摘要:

BackgroundThe purpose of this study was to determine the effects of systemic infusions of nitroglycerin and sodium nitroprusside on flow distribution and wall shear stress in the microcirculation.MethodsWith university approval, the cremaster muscle of 28 anesthetized (70 mg/kg pentobarbital given intraperitoneally) hamsters (Harlan Sprague Dawley: Syrian; weight, 121 ± 11 g [mean ± SD]) was observed usingin vivofluorescence microscopy. Arteriolar diameter, erythrocyte flux, and velocity were measured for a feed arteriole and its sequential branches. Observations were made during control (mean arterial pressure, 88 ± 4 mmHg) and after 30 min of intravenous delivery of sodium nitroprusside or nitroglycerin, titrated to decrease mean arterial pressure by 20 mmHg.ResultsSodium nitroprusside significantly dilated select upstream portions of the network (23 ± 2.6 to 29 ± 2.6 &mgr;m); no arterioles were dilated with nitroglycerin. Erythrocyte flux into the feed (i.e., inflow into the arteriolar network) and into the sequential branches (i.e., distribution within the network) were evaluated. With nitroglycerin, inflow decreased significantly from 1,560 ± 335 to 855 ± 171 cells/s, and flux into the branches decreased evenly. With sodium nitroprusside, inflow increased significantly to 2,600 ± 918 cells/s, yet cells were “stolen” from upstream branches (a decrease from 425 ± 67 to 309 ± 87 cells/s in the first branch). Excess flow passed into a downstream “thorough‐fare channel,” significantly increasing flux from 347 ± 111 to 761 ± 246 cells/s. Wall shear stress decreased uniformly with nitroglycerin infusion, with a decrease in the feed from 8.8 ± 2.5 to 6 ± 1.7 dyn/cm2. With sodium nitroprusside, variable changes occurred that were location specific within the network. For instance, at the inflow point to the network, wall shear stress changed from 8.3 ± 2.5 to 4.2 ± 3.3 dyn/cm2.ConclusionsNitroglycerin infusion promoted homogeneity of flow. Sodium nitroprusside significantly increased the heterogeneity of flow within this arteriolar network; an anatomic location for steal induced by sodium nitroprusside is identified.

ISSN:0003-3022    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

BackgroundClinical studies have implicated surgery in promoting infections and compromising immune functions, including natural killer cell activity. Animal studies indicate that surgery‐induced suppression of natural killer cell activity also promotes tumor metastasis. Hypothermia, a common surgical complication, has been suggested to underlie some of the deleterious consequences of surgery. This study evaluated the effect of hypothermia on the activity and number of blood natural killer cells and on host susceptibility to metastasis. The involvement of adrenergic mechanisms was also considered.MethodsFischer‐344 rats remained awake in their cages (control group) or were anesthetized with 70 mg/kg thiopental and maintained for 2.5 h at core body temperatures of 30–32°C (hypothermia group) or 38°C (normothermia group). Thereafter, at several time points, blood was drawn so natural killer cell activity could be assessed, or rats were injected with syngeneic MADB106 tumor cells that metastasize only to the lungs. Lungs were removed 9 h later for assessment of lung tumor retention, or 4 weeks later for counting of metastases.ResultsNormothermic anesthesia reduced natural killer cell activity (lytic units at 30% specific killing, mean ± SEM) to 39 ± 6.2% of control levels and hypothermia further reduced it to 15 ± 6.6%. These changes were not accompanied by alterations in the numbers of circulating natural killer cells. Hypothermia increased tumor retention to 250% of control levels, and the number of metastases increased from 1.1 ± 0.4 to 4.7 ± 1.2. Normothermia had no significant effects on this index. Nadolol (0.4 mg/kg), a &bgr;‐adrenergic antagonist, significantly attenuated the effect of hypothermia on tumor retention.ConclusionsHypothermia under thiopental anesthesia suppresses natural killer cell activity and compromises host resistance to metastatic formation, possiblyviaadrenergic mechanisms. Such suppression may place patients with metastasizing tumors or dormant viral infections at greater risk for complications after intraoperative hypothermia.

