bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dobutamine Antagonizes Epinephrine's Biochemical and Cardiotonic Effects
Authors: Prielipp Richard C. , MacGregor Drew A. , Royster Roger L. , Kon Neal D. , Hines Michael H. , Butterworth John F. 
Published: November 2003

Background
Patients may receive more than one positive inotropic drug to improve myocardial function and cardiac output, with the assumption that the effects of two drugs are additive. The authors hypothesized that combinations of dobutamine and epinephrine would produce additive biochemical and hemodynamic effects.

Methods
The study was performed in two parts. Phase 1 used human lymphocytes in an in vitro model of cyclic adenosine monophosphate (cAMP) generation in response to dobutamine (10(-8) to 10(-4) M) or epinephrine (10(-9) M to 10(-5) M), and dobutamine and epinephrine together. Phase 2 was a clinical study in patients after aortocoronary artery bypass in which isobolographic analysis compared the cardiotonic effects of dobutamine (1.25, 2.5, or 5 microg x kg(-1) x min(-1)) or epinephrine (10, 20, or 40 ng x kg(-l) x min(-1)), alone or in combination.

Results
In phase 1, dobutamine increased cAMP production 41%, whereas epinephrine increased cAMP concentration approximately 200%. However, when epinephrine (10(-6) M) and dobutamine were combined, dobutamine reduced cAMP production at concentrations between 10(-6) to 10(-4) M (P = 0.001). In patients, 1.25 to 5 microg x kg(-1) x min(-1) dobutamine increased the cardiac index (CI) 15-28%. Epinephrine also increased the CI with each increase in dose. However, combining epinephrine with the two larger doses of dobutamine (2.5 and 5microg x kg(-1) x mi(-1)) did not increase the CI beyond that achieved with epinephrine and the lowest dose of dobutamine (1.25 microg x kg(-1) x min(-1)). In addition, the isobolographic analysis for equieffective concentrations of dobutamine and epinephrine suggests subadditive effects.

Conclusions
Dobutamine inhibits epinephrine-induced production of cAMP in human lymphocytes and appears to be subadditive by clinical and isobolographic analyses of the cardiotonic effects. These findings suggest that combinations of dobutamine and epinephrine may be less than additive.
Peripheral Analgesic Effects of Ketamine in Acute Inflammatory Pain
Authors: Pedersen Juri L. , Galle Tina S. , Kehlet Henrik 
Published: November 2003

Unlabelled
BACKGROUND. This study examined the analgesic effect of local ketamine infiltration, compared with placebo and systemic ketamine, in a human model of inflammatory pain.

Methods
Inflammatory pain was induced by a burn (at 47 degrees C for 7 min; wound size, 2.5 x 5 cm) on the calf in 15 volunteers on 3 separate days with 7-day intervals. They received either (1) subcutaneous infiltration with ketamine in the burn area (local treatment) and contralateral placebo injections, or (2) subcutaneous ketamine contralateral to the burn (systemic treatment) and placebo in the burn area, or (3) placebo on both sides. The study was double-blinded and the order of the treatments was randomized. Hyperalgesia to mechanical and heat stimuli was examined by von Frey hairs and contact thermodes (3.75 and 12.5 cm2), and pain was rated using a visual analog scale (0-100).

Results
The burns produced significant hyperalgesia. Local ketamine infiltration reduced pain during the burn injury compared with systemic treatment and placebo (P < 0.01). Heat pain thresholds were increased by local ketamine treatment compared with placebo immediately after injection (P < 0.03), and so were the mechanical pain thresholds (P = 0.02). Secondary hyperalgesia and suprathreshold pain responses to heat and mechanical stimuli were not significantly affected by local ketamine. No difference between local ketamine and placebo could be detected 1 h and 2 h after the burn.

Conclusions
Ketamine infiltration had brief local analgesic effects, but several measures of pain and hyperalgesia were unaffected. Therefore, a clinically relevant effect of peripheral ketamine in acute pain seems unlikely.
Flow-induced Dilation of Rat Coronary Microvessels Is Attenuated by Isoflurane but Enhanced by Halothane
Authors: Park Kyung W. , Dai Hai B. , Lowenstein Edward , Sellke Frank W. 
Published: November 2003

Background
Volatile anesthetics attenuate agonist-induced endothelium-dependent vasodilation of coronary arteries. This study considered the hypothesis that the anesthetics may also attenuate flow-induced endothelium-dependent vasodilation.

