Heritable differences in respiratory drive and breathing pattern in mice during anaesthesia and emergence

Background. Postanaesthetic hypoxia and ischaemia can lead topostoperative morbidity and mortality. We studied the effectof isoflurane anaesthesia in two inbred mouse strains knownfor phenotypic differences in breathing pattern and respiratorydrive during carbon dioxide challenge and their first-generationoffspring (F₁). Methods. Using whole body plethysmography, we assessed respiratoryrate (RR) and pressure amplitude (Amp) in male B6 (high responderto hypercapnia), C3 (low responder), and F₁ mice at rest, duringanaesthesia with isoflurane, and during recovery from anaesthesia.At each time point, the magnitude and pattern of breathing weredetermined during hypercapnic challenge (FI_CO2 = 0.08).Data (mean (SD)) were analysed by generalized ANOVA with posthoc Bonferroni’s correction (P<0.05). Results. During isoflurane anaesthesia, strain differences betweenB6 and C3 mice in RR were obscured while differences in Amppersisted. In contrast to baseline RR responses to carbon dioxidewere significantly reduced at 0.5 MAC (increase in RR: 175 (33)bpm, 147 (44) bpm, 127 (33) bpm, for B6, C3, and F₁ strainsrespectively) and completely blocked at 1.5 MAC (change in RR:–3 (10) bpm, –2 (1) bpm, –4 (5) bpm, for B6,C3, and F₁ strains, respectively). During recovery, B6 miceshowed a significant increase in RR (77 (33) bpm; P<0.0001)as well as in Amp. This was not observed in either C3 (–22(31) bpm) or F₁ mice (23 (51) bpm). Conclusion. Isoflurane anaesthesia abolished the strain differencesin respiratory drive between B6, C3, and F₁ mice. However, duringrecovery from anaesthesia, significant strain variation in respiratorydrive reappeared and was more pronounced compared with pre-anaestheticlevels. These results suggested, that genetic differences mayhave minimal contribution to decreased respiratory drive duringanaesthesia, but may be a major risk factor for post-operativehypoventilation and the associated morbidity and mortality. Br J Anaesth 2003; 91: 541–5     

Mechanism of thiopental-induced constriction of guinea pig trachea

The authors studied the effects of thiopental on baseline airway tone in intact guinea pig tracheas using a preparation where the epithelial (inside) and serosal (outside) surfaces were isolated. Whole tracheas were excised, cannulated, and mounted in 50-ml tissue baths. The serosal and epithelial surfaces were perfused via separate circuits with Krebs-Henseleit solution. All data were expressed as a percent of constriction produced by 2 X 10(-6) M carbachol (a concentration that elicited a 90 + % of maximal constriction). Thiopental elicited a dose-dependent constriction in all 25 tracheas. Increases in tone were first seen at 10(-5) M (14.3 +/- 1.84%; mean +/- SEM) and reached a peak at 10(-3) M (29 +/- 3.16%; P less than .0001). Responses to thiopental were similar when the epithelium was removed, when thiopental was added to the inner perfusate, and when tracheas were pretreated with 10(-5) M pyrilamine. Constriction was entirely inhibited by pretreatment with indomethacin 10(-5) M. The authors conclude that thiopental, at concentrations in the clinical range, causes a reproducible dose-dependent constriction of guinea pig trachea. This effect is mediated by constrictor prostaglandins.     

Role of Different Replacement Fluids During Extracorporeal Treatment in a Pig Model of Sepsis

In an extracorporeal combination therapy, the impact of different replacement fluids on survival was tested in a bacterial sepsis model in pigs. In an animal study 19 pigs, weighing 7.5–11.1 kg, were included. All groups received an intravenous lethal dose of live Staphylococcus aureus over 1 h. The animals were treated by an extracorporeal circuit consisting of online centrifugation and subsequent plasma filtration for 4 h. The extracorporeal circuit was pre‐filled with 400 mL replacement fluid. In the P0 group 100% hydroxyethyl starch 130/0.4 was used as replacement fluid; in the P30 group 30% pig plasma and 70% hydroxyethyl starch; and in the P100 group 100% pig plasma. The observation time was 7 days. All animals of the group P100 survived, while all animals of group P0 and five out of seven animals of the P30 group died during the observation time. Extracorporeal therapy consisting of online centrifugation and plasma filtration with 100% pig plasma as replacement fluid significantly improved survival in a pig model of sepsis. Further studies with this approach are encouraged.     