ISSN:0003-3022    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

BackgroundInhaled nitric oxide is often used in patients with adult respiratory distress syndrome. However, nitric oxide also may be significantly toxic, especially if administered concurrently with hyperoxia. The authors evaluated the isolated effect of nitric oxide and the combined effects of nitric oxide and hyperoxia on lung injury in rats after acid aspiration.MethodsAnimals were injured by instillation of 1.2 ml/kg hydrogen chloride in low‐pH saline (the acid group) or acidified gastric particles (the casp group) into the lungs under halothane anesthesiaviaa tracheal catheter. Controls received no injury vehicle but rather underwent the surgical process. After recovery from anesthesia, the animals were exposed to 20% or 90% oxygen with or without 20, 40, or 80 ppm nitric oxide for 5 h. The permeability index, alveolar–arterial oxygen difference, the ratio of oxygen pressure to the inspired fraction of oxygen, and the ratio of wet to dry weight were assessed 5 h after injury as indices of lung injury. Data were assessed using analysis of variance.ResultsEach group included 6–10 rats. Exposure to nitric oxide (80 ppm) in air increased protein permeability in the lungs to a permeability index of 1.42 ± 0.12 after acid aspiration. The combination of nitric oxide (80 ppm) and hyperoxia further increased protein leakage to a permeability index of 2.1 ± 0.25. Exposure to lower concentrations of nitric oxide (e.g., 20 and 40 ppm) increased the permeability index of the lungs (1.44 ± 0.21, 1.75 ± 0.29, respectively) in the presence of hyperoxia, although it did not affect the permeability index of the lungs during exposure to air. Pretreatment of animals with deferoxamine and methylene blue partially inhibited the adverse effect of hyperoxia and nitric oxide, which suggested a complex underlying mechanism involving both reactive‐species generation and pulmonary vasomotor changes.ConclusionsThese results show that inhaled nitric oxide at 80 ppm for a short duration (5 h) increases the severity of the inflammatory microvascular lung injury after acid aspiration. The pulmonary damage is exacerbated further in the presence of high oxygen concentrations. Although lower concentrations of nitric oxide did not increase the extent of lung injury, longer exposure times need to be assessed.

ISSN:0003-3022    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

BackgroundPropofol has been shown to produce relaxation of preconstricted airway smooth muscle. Although the inhibition of calcium mobilization is supposed to be the major mechanism of action, the whole picture of the mechanisms is not completely clear.MethodsContractile response was performed using canine tracheal rings. The effects of propofol on carbachol‐induced mobilization of intracellular Ca2+and phosphoinositide hydrolysis were measured using cultured canine tracheal smooth muscle cells by monitoring fura‐2 signal and assessing the accumulation of [3H]‐inositol phosphates. To detect the effect of propofol on muscarinic receptor density and affinity, [3H]N‐methyl‐scopolamine was used as a radioligand for receptor binding assay.ResultsPretreatment with propofol shifts the concentration–response curves of carbachol‐induced smooth muscle contraction to the right in a concentration‐dependent manner without changing the maximal response. Propofol not only decreased the release of Ca2+from internal stores but also inhibited the calcium influx induced by carbachol. In addition, carbachol‐induced inositol phosphate accumulation was attenuated by propofol; the inhibitory pattern was similar to the contractile response. Moreover, propofol did not alter the density of muscarinic receptors. The dissociation constant value was not altered by pretreatment with 100 &mgr;M propofol but was significantly increased by 300 &mgr;M (propofol, 952 ± 229 pM; control, 588 ± 98 pM;P< 0.05).ConclusionsPropofol attenuates the muscarinic receptor–mediated airway muscle contraction. The mechanism underlying these effects was attenuation of inositol phosphate generation and inhibition of Ca2+mobilization through the inhibition of the receptor‐coupled signal‐transduction pathway.

ISSN:0003-3022    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

BackgroundThe authors tested the hypothesis that ketamine and propofol anesthesia would alter the magnitude of hypoxic pulmonary vasoconstriction compared with the conscious state. In addition, they assessed the extent to which cyclooxygenase pathway inhibition and adenosine triphosphate–sensitive potassium channel inhibition modulate hypoxic pulmonary vasoconstriction in the conscious state, and whether these pathways are altered during propofol anesthesia.MethodsTwenty conditioned, male mongrel dogs were chronically instrumented to measure the left pulmonary vascular pressure–flow relationship. Pressure–flow plots were measured during normoxia and hypoxia (systemic arterial PO2reduced to about 60 and about 50 mmHg) on separate days in the conscious state, during ketamine anesthesia, and during propofol anesthesia. The effects of indomethacin and glibenclamide on the magnitude of hypoxic pulmonary vasoconstriction were also assessed in the conscious and propofol‐anesthetized states.ResultsNeither ketamine nor propofol had an effect on the baseline pressure–flow relationship during normoxia compared with the conscious state. Hypoxia resulted in stimulus‐dependent pulmonary vasoconstriction (P< 0.01) in the conscious state. Compared with the conscious state, the magnitude of hypoxic pulmonary vasoconstriction was preserved during ketamine but was potentiated (P< 0.01) during propofol anesthesia. Indomethacin enhanced (P< 0.01) hypoxic pulmonary vasoconstriction in both the conscious and propofol‐anesthetized states. In contrast, glibenclamide only enhanced (P< 0.01) hypoxic pulmonary vasoconstriction in the conscious state and had no effect during propofol anesthesia.ConclusionHypoxic pulmonary vasoconstriction is preserved during ketamine anesthesia but is potentiated during propofol anesthesia. The potentiated response during propofol anesthesia appears to be caused by inhibition of adenosine triphosphate–sensitive potassium channel–mediated pulmonary vasodilation.

