bluuebunny/crossref_metadata_2025 huggingface dataset:
Sources of Error in Noninvasive Pulmonary Blood Flow Measurements by Partial Rebreathing
Authors: Yem Johnny S. , Tang Yongquan , Turner Martin J. , Baker A. Barry
Published: November 2003

Background

Partial rebreathing is a noninvasive method for measuring pulmonary blood flow (PBF). This study examines the systematic errors produced by the partial rebreathing technique utilizing a comprehensive mathematical model of the cardiorespiratory system of a healthy, 70-kg adult male.

Methods

The model simulates tidal breathing through a branched respiratory tree and incorporates the effects on carbon dioxide dynamics of lung tissue mass, vascular transport delays, multiple body compartments, and realistic blood-gas dissociation curves. Four studies were performed: (1) errors produced under standard conditions, (2) effects of recirculation, (3) effects of alveolar-proximal airway partial pressure of carbon dioxide (Pco(2)) differences, and (4) effects of rebreathing time.

Results

Systematic errors are less than 10% when the simulated PBF is between 3 and 6 l/min. At 2 l/min, PBF is overestimated by approximately 35%. At 14 l/min, PBF is underestimated by approximately 40%. At PBF of greater than 6 l/min, recirculation causes approximately 60% of the systematic error, alveolar-proximal airway differences cause approximately 20%, and alveolar-arterial differences cause approximately 20%. The standard rebreathing time of 50 s is shown to be excessive for PBF of greater than 6 l/min. At PBF of less than 3 l/min, errors are caused by inadequate rebreathing time and alveolar-arterial gradients.

Conclusions

Systematic errors in partial rebreathing cardiac output measurements have multiple causes. Our simulations suggest that errors can be reduced by using a variable rebreathing time, which should be increased at low PBF so that quasi-equilibrium in the alveoli can be achieved and decreased at high PBF to reduce the effects of recirculation.
Deactivation of Norepinephrine by Peroxynitrite as a New Pathogenesis in the Hypotension of Septic Shock
Authors: Takakura Ko , Xiaohong Wen , Takeuchi Kenji , Yasuda Yoshikazu , Fukuda Satoru
Published: November 2003

Background

Vascular hyporeactivity to catecholamines limits successful treatment of hypotension in septic shock. Large amounts of nitric oxide (NO) and superoxide anion (O(2)(-1).) are produced in response to bacterial endotoxins and/or inflammatory cytokines. NO reacts with O(2)(-1). to form the potentially toxic NO metabolite, peroxynitrite (ONOO(-1)). The purpose of this study was to investigate whether ONOO(-1) decreases the vasocontractile activity of norepinephrine.

Methods

Norepinephrine was treated with ONOO(-1) or 3-morpholinosydonimine-N-ethyl-carbamine (SIN-1; an ONOO(-1) producer) in a 5 x 10(-2) m sodium phosphate buffer solution at pH 7.4, and absorbance of the product was measured spectrophotometrically at 295 and 370 nm. Norepinephrine pretreated with ONOO(-1) was administered to isolated rat thoracic aortas to observe contractions in functional experiments. The rate constant between norepinephrine and ONOO(-1) was determined via a competition assay with cysteine in functional experiments. Norepinephrine pretreated with ONOO(-1) was injected intravenously into anesthetized rats to measure blood pressure.

Results

Norepinephrine pretreated with ONOO(-1) was confirmed spectrally as oxidized norepinephrine. Norepinephrine pretreated with ONOO(-1) decreased its vasocontractile force in an ONOO(-1) (10(-6), up to 3 x 10(-4) m) concentration-dependent manner (EC(50) = 5.1 x 10(-5) m). The decrease in its force was lower at pretreatment with ONOO(-1) in a lower pH buffer. A rate constant for the ONOO(-1)-norepinephrine reaction was 6 x 10(2) m/s. Norepinephrine (10(-7) m) incubated with SIN-1 (10(-3) m) decreased its vasocontractile force in an incubation time-dependent manner. Administration of norepinephrine pretreated with ONOO(-1) to anesthetized rats caused no significant change in arterial blood pressure.

Conclusions

These results indicate that norepinephrine was oxidized and deactivated by ONOO(-1). This deactivation may, at least in part, account for the hyporeactivities of vasocontraction to norepinephrine in septic shock.
In Vitro and In Vivo Effects of the Phosphodiesterase-III Inhibitor Enoximone on Malignant Hyperthermia–susceptible Swine
Authors: Fiege Marko , Wappler Frank , Weisshorn Ralf , Gerbershagen Mark U. , Kolodzie Kerstin , Schulte am Esch Jochen
Published: November 2003

Background

In human skeletal muscles, the phosphodiesterase-III inhibitor enoximone induces in vitro contracture development, and it has been suggested that enoximone could trigger malignant hyperthermia (MH). In this study, the in vitro and in vivo effects of enoximone in MH-normal (MHN) and MH-susceptible (MHS) swine were investigated.

Methods

Malignant hyperthermia trigger-free general anesthesia was performed in MHS and MHN swine. Skeletal muscle specimens were excised for an in vitro contracture test with 0.6 mm enoximone. Thereafter, MHS and MHN swine were exposed to cumulative administration of 0.5, 1, 2, 4, 8, 16, and 32 mg/kg enoximone intravenously. Clinical occurrence of MH was defined by a Pco(2) greater than 70 mmHg, a pH less than 7.20, and an increase in body temperature of more than 2.0 degrees C.

Results

Enoximone induced marked contractures in all MHS muscle specimens in vitro. In contrast, only small or no contracture development was observed in MHN muscle specimens, without an overlap in contractures between MHS and MHN muscles. However, in vivo, no clinical differences were found between MHS and MHN swine following cumulative enoximone doses. According to the defined criteria, none of the swine developed MH during the experiment. Furthermore, high enoximone doses induced progressive circulatory insufficiency, and after receiving 32 mg/kg enoximone, all animals died of cardiovascular failure.

