Simplified detection of myocardial ischemia by seismocardiography. Differentiation between causes of altered myocardial function.

Seismocardiography (SCG) is a noninvasive technique for recording cardiac vibrations. Changes in these waves have been correlated with chronic and acute alterations in myocardial function. This analysis is complex and clinical integration limited. The current study aimed to simplify the utilization of SCG by fast Fourier transformation for a reliable discrimination between different intra- and postoperative causes of hypotension (i.e., myocardial ischemia or hypovolemia). We operated on nine pigs and recorded SCG at baseline, at hypovolemia (occlusion of the inferior vena cava), and at ischemia (occlusion of the right coronary artery). In conclusion, SCG enables detection and differentiation of ischemia and hypovolemia as important causes of altered myocardial function during and after surgery. Thus, this simple and noninvasive diagnostic tool may be used intra- and postoperatively to identify patients at risk.

A single exposure to hyperbaric oxygen increases levels of circulating nucleosomes but does not induce mononuclear cell apoptosis in divers.

Recent reports that hyperbaric oxygenation (HBO2) induced apoptosis in T-cell lines raised concern about a possible immunosuppressive effect of HBO2. Nucleosomes, DNA fragments wrapped around a histone core, have been observed in the circulation in diseases with increased cell death such as sepsis. Our aim was to investigate, whether HBO2 increases circulating nucleosomes as a marker of cell death and induces apoptosis of peripheral blood mononuclear cells in vivo. After informed consent 29 healthy volunteers were exposed to a 30 minute dive at 2.8 atmospheres absolute in a pressure chamber under resting conditions, while breathing 100% oxygen. Samples were obtained before and 24 hours after exposure. Circulating nucleosomes were measured in serum. Caspase-3 activation, Bcl-2 expression and mRNA of Bcl-2, Bcl-xl and Bax were analyzed in mononuclear cell extracts. Nucleosomes were elevated markedly 24h after exposure (p<0.01), while caspase-3 was not activated significantly. mRNA levels of Bcl-2, Bcl-xl and Bax were not altered. In conclusion, while evidence of elevated levels of circulating nucleosomes was found, mononuclear cell apoptosis was not affected by a single exposure to hyperbaric oxygen.

[Hyperbaric oxygenation: characteristics of intensive care and emergency therapy]. / Hyperbare Sauerstofftherapie: Notfall- und intensivmedizinische Besonderheiten.

Hyperbaric oxygenation (HBO) is a decisive component of a comprehensive interdisciplinary intensive care therapy for numerous disorders, such as gas embolism, severe decompression illness or carbon monoxide (CO) intoxication. However, barochambers with 24 h accessibility are often not readily available, thus, requiring an interhospital transport of critically ill patients. In order to minimise additional risks, a skilled transportation team should be involved. Furthermore, the specific physical and physiological features of HBO require that the transportation personnel must be trained adequately. Specific characteristics of the interhospital transfer of HBO patients are described as well as adverse effects and their specific therapy.

[Hyperbaric oxygen therapy (HBO): current standing]. / Hyperbare Oxygenationstherapie (HBO): eine Standortbestimmung.

For more than thirty years hyperbaric oxygen therapy (HBO) has been an important and ultimate therapeutic tool in special indications. Hyperbaric oxygen improves tissue oxygenation, stimulates important mechanisms in wound healing and exerts beneficial effects on other biochemical and cellular processes. The properties of hyperbaric oxygen have built the rationale for its use as therapy of choice in patients with severe carbon monoxide poisoning, decompression sickness and arterial gas embolism, and as adjunctive therapy for the treatment of osteoradionecrosis, necrotizing fasciitis and compromised skin grafts and flaps. The efficacy of adjunctive hyperbaric oxygen in the treatment of lower extremity problem wounds in diabetic patients seems to be proven. There is little scientific support for other uses of hyperbaric oxygen and its therapeutical benefit should be further investigated. When used according to standard protocols hyperbaric oxygen treatment is a safe therapy with little adverse effects.

Lidocaine pharmacokinetics during hyperbaric hyperoxia in humans.

