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Biomedical subjects

R Rüfer

Publications and source records attributed to R Rüfer.

At least 19 recordsLinked to original sources

Meconium and amniotic fluid embolism: effects on coagulation in pregnant mini-pigs.

OBJECTIVE: A hallmark of amniotic fluid embolism is the induction of coagulation defects. Little is known about the nature of these defects or the causative agent or agents. The purpose of this study was to assess the effects of meconium containing (native) meconium-amniotic-fluid infusion (MAFI) and meconium-free (centrifuged) amniotic-fluid infusion (AFI) on the coagulation system in the mini-pig model. DESIGN: Laboratory study. SETTING: University institute animal laboratory. SUBJECTS: Near-term pregnant Göttingen bred mini-pigs in three groups (control, MAFI, AFI) of six animals each. INTERVENTIONS: After induction of anesthesia, amniotic fluid was collected by cesarean section in all animals. Depending on the group, animals received either Ringer's solution (control), native amniotic fluid (MAFI), or centrifuged amniotic fluid (AFI) via an ear vein. MEASUREMENTS AND MAIN RESULTS: Blood samples were taken from a central vein before infusion (baseline), immediately after infusion, every 10 mins until 90 mins after infusion, and finally, every 20 mins until 150 mins after infusion. The following parameters were measured: Platelets, partial thromboplastin time, prothrombin time, fibrinogen, factors V, VII, VIII, antithrombin III, and protein C. The values relative to baseline in the MAFI and AFI groups were compared with control by rank order test. A p<.05 was considered statistically significant. Compared with the control group, platelets were lower in the MAFI group (p<.005), PTT was prolonged in both the MAFI and AFI groups (p<.005), fibrinogen was lower in both the MAFI and AFI groups (p<.05), prothrombin index was lower (i.e., prothrombin time was prolonged) in the MAFI group (p<.05), and protein C was lower in the MAFI group (p<.005). CONCLUSIONS: Both MAFI and, to a much lesser extent, AFI cause an activation of coagulation in mini-pigs. The changes induced by meconium-free AFI are probably not sufficient to explain the high mortality of the condition.

Amniotic Fluid

Another portable quantitative capnometer.

A new portable quantitative capnometer (Bruker CO2 Module) was tested in an animal lab (mini-pigs) during experiments on air embolism. The end-tidal CO2 values, as measured with this device, showed good agreement with the values of a stationary capnography unit. This device seems suited for quantitative capnometry in the prehospital setting.

Animals

Preliminary observations on the Colibri CO2-indicator.

The performance of a new colorimetric CO2-indicator (Colibri) was assessed in mini-pigs. It performed well during 8-hour procedures. Neither nitrous oxide, nor halothane, nor carbon monoxide, nor intratracheal application of drugs (epinephrine, atropine, lidocaine, and naloxone) interfered with its function. It gave a distinct color change at high ventilation frequencies up to 120/min. The only problem observed was difficulty in matching the colors displayed with the comparison color chart provided. The Colibri's performance seems at least equal to that of the EasyCAP detector, although both devices share some disadvantages (no alarms, semiquantitative, difficult reading in the dark). After initial control of endotracheal tube position by an esophageal detector device, both the Colibri and the EasyCAP seem suited for monitoring of ventilation and circulation if quantitative capnometry is unavailable.

Animals

The influence of an arterial and venous air embolism on the hearing level in laboratory mini pigs.

We examined the influence of an experimental venous and arterial air embolism on the hearing level in laboratory mini pigs. Before and after the injection of air a threshold ABR was measured in anaesthetized mini pigs (n=15). A venous air embolism was performed in 6 animals: no changes in the hearing level or in the interpeak latencies Jewett wave V-I were observed in any of the animals before, during or after the application of air. In 9 animals the arterial embolism was done, 2 animals died and had to be excluded. In 6 animals out of 7 a hearing loss was observed starting after the injection of 40 ml air and finally ending in deafness for these 6 animals. The detected hearing loss is probably of cochlear origin, as no prolongations of the interpeak latencies of Jewett wave V-I at 90 dB HL were observed prior to the deafness. Our results show that air bubbles in the arterial circulation lead to cochlear damage ending in deafness. Our research indicates that decompression sickness, which is comparable to the arterial air embolism, is more often the cause of a sensorineural hearing loss after diving than previously believed.

Animals

[ETICS Study: Empirical therapy of idiopathic chronic singultus].