Conclusions

The cumulative enoximone doses used in this study were 30- to 50-fold higher than therapeutic doses in humans. Enoximone does not trigger MH in genetically determined swine. However, enoximone might be useful for in vitro diagnosis of MH.
Laryngeal Morbidity and Quality of Tracheal Intubation
Authors: Mencke Thomas , Echternach Mathias , Kleinschmidt Stefan , Lux Philip , Barth Volker , Plinkert Peter K. , Fuchs-Buder Thomas
Published: November 2003

Background

Vocal cord sequelae and postoperative hoarseness during general anesthesia are a significant source of morbidity for patients and a source of liability for anesthesiologists. Several risk factors leading to laryngeal injury have been identified in the past. However, whether the quality of tracheal intubation affects their incidence or severity is still unclear.

Methods

Eighty patients were randomized in two groups (n = 40 for each) to receive a propofol-fentanyl induction regimen with or without atracurium. Intubation conditions were evaluated with the Copenhagen Score; postoperative hoarseness was assessed at 24, 48, and 72 h by a standardized interview; and vocal cords were examined by stroboscopy before and 24 and 72 h after surgery. If postoperative hoarseness or vocal cord sequelae persisted, follow-up examination was performed until complete restitution.

Results

Without atracurium, postoperative hoarseness occurred more often (16 vs. 6 patients; P = 0.02). The number of days with postoperative hoarseness was higher when atracurium was omitted (25 vs. 6 patients; P < 0.001). Similar findings were observed for vocal cord sequelae (incidence of vocal cord sequelae: 15 vs. 3 patients, respectively, P = 0.002; days with vocal cord sequelae: 50 vs. 5 patients, respectively, P < 0.001). Excellent intubating conditions were less frequently associated with postoperative hoarseness compared to good or poor conditions (11, 29, and 57% of patients, respectively; excellent vs. poor: P = 0.008). Similar findings were observed for vocal cord sequelae (11, 22, and 50% of patients, respectively; excellent vs. poor: P = 0.02).

Conclusions

The quality of tracheal intubation contributes to laryngeal morbidity, and excellent conditions are less frequently associated with postoperative hoarseness and vocal cord sequelae. Adding atracurium to a propofol-fentanyl induction regimen significantly improved the quality of tracheal intubation and decreased postoperative hoarseness and vocal cord sequelae.
Potentiation of Mivacurium Blockade by Low Dose of Pancuronium
Authors: Motamed Cyrus , Menad Riad , Farinotti Robert , Kirov Krassen , Combes Xavier , Bouleau Daniel , Feiss Pierre , Duvaldestin Philippe
Published: November 2003

Background

Mivacurium is potentiated by pancuronium to a much greater extent than other relaxants. In a previous investigation we suggested that this potentiation could be due to the ability of pancuronium to inhibit plasma cholinesterase activity, but we did not measure plasma concentrations of mivacurium. In the current study we performed a pharmacokinetic analysis by measuring the plasma concentration of mivacurium when preceded by administration of a low dose of pancuronium.

Methods

After induction of general anesthesia with propofol and fentanyl and orotracheal intubation, 10 patients (pancuronium-mivacurium group) received 15 microg/kg pancuronium followed 3 min later by 0.1 mg/kg mivacurium, whereas 10 other patients (mivacurium group) received saline followed by 0.13 mg/kg mivacurium 3 min later. Plasma cholinesterase activity was measured before and 3 and 30 min after pancuronium dosing in the pancuronium-mivacurium group and was measured before and after administration of saline in the mivacurium group. Arterial plasma concentrations of mivacurium and its metabolites were measured at 0.5, 1, 1.5, 2, 4, 10, 20, and 30 min after injection. Neuromuscular blockade was assessed by mechanomyography.

Results

Plasma cholinesterase activity decreased by 26% in the pancuronium-mivacurium group 3 min after injection of pancuronium (P < 0.01) and returned to baseline values 30 min later; however, no significant variation was observed in the mivacurium group. The clearances of the two most active isomers (Cis-Trans and Trans-Trans) were lower in the pancuronium-mivacurium group (17.6 +/- 5.1, 14.7 +/- 5.3 ml. min-1. kg-1, respectively) than in the mivacurium group (32.4 +/- 20.2, 24.8 +/- 13.5 ml. min-1. kg-1; P < 0.05).

Conclusions

A subparalyzing dose of pancuronium decreased plasma cholinesterase activity and the clearance of the two most active isomers of mivacurium. Pancuronium potentiates mivacurium more than other neuromuscular blocking agents because, in addition to its occupancy of postsynaptic acetylcholine receptors, it slows down the hydrolysis of mivacurium.
Biphasic Shocks Compared with Monophasic Damped Sine Wave Shocks for Direct Ventricular Defibrillation during Open Heart Surgery
Authors: Schwarz Birgit , Bowdle T. Andrew , Jett G. Kimble , Mair Peter , Lindner Karl H. , Aldea Gabriel S. , Lazzara Robert G. , O'Grady Sharon G. , Schmitt Paul W. , Walker Robert G. , Chapman Fred W. , Tacker Willis A.
Published: November 2003

Background

Biphasic waveform shocks are more effective than monophasic shocks for transchest ventricular defibrillation, atrial cardioversion, and defibrillation with implantable defibrillators but have not been studied for open chest, intraoperative defibrillation. This prospective, blinded, randomized clinical study compares biphasic and monophasic shock effectiveness and establishes intraoperative energy dose-response curves.

Methods

Patients undergoing cardiothoracic surgery with bypass cardioplegia were randomly assigned to the monophasic or biphasic shock group. Ventricular fibrillation occurring after aortic clamp removal was treated with escalating energies of 2, 5, 7, 10, and 20 J until defibrillation occurred. If ventricular fibrillation persisted, a 20-J crossover shock of the other waveform was used.