METHODS: The disposition of drugs may be influenced by hyperbaric conditions, in particular by changes of liver perfusion. The effect of hyperbaric hyperoxia on the pharmacokinetics of lidocaine, a drug eliminated in the liver with a perfusion-limited clearance, was investigated in human volunteers in a crossover trial. METHODS: A single dose lidocaine i.v. bolus (0.69 or 0.75 mg x kg(-1)) was administered to two volunteers under normobaric conditions (NB: 1 bar or 0.1 MPa, air) and under hyperbaric/hyperoxic conditions (HBO: 2.5 bar or 0.25 MPa, alternating 100% O2-breathing for 20 min and air breathing for 5 min). Blood samples were serially collected for 5 h (NB) or 75 min (HBO), and lidocaine concentration in serum was measured by immunoassay. Data were analyzed assuming linear kinetics and an open two-compartment model. RESULTS: At 1 bar or 0.1 MPa, lidocaine injection caused only slight dizziness and buzzing in the ear. Heart rate and blood pressure were not influenced. Under HBO, lidocaine injection caused marked dizziness and buzzing in the ears, sweating, tremor and coordination-disturbances, even though maximal lidocaine concentrations (0.63 mg x L(-1) and 0.70 mg x L(-1)) were far below therapeutic serum concentrations (1.5-5.0 mg x L(-1)). Pharmacokinetic parameters of lidocaine were similar to those published earlier (T1/2beta: 110+/-16 min; CI: 12.6+/-2.9 ml x min(-1) x kg(-1); Vss: 1.73+/-0.18 L x kg(-1)). There was no indication for effects of HBO on the disposition of lidocaine (p > 0.05). CONCLUSION: The pharmacokinetics of lidocaine do not seem to be influenced in a clinically relevant way in humans by a single HBO-exposure under usual therapeutic conditions. Side effects of lidocaine at 2.5 bar or 0.25 MPa may be caused by pharmacodynamic interactions between lidocaine and hyperbaric/hyperoxic conditions.

Effects of hyperbaric and hyperoxic conditions on the disposition of drugs: theoretical considerations and a review of the literature.

1. Hyperbaric or hyperoxic or both conditions may affect the disposition of drugs by (1) changes in the catalytic activity of drug metabolizing enzymes, (2) hemodynamic changes and (3) changes in membrane permeability, affecting drug distribution. 2. In isolated microsome preparations from rat liver, the metabolism rate of aniline, but not of amidopirin, is reduced by hyperoxia. In vivo, the clearance of salicylic acid is enhanced in the dog at 2.8 ATA and 100% O2, but not at 6 ATA and air, for reasons that are still unknown. The disposition of theophylline, pentobarbital or pethidine is not affected in dogs by hyperbaric or hyperoxic conditions. 3. In human volunteers, hyperbaric or hyperoxic or both conditions do not affect the disposition of gentamycin (2.4 bar, 100% O2), caffeine or lidocaine (2.5 bar, 100% O2). 4. In conclusion, a single exposure to hyperbaric or hyperoxic conditions does not seem to affect single-dose pharmacokinetics of drugs eliminated by the kidney (gentamycin) or by the liver with a capacity-limited clearance (pentobarbital, theophylline, caffeine) or with a perfusion-limited clearance (pethidine, lidocaine). The enhancement of salicylic acid clearance in dogs under hyperoxic conditions remains unclear.

Caffeine pharmacokinetics during hyperbaric hyperoxia in humans.

The effect of hyperbaric hyperoxia on the pharmacokinetics of caffeine was investigated in human volunteers. Some 600 ml of coffee were administered to 2 volunteers and blood samples were serially collected for 24 h. The volunteers entered a hyperbaric chamber 2.5 h following coffee ingestion for a total period of 110 min (0.25 MPa, alternating 100% O2-breathing for 20 min and air breathing for 5 min). The concentrations of caffeine in serum was determined by high pressure liquid chromatography. The caffeine amount ingested was determined by analyzing an aliquot of the coffee beverage. Data were analyzed assuming linear kinetics and an open one-compartment model. Effects of hyperbaric hyperoxia on caffeine disposition were investigated using a runs test. Moreover, a one-population t-test was applied to residuals, separately for data from the initial normobaric period, the hyperbaric period and the terminal normobaric period. Pharmacokinetic parameters were similar to established literature data on caffeine [Volunteer 1: maximal concentration (Cmax: 6.13 mg.L-1 at Tmax: 55 min, half-time of elimination (T1/2: 180 min, total clearance (Cl): 3.41 ml.min-1.kg-1; volume of distribution (Vd: 0.88 I.kg-1; Volunteer 2: Cmax: 6.23 mg.L-1, Tmax: 94 min, T1/2: 283 min, Cl: 1.90 ml.min-1.kg-1, Vd: 0.77 L.kg-1). The runs test as well as the analysis of residuals gave no evidence for alterations of caffeine disposition by hyperoxia (p > 0.05). The pharmacokinetics of caffeine do not seem to be influenced in a clinically relevant way in humans during a stay for 100 min at 0.25 MPa, alternating 100% O2 and air breathing.

