The effect of surgery and anesthetic agents on granulocyte-chemiluminescence in whole blood

The effect of anesthesia and major abdominal surgery on zymosan-induced chemiluminescence (CL) of neutrophil granulocytes was evaluated. CL was measured in diluted whole blood taken at distinct intervals within the perioperative period. In addition, blood samples from healthy volunteers were supplemented with ether and halothane to investigate the in vitro effect of these agents. The phagocytosis-induced CL was not found to be depressed by anesthesia and surgery. Only at supranarcotic concentrations was CL reduced. Surgery and anesthesia, therefore, do not appear to impair this defense system significantly under the conditions of this investigation.     

Influence of ventilatory and circulatory changes on the pharmacokinetics of halothane and isoflurane

In two groups of dogs, uptake and elimination of halothane and isoflurane were studied using a closed-loop anesthesia system which automatically controlled end-tidal halothane or isoflurane partial pressure at minimal alveolar concentration (MAC) equivalent levels. Hemodynamic and respiratory variables were recorded and the anesthetic partial pressure was measured in the inspired and expired air, as well as in the arterial, cerebrovenous and mixed venous blood. Data were recorded during wash-in, hyperventilation, hypercirculation, hypotension and wash-out. For halothane, the controller delivered a higher inspired partial pressure than for isoflurane to compensate for the higher blood/gas partition coefficient. This was especially pronounced during the wash-in and the hypercirculation periods. Smaller differences between halothane and isoflurane partial pressures occurred during hyperventilation, hypotension and the wash-out period and could be explained by the lower solubility of isoflurane. These results show that even under unstable ventilatory and hemodynamic conditions, the inspired concentration of isoflurane has to be adjusted less often and to a smaller degree than that of halothane if end-tidal concentrations are to be maintained constant.     

The effect of surgery and anesthetic agents on granulocyte-chemiluminescence in whole blood

Summary The effect of anesthesia and major abdominal surgery on zymosan-induced chemiluminescence (CL) of neutrophil granulocytes was evaluated. CL was measured in diluted whole blood taken at distinct intervals within the perioperative period. In addition, blood samples from healthy volunteers were supplemented with ether and halothane to investigate the in vitro effect of these agents. The phagocytosis-induced CL was not found to be depressed by anesthesia and surgery. Only at supranarcotic concentrations was CL reduced. Surgery and anesthesia, therefore, do not appear to impair this defense system significantly under the conditions of this investigation.     

Brain cyclic nucleotide and energy metabolite responses to subanesthetic and anesthetic concentrations of halothane

Adult rats were exposed to 0.5, 1.0 and 1.5% halothane, delivered in air, for 1 h. Whole brain 3',5'-cyclic adenosine monophosphate (cAMP) of halothane-exposed rats showed only a slight increase relative to control values. 3',5'-Cyclic guanosine monophosphate (cGMP) was increased significantly in halothane-exposed rats, and the response was directly related to the halothane concentrations. Adenosine triphosphate (ATP) and phosphocreatine (PC) remained unchanged relative to control values. Correspondence of these values to apparent discrepancies in the literature is discussed.     

The effects of naloxone on the analgesic activities of general anaesthetics

Summary Inhaled concentrations of nitrous oxide (80%), halothane (0.5%), trichloroethylene (0.5%) and s.c. ethanol (1 ml/kg) caused similar degrees of excitation and ataxia in mice. Nitrous oxide, tricholoroethylene and ethanol caused analgesia (hot plate and writhing tests), but only that caused by nitrous oxide was antagonized by naloxone (20 mg/kg). Halothane lacked analgesic activity.     

The effect of halothane on the action of alcuronium in the dog.

The effect of halothane on the action of alcuronium on neuromuscular transmission was studied in the intact dog. Electrical and mechanical evoked responses from stimulation of the ulnar nerve were recorded. The administration of 0.5% halothane prolonged the duration of action of alcuronium by about 50%.     