Methods
Rat subepicardial arteries of approximately 100 microm were monitored for diameter changes in vitro by a video detection system, with the midpoint luminal pressure held constant at 40 mmHg but the pressure gradient (and therefore flow) across each vessel increased from 0 to 80 mmHg, in the presence or absence of 1 or 2 minimum alveolar concentration (MAC) isoflurane or 1 or 2 MAC halothane, with or without 10 microM of the nitric oxide (NO) synthase inhibitor NG-nitro-L-arginine (L-NNA) or 10 microM of the cyclooxygenase inhibitor indomethacin.

Results
Flow-induced dilation was attenuated by L-NNA or indomethacin (p < 0.001 each). It was attenuated by isoflurane in a concentration-dependent manner (P < 0.001). Attenuation by 2 MAC isoflurane persisted even in the presence of L-NNA (P < 0.01) or indomethacin (P < 0.05). On the other hand, flow-induced dilation was enhanced by 2 MAC halothane (P < 0.05). Halothane at 1 MAC had no significant effect. Enhancement by 2 MAC halothane was evident in the presence of indomethacin (P < 0.05) but not L-NNA (P = 0.40).

Conclusions
In rat subepicardial arteries, flow-induced dilation is endothelium-dependent and mediated by both NO and a prostanoid. Isoflurane attenuates flow-induced dilation, possibly by decreasing synthesis, the action of NO and a prostanoid, or both, whereas halothane enhances it, possibly by increasing synthesis, the action of NO, or both.
Anesthetic-induced Alteration of Ca2+Homeostasis in Neural Cells
Authors: Franks John J. , Wamil Artur W. , Janicki Piotr K. , Horn Jean-Louis , Franks William T. , Janson Victoria E. , Vanaman Thomas C. , Brandt Paul C. 
Published: November 2003

Background
Many inhalation anesthetics at clinically relevant concentrations inhibit plasma membrane Ca2+-adenosine triphosphatase (PMCA) ion pumping in brain synaptic membranes and in cultured cells of neural origin. In this study, the authors investigated the effect of inhalation anesthetics on cytosolic calcium homeostasis in cortical neurons maintained at physiologic and room temperatures and on cortical neurons and pheochromocytoma cells with antisense blockade of specific PMCA isoforms.

Methods
Using Ca2+-specific confocal microfluorimetry, the anesthetic effects on Ca2+ dynamics were examined in mouse embryonic cortical neurons in association with ligand-stimulated Ca2+ influx. Studies were done at 21 degrees C and 37 degrees C. Mouse embryonic cortical neurons with oligodeoxyribonucleotide blockade of PMCA2 expression and transfected rat pheochromocytoma cells with blocked expression of PMCA1 were also examined.

Results
Baseline and poststimulation peak cytosolic calcium concentrations ([Ca2+]i) were increased, and Ca2+ clearance was delayed in cells exposed at 37 degrees C, but not at 21 degrees C, to concentrations < or = 1 minimum alveolar concentration (MAC)-equivalent of halothane, isoflurane, and sevoflurane. Neurons exposed to xenon solutions < or = 0.4, 0.6, and 0.8 MAC showed dose-related perturbations of cytosolic Ca2+. Calcium dynamics were altered in neural cells with blocked PMCA isoform production, but at much lower halothane concentrations: 0.5 MAC for cortical neurons and 0.1 MAC for pheochromocytoma cells.

Conclusions
By extruding Ca2+ through the plasma membrane, PMCA maintains resting neuronal [Ca2+]i at low levels and clears physiologic loads of Ca2+ after influx through calcium channels. Inhalation anesthetics perturb this process and thus may interfere with neurotransmitter release, altering interneuronal signaling.
Role of Intracellular Ca2+Stores in the Inhibitory Effect of Halothane on Airway Smooth Muscle Contraction
Authors: Yamakage Michiaki , Kohro Shinji , Matsuzaki Takashi , Tsuchida Hideaki , Namiki Akoyoshi 
Published: November 2003

Background
Halothane directly inhibits contraction of airway smooth muscle, mainly by decreasing the intracellular concentration of free Ca2+ ([Ca2+]i). The role of intracellular Ca2+ stores, sarcoplasmic reticulum, is still unclear. We investigated the role of sarcoplasmic reticulum in the inhibitory effect of halothane on contraction of airway smooth muscle by measuring [Ca2+]i and intracellular concentration of inositol 1,4,5-triphosphate ([IP3]i), a second messenger for release of Ca2+ from sarcoplasmic reticulum.