Results

Cumulative defibrillation success at 5 J, the primary end point of the study, was higher in the biphasic group than in the monophasic group (25 of 50 vs. 9 of 41 defibrillated; P = 0.011). In addition, the biphasic group required lower threshold energy (6.8 vs. 11.0 J; P = 0.003), less cumulative energy (12.6 vs. 23.4 J; P = 0.002), and fewer shocks (2.5 vs. 3.5; P = 0.002). Crossover-shock effectiveness did not differ between groups. Dose-response curves show biphasic shocks to have higher cumulative success rates at all energies tested.

Conclusions

Biphasic shocks are substantially more effective than monophasic shocks for direct defibrillation. The dose-response curve guides selection of first-shock energy for traditional step-up protocols. Starting at 5 J optimizes for lowest threshold and cumulative energy, whereas 10 or 20 J optimizes for more rapid defibrillation and fewer shocks.
Echocardiographic Doppler Assessment of Pulmonary Capillary Wedge Pressure in Surgical Patients with Postoperative Circulatory Shock and Acute Lung Injury
Authors: Bouhemad Bélaïd , Nicolas-Robin Armelle , Benois Alain , Lemaire Sacha , Goarin Jean-Pierre , Rouby Jean-Jacques
Published: November 2003

Background

In cardiac patients, pulmonary capillary wedge pressure (PCWP) is estimated using color M-mode Doppler study of left ventricular filling and Doppler tissue imaging. The goal of this study was to assess whether echocardiography accurately estimates PCWP in critically ill patients.

Methods

Sixty ventilated patients admitted for septic shock and acute lung injury were prospectively studied using simultaneously transesophageal echocardiography and pulmonary artery catheterization. Initial PCWP values and their changes measured invasively were compared to initial values and corresponding changes of early diastolic velocity of mitral annulus displacement measured by Doppler tissue imaging (Ea), flow propagation velocity of early diastolic mitral inflow measured by color M-mode Doppler (Vp), and their respective ratio to early mitral inflow velocity (E) measured by conventional Doppler: E/Ea and E/Vp. Relations between E/Ea, E/Vp, and PCWP were prospectively tested in 20 additional patients.

Results

E/Ea and E/Vp gave a rough estimate of initial PCWP values with mean biases of 0.4 +/- 2.2 and 0.1 +/- 2.9 mmHg, respectively. Receiving operating characteristic curves demonstrated that an E/Ea of 6 or greater is an accurate predictor of a PCWP of 13 mmHg or greater and that an E/Ea of 5.4 is a good predictor of a PCWP of 8 mmHg or less. Changes in PCWP were significantly correlated to changes in E/Ea (Rho = 0.84, P < 0.0001).

Conclusions

In patients with postoperative circulatory shock and acute lung injury, transesophageal echocardiography estimates noninvasively PCWP. However, echocardiographic estimation of PCWP may not be accurate enough for adjusting therapy.
Apoptotic Neuronal Death following Deep Hypothermic Circulatory Arrest in Piglets
Authors: Ditsworth Dara , Priestley Margaret A. , Loepke Andreas W. , Ramamoorthy Chandra , McCann John , Staple Lauren , Kurth C. Dean
Published: November 2003

Background

Deep hypothermic circulatory arrest (DHCA), as used in infant heart surgery, carries a risk of brain injury. In a piglet DHCA model, neocortical neurons appear to undergo apoptotic death. Caspases, cytochrome c, tumor necrosis factor (TNF), and Fas play a role in apoptosis in many ischemic models. This study examined the expression of these factors in a DHCA piglet model.

Methods

Thirty-nine anesthetized piglets were studied. After cardiopulmonary bypass (CPB) cooling of the brain temperature to 19 degrees C, DHCA was induced for 90 min, followed by CPB rewarming. After separation from CPB, piglets were killed at 1, 4, 8, 24, and 72 h and 1 week. Caspase-8 and -3 activity, and concentrations of TNF-alpha, Fas, Fas-ligand, cytochrome c, and adenosine triphosphate (ATP) were measured in the neocortex by enzymatic assay and Western blot analysis. Caspase-8 and -3 activity and cell death were examined histologically. Significance was set at P < 0.05.

Results

In neocortex, damaged neurons were not observed in control (no CPB), rarely observed in CPB (no DHCA), and rarely observed in the DHCA 1-h, 4-h, and 1-week reperfusion groups. However, they were seen frequently in the DHCA 8-, 24-, and 72-h reperfusion groups. Although neuronal death was widespread 8-72 h after DHCA, cortical ATP concentrations remained unchanged from control. Both caspase-3 and -8 activities were significantly increased at 8 h after DHCA, and caspase-3 concentration remained elevated for as long as 72 h. Caspase-3 and -8 activity was also observed in damaged neocortical neurons. Cytosolic cytochrome c and Fas were significantly expressed at 1 h and 4 h after DHCA, respectively. Fas-ligand and TNF-alpha were not observed in any group.

Conclusion

After DHCA, induction of apoptosis in the neocortex occurs within a few hours of reperfusion and continues for several days. Increased Fas, cytochrome c, and caspase concentrations, coupled with normal brain ATP concentrations and apoptotic histologic appearance, are consistent with the occurrence of apoptotic cell death.
Local Anesthetics Modulate Neuronal Calcium Signaling through Multiple Sites of Action
Authors: Xu Fang , Garavito-Aguilar Zayra , Recio-Pinto Esperanza , Zhang Jin , J. Blanck Thomas J.
Published: November 2003

Background

Local anesthetics (LAs) are known to inhibit voltage-dependent Na+ channels, as well as K+ and Ca2+ channels, but with lower potency. Since cellular excitability and responsiveness are largely determined by intracellular Ca2+ availability, sites along the Ca2+ signaling pathways may be targets of LAs. This study was aimed to investigate the LA effects on depolarization and receptor-mediated intracellular Ca2+ changes and to examine the role of Na+ and K+ channels in such functional responses.

