bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparative Effects of Hypotension Due to Isoflurane, Nitroglycerin, and Adenosine on Subendocardial Microcirculation
Authors: Fujita Yoshihisa , Habazettl Helmut , Corso Carlos O. , Messmer Konrad , Yada Toyotaka 
Published: November 2003

Background
Although isoflurane may cause subendocardial hypoperfusion in the presence of coronary stenosis because of its coronary arteriolar dilatory effects, it is not known how the subendocardial microcirculation is affected. The authors examined the effects of isoflurane on poststenotic subendocardial microvessels with coronary stenosis.

Methods
The authors observed subendocardial microvessels in in situ beating swine hearts with or without critical stenosis of the left anterior descending coronary artery (LAD) with a needle-type videomicroscope during isoflurane- (ISO-H), adenosine- (ADE-H), and nitroglycerin- (NTG-H) induced hypotension (mean arterial pressure, 55 mmHg). Regional myocardial function, oxygen balance, and lactate metabolism in the region perfused by the LAD also were determined.

Results
In swine with stenosis, there were no differences in heart rate, cardiac output, and LAD blood flow among the three types of hypotension. Regional lactate production and anterior interventricular venous pO2 were similar during ISO-H and NTG-H but higher during ADE-H. With videomicroscopy, about half as many subendocardial microvessels could be visualized during ADE-H as with ISO-H and NTG-H. The average decrease in the systolic diameter of subendocardial microvessels of greater than 100 microm was 9 +/- 6% during ISO-H and 12 +/- 5% during NTG-H, but no consistent phasic diameter changes were observed during ADE-H. In swine without stenosis, a systolic diameter decrease was observed during all three types of hypotension.

Conclusions
These findings suggest that hypotension induced by isoflurane or nitroglycerin preserves phasic diameter changes in subendocardial microvessels in the presence of critical coronary stenosis, whereas that induced by adenosine does not.
Antinociceptive Interaction of Intrathecal α2-adrenergic Agonists, Tizanidine and Clonidine, with Lidocaine in Rats
Authors: Kawamata Tomoyuki , Omote Keiichi , Kawamata Mikito , Iwasaki Hiroshi , Namiki Akiyoshi 
Published: November 2003

Background
The intrathecal alpha2-adrenergic agonist, clonidine, has been shown to have considerable antinociceptive effect, although clonidine causes hypotension and bradycardia. The combination of intrathecal clonidine and local anesthetics enhances analgesic effects, whereas the combination may cause marked hypotension and motor blockade, which may limit the clinical application of the combination. Tizanidine, another alpha2-adrenergic agonist, has also provided antinociception without producing pronounced hemodynamic changes. This study was designed to evaluate the antinociceptive and hemodynamic interactions of tizanidine and clonidine with lidocaine.

Methods
Male Sprague Dawley rats were chronically implanted with lumbar intrathecal catheters. The tail-flick test was used to assess the thermal nociceptive threshold. The ability of intrathecal tizanidine, clonidine, lidocaine, or the combinations of alpha2-adrenergic agonist and lidocaine to alter the tail-flick latency was examined. To characterize the antinociceptive interaction, the isobolographic analysis was applied. Additionally, the motor function, blood pressure and heart rate after intrathecal administration of drugs and combinations were also monitored.

Results
Intrathecal tizanidine, clonidine, or the combinations increased the tail-flick latency in dose- and time-dependent fashion without affecting motor function. The order potencies (dose producing a 50% of peak effect, in microg) of tizanidine and clonidine were 1.8 and 0.75, respectively. With isobolographic analysis, tizanidine with lidocaine and clonidine with lidocaine showed significantly synergistic antinociceptive interaction. Potency ratio analysis and fractional analysis also confirmed the synergistic interaction. At the doses in the combinations showing comparable antinociception, tizanidine with lidocaine, unlike clonidine with lidocaine, did not affect motor function or blood pressure.

Conclusion
The authors' results show that intrathecal tizanidine and clonidine synergistically interact with lidocaine so that the degree of antinociception to somatic noxious stimuli are enhanced. The antinociceptive synergistic interaction between tizanidine and lidocaine may be useful in clinical practice without affecting blood pressure, heart rate, or motor function.
Effects of Positive End-expiratory Pressure and Different Tidal Volumes on Alveolar Recruitment and Hyperinflation
Authors: Dambrosio Michele , Roupie Eric , Mollet Jean-Jacques , Anglade Marie-Christine , Vasile Norbert , Lemaire Francois , Brochard Laurent 
Published: November 2003

Background
The morphologic effect of positive end-expiratory pressure (PEEP) and of two tidal volumes were studied by computed tomography to determine whether setting the tidal volume (Vt) at the upper inflection point (UIP) of the pressure-volume (P-V) curve of the respiratory system or 10 ml/kg have different effects on hyperinflation and alveolar recruitment.

