81,000+/-69,000 to 117,000+/-64,000 dynes x s x cm(-5), P = 0.05), and graft blood flow (L-arginine, 55+/-25 to 50+/-19 ml/min vs. placebo, 60+/-34 to 46+/-18, P = 0.05) remained more stable in the L-arginine-treated patients.

Conclusions
Systemic L-arginine infusion reduced postbypass coronary vasoconstriction. There were no adverse events associated with the drug infusion.
The effect of Pyrogen Administration on Sweating and Vasoconstriction Thresholds during Desflurane Anesthesia
Authors: Lenhardt Rainer , Negishi Chiharu , Sessler Daniel I. , Ozaki Makoto , Ettinger Katharine , Bastanmehr Hiva , Lobo Errol 
Published: November 2003

Background
General anesthetics increase the sweating-to-vasoconstriction interthreshold range (temperatures not triggering thermoregulatory defenses), whereas fever is believed to only increase the setpoint (target core temperature). However, no data characterize thresholds (temperatures triggering thermoregulatory defenses) during combined anesthesia and fever. Most likely, the combination produces an expanded interthreshold range around an elevated setpoint. The authors therefore tested the hypothesis that thermoregulatory response thresholds during the combination of fever and anesthesia are simply the linear combination of the thresholds resulting from each intervention alone.

Methods
The authors studied eight healthy male volunteers. Fever was induced on the appropriate days by intravenous injection of 30 IU/g human recombinant interleukin 2 (IL-2), followed 2 h later by an additional 70 IU/g. General anesthesia consisted of desflurane 0.6 minimum alveolar concentration (MAC). The volunteers were randomly assigned to the following groups: (1) control (no desflurane, no IL-2); (2) IL-2 alone; (3) desflurane alone; and (4) desflurane plus IL-2. During the fever plateau, volunteers were warmed until sweating was observed and then cooled to vasoconstriction. Sweating was evaluated from a ventilated capsule and vasoconstriction was quantified by volume plethysmography. The tympanic membrane temperatures triggering significant sweating and vasoconstriction identified the respective response thresholds. Data are presented as the mean +/- SD; P < 0.05 was considered significant.

Results
The interthreshold range was near 0.40 degrees C on both the control day and during IL-2 administration alone. On the IL-2 alone day, however, the interthreshold range was shifted to higher temperatures. The interthreshold range increased significantly during desflurane anesthesia to 1.9+/-0.6 degrees C. The interthreshold range during the combination of desflurane and IL-2 was 1.2+/-0.6 degrees C, which was significantly greater than on the control and IL-2 alone days. However, it was also significantly less than during desflurane alone.

Conclusion
The combination of desflurane and IL-2 caused less thermoregulatory inhibition than would be expected based on the effects of either treatment alone. Fever-induced activation of the sympathetic nervous system may contribute by compensating for a fraction of the anesthetic-induced thermoregulatory impairment.
Comparison of Ropivacaine and Lidocaine for Intravenous Regional Anesthesia in Volunteers
Authors: Chan Vincent W. S. , Weisbrod Mitchell J. , Kaszas Zsuzsanna , Dragomir Camelia 
Published: November 2003

Background
Ropivacaine may be useful for intravenous regional anesthesia, but its anesthetic effectiveness and toxicity have not been evaluated.

Methods
Two doses of ropivacaine (1.2 and 1.8 mg/kg) and one dose of lidocaine (3 mg/kg) were compared for intravenous regional anesthesia in 15 volunteers. An arm tourniquet was inflated for 30 min after injection and then deflated in two cycles. Sensory block was measured by response to touch, cold, pinprick, and transcutaneous electric stimulation, and motor function was measured by hand grip strength and muscle power. Median, ulnar, radial, and musculocutaneous nerve functions were tested before local anesthetic injection and then at 5-min intervals until blocks resolved. The plasma ropivacaine and lidocaine concentrations were determined from arterial and venous blood samples drawn from the unanesthetized arm.