Methods
[Ca2+]i was monitored by measuring the 500-nm light emission ratio (F340/F380) of a Ca2+ indicator fura-2 with isometric tension of canine tracheal smooth muscle strip. During Ca2+-free conditions, carbachol (10(-5) M) was introduced with pretreatment of halothane (0-3%). During Ca2+-free conditions, 20 mM caffeine, a Ca2+-induced Ca2+ release channel opener, was introduced with or without halothane. We measured [IP3]i during exposure to carbachol and halothane by radioimmunoassay technique.

Results
Pretreatment with halothane significantly diminished carbachol-induced increases in [Ca2+]i by 77% and muscle tension by 83% in a dose-dependent manner. Simultaneous administration of halothane significantly enhanced caffeine-induced transient increases in [Ca2+]i and muscle tension in a dose-dependent manner, by 97% and 69%, respectively. Pretreatment with halothane abolished these responses. Rapid increase in [IP3]i produced by carbachol was significantly inhibited by 32% by halothane in a dose-dependent manner.

Conclusions
Halothane, during Ca2+-free conditions, inhibits transient contraction of airway smooth muscle induced by muscarinic receptor stimulation, mainly by attenuating the increase in [Ca2+]i. Depletion of Ca2+ from sarcoplasmic reticulum via Ca2+-induced Ca2+ release channels also may contribute to the attenuation of the increase in [Ca2+]i by halothane.
Effects of Volatile Anesthetics on Atrial and AV Nodal Electrophysiological Properties in Guinea Pig Isolated Perfused Heart
Authors: Raatikainen Pekka M. J. , Trankina Mark F. , Morey Timothy E. , Dennis Donn M. 
Published: November 2003

Background
Knowledge of the anesthetic effects on atrial and atrioventricular (AV) nodal electrophysiologic properties is fundamental to understand the modulatory role of anesthetics on the pathogenesis of supraventricular tachycardias, and to individualize the perioperative management of patients with supraventricular tachycardias or AV nodal conduction disturbances. Therefore the authors studied the effects of three commonly used volatile anesthetics on the electrophysiologic properties of the atrium and AV node.

Methods
The concentration-dependent electrophysiologic effects of halothane, isoflurane, and desflurane (0-2 minimum alveolar concentration [MAC]) were studied in guinea pig Langendorff-perfused hearts fit with instruments to simultaneously measure atrial and AV nodal conduction times and atrial monophasic action potential duration. Atrial and AV nodal effective refractory periods were measured simultaneously using a computer-assisted premature stimulation protocol. The concentrations of anesthetics in the gas phase were monitored by an infrared gas analyzer.

Results
Volatile anesthetics caused markedly different concentration-dependent effects on atrial conduction, repolarization, and refractoriness, and on AV nodal function. At equianesthetic concentrations, halothane depressed atrial conduction the most, whereas desflurane caused the greatest shortening of atrial monophasic action potential duration. Halothane had no significant effect on atrial refractoriness, whereas at 2 MAC desflurane significantly shortened and isoflurane significantly prolonged atrial effective refractory periods by 18.1+/-13.5% and 13.2+/-14.7%, respectively. On an equi-MAC basis, the rank order of potency for the anesthetics to prolong AV nodal conduction time and AV nodal ERP was halothane > desflurane > isoflurane.

Conclusion
The different electrophysiologic effects of volatile anesthetics in the atrium and AV node suggest that these agents may modulate atrial dysrhythmogenesis in distinctly different ways.
Transmural Pressure of Epidural Veins in the Thoracic and Lumbar Spine of Pigs
Authors: Nystrom Elisabet U. M. , Blomberg Sture G. , Buffington Charles W. 
Published: November 2003

Background
The aim of this study was to determine the transmural pressure gradient of epidural veins located within the spinal column and to investigate the effects of increased intra-abdominal and intrathoracic pressure on this gradient.

Methods
Fourteen pigs were sedated with ketamine and anesthetized with halothane. Ventilation was controlled after tracheotomy. Needles were inserted into the epidural and subarachnoid space, and a catheter was threaded into an epidural vein. Pressures in these structures were measured during controlled and spontaneous ventilation, increased abdominal pressure, and thoracic compression. Measurements were made in both the thoracic and lumbar regions.

Results
The pressure gradient between the epidural vein and the surrounding epidural space was low-11 or 2 mmHg--in both the lumbar and thoracic areas. This gradient was not affected by the mode of ventilation or increased abdominal or thoracic pressure (or both), even though the absolute intramural pressure increased.