Idiopathic chronic singultus (ICS) describes recurring episodes of persistent hiccuping lasting longer than an arbitrary time limit (e.g. one month) for which no organic cause or consistently effective treatment can be found. It has been suggested that ICS may result from chronic stimulation of a supraspinal "hiccup center" by impulses originating from receptors in the gastrointestinaltract. This hypotesis implies the possibility of treating ICS by reducing gastric acid (via omeprazole), facilitating gastric emptying (via cisapride), or suppressing of the "hiccup centre" (via GABA-ergic offects of baclofen or gabapentin). 29 patients (28 male, one female; age 71 +/- 10 years) suffering from ICS for four to 564 months were treated with a combination of cisapride (30 mg/d), omeprazole (20 mg/d) and baclofen (45 mg/d) (COB). The patients rated the severity of hiccuping on a subjective assessment scale (SAS) that ranged from 0 (= no hiccuping) to 10 (= unbearable hiccuping). Hiccuping ceased in 38% (11/29) of the treated patients and decreased in severity in an additional 24% (7/29). Mean SAS-scores following 20 to 24 weeks of therapy (3.7 +/- 3.4) were significantly lower compared to before therapy (8.8 +/- 1.3) (Mann-Whitney rank order test [p < 0.02]). In the patients that failed to respond to COB, gabapentin (1.200 mg/d) was substituted for baclofen. Hiccuping ceased in one and improved in two of these ten subjects. We conclude that COB is an effective empirical therapy in the majority of patients with ICS. It may be useful to substitute gabapentin for baclofen in those not responding to COB.

Acetates

In vitro paraoxon (E 600) exposure: no activating effect on human blood coagulation.

The in vitro effects of the organophosphorus compound (OPC) paraoxon (POX) on human blood coagulation were assessed by fibrin monomer (FM) concentration measurements and thrombelastographic (TEG) determinations. Increasing doses of POX dissolved in alcohol (POX + ALO) or alcohol (ALO) only in corresponding quantities were added to blood drawn from six human volunteers. In both series (POX + ALO and ALO-only) FM concentrations increased in comparison to the baseline levels. No statistically significant differences exist, however, between FM measurements performed on blood with POX + ALO and those performed on blood with ALO-only. No coagulation-activating effect of POX in vitro was demonstrable; the changes seen in vitro are due to the ALO used as a vehicle. The thrombelastographic parameters showed several changes in the POX + ALO series as dosage increased. At high POX levels, reaction time r and clot formation time k became longer than in the baseline measurements, the clot formation rate alpha and the maximum amplitude MA were reduced. The TEG changes indicate a hypocoagulable state, probably due to the POX effect on platelet function and/or inhibition of clotting factors (serine proteases).

Blood Coagulation

Transplacental kinetics of lead in pregnant mini-pigs.

This study examined the maternal and fetal blood kinetics of lead in pregnant, near term mini-pigs. A lead dose of 1 mg/kg was administered to the animals by i.v. injection as bolus. During the 5-h sampling period, the two-compartment maternal pharmacokinetics demonstrated a rapid phase T1/2 of 8 min and a slower phase T1/2 of 199 min. Lead reached the fetus with a time lag of 81 min. At 24 h after administration the ratio of fetal to maternal blood lead concentration seemed to become stable. When lead was injected directly into the fetal blood circulation, the decay of fetal blood lead fitted one-compartment model. The disappearance half-life was 92 min. Lead can obviously accumulate in fetal liver; the lead level in fetal brain showed no detectable changes. This study confirmed that lead can also pass through the epitheliochorial placenta.

Animals

[Stress free anesthesia induction ZESTRANI (ZEro STRess ANesthesia Induction) in Göttingen minipigs. An experimental method].

The Göttingen Mini-pig is a popular laboratory animal, that is used i.a. in experimental surgery and anaesthesia. For ethical and scientific reasons it is mandatory to minimize the stress the laboratory animals are exposed to. The presented stress-free experimental anaesthesia induction (ZESTRANI) is based on innovative means to achieve adequate analgesia using different substances appropriate for the animal's state of consciousness. Markedly lower heart rates and mean arterial pressures are seen when the ZESTRANI-method is used as compared retrospectively to the previously used "conventional" anaesthesia induction. With the ZESTRANI method no "fight or flight"-reactions are seen.

Anesthesia, General

A portable quantitative capnometer in test.