Methods

Effects of bupivacaine, ropivacaine, mepivacaine, and lidocaine (0.1-2.3 mm) on evoked [Ca2+](i) transients were investigated in neuronal SH-SY5Y cell suspensions using Fura-2 as the intracellular Ca2+ indicator. Potassium chloride (KCl, 100 mm) and carbachol (1 mm) were individually or sequentially applied to evoke increases in intracellular Ca2+. Coapplication of LA and Na+/K+ channel blockers was used to evaluate the role of Na+ and K+ channels in the LA effect on the evoked [Ca2+](i) transients.

Results

All four LAs concentration-dependently inhibited both KCl- and carbachol-evoked [Ca2+](i) transients with the potency order bupivacaine > ropivacaine > lidocaine >/= mepivacaine. The carbachol-evoked [Ca2+](i) transients were more sensitive to LAs without than with a KCl prestimulation, whereas the LA-effect on the KCl-evoked [Ca2+](i) transients was not uniformly affected by a carbachol prestimulation. Na+ channel blockade did not alter the evoked [Ca2+](i) transients with or without a LA. In the absence of LA, K+ channel blockade increased the KCl-, but decreased the carbachol-evoked [Ca2+](i) transients. A coapplication of LA and K+ channel blocker resulted in larger inhibition of both KCl- and carbachol-evoked [Ca2+](i) transients than by LA alone.

Conclusions

Different and overlapping sites of action of LAs are involved in inhibiting the KCl- and carbachol-evoked [Ca2+](i) transients, including voltage-dependent Ca2+ channels, a site associated with the caffeine-sensitive Ca2+ store and a possible site associated with the IP(3)-sensitive Ca2+ store, and a site in the muscarinic pathway. K+ channels, but not Na+ channels, seem to modulate the evoked [Ca2+](i) transients, as well as the LA-effects on such responses.
Anesthetic Preconditioning Improves Adenosine Triphosphate Synthesis and Reduces Reactive Oxygen Species Formation in Mitochondria after Ischemia by a Redox Dependent Mechanism
Authors: Novalija Enis , Kevin Leo G. , Eells Janis T. , Henry Michele M. , Stowe David F.
Published: November 2003

Background

Mitochondrial changes that characterize the heart after anesthetic preconditioning (APC) or the mechanisms by which mitochondrial triggering factors lead to protection are unknown. This study hypothesized that generation of reactive oxygen species (ROS) during APC is required to initiate the mitochondrial protective effects, and that APC leads to improved mitochondrial electron transport chain function and cardiac function during reperfusion.

Methods

Isolated guinea pig hearts were subject to 30 min ischemia and 120 min reperfusion. Prior to ischemia hearts were either untreated (I/R), or treated with sevoflurane (APC), in the presence or absence of the ROS scavenger tiron (TIR), or the superoxide dismutase mimetic MnTBAP (TBAP). Intracellular ROS were measured by spectrofluorometry using the fluorescent probe dihydroethidium (DHE). In another series of experiments, using the same protocol, hearts were reperfused for only 5 min and removed for measurement of adenosine triphosphate (ATP) synthesis by luciferin-luciferase luminometry and ROS generation by dichlorohydro-fluorescein (DCF) fluorescence in isolated mitochondria.

Results

The APC improved cardiac function and reduced infarction. Tiron or MnTBAP abrogated the protection afforded by APC. Mitochondrial ATP synthesis was decreased by 70 +/- 3% after IR alone, by only 7 +/- 3% after APC, by 69 +/- 2% after APC+TIR, and by 71 +/- 3% after APC + TBAP. Mitochondrial ROS formation (DCF) increased by 48 +/- 3% after IR alone, by 0 +/- 2% after APC, by 43 +/- 4% after APC + TIR, and by 46 +/- 3% after APC + TBAP. ROS generation (DHE) was increased in I/R group at 5 and 120 min reperfusion. This was attenuated by APC but this protective effect was abrogated in APC + TIR and APC + TBAP groups.

Conclusions

The results indicate that ROS are central both in triggering and mediating APC, and that the mitochondrion is the target for these changes.
Role of Endothelium-derived Hyperpolarizing Factor in Phenylephrine-induced Oscillatory Vasomotion in Rat Small Mesenteric Artery
Authors: Okazaki Kayoko , Seki Sumihiko , Kanaya Noriaki , Hattori Jun-ichi , Tohse Noritsugu , Namiki Akiyoshi
Published: November 2003

Background

In small mesenteric arteries, endothelium-derived hyperpolarizing factor (EDHF) in addition to endothelium-derived relaxing factors (EDRFs) including NO plays an important role in acetylcholine-induced vasodilation. It has been reported that EDRFs play an important role in alpha(1)-adrenoceptor agonist-induced oscillatory vasomotion and in limiting vasoconstrictor response to the agonists; however, contribution of EDHF to the alpha(1)-agonist-induced oscillation is unknown.

Methods

Rat small mesenteric arteries were isolated and cannulated at each end with a glass micropipette. The vessels were immersed in a bath (37 degrees C) containing physiologic saline solution. Changes in vessel diameter were measured using an optical density video detection system.

Results

Denudation of the endothelium and inhibition of NO synthesis caused a leftward shift in the concentration-response relation for phenylephrine in the mesenteric arteries, whereas inhibition of cyclooxygenase by indomethacin had no effect. Blockade of Ca2+-activated K+ (K(Ca)) channels by charybdotoxin and apamin caused a further leftward shift in the concentration-response relation in the vessels pretreated with Nomega-nitro-l-arginine methylester and indomethacin. Phenylephrine at concentrations higher than 10(-6) m caused endothelium-dependent oscillatory vasomotion, which was reduced but not abolished after combined inhibition of the cyclooxygenase and NO synthase pathways. However, the K(Ca) channel blockers completely abolished the remaining component of oscillation.