Methods
Alveolar recruitment and hyperinflation were quantified by computed tomography in nine patients with the acute respiratory distress syndrome (ARDS). First, end expiration was compared without PEEP and with PEEP set at the lower inflection point of the P-V curve; second, at end inspiration above PEEP, a reduced Vt set at the UIP (rVt) and a standard 10 ml/kg Vt (Vt) ending above the UIP were compared. Three lung zones were defined from computed tomographic densities: hyperdense, normal, and hyperinflated zones.

Results
Positive end-expiratory pressure induced a significant decrease in hyperdensities (from 46.8 +/- 18% to 38 +/- 15.1% of zero end-expiratory pressure (ZEEP) area; P < 0.02) with a concomitant increase in normal zones (from 47.3 +/- 20.9% to 56.5 +/- 13.2% of the ZEEP area; P < 0.05), and a significant increase in hyperinflation (from 8.1 +/- 5.9% to 17.8 +/- 12.7% of ZEEP area; P < 0.01). At end inspiration, a significant increase in hyperinflated areas was observed with Vt compared with rVt (33.4 +/- 17.8 vs. 26.8 +/- 17.3% of ZEEP area; P < 0.05), whereas no significant difference was observed for both normal and hyperdense zones.

Conclusions
Positive end-expiratory pressure promotes alveolar recruitment; increasing Vt above the UIP seems to predominantly increase hyperinflation.
A Rapid Increase in Foot Tissue Temperature Predicts Cardiovascular Collapse during Anaphylactic and Anaphylactoid Reactions
Authors: Kotani Naoki , Kushikata Tetsuya , Matsukawa Takashi , Sessler Daniel I. , Muraoka Masatoshi , Hashimoto Hiroshi , Ishihara Hironori , Matsuki Akitomo 
Published: November 2003

Background
Cardiovascular collapse during anaphylactic and anaphylactoid reactions results from release of histamine and other vasoactive substances. Intense arteriolar vasodilation associated with severe allergic reactions is likely to increase convective transfer of heat and peripheral tissue temperature, and finally to provoke cardiovascular collapse. Therefore the authors tested the hypothesis that during anaphylactic and anaphylactoid reactions, an acute increase in peripheral tissue temperature precedes cardiovascular collapse and that the magnitude of the increase correlates with the severity of the reaction.

Methods
During a 13-yr period, approximately 120,000 patients were screened for clinical evidence of intraoperative anaphylactic and anaphylactoid reactions. Core temperature was measured in the distal esophagus, and "deep" foot tissue temperature was measured on the sole of one foot in all these patients. Otherwise unexplained cardiovascular collapse accompanied by bronchospasm and/or cutaneous signs such as urticaria, flushing, or angioedema occurred in 32 patients who were entered into a prospective diagnostic protocol. Among these, 15 met laboratory criteria for anaphylactic or anaphylactoid reactions. Anaphylaxis was confirmed in nine of them by a positive skin test to the suspected agent, the in vitro leukocyte histamine-release test, or the Praunitz-Küstner test. Reactions were considered anaphylactoid in six others when laboratory evidence did not support anaphylaxis, but plasma histamine or tryptase concentrations were much greater during episodes than 6 weeks later.

Results
Development of anaphylactic and anaphylactoid reactions followed a characteristic pattern: (1) Foot temperature, which was initially 3.3 +/- 1.7 degrees C less than core temperature, increased to within 0.3 degrees C of core temperature 3.2 +/- 1.4 min after drug administration; (2) onset of cardiovascular collapse ensued 1.8 +/- 0.8 min later; and (3) core temperature increased from 34.7 +/- 1.0 degrees C to peak values 37.1 +/- 0.6 degrees C 13 +/- 5 min after drug administration. The most severe reactions were associated with shorter times to comparable core and foot temperatures, faster onset of cardiovascular collapse, and higher maximum core temperatures.