ISSN:0003-3022    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

BackgroundTo learn more about pain mechanisms produced by surgery, responses of wide dynamic range (WDR) and high threshold (HT) dorsal horn neurons were studied before and after an incision. For this study, an incision was made in a mechanically insensitive area of the receptive field (RF) of the dorsal horn neuron in the plantar aspect of the foot and changes in mechanical response properties were studied.MethodsAction potentials from single dorsal horn neurons were recorded in halothane anesthetized rats and these neurons were characterized as WDR or HT. Changes in background activity and responses to a variety of mechanical stimuli adjacent to the incision, distant to the injury, and in areas throughout the hindquarters were recorded.ResultsFifty neurons were recorded (29 WDR, 21 HT cells); only nine of these had a sustained increase in background activity after incision. Marked decreases in threshold to von Frey filaments applied adjacent to the wound occurred in 9 of 28 WDR neurons but in none of 21 HT cells. Von Frey filament thresholds distant to the incision were largely not changed. A blunt mechanical stimulus activated 18 of 22 WDR neurons when applied directly on the incision. HT cells were largely not excited by this mechanical stimulus after incision. The RF to pinch was enlarged in 31 neurons to include areas outside the injury. Pinch RFs of both WDR and HT cells expanded.ConclusionThese results suggest that incisions in mechanically insensitive areas of the RF of dorsal horn neurons produced little change in background activity; expansion of pinch RFs outside the injury was common. Changing a mechanically insensitive area of the RF of WDR neurons to a mechanically sensitive area by an incision could contribute to pain behaviors that indicate primary mechanical hyperalgesia in behavioral studies.

ISSN:0003-3022    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

BackgroundThe local anesthetic bupivacaine exists in two stereoisomeric forms, R(+)‐ and S(−)‐bupivacaine. Because of its lower cardiac and central nervous system toxicity, attempts were made recently to introduce S(−)‐bupivacaine into clinical anesthesia. We investigated stereoselective actions of R(+)‐ and S(−)‐bupivacaine toward two local anesthetic‐sensitive ion channels in peripheral nerve, the Na+and the flicker K+channel.MethodsIn patch‐clamp experiments on enzymatically demyelinated peripheral amphibian nerve fibers, Na+and flicker K+channels were investigated in outside‐out patches. Half‐maximum inhibiting concentrations (IC50) were determined. For the flicker K+channel, simultaneous block by R(+)‐bupivacaine and S(−)‐bupivacaine was analyzed for competition and association (k1) and dissociation rate constants (k−1) were determined.ResultsBoth channels were reversibly blocked by R(+)‐ and S(−)‐bupivacaine. The IC50values (±SEM) for tonic Na+channel block were 29 ± 3 &mgr;M and 44 ± 3 &mgr;M, respectively. IC50values for flicker K+channel block were 0.15 ± 0.02 &mgr;M and 11 ± 1 &mgr;M, respectively, resulting in a high stereopotency ratio (±) of 73. Simultaneously applied enantiomers competed for a single binding site. Rate constants k1and k−1were 0.83 ± 0.13 × 106M−1· s−1and 0.13 ± 0.03 s−1, respectively, for R(+)‐bupivacaine and 1.90 ± 0.20 × 106M−1· s−1and 8.3 ± 1.0 s−1, respectively, for S(−)‐bupivacaine.ConclusionsBupivacaine block of Na+channels shows no salient stereoselectivity. Block of flicker K+channels has the highest stereoselectivity ratio of bupivacaine action known so far. This stereoselectivity derives predominantly from a difference in k−1, suggesting a tight fit between R(+)‐bupivacaine and the binding site. The flicker K+channel may play an important role in yet unknown toxic mechanisms of R(+)‐bupivacaine.

