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H C Pape

Publications and source records attributed to H C Pape.

14 recordsLinked to original sources
PubMed1992

Nitric oxide controls oscillatory activity in thalamocortical neurons.

Nitric oxide (NO) is considered a diffusible messenger involved in neuronal communication, although the post-synaptic target cells of NO action and the associated biological function in the CNS are still a matter of controversy. Within the discrete pattern of NO-synthesizing neurons in the brain, NO synthase is specifically colocalized with the cholinergic brain stem-thalamic system, which is thought to regulate the state-dependent activity of the thalamocortical circuit. Here we report evidence indicating that the release of NO onto thalamocortical neurons results in an alteration in voltage dependence of the hyperpolarization-activated cation conductance, probably mediated via the cGMP system. NO selectively dampens oscillatory neuronal activity, indicating a rapidly diffusing signaling mechanism that controls the functional state of the thalamocortical network.

Animals↗
PubMed1992

Pulmonary damage after intramedullary femoral nailing in traumatized sheep--is there an effect from different nailing methods?

Stabilization of femoral shaft fractures is a controversial issue in the management of patients with multiple trauma. Intramedullary nailing usually is preferred primarily; in recent years, however, pulmonary complications (e.g., ARDS) have been reported that were attributed to the reaming procedure. To study the effects of different nailing methods in a model of severe trauma, hemorrhagic shock and lung contusion were created at day 1 in sheep prepared by the method described by Staub. After recuperation (day 3) the animals in the study group (group 1) underwent intramedullary nailing of a closed femur without prior reaming; group 2 was treated with reaming and nailing according to AO standards. The reaming procedure led to an acute increase of pulmonary arterial pressure only in group 2 (19.8 +/- 2.1 to 31.0 +/- 4.6 mm Hg). Pulmonary triglyceride levels increased at parallel time points from 18.27 +/- 2.3 to 33.04 +/- 7.37 mg/dL only in group 2. Stimulatory capacity of polymorphonuclear leukocytes (PMNL) increased in the study group and decreased in controls (group 1: 2.652 +/- 0.23 x 10(6) cpm to 3.387 +/- 1.34 x 10(6) cpm; group 2: 2.699 +/- 0.34 x 10(6) cpm to 2.460 +/- 0.187 x 10(6) cpm). Intramedullary nailing caused an increase of lung capillary permeability in both groups; in the study group less damage was seen (group 1: 0.390 +/- 0.0006 to 0.354 +/- 0.011; group 2: 0.391 +/- 0.0004 to 0.336 +/- 0.015; p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylglucosaminidase↗
PubMed1992

Adenosine promotes burst activity in guinea-pig geniculocortical neurones through two different ionic mechanisms.

1. The mechanisms of action of adenosine were examined in relay neurones of the dorsal lateral geniculate nucleus (LGND) using in vitro intracellular recording techniques in guinea-pig thalamic slices. 2. Adenosine hyperpolarized LGND relay neurones due to an increase in membrane potassium conductance. The K+ currents generated by near maximal stimulation of adenosine and GABAB receptors were non-additive. 3. Blockage of membrane K+ conductances by barium unmasked a second response to adenosine; an outward shift of the current versus voltage relationship negative to -65 mV associated with an increase in membrane input resistance. The beta-adrenoceptor agonist isoprenaline elicited an inward current in the same voltage range, which was inhibited and replaced by an outward current during activation of adenosine receptors. The effects of adenosine were due to a decrease in amplitude and rate of rise of the hyperpolarization-activated cation current, Ih. Maximal reduction by 66% of Ih amplitude occurred near the range of half-activation. 4. Both responses to adenosine were mimicked by the selective A1 receptor agonists N6-cyclopentyladenosine or N6-cyclohexyladenosine, and reversibly blocked by the selective A1 receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX). 5. The decrease in Ih by adenosine may be mediated by an inhibition of adenylyl cyclase activity and hence a decrease in the intracellular level of cyclic AMP, since local application of the adenylyl cyclase inhibitor 2',3'-dideoxyadenosine imitated the decrease in Ih. Local application of the adenylyl cyclase stimulant forskolin or 8-bromo-cyclic AMP resulted in an enhancement in Ih, and forskolin inhibited the action on Ih evoked by N6-cyclopentyladenosine. 6. The adenosine-induced effects interacted with the intrinsic electrophysiological properties of LGND neurones in that (i) the hyperpolarization due to an increase in K+ conductance inhibited single spike firing and promoted calcium-mediated burst discharges, and (ii) the decrease in Ih inhibited the dampening effect on Ca(2+)-mediated rebound activity of beta-adrenergic receptor stimulation. 7. It is suggested that during increased levels of extracellular adenosine the response of LGND relay neurones to activating brainstem influences will be depressed, and a pattern of Ca(2+)-mediated burst firing will be favoured.