Therapeutic Plasma Exchange in Glucocorticosteroid‐Unresponsive Patients With Clinically Isolated Syndrome

Clinically Isolated Syndromes (CIS) summarize clinical features of possible multiple sclerosis (MS) as a first clinical event of the disease. Escalation therapy in CIS episodes comprises high dose glucocorticosteroid (GCS) treatment followed by therapeutic plasma exchange (TPE) in patients unresponsive to GCS. The aim of our study was to analyze TPE effects in CIS patients. Eleven GCS‐unresponsive patients exhibiting CIS were treated with TPE. A median of 5.0 (range 3–8) treatments were performed with a median exchange volume of 3.0 L (range 2.2–3.5 L). Standard diagnostic results in CIS patients were collected. In 10 out of 11 patients clinical improvement was observed. In Expanded Disability Status Scale (EDSS) Scoring, a commonly used score to assess disability in MS and CIS patients, significant improvement was shown as well. One patient was a non‐responder to TPE. Apheresis treatments were well tolerated in all patients. In the medical control of GCS‐unresponsive CIS episodes, TPE appears to be an effective and well‐tolerated treatment option. TPE response in CIS patients is comparable to TPE results in GCS‐unresponsive MS relapses. Further prospective studies are indicated.     

Plasma Separation by Centrifugation and Subsequent Plasma Filtration: Impact on Survival in a Pig Model of Sepsis

The impact on survival of a combination of plasma separation by centrifugation and subsequent plasma filtration was tested in a bacterial sepsis model in pigs. In this animal study 19 pigs were included. Groups II and III received an intravenous lethal dose of live Staphylococcus aureus over 1 h; group I received saline (non‐septic control—NC). Groups I and II were treated by an extracorporeal circuit consisting of online centrifugation and subsequent plasma filtration (group II: treated group—TG) for 4 h; group III had no specific treatment (septic control, SC). The observation time was 7 days. All animals of group I (NC) and group II (TG) survived, while all animals of group III (SC) died during the observation time. Extracorporeal therapy with online centrifugation and plasma filtration significantly improved survival in a pig model of sepsis. Further studies with this approach are encouraged.     

The purification and characterization of Cordemcura

3-Amino-5-(4-pyridinyl)-1,2-dihydro-pyrid-2-one (1) is an amphoteric compound and forms one crystalline sodium salt and two hydrochlorides. Physicochemical properties UV, NMR and MS are described. TLC has been used mainly and is the most sensitive method for estimation of 1-byproducts. Coloured byproducts, generated by hypochlorite or air oxidation during synthesis and handling in solution, are monitored by vis-spectra, diminished by sulfite addition and removed by alkaline precipitation. The purification procedure is able to produce 1 with only 0.1% of precursors or byproducts.     

Use of human preconditioned phagocytes for extracorporeal immune support: introduction of a concept.

Neutrophils are critical effector cells in humoral and innate immunity and play a vital role in phagocytosis and bacterial killing. If they and/or their specific functions are lacking, then immunoparalysis may occur, and severe diseases like systemic inflammatory response syndrome (SIRS) or sepsis can take a fatal course. In this paper, we discuss the possibility of using preconditioned cells in an extracorporeal biohybrid immune support system. A human promyelocytic cell line was stimulated for different times with all-trans retinoic acid. The resulting cells displayed major signs and functions of mature neutrophilic granulocytes including oxygen radical production, phagocytosis of living and dead Escherichia coli, Staphylococcus aureus, Candida albicans, intracellular killing, and interleukin production. The cells can be expanded to yield a sufficient cell mass, and subsequent prestimulation results in an expression of specific neutrophil functions. Extracorporeal bioreactor experiments seem to be feasible to test the benefit in immunoparalysis-associated diseases like SIRS or sepsis.     

In vivo hysteresis of airspace dimensions measured by aerosol recovery

In anesthetized mongrel dogs, we made measurements of single breath aerosol recovery (RC) at equal volume points on the inflation and deflation limb of the quasi-static pressure-volume (P-V) curve of the lungs. Using a 1.2 micron monodisperse aerosol, a large aerosol tidal volume (Vt), and a breathing period of 5 sec, we found that losses of particles were primarily due to sedimentation in pulmonary airspaces distal to anatomic dead space. Thus, the RC measurements could be related to a mean radius (R) of airspaces filled with aerosol over the course of the breath. Furthermore, at a given volume, differences between inflation and deflation limb RC could be attributed to differences in R for the two measurements (i.e., RI vs RD). We found that at isovolume, RC as measured from the inflation limb was larger than that measured from the deflation limb for low lung volumes (less than 0.75 TLC). However, the recoveries were similar as lung volume approached TLC (greater than 0.75 TLC). These results implied that at the same volume, RI greater than RD expect at volumes approaching TLC, i.e. a larger mean airspace dimension on the inflation limb than on the deflation limb at equal volume. The findings of this study support a model of nonuniform changes in airspace dimensions associated with in vivo inflation and deflation of the lungs.