Results
Sensory and motor blocks were complete within 25 min and 30 min, respectively, in all three treatment groups. However, recovery of sensory and motor block after tourniquet release was slowest in the high-dose ropivacaine group. Anesthesia to pinprick and transcutaneous electric stimulation was sustained in all the volunteers in the high-dose ropivacaine group for 55 min and 85 min, respectively, whereas complete recovery was observed in the lidocaine group (P = 0.008) and partial recovery in the low-dose ropivacaine group (P < 0.05) during the same period. Motor block also was sustained in the high-dose ropivacaine group for 70 min, which was significantly longer than in the lidocaine group (P < 0.05). All volunteers (five of five) given lidocaine and one volunteer given high-dose ropivacaine reported light-headedness and hearing disturbance during tourniquet release when the arterial plasma lidocaine and ropivacaine concentrations were 4.7+/-2.1 microg/ml (mean) and 2.7 micro/ml, respectively.

Conclusion
Compared with lidocaine, intravenous regional anesthesia with ropivacaine appears to be comparable but has longer-lasting residual anesthesia.
Shivering and Shivering-like Tremor during Labor with and without Epidural Analgesia
Authors: Panzer Oliver , Ghazanfari Naghme , Sessler Daniel I. , Yucel Yuksel , Greher Manfred , Akca Ozan , Donner Andrew , Germann Peter , Kurz Andrea 
Published: November 2003

Background
Effective treatment and prevention of hyperthermia and shivering-like tremor during labor is hindered by a poor understanding of their causes. The authors sought to identify the incidence of nonthermoregulatory shivering-like tremor and the factors associated with this activity.

Methods
The authors studied women in spontaneous full-term labor who chose epidural analgesia (n = 21) or opioid sedation (n = 31). Shivering-like tremor and sweating were evaluated by observation. Core temperature was recorded in the external auditory canal using a compensated infrared thermometer. Arteriovenous shunt tone was evaluated with forearm minus fingertip skin temperature gradients; gradients less than 0 were considered evidence of vasodilation. Tremor was considered nonthermoregulatory when core temperature exceeded 37 degrees C and the arms were vasodilated. Pain was evaluated using a visual analog scale.

Results
Shivering-like tremor was observed in 18% of 290, 30-min data-acquisition epochs before delivery. The patients were both normothermic and vasodilated during 15% of these epochs. Shivering was observed in 16% of 116 postdelivery epochs and was nonthermoregulatory in 28%. Sweating was observed in 30% of predelivery epochs, and the patients were both hypothermic and vasoconstricted during 12%. The mean core temperature in patients given epidural analgesia was approximately 0.2 degrees C greater than in those given sedation. Hyperthermia was observed during 10 epochs (38.4+/-0.3 degrees C) during epidural analgesia and during 10 epochs (38.4+/-0.3 degrees C) with sedation. The patients were vasoconstricted in more than 50% of these epochs in each group. Multivariate mixed-effects modeling identified high pain scores and vasoconstriction as significant predictors of shivering. There were no predictors for shivering epochs in patients who were simultaneously normothermic and vasodilated. Significant predictors of sweating were time before delivery, high pain scores, hypothermia with vasoconstriction, high thermal comfort, and low mean skin temperature. There were no predictors for sweating epochs in patients who were simultaneously hypothermic and vasoconstricted.

Conclusions
This study confirms the clinical impression that some peripartum shivering-like tremor is nonthermoregulatory. The authors also identified nonthermoregulatory sweating. These data indicate that shivering-like tremor and sweating in the peripartum period is multifactorial.
Pharmacokinetics of ε-aminocaproic Acid in Patients Undergoing Aortocoronary Bypass Surgery
Authors: Butterworth John , James Robert L. , Lin Yonggu , Prielipp Richard C. , Hudspeth Allen S. 
Published: November 2003

Background
Epsilon-aminocaproic acid (EACA) is commonly infused during cardiac surgery using empiric dosing schemes. The authors developed a pharmacokinetic model for EACA elimination in surgical patients, tested whether adjustments for cardiopulmonary bypass (CPB) would improve the model, and then used the model to develop an EACA dosing schedule that would yield nearly constant EACA blood concentrations.