Adenosine↗
PubMed1992

[Effects of different intramedullary stabilizing procedures of the femur on lung function in polytrauma].

We investigated the effects of primary (< 24 h) intramedullary femoral nailing on lung function and pulmonary hemodynamics in multiple trauma patients. The standard procedure following reaming of the medullary canal (AFN) was compared with a new procedure using a small, solid nail without prior reaming (UFN). Pulmonary hemodynamics were determined using a pulmonary artery catheter. Global lung function was assessed by means of the oxygenation ratio (PaO2/FiO2). Concentrations of elastase and the platelet count as a general parameter of the clinical course were determined from central venous blood during and 3 days after surgery. The lung function was stable in UFN patients (n = 6), but decreased significantly in AFN patients (n = 10) from 353 +/- 24 (PaO2/FiO2 preoperative) to 260 +/- 28 (PaO2/FiO2 postoperative) and did not improve until 48 h later. Pulmonary artery pressure (Pap) remained within normal limits in UFN patients, whereas in AFN patients Pap increased from 27.4 +/- 3 mm Hg (preoperative) to 37 +/- 3 mm Hg during reaming and did not normalize until 1 h after insertion of the nail. The platelet count remained unchanged in UFN patients and dropped in AFN patients from 143 +/- 25 x 1000 cells/ml blood (preoperative) to 87.5 +/- 15 x 1000 cells/ml blood 2 days after surgery. Our measurements did not show an increase in central venous triglycerides in the AFN group, probably because bone marrow does not become immediately soluble. There was no significant difference between the increase of elactase levels in the two groups. The femoral nailing procedure with reaming in multiple trauma patients involves a potential risk to the lung.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1992

[Can post-traumatic renal failure be modified therapeutically?].

Acute renal failure in the late phase after severe trauma is particularly dangerous, since it is resistant to therapy and contributes to the development of post-traumatic multiple organ failure. We have studied different treatment regimes in order to establish whether late renal failure can be prevented (study A: colloidal and crystalloid solutions; study B greater than: crystalloid solutions and dopamine; continuous infusion 3 micrograms/kg body weight). Renal function was assessed by means of the score by Goris as well as by creatinine clearance over a period of 14 days. Haemodynamics and cardiac function were determined on a daily basis. The demographic parameters were comparable in both groups. In group A 37 of 61 patients died (60.6%), and in group B 17 of 38 patients (44.7%) (P less than 0.05). The incidence of impairment of renal function was comparable; in group A there was significantly more severe damage (18%) compared to group B (2.6%). This coincided with significantly higher mortality in group A (group A: 60.65%; group B: 44.7%). In group A a lesser volume was given during the preclinical and clinical course, even after correcting for the volume-saving effect of colloidal solutions. In addition, cardiac index was higher in group B (day 9: 5.9 +/- 0.61 l/min) than in group A (day 9: 4.4 +/- 0.5 l/min) and pulmonary capillary wedge pressure (PCWP) was lower and systemic vascular resistance (SVR) higher over the whole period. Also, the arterio-venous oxygen difference (AvDO2) was higher following day 9 in patients in group A, but creatinine clearance was better in group B patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Kidney Injury↗
PubMed1992

Determination of human neutrophil elastase in bronchoalveolar lavage fluid: homogeneous immunoactivation versus heterogeneous enzyme immunoassay.