[Changes in hemodynamic values in various phases of pelviscopy]. / Veränderungen hämodynamischer Kenngrössen in den verschiedenen Phasen der Pelviskopie.

In 57 patients the effects of various stages during routine laparoscopy (induction of anaesthesia, intraabdominal insufflation of carbon dioxide, changes in body position) on cardiac performance were investigated. For the measurement of cardiac output we used the noninvasive thoracic impedance cardiography. After induction of anaesthesia and with terminated CO2 insufflation cardiac index significantly decreased compared to the reference values prior to surgical intervention (3.21 L/m2 vs. 1.96 L/m2; p less than 0.0001). At the end of laparoscopy in Trendelenburg position there was a slight increase in cardiac index with 2.26 L/m2. After the patients had been returned to the horizontal position and the abdomen was then deflated cardiac index almost reached the values at the beginning of laparoscopy. We demonstrated a high reproducibility in cardiac output measurements using impedance cardiography when comparing the respective values 24 hours prior to laparoscopy and those results investigated 24-48 hours after the surgical intervention. With regard to clinical situations of hypovolemia, f.e. ruptured ectopic pregnancies it is evident that the described alterations in cardiac performance should be considered.

Decreased myometrial beta-adrenoceptors in women receiving beta 2-adrenergic tocolytic therapy: correlation with lymphocyte beta-adrenoceptors.

We have determined simultaneously the density of beta-adrenoceptors in human myometria (by (-)-[125I]iodopindolol binding) derived from 36 women undergoing cesarean section and in the corresponding circulating lymphocytes (by (-)-[125I]iodocyanopindolol binding). In myometrial membranes about 80% to 85% of the beta-adrenoceptors were of the beta 2-subtype. The density of myometrial and lymphocyte beta-adrenoceptors in women treated with the beta 2-adrenoceptor agonist hexoprenaline to prevent preterm labor was about 65% to 70% lower than that in nontreated women. Concomitantly, in hexoprenaline-treated women the 10 mumol/L isoproterenol-evoked increase in lymphocyte cyclic adenosine monophosphate content (as index for lymphocyte beta-adrenoceptor responsiveness) was diminished to a similar extent. Combining all data resulted in a significant positive correlation between myometrial and lymphocyte beta-adrenoceptor densities (r = 0.7303; n = 36; p less than 0.001). It is possible that determination of beta-adrenoceptor function in circulating lymphocytes may be a useful model to monitor myometrial beta-adrenoceptor changes during tocolytic therapy.

Hemodynamic and hemorheological profiles in women with proteinuric hypertension of pregnancy and in pregnant controls.

We obtained blood samples from 52 patients with pre-eclampsia and from 40 pregnant controls for measurement of plasma urate levels, hematocrit, white cell count and various hemorheological parameters. We also used impedance cardiography to measure cardiac output in both groups and from the results derived values for total peripheral resistance and oxygen transport. Central venous pressure was measured with a superior vena cava catheter in patients with pre-eclampsia but not in controls. Women with pre-eclampsia had significantly lower cardiac output and central venous pressure when compared with a control group. A modest correlation was observed between central venous pressure and cardiac output. The majority of pre-eclamptic patients had significantly raised hematocrit, leucocyte count, uric acid and red cell aggregation. Red cell deformability was significantly decreased in patients with pre-eclampsia. Most patients with severe pre-eclampsia (BP diast. greater than 100 mmHg) had a low Antithrombin III and colloid osmotic pressure level. The leucocyte count was raised when compared with the women with moderate pre-eclampsia. Oxygen delivery was reduced in patients with pre-eclampsia because of impaired rheological properties of their blood.

[Seminar: electronic data processing in gynecology and obstetrics]. / Seminar: EDV in Gynäkologie und Geburtshilfe.

Several possible procedures were discussed for computerizing clinical research and basic documentation. All approaches were evaluated with regard to available performance and installation effort. Additionally examples for personal computer aided data collection in the field of perinatology, oncology, endocrinology and expert systems were presented.

[Prenatal sonographic diagnosis of abnormalities and the significance of prepartum therapeutic procedures]. / Geburtshilflich-sonographische Diagnostik von Fehlbildungen und Bedeutung präpartualer Therapieverfahren.