Conclusions

Endothelially-derived NO is an important modulator of sustained agonist-induced vasoconstriction. NO, as well as endothelially-derived cyclooxygenase products and EDHF, also contribute significantly to phenylephrine-induced oscillatory vasomotion.
Direct Myocardial Depressant Effect of Methylmethacrylate Monomer
Authors: Kim Ki Jun , Chen Da Guang , Chung Namsik , Lynch Carl , Park Wyun Kon
Published: November 2003

Background

The present study explored the mechanism of direct myocardial depression by methylmethacrylate monomer (MMA).

Methods

Isometric contraction of isolated guinea pig right ventricular papillary muscle was measured in modified normal and 26 mm K+ Tyrode solutions at various stimulation rates. Normal and slow action potentials were evaluated by conventional microelectrode technique. MMA effects on various aspects of sarcoplasmic reticulum function were evaluated by its effect on rapid-cooling contractures, rested-state contraction in rat papillary muscle in modified normal Tyrode solution, and in guinea pig papillary muscle under low Na+ (25 mm) Tyrode solution. Whole cell patch clamp techniques were applied to measure the inward Ca2+ currents (I(Ca)).

Results

MMA (0.5, 1.5, and 4.7 mm) caused concentration-dependent depression of peak force and maximal rate of force development to approximately 70, 50, and 20% of baseline from rested state to 3 Hz stimulation rates, respectively. Depression of peak force and maximal rate of force development by MMA was dependent on stimulation frequency, with less depression at higher stimulation rates. In low Na+ Tyrode solution, 1.5 mm MMA depressed peak force of rat and guinea pig myocardium by 20-30%. In 26 mm K+ Tyrode solution, 0.5 and 1.5 mm MMA caused selective and marked concentration-dependent depression of late force development (0.5 mm: approximately 60% of baseline, 1.5 mm: approximately 30% of baseline) with no alteration in early force development. MMA (1.5 mm) depressed rapid-cooling contracture to 53 +/- 10% of baseline, accompanied by approximately 63% prolongation of time to peak contracture. In patch clamp studies, MMA reduced I(Ca) in a concentration-dependent manner.

Conclusions

The direct myocardial depressant effect of MMA seems to be caused in part by depression of Ca2+ influx through cardiac membrane, while depolarization-activated sarcoplasmic reticulum Ca2+ release appears modestly depressed.
Femoral-Sciatic Nerve Blocks for Complex Outpatient Knee Surgery Are Associated with Less Postoperative Pain Before Same-day Discharge
Authors: Williams Brian A. , Kentor Michael L. , Vogt Molly T. , Williams John P. , Chelly Jacques E. , Valalik Stacey , Harner Christopher D. , Fu Freddie H.
Published: November 2003

Background

Outpatient knee surgery has come to involve increasingly complex procedures. The authors present observational data from a nerve block algorithm designed for the care of outpatients undergoing knee surgery. The aim of this report is to demonstrate differences in pain and unplanned hospital admission associated with surgical complexity and nerve blocks used.

Methods

Day-of-surgery outcomes were studied for 1,200 consecutive outpatients undergoing routine arthroscopy or one of six complex outpatient knee procedures. Nerve blocks were administered on the basis of anticipated pain from open incisions in the femoral and sciatic nerve distributions. Regression analysis was used to determine factors associated with postoperative pain and unplanned hospital admissions, and patients were categorized as having received femoral and sciatic nerve blocks (FSB), femoral nerve block only (FNB), or no nerve blocks.

Results

Patients undergoing more complex (vs. less invasive) knee surgery were at greater risk for pain (P </= 0.004), whereas the use of FSB (vs. FNB or no block) was associated with less pain (P < 0.01). When no nerve blocks were used, more complex (vs. less invasive) knee surgery was associated with a 10-fold greater risk of hospital admission (P = 0.001). In the regression analyses, more complex surgery (P < 0.001) was associated with increased risk of admission, and the use of FNB or FSB (vs. no block) was associated with a 2.5-fold reduction in unplanned admissions (P = 0.009).

Conclusions

For complex knee surgery, the use of FSB was associated with less pain; the use of FNB or FSB (vs. no block) was associated with fewer hospital admissions.
Quantitative Sensory Testing and Human Surgery
Authors: Wilder-Smith Oliver H. G. , Tassonyi Edömer , Crul Ben J. P. , Arendt-Nielsen Lars
Published: November 2003

Background

Altered central nervous system sensory processing (neuroplasticity) is a basic mechanism underlying postoperative pain that can be made visible using quantitative sensory testing. Using quantitative sensory testing, the authors investigated how perioperative analgesia affects postoperative neuroplasticity and how this relates to clinical pain measures.

Methods

Patients undergoing back surgery received placebo, fentanyl, or ketorolac (n = 15 per group) before isoflurane-nitrous oxide anesthesia. Preoperatively to 5 days postoperatively, we measured thresholds to electrical skin stimulation at the incision site, arm, and leg; pain scores; and morphine patient-controlled analgesia consumption.

Results

Decreased pain thresholds versus preoperatively were seen 5 days postoperatively, with decreases greater for ketorolac (-63%; P = 0.00005 vs. preoperatively) than placebo (-45%; P = 0.008 vs. preoperatively) but nonsignificant for fentanyl (-36%; P = 0.9 vs. preoperatively). Mainly nonnociceptive thresholds were increased up to 24 h postoperatively. Postoperative clinical pain measures were similar across drug groups. Postoperative pain tolerance threshold changes did not correlate with preoperative clinical pain measures but were inversely related to preoperative thresholds for placebo and ketorolac but not fentanyl.