Elastase mass concentrations of bronchoalveolar lavage fluid were determined by a homogeneous immunoactivation and a heterogeneous enzyme immunoassay. There was an excellent correlation between both assay systems (y = 1.0376 . x + 1.311; r = 0.9901; n = 43) indicating the suitability of the immunoactivation method for the determination of elastase concentrations in bronchoalveolar lavage fluid as a matrix. Furthermore, dilution of bronchoalveolar lavage fluid samples did not influence the elastase recovery of either assay system.

Bronchoalveolar Lavage Fluid↗
PubMed1991

Actions of norepinephrine in the cerebral cortex and thalamus: implications for function of the central noradrenergic system.

Norepinephrine (NE) has potent and long-lasting ionic effects on cortical and thalamic neurons. In cortical pyramidal cells, activation of beta-adrenergic receptors results in an enhanced excitability and responsiveness to depolarizing inputs. This enhanced excitability is expressed as a reduction in spike frequency adaptation and is mediated by a marked suppression of a slow Ca(++)-activated potassium current known as IAHP. In the thalamus, application of NE results in the suppression of ongoing rhythmic burst activity and a switch to the single spike firing mode of action potential generation. This effect is mediated through an alpha 1-adrenergic suppression of a resting leak potassium current, IKL, and through a beta-adrenoceptor-mediated enhancement of the hyperpolarization activated cation current Ih. Together with the actions of other neuromodulatory neurotransmitters (i.e., acetylcholine, histamine, serotonin) these effects facilitate the switch of these neurons from a state of rhythmic oscillation and low excitability during drowsiness and slow-wave sleep to a state of increased excitability and responsiveness during periods of waking, attentiveness and cognition.

Action Potentials↗
PubMed1991

[Does lung contusion and general injury severity have an effect on the lung following intramedullary femoral nailing? An animal model].

We evaluated changes in lung function after closed intramedullary femoral nailing (IMN) in sheep. The effects of isolated IMN were compared with those of nailing after lung contusion and hemorrhagic shock. In adult female merino sheep a chronic lung lymph fistula was prepared according to the method described by Staub. At day 1, group 1 received right-sided lung contusion and hemorrhagic shock to a mean blood pressure of 50 mmHg for 2 h. Group 2 was the control group. At day 3 both groups were submitted to IMN, followed by a 2-h observation period. IMN caused a transient significant increase in pulmonary artery pressure and central venous triglycerides in both groups. Chemiluminescence of isolated polymorphonuclear leukocytes (PMNL) decreased in group 1 from 2.699 +/- 0.344 to 2.460 +/- 0.187 x 10(6) cpm/25000 PMNL and increased in group 2 from 2.757 +/- 0.127 to 3.824 +/- 0.439 x 10(6) cpm/25000 PMNL. Lymph flow in group 1 increased 1.5-fold while microvascular pressure decreased. In group 2 lymph flow increased less, while MVP increased. The filtration coefficient in group 1 was 5 times (7.533 +/- 0.044) that in the control group (1.45 +/- 0.133). Calculations of permeability indicated a 2-fold increase (0.044 group 1 vs 0.026 group 2). In the presence of previous lung contusion and hemorrhagic shock there is definite lung damage from IMN. This is probably mediated by stimulation of PMNL.

Animals↗
PubMed1991

[Multiple organ failure. Reflection of generalized cell damage of all organs following severe trauma].