Brain cyclic nucleotide and energy metabolite responses to subanesthetic and anesthetic concentrations of halothane

Summary Adults rats were exposed to 0.5, 1.0 and 1.5% halothane, delivered in air, for 1 h. Whole brain 3,5-cyclic adenosine monophosphate (cAMP) of halothane-exposed rats showed only a slight increase relative to control values. 3,5-Cyclic guanosine monophosphate (cGMP) was increased significantly in halothane-exposed rats, and the response was directly related to the halothane concentrations. Adenosine triphosphate (ATP) and phosphocreatine (PC) remained unchanged relative to control values. Correspondence of these values to apparent discrepancies in the literature is discussed.Acknowledgments. This research was supported by Public Health Service Grant NS-14355.     

Der Einfluss von Halothan und Chloroform auf die Feinstruktur und Proteinsynthese der Rattenleber

Summary Examinations by electron microscopic and autoradiographic techniques of whether chloroform and halothane alter protein synthesis in rat liver, demonstrate, that chloroform causes an early destruction of the granular endoplasmatic reticulum accompanied by a marked decrease of the protein synthesis in the centre of the acini. After anaesthesia with halothane, the granular endoplasmatic reticulum and the protein synthesis proved to remain unaffected.     

The effect of halothane on the action of alcuronium in the dog

Summary The effect of halothane on the action of alcuronium on neuromuscular transmission was studied in the intact dog. Electrical and mechanical evoked responses from stimulation of the ulnar nerve were recorded. The administration of 0.5% halothane prolonged the duration of action of alcuronium by about 50%.We are indebted to Professor A. Mueller for facilities, help and encouragement. R.S. Jones was the holder of a Royal Society European Exchange Fellowship.     

Effect of recombinant human granulocyte colony-stimulating factor on human neutrophil adherence in vitro.

We measured the effects of recombinant human granulocyte-colony stimulating factor (rhG-CSF) on the adherence of human neutrophils by using a dacron fiber system to assay the adhesive ability of neutrophils. rhG-CSF enhanced neutrophil adherence to dacron fibers. N-formyl-methionyl-leucyl-phenylalanine (fMLP) induced neutrophil-neutrophil interaction (neutrophil aggregation) in addition to neutrophil-dacron interaction, whereas rhG-CSF did not cause neutrophil aggregation. These results indicated that rhG-CSF increases the adhesive ability of neutrophils without neutrophil-neutrophil interaction, and the action of rhG-CSF in neutrophil activation is different from the neutrophil activation caused by fMLP.     

Effect of recombinant human granulocyte colony-stimulating factor on human neutrophil adherence in vitro

Summary We measured the effects of recombinant human granulocyte-colony stimulating factor (rhG-CSF) on the adherence of human neutrophils by using a dacron fiber system to assay the adhesive ability of neutrophils. rhG-CSF enhanced neutrophil adherence to dacron fibers. N-formyl-methionyl-leucyl-phenylalanine (fMLP) induced neutrophil-neutrophil interaction (neutrophil aggregation) in addition to neutrophil-dacron interaction, whereas rhG-CSF did not cause neutrophil aggregation. These results indicated that rhG-CSF increases the adhesive ability of neutrophils without neutrophil-neutrophil interaction, and the action of rhG-CSF in neutrophil activation is different from the neutrophil activation caused by fMLP.     

Regulation of neutrophil trafficking from the bone marrow

Neutrophils are an essential component of the innate immune response and a major contributor to inflammation. Consequently, neutrophil homeostasis in the blood is highly regulated. Neutrophil number in the blood is determined by the balance between neutrophil production in the bone marrow and release from the bone marrow to blood with neutrophil clearance from the circulation. This review will focus on mechanisms regulating neutrophil release from the bone marrow. In particular, recent data demonstrating a central role for the chemokines CXCL12 and CXCL2 in regulating neutrophil egress from the bone marrow will be discussed.     

Chemotactic and random movement of cord-blood granulocytes

Summary Chemotactic responsiveness and random movement of cord-blood granulocytes were studied with a modified Boyden's method. Cord-blood granulocytes were less active chemotactically than granulocytes from healthy children and adults, whereas the random filter movement of the cells from all three sources was about the same. In cord sera, concentrations of cell directed chemotaxis inhibitors were equal to those in sera from other age groups. Compared with the situation in healthy children and adults, the generation of chemotactic factors in cord-blood sera was impaired. This impairment was not related to an increased activity of chemotactic factor inactivators. Measurement of the cyclic nucleotide levels in granulocytes from cord-blood and from children belonging to various age groups revealed that the cord granulocytes have significantly lower concentrations of cAMP and cGMP, which could have been responsible for the decreased chemotactic responsiveness.     