Conclusions

Without analgesia, neuroplasticity after surgery was inhibitory the first 24 h and followed at 5 days by excitation. Fentanyl efficiently preempted this hyperalgesia, but hyperalgesia was greater with ketorolac than with placebo. Clinical pain measures neither reflected the different effects of ketorolac and fentanyl on postoperative neuroplasticity nor permitted prediction of postoperative neuroplasticity. The information obtained by perioperative quantitative sensory testing is separate from and additional to that from clinical pain measures and may enable more mechanism-based approaches to surgical analgesia management in the future.
Supraspinal Contribution to Development of Both Tonic Nociception and Referred Mirror Hyperalgesia
Authors: Chen Hui-Sheng , Li Meng-Meng , Shi Juan , Chen Jun
Published: November 2003

Background

The roles of descending facilitatory pathway from the rostral medial medulla (RMM) in development of persistent spontaneous nociception and hyperalgesia were evaluated in the bee venom (BV) test and the formalin test.

Methods

Bilateral lesions of the RMM with ibotenic acid, a soma-selective neurotoxin, were performed to study their effects on the spontaneous pain-related behaviors and hyperalgesia, which were determined by counting the number of flinching reflex per 5 min (1 h) and by measuring paw withdrawal thermal latency (PWTL) and mechanical threshold (PWMT) to radiant heat and von-Frey filaments to both hind paws in conscious rats, respectively.

Results

1) Bilateral lesions of the RMM produced a similarly significant inhibition of persistent spontaneous flinching reflexes in the BV test and the formalin test; however, the inhibitory effect occurred in the late 50 min (11-60 min), but not the first 10 min (0-10 min) following intraplantar injection of either BV or formalin. 2) Bilateral lesions of the RMM prevented the development of the BV-induced referred mirror heat hyperalgesia occurred in the noninjected paw, but had no effect on the primary heat and mechanical hyperalgesia occurred in the injected paw.

Conclusions

The present results provide a new line of behavioral evidence that tonic activation of descending facilitatory pathway contributes to the establishment of 1) the BV and formalin-induced persistent spontaneous nociception; and 2) the BV-induced referred mirror heat hyperalgesia and the central sensitization, but not the primary heat and mechanical hyperalgesia.
Spinal Adrenergic and Cholinergic Receptor Interactions Activated by Clonidine in Postincisional Pain
Authors: Duflo Frédéric , Conklin Dawn , Li Xinhui , Eisenach James C.
Published: November 2003

Background

Previous pharmacologic and molecular studies suggest that the alpha(2)-adrenoceptor subtype A is the target for spinally administered alpha(2)-adrenergic agonists, i.e., clonidine, for pain relief. However, intrathecally administered alpha(2) C antisense oligodeoxynucleotide was recently reported to decrease antinociception induced by clonidine in the rat, suggesting non-A sites may be important as well. The current study sought to determine the subtype of alpha(2) adrenoceptors activated by clonidine in a rodent model for human postoperative pain, and to examine its interaction with spinal cholinergic receptors.

Methods

Postoperative hypersensitivity was produced in rats by plantar incision of the hind paw and punctuate mechanical stimuli were applied around the wound 24 h after surgery. Effects of intrathecal clonidine and 2-(2,6-diethylphenylamino)-2-imidazoline (ST91) on withdrawal thresholds to the stimulus were determined. To examine the adrenoceptor subtype and its interaction with spinal cholinergic receptors, animals were intrathecally pretreated with vehicles BRL44408 (an alpha(2) A subtype-preferring antagonist), ARC239 (an alpha(2) non-A subtype-preferring antagonist), atropine (a muscarinic antagonist), and mecamylamine (a nicotinic antagonist).

Results

Intrathecal ST91 showed a significantly greater efficacy when compared with clonidine. The analgesic effect of clonidine was diminished by pretreatment with either adrenoceptor antagonist, whereas the effect of ST91 was solely blocked by ARC239 pretreatment. Atropine and mecamylamine abolished the effect of clonidine effect but not the effect of ST91.

Conclusions

Both alpha(2) A and alpha(2) non-A adrenoceptors, as well as spinal cholinergic activation, are important to the antihypersensitivity effect of clonidine after surgery. ST91 is more efficacious in this model than clonidine and relies entirely on alpha(2) non-A adrenoceptors.
Operating Room Utilization Alone Is Not an Accurate Metric for the Allocation of Operating Room Block Time to Individual Surgeons with Low Caseloads
Authors: Raja Srinivasa N. , Dexter Franklin , Macario Alex , Traub Rodney D. , Lubarsky David A.
Published: November 2003

Introduction

Many surgical suites allocate operating room (OR) block time to individual surgeons. If block time is allocated to services/groups and yet the same surgeon invariably operates on the same weekday, for all practical purposes block time is being allocated to individual surgeons. Organizational conflict occurs when a surgeon with a relatively low OR utilization has his or her allocated block time reduced. The authors studied potential limitations affecting whether a facility can accurately estimate the average block time utilizations of individual surgeons performing low volumes of cases.

Methods

Discrete-event computer simulation.

Results

Neither 3 months nor 1 yr of historical data were enough to be able to identify surgeons who had persistently low average OR utilizations. For example, with 3 months of data, the widths of the 95% CIs for average OR utilization exceeded 10% for surgeons who had average raw utilizations of 83% or less. If during a 3-month period a surgeon's measured adjusted utilization is 65%, there is a 95% chance that the surgeon's average adjusted utilization is as low as 38% or as high as 83%. If two surgeons have measured adjusted utilizations of 65% and 80%, respectively, there is a 16% chance that they have the same average adjusted utilization. Average OR utilization can be estimated more precisely for surgeons performing more cases each week.