A new hand-held quantitative capnometer (BCI Capnocheck) was tested in the animal lab setting. The end-tidal CO2 values, as measured with this device, showed good agreement with arterial (Paco2) values. This device seems suited for quantitative capnometry in the prehospital setting. It must be noted, however, that this device has no alarms.

Animals

Oximetry for amniotic fluid embolism detection in mini-pigs: tail or snout?

The continuous, non-invasive real-time monitoring of arterial oxygenation (pulse oximetry) has become a standard of care in both human and veterinary medicine. It allows reliable, simple and inexpensive assessment of the arterial oxygenation status. In pigs, commonly used sites for oximetry-probe placement are the ear, snout or tongue, while more recently the 'pig-tail oximetry' has been suggested. In a study regarding the coagulation system during amniotic fluid embolism (AFE) in mini-pigs, we compared tail and snout for oximetry-probe placement and compared them with the 'gold standard': blood-gas analysis (BGA). In both the AFE group and the control group, the tail measurements were slightly lower and the snout measurements were slightly higher than the BGA results. In the experimental model used, both tail and snout measurements were able to detect a temporary desaturation immediately after amniotic fluid embolism (AFE). Blood-gas analysis (BGA) performed on blood drawn from a large artery missed the event. Clinically, there is no significant difference between snout and tail as oximetry-probe placement sites: both are reliable oximetry sites in mini-pigs.

Animals

[Preclinical control of intubation and artificial respiration. Animal experiment and literature review].

Oesophageal malposition of an endotracheal tube is among the leading causes of anaesthesia incidents. While clinical manoeuvres for detection of tube malposition are unreliable, monitoring (i.e. capnography) can prevent such incidents. The problem is particularly important in prehospital care, where capnography is not (yet) widely available. We tested three devices used for differentiating oesophageal from endotracheal intubation: 1. Non-CO2-dependent Oesophageal Detector Device (ODD) as described by Pollard and Wee, 2. Semi-quantitative chemical disposable capnometer EasyCAP (Nellcor), 3. Non-quantitative infrared miniaturised capnometer MiniCAP (MSA). METHODS. 50 anaesthetised minipigs were intubated with a Magill tube. An identical additional tube was placed in the oesophagus. The cuffs of both tubes were inflated. Unexperienced personnel (students, laboratory technicians) were asked to determine the position of one of the tubes by using one of the devices according to the randomisation plan. The decision had to be taken within 30 s. Using the ODD, the proband first injected 100 ml air into the lung (or stomach) and then tried to aspirate the same volume. EasyCAP and MiniCAP were used according to manuals. RESULTS. Each device was used 25 times with a tracheal tube and 25 times with an oesophageal tube. All tube position identifications were correct. When ventilating the oesophagus/stomach for capnometric control, regurgitation into the tube occurred six times (five times with the EasyCAP and once with the MiniCAP). In these cases, the decision was based on this occurrence and not on the display of the device. While using the ODD no regurgitation occurred. CONCLUSION. These devices are useful for preclinical practice. According to the literature and our experience, the ODD is superior for the initial control of tube position, especially in cardiac arrest. Capnometry is needed, however, for continuous control of ventilation.

Anesthesiology

Influence of intratracheal application of fluorocarbon 72 and different lipid-mixtures on mechanical behavior of isolated immature pig lungs.

Substitution of surfactant in immature lungs has two functional targets: the reduction of the overall alveolar surface tension and the mechanical stabilization of the system of alveoli having different diameters. Indeed, the lowering of the surface tension facilitates the inflation of the lungs, but according to Laplace's law small and large alveoli are not in pressure equilibrium as long as the surface tension is equal in both small and large alveoli. In the present work, we tried to stabilize the lungs and to compare the effect of bolus surfactant substitution with the two-step substitution of fluorocarbons and surfactant. In all, 24 fetal immature lungs were used. For our experiments we used fluorocarbon 72 (FC-72) with a surface tension of 12 mN/m. In groups 1 and 2, a mixture of dipalmitoylphosphatidylcholine (DPPC): cholesterol 9:1 (molar ratio) or DPPC: phosphatidylglycerol (PG) 9:1 (molar ratio) was administered intratracheally as a bolus. In the case of groups 3 and 4, the immature lungs were rinsed first with FC-72. After removing the fluorocarbon, the lungs were artificially ventilated and the DPPC: cholesterol 9:1 (group 3) or DPPC:PG 9:1 mixture (group 4) was given in aerosol form. Static pressure-volume curves (p-v) of the mean values of the 6 lungs in each group were registered at the beginning (0 min) and after 20 and 40 min of artificial ventilation. Airway opening pressure, weight-specific end-inspiratory lung compliance, and phospholipid contents were investigated.(ABSTRACT TRUNCATED AT 250 WORDS)

1,2-Dipalmitoylphosphatidylcholine

Positive influence of nifedipine on early-stage minipig shock lung.