Conclusions
The normal core-to-peripheral tissue temperature gradient was obliterated several minutes before hemodynamic consequences associated with anaphylactic and anaphylactoid reactions. Further, a rapid increase in deep foot temperature and maximum core temperature correlated with clinical severity.
Dexmedetomidine Does Not Alter the Sweating Threshold, But Comparably and Linearly Decreases the Vasoconstriction and Shivering Thresholds
Authors: Talke Pekka , Tayefeh Farzin , Sessler Daniel I. , Jeffrey Renee , Noursalehi Mojtaba , Richardson Charles 
Published: November 2003

Background
Clonidine decreases the vasoconstriction and shivering thresholds. It thus seems likely that the alpha2 agonist dexmedetomidine will also impair control of body temperature. Accordingly, the authors evaluated the dose-dependent effects of dexmedetomidine on the sweating, vasoconstriction, and shivering thresholds. They also measured the effects of dexmedetomidine on heart rate, blood pressures, and plasma catecholamine concentrations.

Methods
Nine male volunteers participated in this randomized, double-blind, cross-over protocol. The study drug was administered by computer-controlled infusion, targeting plasma dexmedetomidine concentrations of 0.0, 0.3, and 0.6 ng/ml. Each day, skin and core temperatures were increased to provoke sweating and then subsequently reduced to elicit vasoconstriction and shivering. Core-temperature thresholds were computed using established linear cutaneous contributions to control of sweating, vasoconstriction, and shivering. The dose-dependent effects of dexmedetomidine on thermoregulatory response thresholds were then determined using linear regression. Heart rate, arterial blood pressures, and plasma catecholamine concentrations were determined at baseline and at each threshold.

Results
Neither dexmedetomidine concentration increased the sweating threshold from control values. In contrast, dexmedetomidine administration reduced the vasoconstriction threshold by 1.61 +/- 0.80 degrees C x ng(-1) x ml (mean +/- SD) and the shivering threshold by 2.40 +/- 0.90 degrees C x ng(-1) x ml. Hemodynamic responses and catecholamine concentrations were reduced from baseline values, but they did not differ at the two tested dexmedetomidine doses.

Conclusions
Dexmedetomidine markedly increased the range of temperatures not triggering thermoregulatory defenses. The drug is thus likely to promote hypothermia in a typical hospital environment; it is also likely to prove an effective treatment for shivering.
Estrogen-induced Changes in Protein Binding of Bupivacaine during in Vitro Fertilization
Authors: Tsen Lawrence C. , Arthur G. Richard , Datta Sanjay , Hornstein Mark D. , Bader Angela M. 
Published: November 2003

Background
Patients having in vitro fertilization (IVF) procedures that use gonadotropin-releasing hormone agonist down-regulation undergo hormonal manipulation of estrogen concentrations to induce oocyte maturation. After achieving minimal estrogen concentrations (baseline), stimulation increases estrogen concentrations to supraphysiologic levels, leading to egg retrieval. The isolated effect of estrogen on protein binding has not previously been reported. This study was conducted to measure the effect of estrogen concentrations on protein binding of two concentrations of bupivacaine, 1 microg/ml and 5 microg/ml, corresponding, respectively, to systemic concentrations expected after administration of epidural anesthesia and associated with bupivacaine toxicity. Serum proteins were measured to address the mechanism.

Methods
Twenty-nine healthy women undergoing IVF procedures were enrolled and venous samples were drawn at times of minimal and maximal estrogen concentrations. The percentage of free bupivacaine was determined at fixed concentrations of 1 and 5 microg/ml. Serum albumin and alpha1-acid glycoprotein concentrations were measured at baseline and at retrieval in a group of 24 women.

Results
The percentage of free bupivacaine increased between times of minimal and maximal serum estrogen concentrations, corresponding to decreased protein binding. Concentrations of serum albumin and alpha1-acid glycoprotein decreased between baseline and retrieval times.

Conclusions
Patients undergoing IVF procedures demonstrate a decrease in protein binding of bupivacaine from baseline concentrations. These changes may be explained by a decrease in albumin and alpha1-acid glycoprotein. During anesthesia for egg retrieval, clinicians should consider the implications of increased free fraction of drug, especially for highly protein-bound agents.
The Effect of Imidazoline Receptors and α2-adrenoceptors on the Anesthetic Requirement (MAC) for Halothane in Rats
Authors: Kagawa Kiyokazu , Mammoto Tadanori , Hayashi Yukio , Kamibayashi Takahiko , Mashimo Takashi , Yoshiya Ikuto 
Published: November 2003

Background
Recent evidences have documented that several pharmacologic actions of alpha2-adrenoceptor agonists are mediated via activation of not only alpha2-adrenoceptors, but also by imidazoline receptors, which are nonadrenergic receptors in the central nervous system. However, the effect of imidazoline receptors on the anesthesia is not well known, and it is important to clarify the effects of both receptors on anesthesia.