Between 1981 and October 1985, prenatal ultrasound examinations revealed 19 malformations of the central nervous system, 13 intestinal malformations, 15 malformations of the urogenital tract, four non-immunological cases of hydrops fetalis, two sacral teratomas and one cardiac malformation. In only one of eleven cases of hydrocephalus were all preconditions fulfilled for considering an intra-uterine ventriculo-amniotic shunt insertion. In bilateral obstructive uropathy the dynamics of amniotic fluid volume both before and after intra-amniotic administration of an infusion is decisive for any further prognostic assessment. There are marked differences regarding the neonatal survival rate between the various organ-specific malformations (gastro-intestinal: 31%; hydrocephalus: 55%; obstructive uropathy: 89%). Personal experience suggests that there are only a few cases requiring intra-uterine, predominantly invasive, treatment. The value of prenatal ultrasound examination lies mainly in early diagnosis and the resulting choice of subsequent obstetric measures. Of particular importance is an interdisciplinary collaboration with specialists in allied fields.

Simultaneous investigations of maternal cardiac output and fetal blood flow during hypervolemic hemodilution in preeclampsia--preliminary observations.

In pre-eclampsia hemodynamic alterations are characterized by a lack of plasma volume expansion and a raised peripheral vascular resistance. For the compensation of plasma volume deficit and to restitute blood fluidity the therapeutic use of plasma volume expanders (f.e. low molecular dextran) is recommended. Several groups (Goodlin et al., Cloeren et al., Heilmann et al., Seghal et al., Schröck) have demonstrated benefitial effects on fetal status and development in the course of hypervolemic hemodilution in preeclampsia. This therapeutic procedure presumes the continuous surveillance of maternal hemodynamics to early recognize heart insufficiency or fluid overload in the lungs. We use the noninvasive thoracic impedance cardiography for continuous monitoring of maternal heart performance. The effect of hypervolemic hemodilution on fetal circulation has not been quantitatively investigated yet. Meanwhile pulsed doppler ultrasonography offers the possibility of estimating quantitative changes on fetal blood flow. We used both noninvasive techniques--thoracic impedance cardiography and pulsed doppler imaging system--for the simultaneous evaluation of maternal and fetal hemodynamic parameters during hypervolemic hemodilution. This preliminary report summarizes the investigations in 5 patients with pre-eclampsia (mean arterial blood pressure greater than or equal to 103.3 mm Hg, hemoconcentration with elevated hematocrit levels greater than or equal to 38%). The patients received an infusion of 500 ml dextran 40 over a period of exactly 60 minutes. The simultaneous measurements of maternal and fetal cardiovascular parameters were performed in 15-minutes intervals during dextran application and 15 minutes (p 15), 30 minutes (p 30) and 60 minutes (p 60) after the end of infusion.(ABSTRACT TRUNCATED AT 250 WORDS)

Different mechanisms underlying reduced beta 2-adrenoceptor responsiveness in lymphocytes from neonates and old subjects.

To investigate the mechanism underlying age-dependent changes in beta-adrenoceptor function we have determined beta 2-adrenoceptor density (by (+/-)-125iodocyanopindolol (ICYP) binding) and beta 2-responsiveness (cyclic AMP responses to isoprenaline stimulation) in lymphocytes derived from 20 neonates, 54 young adults (19-30 years) and 15 old subjects (60-86 years). In young adults the mean number of lymphocyte beta 2-adrenoceptors amounted to 862 +/- 36 (range 500-1560) ICYP binding sites/cell (N = 54); it was slightly higher in old subjects with 1230 +/- 94 (698-1980) ICYP binding sites/cell (N = 15). In contrast, lymphocytes derived from neonatal blood had a significantly lower mean beta 2-adrenoceptor number (385 +/- 35 (130-608) ICYP binding sites/cell, N = 20, P less than 0.01). (-)-Isoprenaline (0.01-100 microM)-induced increases in lymphocyte cyclic AMP content were significantly lower in neonates and old subjects than in young adults. While for neonates and young adults significant positive correlations between beta 2-adrenoceptor density and 10 microM (-)-isoprenaline-induced cyclic AMP increases exist, in old subjects cyclic AMP increases were much lower than could be expected from the beta 2-adrenoceptor number. It is concluded that the mechanism underlying reduced beta 2-adrenoceptor responsiveness in neonates and old subjects is different: while in neonates it seems to be due to the reduced beta-adrenoceptor number, in old subjects it is caused by a post-receptor defect--presumably by a decreased activity of the adenylate cyclase.

[Chorioamniotic infections following diagnostic amniocentesis in the 2d trimester]. / Chorioamniale Infektionen nach diagnostischer Amniocentese im II. Trimenon.