Mechanical and biochemical lesions can be observed in shock lung. To investigate the influence of the calcium antagonist nifedipine on these lesions, we produced shock lung in male minipigs. Three groups (control, thrombin, and thrombin + nifedipine; n = 5) were formed. In the second and third group thrombin was administered intravenously (400 IU/kg body weight) over a period of 2 h. After that the animals received aminocaproic acid (100 mg/kg body weight/h) throughout the rest of the study. Nifedipine was administered in the third group at a dosage of 46 micrograms/kg body weight/h. During the investigation period coagulation and hemodynamic status were examined as well as blood gas levels. Then the isolated lungs were examined. Without nifedipine there was a significant decrease in arterial PO2, an increase in airway opening pressure (Pi), and a decrease in weight-specific end-inspiratory lung compliance (Ci). These changes were not observed under the influence of nifedipine, after which the results were similar to the control group. This demonstrates a positive influence of nifedipine on the acid-base status and the investigated lung mechanical parameters.

Animals

Mechanical properties of isolated fetal miniature pig lungs after substitution with fluorocarbons.

In our present study we tried to inflate and stabilize isolated immature lungs of fetal minipigs in gestation age of 95 days (= 85% of total normal gestation period) with different fluorocarbons. Based on our previous experiences, the immature lungs at day 95 are almost non inflatable with air. For our experiments we used fluorocarbon 43 (FC-43) with a surface tension of 16 mN/m and fluorocarbon 72 (FC-72) with a surface tension of 12 mN/m. Eighteen fetal immature lungs were used. In group 1 the lungs were rinsed with FC-43; in group 2 the rinse solution was FC-72, and in group 3 the lungs were untreated. After removing the fluorocarbon, in the case of groups 1 and 2, the lungs were artificially ventilated. Pressure-volume (p-v) curves were registered in the beginning (immediately after FC lavage), after 10 and 20 min of artificial ventilation. Airway opening pressure (pi) and weight-specific end-inspiratory lung compliance (ci) were investigated. Statistically significant differences in weight-specific end-inspiratory compliance were found between FC groups and untreated group 3, but no stabilization could be seen during the investigation period of 20 min. No statistically significant improvement in weight-specific end-inspiratory compliance was observed between group 1 and 2, although the compliances of group 2 with FC-72 were better than those of group 1 with FC-43 in three p-v diagrams registered in the beginning and after 10 and 20 min of artificial ventilation.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Mechanical properties of fetal minipig lungs after substitution of surfactant with fluorocarbon and dipalmitoylphosphatidylcholine.

Respiratory distress syndrome (RDS) is characterized by quantitative and qualitative disturbances of surface active substances (surfactant). Therefore, intratracheal surfactant substitution is a favored subject of clinical investigations. In our study we tried to inflate and stabilize lungs in two steps: first, lungs were rinsed with a fluorocarbon and, second, artificially ventilated with a dipalmitoylphosphatidylcholine (DPPC) aerosol, the mean component of surfactant. Sixteen isolated fetal minipig lungs of day 95 (85% of the total gestation period) were used. From one pair of lungs one lung served as control (group 1), whereas the other was treated with DPPC (group II). In both groups the lungs were rinsed first with a fluorocarbon (FC-72, surface tension 12 mN/m). This maneuver was followed by an artificial ventilation with an aerosol of either salt solution (group I) or DPPC (group II) for 40 min. To characterize lung mechanics, static pressure volume curves were registered at 0, 20, and 40 min after fluorocarbon lavage. Airway opening pressure (pi), end-inspiratory volume (vi), and weight-specific end-inspiratory lung compliance (ci) were investigated. As biochemical parameters of the lungs we determined phospholipidphosphate content and DPPC, sphingomyelin (SM), and lysophosphaditylcholine (LPC) of the lung tissue. Significant differences were found with regard to phospholipidphosphate and DPPC content. No difference was seen in static pressure volume diagrams at the end of the investigation period.

1,2-Dipalmitoylphosphatidylcholine