Methods
Seventy-two rats were anesthetized with halothane, and the anesthetic requirement for halothane was evaluated as minimum alveolar concentration (MAC). The MAC for halothane was determined in the presence of dexmedetomidine (0, 10, 20, and 30 microg/kg, intraperitoneally [IP]), a selective alpha2-adrenoceptor agonist with weak affinity for imidazoline receptors. Then, the authors evaluated the inhibitory effect of rauwolscine (20 mg/kg, IP), an alpha2-adrenoceptor antagonist with little affinity for imidazoline receptors, on the MAC-reducing action of dexmedetomidine (30 microg/kg). Further, the effect of rilmenidine (20, 50, 100, 1000 microg/kg, IP), a selective imidazoline receptor agonist, on the MAC for halothane was also investigated.

Results
Dexmedetomidine decreased the MAC for halothane dose-dependently, and this MAC-reducing action of dexmedetomidine was completely blocked by rauwolscine. Rilmenidine alone did not change the MAC for halothane.

Conclusions
The present data indicate that the anesthetic sparing action of dexmedetomidine is most likely mediated through alpha2- adrenoceptors, and the stimulation of imidazoline receptors exerts little effect on the anesthetic requirement for halothane.
Subjective, Psychomotor, Cognitive, and Analgesic Effects of Subanesthetic Concentrations of Sevoflurane and Nitrous Oxide
Authors: Galinkin Jeffrey L. , Janiszewski Debra , Young Christopher J. , Klafta Jerome M. , Klock P. Allan , Coalson Dennis W. , Apfelbaum Jeffrey L. , Zacny James P. 
Published: November 2003

Background
Sevoflurane is a volatile general anesthetic that differs in chemical nature from the gaseous anesthetic nitrous oxide. In a controlled laboratory setting, the authors characterized the subjective, psychomotor, and analgesic effects of sevoflurane and nitrous oxide at two equal minimum alveolar subanesthetic concentrations.

Methods
A crossover design was used to test the effects of two end-tidal concentrations of sevoflurane (0.3% and 0.60%), two end-tidal concentrations of nitrous oxide (15% and 30%) that were equal in minimum alveolar concentration to that of sevoflurane, and placebo (100% oxygen) in 12 healthy volunteers. The volunteers inhaled one of these concentrations of sevoflurane, nitrous oxide, or placebo for 35 min. Dependent measures included subjective, psychomotor, and physiologic effects, and pain ratings measured during a cold-water test.

Results
Sevoflurane produced a greater degree of amnesia, psychomotor impairment, and drowsiness than did equal minimum alveolar concentrations of nitrous oxide. Recovery from sevoflurane and nitrous oxide effects was rapid. Nitrous oxide but not sevoflurane had analgesic effects.

Conclusions
Sevoflurane and nitrous oxide produced different profiles of subjective, behavioral, and cognitive effects, with sevoflurane, in general, producing an overall greater magnitude of effect. The differences in effects between sevoflurane and nitrous oxide are consistent with the differences in their chemical nature and putative mechanisms of action.
Effects of Intrathecally Administered Nociceptin, and Opioid Receptor-like1Receptor Agonist, and N-methyl-D-aspartate Receptor Antagonistst on the Thermal Hyperalgesia Induced by Partial Sciatic Nerve Injury in the Rat
Authors: Yamamoto Tatsuo , Nozaki-Taguchi Natsuko 
Published: November 2003

Background
Nociceptin is a 17-amino acid peptide and acts as a potent endogenous agonist of the opioid receptor-like1 receptor. Nociceptin is reported to depress glutamatergic transmission and to block the spinal facilitation that is thought to be mediated by the N-methyl-D-aspartate (NMDA) receptor. In the present study, the authors investigated the effect of intrathecally administered nociceptin and NMDA antagonists on the level of thermal hyperalgesia after partial sciatic nerve injury in the rat.

Methods
Partial sciatic nerve injury was created by tight ligation of one third to one half of the right sciatic nerve. The level of thermal hyperalgesia was evaluated by the difference score, which was calculated by subtracting the paw withdrawal latency against thermal nociceptive stimulation in the uninjured paw from that in the injured paw. Drugs were administered intrathecally 7 or 11 days after the nerve injury, and the level of thermal hyperalgesia was measured 5, 15, 30, 60, and 90 min after the drug injection.