ISSN:0003-3022    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

BackgroundPartial liquid ventilation (PLV) and prone position can improve arterial oxygen tension (PaO2) in acute lung injury (ALI). The authors evaluated additive effects of these techniques in a saline lung lavage model of ALI.MethodsALI was induced in 20 medium‐sized pigs (29.2 ± 2.5 kg body weight). Gas exchange and hemodynamic parameters were determined in both supine and prone position in all animals. Thereafter, one group was assigned to PLV with two sequential doses of 15 ml/kg of perfluorocarbon (n = 10); the second group was assigned to gaseous ventilation (n = 10). Gas‐exchange and hemodynamic parameters were determined at corresponding time points in both groups in prone and supine position.ResultsIn the PLV group, positioning the animals prone resulted in an increase of PaO2prior to PLV and during PLV with both doses of perfluorocarbon when compared to ALI. PLV in supine position was only effective if 30 ml/kg of perfluorocarbon was applied. In the gaseous ventilation group, PaO2increased reproducibly compared with ALI when the animals were turned prone. A significant additive improvement of arterial oxygenation was observed during combined therapy with 30 ml/kg of perfluorocarbon and prone position in the PLV group compared with either therapy alone.ConclusionsThe authors conclude that combining PLV with prone position exerts additive effects on pulmonary gas exchange in a saline lung lavage model of ALI in medium‐sized pigs.

ISSN:0003-3022    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

BackgroundThe activity of canine expiratory neurons is primarily dependent onN‐methyl‐D‐aspartic acid (NMDA)‐receptor mediated excitatory chemodrive inputs and a powerful inhibitory gain modulatory mechanism mediated via &ggr;‐aminobutyric acidA(GABAA) receptors. We examined whether the depressant effect of halothane on expiratory neuronal activity is primarily caused by a reduction in glutamatergic excitation or a potentiation of the inhibitory mechanism.MethodsExperiments were performed in halothane‐anesthetized, vagotomized, paralyzed, and mechanically ventilated dogs during hypercapnic hyperoxia. The effect of a halothane dose increase from one minimum alveolar concentration (MAC) to 2 MAC on extracellularly recorded expiratory neuronal activity was studied before and during complete GABAAreceptor blockade by localized picoejection of bicuculline close to the neuron. Complete blockade of the inhibitory mechanism allowed differentiation between the effects of halothane on overall NMDA‐mediated excitation and on GABAA‐mediated inhibition.ResultsThe spontaneous activity of 12 expiratory neurons was significantly depressed (18.1%) by the 1‐MAC halothane dose increase. Overall glutamatergic excitation was depressed 38.3 ± 12.3% (mean ± SD) by the 1‐MAC halothane increase. The prevailing GABAAergic attenuation of neuronal output decreased significantly from 49.5 ± 10 to 32.0 ± 10.4%. Thus overall inhibition was reduced by halothane by 33.5 ± 17.2%.ConclusionsThese results suggest that the depressive effect of a 1‐MAC halothane dose increase on expiratory neuronal activity in ourin vivopreparation with an intact neural network was mainly caused by a reduction of synaptic excitatory mechanisms and not an enhancement of synaptic inhibitory mechanisms.

ISSN:0003-3022    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

BackgroundPrevious work showed a twofold increase in stiffness of nonischemic myocardium at the base during ischemia of the left anterior wall. Whether the diastolic response of nonischemic myocardium to remote ischemia depends on the localization of the ischemic or the nonischemic area is unknown.MethodsIn dogs with open chests, regional function in ischemic and nonischemic myocardium was assessed (sonomicrometry) before and 5 min after occlusion of the left anterior descending coronary artery (LAD; n = 7) or the left circumflex coronary artery (LCX; n = 7).ResultsIn nonischemic myocardium at the base, left anterior descending and left circumflex coronary artery occlusion both resulted in a twofold increase in chamber stiffness, whereas contractility and peak lengthening rate remained unchanged. In nonischemic myocardium of the posterior wall, left anterior descending coronary artery occlusion resulted in a significant (P< 0.05vs. control,P< 0.05vs.base) increase (mean ± SD) in chamber stiffness (25 ± 6%), contractility (17 ± 5%), and peak lengthening rate (28 ± 6%). In nonischemic myocardium at the apex, left circumflex coronary artery occlusion resulted in a significant (P< 0.05vs.control,P< 0.05vs.base) increase in chamber stiffness (15 ± 5%), contractility (16 ± 4%), and peak lengthening rate (19 ± 6%).ConclusionsStiffening of remote nonischemic myocardium occurs regardless of the localization of the ischemic and nonischemic area. The systolic and diastolic responses of nonischemic myocardium are not necessarily homogenous but may vary among different regions.

ISSN:0003-3022    

出版商:OVID    

年代:1999

数据来源: OVID