Conclusions

Average OR utilization probably cannot be estimated precisely for low-volume surgeons based on 3 months or 1 yr of historical OR utilization data. The authors recommend that at surgical suites trying to allocate OR time to individual low-volume surgeons, OR allocations be based on criteria other than only OR utilization (e.g., based on OR efficiency).
Criteria of Adequate Clinical Recovery from Neuromuscular Block
Authors: Raja Srinivasa N. , Ali Hassan H.
Published: November 2003

This study was undertaken to compare the sensitivities of the train-of-four response (2 Hz for 2 s), the single twitch (0.15 Hz), and the tetanic response (50 Hz for 5 s) as indices of residual nondepolarizing block. Spontaneous or induced recovery of evoked thumb adduction in response to ulnar nerve stimulation was studied. One hundred and seven adult surgical patients were divided according to the relaxant used, into six groups. We found that when the single twitch recovered to control height, the train-of-four ratio was well below 1.0. This ratio was significantly lower during spontaneous recovery than following neostigmine antagonism of the block (P < 0.01). The tetanic response was fully sustained when the train-of-four ratio was above 0.7. When the ratio was less than 0.7, variable degrees of fade of tetanus were evident. Analysis of variance indicated similar train-of-four ratios among the six groups at complete recovery of the single twitch irrespective of the relaxant technique used (P < 0.1). It is concluded that a train-of-four ratio of 0.7 or higher reliably indicates the recovery of the single twitch to control height and a sustained response to tetanic stimulation at 50 Hz for 5 s. The clinical significance of this study is as follows: the train-of-four response provides the same indication of clinical recovery from nondepolarizing block as obtained from tetanic stimulation at a physiological frequency; and reliance on the recovery of the single twitch to control height as a criterion of spontaneous return to normal clinical neuromuscular function may be misleading.
Simulation Study of Rested Versus Sleep-deprived Anesthesiologists
Authors: Howard Steven K. , Gaba David M. , Smith Brian E. , Weinger Matthew B. , Herndon Christopher , Keshavacharya Shanthala , Rosekind Mark R.
Published: November 2003

Background

Sleep deprivation causes physiologic and subjective sleepiness. Studies of fatigue effects on anesthesiologist performance have given equivocal results. The authors used a realistic simulation environment to study the effects of sleep deprivation on psychomotor and clinical performance, subjective and objective sleepiness, and mood.

Methods

Twelve anesthesia residents performed a 4-h anesthetic on a simulated patient the morning after two conditions of prior sleep: sleep-extended (EXT), in which subjects were allowed to arrive at work at 10:00 AM for 4 consecutive days, thus allowing an increase in nocturnal sleep time, and total sleep deprivation (DEP), in which subjects were awake at least 25 h. Psychomotor testing was performed at specified periods throughout the night in the DEP condition and at matched times during the simulation session in both conditions. Three types of vigilance probes were presented to subjects at random intervals as well as two clinical events. Task analysis and scoring of alertness were performed retrospectively from videotape.

Results

In the EXT condition, subjects increased their sleep by more than 2 h from baseline (P = 0.0001). Psychomotor tests revealed progressive impairment of alertness, mood, and performance in the DEP condition over the course of the night and when compared with EXT during the experimental day. DEP subjects showed longer response latency to vigilance probes, although this was statistically significant for only one probe type. Task analysis showed no difference between conditions except that subjects "slept" more in the DEP condition. There was no significant difference in the cases' clinical management between sleep conditions. Subjects in the DEP condition had lower alertness scores (P = 0.02), and subjects in the EXT condition showed little video evidence of sleepiness.

Conclusions

Psychomotor performance and mood were impaired while subjective sleepiness and sleepy behaviors increased during simulated patient care in the DEP condition. Clinical performance between conditions was similar.
Propofol Increases Phosphorylation of Troponin I and Myosin Light Chain 2 via Protein Kinase C Activation in Cardiomyocytes
Authors: Kanaya Noriaki , Gable Brad , Murray Paul A. , Damron Derek S.
Published: November 2003

Background

Troponin I (TnI) and myosin light chain 2 (MLC2) are important myofibrillar proteins involved in the regulation of myofilament calcium (Ca2+) sensitivity and cardiac inotropy. The objectives of this study were to determine the role of protein kinase C (PKC) in mediating propofol-induced changes in actomyosin adenosine triphosphatase activity in cardiac myofibrils and to examine the extent to which propofol alters the phosphorylation of TnI and MLC2 in cardiomyocytes.

Methods

Freshly isolated adult rat ventricular myocytes were used for the study. Cardiac myofibrils were extracted for assessment of actomyosin adenosine triphosphatase activity and phosphorylation of TnI and MLC2. Western blot analysis for PKC-alpha was performed on cardiomyocyte subcellular fractions. Simultaneous measurement of intracellular free Ca2+ concentration ([Ca2+](i)) and myocyte shortening was assessed using fura-2 and video edge detection, respectively.

Results

Propofol (30 microM) reduced the Ca2+ concentration required for activation of actomyosin adenosine triphosphatase activity, and this effect was abolished by bisindolylmaleimide I. In addition, propofol stimulated dose-dependent phosphorylation of TnI and MLC2. PKC activation with phorbol myristic acetate also stimulated an increase in phosphorylation of TnI and MLC2. The actions of propofol and phorbol myristic acetate together on phosphorylation of TnI and MLC2 were not additive. PKC inhibition with bisindolylmaleimide I attenuated phorbol myristic acetate- and propofol-induced phosphorylation of TnI and MLC2. Propofol stimulated translocation of PKC-alpha from cytosolic to membrane fraction. Propofol caused a shift in the extracellular Ca2+-shortening relationship, and this effect was abolished by bisindolylmaleimide I.