Results
Intrathecal injection of nociceptin, but not of NMDA antagonists, attenuated the level of thermal hyperalgesia in a dose-dependent manner at a dose of 0.17-17 nM (post-drug difference score: saline-treated rats, -4.9 +/- 2.2 s; 17 nM nociceptin-treated rats, -1.3 +/- 0.9 s).

Conclusions
Intrathecal injection of nociceptin attenuated the level of thermal hyperalgesia induced by partial sciatic nerve injury, and NMDA receptor-dependent spinal facilitation does not play an important role in maintaining thermal hyperalgesia in rats with partial sciatic nerve injury.
Anesthetic-induced Preconditioning
Authors: Cason Brian A. , Gamperl A. Kurt , Slocum Robert E. , Hickey Robert F. 
Published: November 2003

Background
Experimental evidence suggests that ATP-sensitive potassium channels are involved in myocardial ischemic preconditioning. Because some pharmacologic effects of isoflurane are mediated by K(ATP) channels, the authors tested the hypothesis: Isoflurane administration, before myocardial ischemia, can induce or mimic myocardial preconditioning.

Methods
Myocardial infarct size was measured in three groups of propofol-anesthetized rabbits, each subjected to 30 min of anterolateral coronary occlusion followed by 3 h of reperfusion. Groups differed in their pretreatment: Group 1 (control, N = 13) no pretreatment, Group 2 (ischemic preconditioning, N = 8), 5 min of coronary occlusion and 15 min of reperfusion; Group 3 (isoflurane pretreatment; N = 15), 15 min of isoflurane (1.1% end-tidal) and 15 min of washout. Hemodynamics were monitored serially. Myocardial infarct size and the area at risk were defined using triphenyltetrazolium chloride staining and fluorescent microspheres, respectively, and both were measured using computerized planimetry.

Results
Infarct size expressed as a percentage of area at risk was 23.4 +/- 8.5% (mean +/- SD) in the isoflurane group compared with 33.1 +/- 13.3% in controls, and 8.7 +/- 6.2% in the ischemia-preconditioned group. Analysis for coincidental regressions, followed by tests for equality of slope and elevation, showed that the linear relationship between infarct size and area at risk was significantly (P < 0.05) different in all three groups because of differences in line elevation. Minor differences in hemodynamic variables were found between groups, which were unlikely to account for the significant differences in infarct size.

Conclusion
Preadministration of isoflurane, before myocardial ischemia, reduces myocardial infarct size, and mimics myocardial preconditioning.
Differential Effects of Thiopental on Neuronal Nicotinic Acetylcholine Receptors and P2XPurinergic Receptors in PC12 Cells
Authors: Andoh Tomio , Furuya Ryousuke , Oka Keikou , Hattori Satoshi , Watanabe Itaru , Kamiya Yoshitaka , Okumura Fukuichiro 
Published: November 2003

Background
PC12 cells, derived from rat pheochromocytoma, express neuronal nicotinic acetylcholine receptors (nAchRs) and P2X purinergic receptors, both of which resemble the receptors in postganglionic sympathetic neurons. The former is the established and the latter is the putative receptor to mediate fast synaptic transmission. The authors investigated effects of thiopental on these two ligand-gated ion channels.

Methods
Whole cell currents were recorded in PC12 cells without treatment of nerve growth factor, using conventional whole cell patch clamp technique. Nicotine or adenosine triphosphate (ATP) 30 microM was applied for 4-5 s in the absence or presence of thiopental 3-300 microM.

Results
Nicotine induced the rapidly decaying inward current at -60 mV, which exhibited the characteristics of the neuronal nAchR-mediated current. Thiopental inhibited the nicotine-induced inward current and accelerated the current decay in a dose-dependent manner, resulting in the greater effects on the steady current than the peak current. IC50s for the peak and steady current were 56.7 and 7.4 microM, when the anesthetic was coapplied with nicotine. Thiopental's inhibition was not associated with a change in the reversal potential and was voltage-independent at membrane potential of -30 to -70 mV. Most of thiopental's effects seemed to require channel opening. In contrast to the nicotine-induced current, thiopental had little effect on the current elicited by ATP.

Conclusions
Thiopental, whose reported EC50 for general anesthesia is 25 microM, inhibited the neuronal nAchR-mediated current but not the P2X receptor-mediated response in PC12 cells at clinically relevant concentrations. Inhibition may result in suppression of synaptic transmission in sympathetic ganglia.