bluuebunny/crossref_metadata_2025_split huggingface dataset:
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.