Between 1978 and 1984 we performed 3 122 amniocentesis for prenatal diagnosis in second trimester. Based on a four week follow-up in more than 96% of all amniocentesis the percentage of fetal loss was 0.74% (n = 23). In 13 cases abortion was accompanied by chorioamnionitis. These cases were examined for various technical details and it could be concluded, that the incidence of febrile abortion is related to the early gestational age for amniocentesis. On the other hand, multiple insertions or the localisation of placenta both show no relation to the short-time febrile complications. To investigate the maternal-fetal transfer of mezlocillin, a single dose of 5 g mezlocillin was administered intravenously in 25 patients. In amniotic fluid mezlocillin levels exceeded 2 micrograms/ml nearly 120 minutes after administration. These pharmacokinetic data suggest, that a prophylactic regimen with antibiotics in the course of amniocentesis seems not to be beneficial for the prevention of chorio-amniotic infections.

[Hexoprenaline--a new tocolytic for treatment of premature labor]. / Hexoprenalin--ein neues Tokolytikum zur Behandlung der vorzeitigen Wehentätigkeit.

Hexoprenaline is a selective beta 2-mimetic drug used in tocology for the prevention of premature labor and immature birth. From clinical application of the drug in bronchospasm therapy its selectivity, which is due to the elongated nitrogen substituent, is well-known. Because of the relatively small stimulation of cardiac beta 1-receptors the side-effects related therewith are less pronounced than with other beta-mimetics. The extent of tachycardia depends on the initial sympathomimetic condition of the patients. The success rate for hexoprenaline tocolyses is 34-78%, dependent on the initial tocological condition. The advantage of hexoprenaline compared with other tocolytics on the basis of experience made so far seems to relate to the smaller increase in chronotropy and the better tolerability.

[Maternal and fetal hemodynamics under simultaneous beta stimulation and beta1 blockade in a tocolysis model. Considerations on status of the neonatal beta receptor and transplacental passage of metoprolol]. / Maternale und fetale Hämodynamik unter gleichzeitiger beta-Stimulation und beta1-Blockade am Tokolysemodell. Berücksichtigung des neonatalen beta-Rezeptorenstatus und der transplazentaren Metoprolol-Passage).

This report summarizes the clinical experiences in the treatment of preterm labor using the combination of hexoprenaline and the beta 1-antagonist metoprolol. We found a dose dependency in the antagonism of positive inotropic effects primarily induced by the beta-stimulator hexoprenaline. To verify the pharmacological properties of metoprolol in transplacental passage we evaluated the plasma concentration of metoprolol in umbilical cord blood. There is quite a low concentration of the beta-blocker nearly 24 h after the last course of administration. The beta 2-receptor density--determined by (+/-)-125-iodocyanopindolol (ICYP) binding--and beta 2-receptor responsiveness--assessed by cyclic AMP response to isoprenaline stimulation--in lymphocytes derived from neonatal blood were also investigated. These results were compared with identical investigations in adult lymphocytes. The results indicate that in neonates beta 2-receptor density and responsiveness is significantly diminished in comparison to the adult controls. The present investigations induce a new concept for the estimation of concomitant fetal cardiovascular reactions under maternal beta-blockade.

[Effect of metoprolol on the flow properties of blood]. / Der Effekt von Metoprolol auf die Fliesseigenschaften des Blutes.

In the present article the interaction of 1- isopropylamino-3-[4-(2-methoxyethyl)-phenoxy]-2-propanol (metoprolol, Beloc) with human erythrocytes is reported. Metoprolol is well known and acts mainly as a selective beta-1-antagonist. While erythrocyte aggregation, suspension osmolality and pH-values were unchanged, red cell deformability was markedly improved. Investigation into the furosemide-sensitive fluxes resulted in an inhibition of sodium efflux and in a constant water content of human erythrocytes. These in vitro results suggest that metoprolol induced improvement of red cell deformability cannot be explained by shape changes of erythrocytes.

[Treatment results in malignant tumors of the vulva, a retrospective analysis of 119 cases]. / Behandlungsergebnisse beim Malignom der Vulva, eine retrospektive Analyse an 119 Fällen.

Between 1960 and 1980 111 patients with malignomas of the vulva were treated. Among these 86 cases were admitted primarily with view of treatment. Within the period conception of therapy was changed drastically. Where as in former time treatment consists in excision of the tumour with following conventional X-ray therapy, since 1973 therapy of choice was radical vulvectomy with inguinal lymphonodectomy. Based on these facts a retrospective comparison of the survival rates in possible, particularly distribution of stages is likely the same in the two groups. The group treated since 1973 has essential better survival rates. This can be attributed to the conception of radical operative treatment preferred in literature predominantly. Mortality rate is below 5 per cent which will be favourable in the geriatric clientele. To make the results of treatment comparable internationally a postoperative classification should be proposed like in breast cancer. The question of the position of an additional postoperative irradiation is to be answered only with aid of a prospective multicenter study.