Methods
Consenting patients undergoing elective coronary artery surgery received one of two loading doses of EACA, 30 mg/kg (group I, n = 7) or 100 mg/kg (group II, n = 6) after CPB, or (group III) a 100 mg/kg loading dose before CPB and a 10 mg x kg(-1) x h(-1) maintenance infusion continued for 4 h during and after CPB (n = 7). Two patients with renal failure received EACA in the manner of group III. Blood concentrations of EACA, measured by high-performance liquid chromatography, were subjected to mixed-effects pharmacokinetic modeling.

Results
The EACA concentration data were best fit by a model with two compartments and corrections for CPB. The elimination rate constant k10 fell from 0.011 before CPB to 0.0006 during CPB, returning to 0.011 after CPB. V1 increased 3.8 l with CPB and remained at that value thereafter. Cl1 varied from 0.08 l/min before CPB to 0.007 l/min during CPB and 0.13 l/min after CPB. Cl2 increased from 0.09 l/min before CPB to 0.14 l/min during and after CPB. Two patients with renal failure demonstrated markedly reduced clearance. Using their model, the authors predict that an EACA loading infusion of 50 mg/kg given over 20 min and a maintenance infusion of 25 mg x kg(-1) x h(-1) would maintain a nearly constant target concentration of 260 microg/ml.

Conclusions
EACA clearance declines and volume of distribution increases during CPB. The authors' model predicts that more stable perioperative EACA concentrations would be obtained with a smaller loading dose (50 mg/kg given over 20 min) and a more rapid maintenance infusion (25 mg x kg(-1) x h(-1)) than are typically employed.
Neurokinin-1 Receptors Are Involved in Behavioral Responses to High-intensity Heat Stimuli and Capsaicin-induced Hyperalgesia in Mice
Authors: Mansikka Heikki , Shiotani Masako , Winchurch Richard , Raja Srinivasa N. 
Published: November 2003

Background
The neurokinin-1 (NK-1) receptor and its ligand, substance P, are thought to play important roles in nociception and hyperalgesia. This study evaluated the role of the NK-1 receptor in processing noxious stimuli in normal and inflammatory states.

Methods
Behavioral responses to heat and mechanical and chemical stimuli were studied in NK-1 receptor knockout mice and wild-type control mice. Thermal nociception was evaluated by measuring paw lick or jump latencies to hot plate (52, 55, and 58 degrees C) and paw withdrawal latencies to radiant heat applied to the hind paws. Mechanical nociception was measured by von Frey monofilament applications to the hind paws. Intraplantar capsaicin-induced (10 microg/20 microl) paw licking and mechanical and heat hyperalgesia were compared in NK-1 knockout and wild-type mice.

Results
Withdrawal responses to radiant heat (4.3+/-0.18 s for knockout and 4.4+/-0.8 s for wild-type mice) and von Frey monofilaments were similar in knockout and wild-type mice. In the hot plate test, increasing the hot plate temperature from 52 degrees C to 58 degrees C resulted in a decrease in the response latency in the wild-type mice (30.4+/-17.5 s to 15.2+/-6.8 s, P < 0.05), whereas in the knockout mice the response latencies remained constant (28.2+/-19.8 s to 29+/-15.1 s, not significant). Capsaicin-induced paw licking (14.5+/-12.8 s for knockout and 41.3+/-37.3 s for wild-type mice, P < 0.05) and mechanical and heat hyperalgesia were attenuated in the knockout mice.

Conclusion
NK-1 receptors contribute to the withdrawal responses to high-intensity heat stimuli and to capsaicin-induced mechanical and heat hyperalgesia.