Conclusion
The pressure gradient between the epidural vein and the surrounding space is low and does not change when abdominal or thoracic pressures are increased.
Pulmonary Blood Flow Does Not Redistribute in Dogs with Reposition from Supine to Left Lateral Position
Authors: Mure Margareta , Domino Karen B. , Robertson Thomas , Hlastala Michael P. , Glenny Robb W. 
Published: November 2003

Background
Recent studies have questioned the classical gravitational model of pulmonary perfusion. Because the lateral position is commonly used during surgery, the authors studied the redistribution of pulmonary blood flow in the left lateral decubitus position using a high spatial resolution technique.

Methods
Distributions of pulmonary blood flow were measured using intravenously injected 15-microm diameter radioactive-labeled microspheres in eight halothane-anesthetized dogs, which were studied in the supine and left lateral decubitus positions in random order. Lungs flushed free of blood were air-dried at total lung capacity and sectioned into 1,498-2,396 (1.7 cm3) pieces per animal. Radioactivity was measured by a gamma counter, and signals were corrected for piece weight and normalized to mean flow.

Results
Blood flow to the dependent left lung did not increase, and blood flow to the nondependent right lung did not decrease in the lateral position. The left lung received 39.3 +/-7.0% and 39.2+/-8.8% (mean +/- SD) of perfusion in the supine and left lateral positions, respectively. Detailed assessment of the spatial distributions of pulmonary blood flow revealed the lack of a gravitational gradient of blood flow in the lateral position. The distributions of blood flow did not differ in the supine and left lateral decubitus positions.

Conclusions
Perfusion to each lung did not change with movement from the supine to the left lateral position. These findings contradict the prediction of increased dependent lung and decreased nondependent lung blood flow based on the gravitational model. It was concluded that the distribution of blood flow in the lateral position in dogs is dominated by pulmonary vascular structure.
Acute Depression of Myocardial β-Adrenergic Receptor Signaling during Cardiopulmonary Bypass
Authors: Booth John V. , Landolfo Kevin P. , Chesnut Lynn C. , Bennett-Guerrero Elliott , Gerhardt Mark A. , Atwell Darryl M. , El-Moalem Habib E. , Smith Mark Stafford , Funk Bonita L. , Kuhn Cynthia M. , Kwatra Madan M. , Schwinn Debra A. 
Published: November 2003

Background
Previously the authors showed that myocardial beta-adrenergic (betaAR) function is reduced after cardiopulmonary bypass (CPB) in a canine model Whether CPB results in similar effects on betaAR function in adult humans is not known. Therefore the current study tested two hypotheses: (1) That myocardial betaAR signaling is reduced in adult humans after CPB, and (2) that administration of long-term preoperative betaAR antagonists prevents this process.

Methods
After they gave informed consent, 52 patients undergoing aortocoronary surgery were enrolled. Atrial biopsies were obtained before CPB and immediately before discontinuation of CPB. Plasma catecholamine concentrations, myocardial betaAR density, and functional responsiveness (basal, isoproterenol, zinterol, sodium fluoride, and manganese-stimulated adenylyl cyclase activity) were assessed.

Results
Catecholamine levels increased significantly during CPB (P < 0.005). Myocardial betaAR adenylyl cyclase coupling decreased during CPB, as evidenced by a 21% decrease in isoproterenol-stimulated adenylyl cyclase activity (750 [430] pmol cyclic adenosine monophosphate per milligram total protein 15 min before CPB compared with 540 [390] at the end of CPB, P = 0.0062, medians [interquartile range]) despite constant betaAR density. Differential activation along the betaAR signal transduction cascade localized the defect to the adenylyl cyclase moiety. Administration of long-term preoperative betaAR antagonists did not prevent acute CPB-induced myocardial betaAR dysfunction.

Conclusions
These data indicate that the myocardial adenylyl cyclase response to betaAR agonists decreases acutely in adults during aortocoronary surgery requiring CPB, regardless of whether long-term preoperative betaAR antagonists are administered. The mechanism underlying acute betaAR dysfunction appears to be direct impairment of the adenylyl cyclase moiety. Similar increases in manganese-stimulated activity before and at the end of CPB show preserved adenylyl cyclase catalytic activity, suggesting that other mechanisms (such as decreased protein levels or altered isoform expression or function) may be responsible for decreased adenylyl cyclase function.
Paralysis Only Slightly Reduces the Febrile Response to Interleukin-2 during Isoflurane Anesthesia
Authors: Lenhardt Rainer , Negishi Chiharu , Sessler Daniel I. , Ozaki Makoto , Tayefeh Farzin , Kurz Andrea 
Published: November 2003

Background
Fever sometimes occurs during anesthesia. However, it is rare considering how often pyrogenic causes are likely to be present and how common fever is after surgery. This low incidence results in part from dose-dependent inhibition of fever by volatile anesthetics. Paralysis, however, may contribute by preventing shivering and the associated increase in metabolic heat production. Therefore the authors tested the hypothesis that paralysis during anesthesia decreases the febrile response to pyrogen administration.