Chemotactic and random movement of cord-blood granulocytes

Chemotactic responsiveness and random movement of cord-blood granulocytes were studied with a modified Boyden's method. Cord-blood granulocytes were less active chemotactically than granulocytes from healthy children and adults, whereas the random filter movement of the cells from all three sources was about the same. In cord sera, concentrations of cell directed chemotaxis inhibitors were equal to those in sera from other age groups. Compared with the situation in healthy children and adults, the generation of chemotactic factors in cord-blood sera was impaired. This impairment was not related to an increased activity of chemotactic factor inactivators. Measurement of the cyclic nucleotide levels in granulocytes from cord-blood and from children belonging to various age groups revealed that the cord granulocytes have significantly lower concentrations of cAMP and cGMP, which could have been responsible for the decreased chemotactic responsiveness.     

Lack of substrate specificity on the speed of amoeboid locomotion inNaegleria gruberi

Summary Comparison of locomotory rates ofNaegleria on glass, agar, plastic and fluorocarbon oil under a range of defined electrolyte concentrations showed the speed of amoeboid movement to be independent of the substrate's nature.Acknowledgments. We would like to thank Les Cooper for technical assistance, the Science Research Council for support and the 3M Company for the gift of FC75 oil.     

Surface molecules regulating rolling and adhesion to endothelium of neutrophil granulocytes and MDA-MB-468 breast carcinoma cells and their interaction

The extravasation of leukocytes and tumor cells is a multi-step process with the involvement of various adhesion molecules depending on the three steps rolling, adhesion, and diapedesis. We have developed an in vitro model, by which we investigated the rolling and adhesion of neutrophil granulocytes and MDA-MB-468 human breast carcinoma cells to lung endothelial cells under physiological flow-conditions. We found that norepinephrine had an inhibitory function on the fMLP-promoted adhesion of neutrophil granulocytes due to a down-regulation of β2-integrin. Furthermore, neutrophil granulocytes serve as linking cells for the interaction of the MDA-MB-468 cells with the endothelium, which are both β2-integrin negative, but express the β2-integrin ligand ICAM-1. In addition, we show here that N-cadherin is up-regulated on the endothelial cells and on neutrophil granulocytes in response to fMLP. This up-regulation resulted in a significant increase of adherent MDA-MB-468 cells, which are also N-cadherin positive. Received 3 September 2007; received after revision 17 October 2007; accepted 22 October 2007     

Effect of volatile anesthetics on the circular dichroism of bilirubin bound to human serum albumin

The characteristic circular dichroism of bilirubin bound to human serum albumin undergoes a remarkable sign inversion on addition of halothane, chloroform and other volatile anesthetics. This sign inversion, which is completely reversed by removal of the anesthetic, reflects a pronounced conformational change of the bound ligand; probably a complete inversion of chirality. The observation suggests that association of volatile anesthetics with proteins can markedly alter the internal topography of receptor sites and potentially influence the stereoselectivity of ligand binding.     

Effect of volatile anesthetics on the circular dichroism of bilirubin bound to human serum albumin.

The characteristic circular dichroism of bilirubin bound to human serum albumin undergoes a remarkable sign inversion on addition of halothane, chloroform and other volatile anesthetics. This sign inversion, which is completely reversed by removal of the anesthetic, reflects a pronounced conformational change of the bound ligand; probably a complete inversion of chirality. The observation suggests that association of volatile anesthetics with proteins can markedly alter the internal topography of receptor sites and potentially influence the stereoselectivity of ligand binding.     

The effects of continuous chloroform and halothane anesthesia on plasma prolactin levels in ovariectomized estrogen-treated rats

Summary In ovariectomized, estrogen-treated rats bearing indwelling aortic catheters, continuous inhalation of chloroform or halothane resulted in increases in plasma prolactin levels 10 min after the exposure to the anesthetics. The plasma prolactin levels over the subsequent 2 h, however, were not significantly different from that of the control animals.Supported by NSF Research Grant BMS 74-17332.The authors wish to express their appreciation to Mrs Cynthia Van De Walle for her outstanding assistance in the performance of the prolactin RIA and the art work.