Conclusions

These results suggest that propofol increases myofilament Ca2+ sensitivity via a PKC-dependent pathway involving the phosphorylation of MLC2.
Fetal Plasma Concentrations after Intraamniotic Sufentanil in Chronically Instrumented Pregnant Sheep
Authors: Strümper Danja , Durieux Marcel E. , Gogarten Wiebke , Van Aken Hugo , Hartleb Kristian , Marcus Marco A. E.
Published: November 2003

Background

Rapid progress is being made in fetal surgery. Because the fetus is capable of pain perception after the 26th week of gestation, adequate postoperative fetal pain management is essential. The preferred approach would provide fetal analgesia without affecting the mother. Intraamniotically administered sufentanil may be an interesting option if it achieves therapeutic plasma concentrations (PCs) in the fetus but not the mother.

Methods

After approval of the study, 25 or 50 microg sufentanil was administered intraamniotically in 10 chronically instrumented pregnant ewes. Maternal and fetal vital signs, arterial blood gases, and uterine blood flow were recorded over 120 min. Sufentanil PCs were determined before and 1, 3, 5, 10, 15, 30, 45, 60, 90, and 120 min after injection. Statistical analysis was performed using one- or two-way analysis of variance followed by Dunnett or Tukey test, as appropriate (P < 0.05; data presented as median [95% confidence interval]).

Results

After 25 microg sufentanil, fetal PC stabilized at 134 +/- 89 pg/ml (after 10 min), and maternal PCs stabilized at 44 +/- 11 pg/ml (after 15 min). After 50 microg sufentanil, fetal PCs stabilized at 134 +/- 35 pg/ml (after 15 min), and maternal PCs reached 80 +/- 25 pg/ml (at 30 min). Injection of 25 microg sufentanil intraamniotically did not affect maternal or fetal hemodynamics, uterine blood flow, or arterial blood gases. Fetal heart rate increased after administration of 50 microg sufentanil (maximum change at 10 min: +16 +/- 12%).

Conclusion

The sheep fetus absorbs sufentanil after intraamniotic instillation. Significantly greater PCs were obtained in the fetal lamb as compared with the ewe. This suggests that investigation of intraamniotic opioids for fetal analgesia might be worthwhile.
Intraspinal Adenosine Induces Spinal Cord Norepinephrine Release in Spinal Nerve-ligated Rats but not in Normal or Sham Controls
Authors: Bantel Carsten , Li Xinhui , C. Eisenach James
Published: November 2003

Background

Intrathecal adenosine is antinociceptive under conditions of central sensitization, but not in response to acute stimuli in normals. The reasons for this selective circumstance of action remain unclear, but some evidence links adenosine's antinociceptive effects to release of norepinephrine by terminals in the spinal cord. The purpose of this study was to test whether spinal adenosine induces norepinephrine release selectively in settings of hypersensitivity.

Methods

Rats randomly assigned to spinal nerve ligation, sham operation, or no operation were anesthetized. A microdialysis fiber was implanted in the spinal cord dorsal horn at the L5-L6 level and perfused with artificial cerebrospinal fluid. After washout and a baseline sample period, adenosine at various concentrations was infused through the fiber for 150 min, and samples were collected every 15 min.

Results

In ligated, but not in sham or normal animals, adenosine perfusion increased norepinephrine in spinal cord microdialysates in a concentration-dependent manner. The effects of adenosine plateaued after 75 min and remained stable until the end of the experiment. Intravenous injection of selective adenosine A1 and A2 receptor antagonists revealed that adenosine's effect on spinal norepinephrine release was A1 receptor mediated.

Conclusions

This is the first study to provide direct evidence that adenosine is able to release norepinephrine in spinal cord dorsal horns in living animals. However, this effect was only seen in animals after spinal nerve ligation. These data are consistent with behavioral studies demonstrating that adenosine's antinociceptive effects in rats after spinal nerve ligation is totally dependent on intact spinal noradrenergic terminals and can be blocked by spinal alpha 2-adrenergic receptor antagonists.
Antihyperalgesic and Side Effects of Intrathecal Clonidine and Tizanidine in a Rat Model of Neuropathic Pain
Authors: Kawamata Tomoyuki , Omote Keiichi , Yamamoto Hiroki , Toriyabe Masaki , Wada Kohsuke , Namiki Akiyoshi
Published: November 2003

Background

Although intrathecal clonidine produces pronounced analgesia, antinociceptive doses of intrathecal clonidine produce several side effects, including hypotension, bradycardia, and sedation. Intrathecal tizanidine, another alpha(2)-adrenergic agonist, has provided antinociception without producing pronounced hemodynamic changes in animal studies. However, it has been unclear whether antihyperalgesic doses of intrathecal clonidine and tizanidine produce hypotension and bradycardia in a neuropathic pain state. This study was designed to evaluate the antihyperalgesic effects and side effects of intrathecal clonidine and tizanidine in a rat model of neuropathic pain.

Methods

Male Sprague-Dawley rats were chronically implanted with lumbar intrathecal catheters, and the sciatic nerve was loosely ligated. After 21-28 days after surgery, the rats received intrathecal clonidine (0.3, 1.0, and 3.0 microg) and tizanidine (1.0, 2.0, and 5.0 microg), and the antihyperalgesic effects of thermal and mechanical stimuli were examined. In addition, the changes in blood pressure and heart rate, sedation level, and other side effects after intrathecal administration of drugs were recorded.

Results

The administration of 3.0 microg intrathecal clonidine or 5.0 microg tizanidine significantly reversed both thermal and mechanical hyperalgesia. The administration of 3.0 microg intrathecal clonidine, but not 5.0 microg tizanidine, significantly decreased mean blood pressure and heart rate and produced urinary voiding. A greater sedative effect was produced by 3.0 microg intrathecal clonidine than by 5.0 microg tizanidine.

Conclusion

The antihyperalgesic dose of intrathecal clonidine and the antinociceptive doses produced several side effects. Intrathecal tizanidine at the dose that reversed hyperalgesia would be preferable for neuropathic pain management because of absence of hypotension and bradycardia and lower incidence of sedation.