Methods
Seven volunteers each participated on two study days. They were given 30 IU/g intravenous interleukin-2, followed 90 min later by an additional 70 IU/g dose. Anesthesia was induced 30 min after the second dose and maintained for 6 h with 0.6 minimum alveolar concentration isoflurane. The volunteers were randomly assigned to (1) paralysis with vecuronium or (2) no muscle relaxants. Body heat content and distribution were determined from measured tissue and skin temperatures. Data are presented as mean +/- SD; P < 0.05 was considered significant.

Results
There was no clinically important difference in peak core (tympanic membrane) temperatures on the unparalyzed (37.6+/-0.9 degrees C) and paralyzed (37.2+/-0.6 degrees C) days. Core heat content increased 1.2+/-0.7 kcal/kg over the last 5 h of anesthesia on the unparalyzed day, but only by 0.9+/-0.4 kcal/kg when the volunteers were paralyzed. Peripheral tissue heat content increased 0.1+/-1.1 kcal/kg on the unparalyzed day but decreased 1.1+/-0.7 kcal/kg when the volunteers were paralyzed. Consequently, body heat content increased 1.3+/-1.3 kcal/kg on the unparalyzed day but decreased significantly by 0.2+/-0.8 kcal/kg when the volunteers were paralyzed.

Conclusions
Paralysis prevented shivering from increasing the metabolic rate. Consequently, body heat content decreased during paralysis, whereas otherwise it increased. Thermoregulatory vasoconstriction was nonetheless able to maintain similar peak and integrated core temperatures on each study day. Administration of muscle relaxants thus is not the primary explanation for the relative paucity of intraoperative fever.
Concentration-Response Relationships for Fentanyl and Sufentanil in Patients Undergoing Coronary Artery Bypass Grafting
Authors: Thomson Ian R. , Henderson Blair T. , Singh Karanbir , Hudson Robert J. 
Published: November 2003

Background
Concentration-response relationships for sufentanil and fentanyl are undefined in patients undergoing coronary artery bypass grafting.

Methods
Separate studies of sufentanil and fentanyl were performed in lorazepam-premedicated patients undergoing coronary artery bypass grafting. Patients were assigned randomly to groups with different prebypass effect-site opioid concentrations targeted by computer-assisted infusion. The target sufentanil concentrations were 0.4 ng/ml (group LS, n = 11), 0.8 ng/ml (group MS, n = 10), and 1.2 ng/ml (group HS, n = 11); the target fentanyl concentrations were 5 ng/ml (group LF, n = 7), 10 ng/ml (group MF, n = 7), and 15 ng/ml (group HF, n = 6). Propofol at a dose of 1 mg/kg was administered at induction of anesthesia and isoflurane was used for hemodynamic control Hemodynamics, end-tidal isoflurane concentration, and opioid concentration in arterial blood were measured at specific intervals.

Results
Intraoperative opioid concentrations were constant, averaging 0.71 +/- 0.13, 1.25 +/- 0.21, and 2.03 +/- 0.46 ng/ml for groups LS, MS, and HS, respectively, and 7.3 +/- 1.1, 13.2 +/- 2.2, and 24.4 +/- 5.8 ng/ml for groups LF, MF, and HF, respectively (all mean +/- SD). Isoflurane requirements were significantly greater in group LS than in groups MS and HS and greater in group LF than in groups MF and HF. The serum opioid and end-tidal isoflurane concentrations were correlated significantly. There were no intergroup differences in hemodynamics.

Conclusions
Serum sufentanil and fentanyl concentrations of 0.71 +/- 0.13 ng/ml and 7.3 +/- 1.3 ng/ml, respectively, are on the steep parts of the concentration-response relationships and facilitate prebypass hemodynamic control in patients undergoing coronary artery bypass grafting with opioid-isoflurane anesthesia. Concentrations of sufentanil > or = 1.25 +/- 0.21 ng/ml and of fentanyl > or = 13.3 +/- 2.2 ng/ml minimize isoflurane requirements but do not improve hemodynamic control.