Multiple organ failure (MOF) is presently recognized as the most severe, and often lethal, complication after multiple trauma. Causal factors and pathomechanisms remain unclear, however. Generalized inflammatory cell tissue injury with a subsequent increase in permeability in all organs has been suggested. For this reason, 38 polytraumatized patients were examined in a prospective study. Organ function was analyzed, and specific clinical and histological studies were performed to check for generalized cell tissue damage and increased respiratory permeability. In all organs we found signs of tissue damage immediately after trauma. Disturbances of organ function were seen consistently, starting precisely from day 4. It was not possible to confirm an influence of blunt organ trauma on organ function during follow-up. The severity of injury (especially intrathoracic and intraabdominal) and massive bleeding increases the risk of MOF. MOF was not always associated with the onset of sepsis, and no temporal dependence could be shown. Histological studies demonstrated an inflammatory change in organ tissues, which is probably the result of toxic substances (endotoxin, TNF, oxygen radicals, proteases and eicanosoids) released into the blood circulation after trauma. Insufficient neutralization of these toxic metabolites leads to generalized permeability damage and consequently to progressive organ failure. Therefore, even with optimized initial treatment of multiple trauma patients, MOV and mortality can only be reduced with a causal approach to therapy.

Adolescent↗
PubMed1990

Properties of a hyperpolarization-activated cation current and its role in rhythmic oscillation in thalamic relay neurones.

1. The physiological and functional features of time-dependent anomalous rectification activated by hyperpolarization and the current which underlies it, Ih, were examined in guinea-pig and cat thalamocortical relay neurones using in vitro intracellular recording techniques in thalamic slices. 2. Hyperpolarization of the membrane from rest with a constant-current pulse resulted in time-dependent rectification, expressed as a depolarizing sag of the membrane potential back towards rest. Under voltage clamp conditions, hyperpolarizing steps to membrane potentials negative to approximately -60 mV were associated with the activation of a slow inward current, Ih, which showed no inactivation with time. 3. The activation curve of the conductance underlying Ih was obtained through analysis of tail currents and ranged from -60 to -90 mV, with half-activation occurring at -75 mV. The time course of activation of Ih was well fitted by a single-exponential function and was strongly voltage dependent, with time constants ranging from greater than 1-2 s at threshold to an average of 229 ms at -95 mV. The time course of de-activation was also described by a single-exponential function, was voltage dependent, and the time constant ranged from an average of 1000 ms at -80 mV to 347 ms at -55 mV. 4. Raising [K+]o from 2.5 to 7.5 mM enhanced, while decreasing [Na+]o from 153 to 26 mM reduced, the amplitude of Ih. In addition, reduction of [Na+]o slowed the rate of Ih activation. These results indicate that Ih is carried by both Na+ and K+ ions, which is consistent with the extrapolated reversal potential of -43 mV. Replacement of Cl- in the bathing medium with isethionate shifted the chloride equilibrium potential positive by approximately 30-70 mV, evoked an inward shift of the holding current at -50 mV, and resulted in a marked reduction of instantaneous currents as well as Ih, suggesting a non-specific blocking action of impermeable anions. 5. Local (2-10 mM in micropipette) or bath (1-2 mM) applications of Cs+ abolished Ih over the whole voltage range tested (-60 to -110 mV), with no consistent effects on instantaneous currents. Barium (1 mM, local; 0.3-0.5 mM, bath) evoked a steady inward current, reduced the amplitude of instantaneous currents, and had only weak suppressive effects on Ih. 6. Block of Ih with local application of Cs+ resulted in a hyperpolarization of the membrane from the resting level, a decrease in apparent membrane conductance, and a block of the slow after-hyperpolarization that appears upon termination of depolarizing membrane responses, indicating that Ih contributes substantially to the resting and active membrane properties of thalamocortical relay neurones.(ABSTRACT TRUNCATED AT 400 WORDS)

Action Potentials↗
PubMed1990

Noradrenergic and serotonergic modulation of a hyperpolarization-activated cation current in thalamic relay neurones.

1. Modulation of the hyperpolarization-activated cation current, Ih, by noradrenaline (NA) and serotonin (5-HT) was examined in guinea-pig and cat medial and lateral geniculate relay neurones using the in vitro slice technique. 2. In the absence of pharmacological antagonists, local application of NA resulted in a slow depolarization and decrease in apparent input conductance, a response which was blocked by local or bath application of the alpha 1-adrenoceptor antagonist prazosin. Application of NA after pharmacological block of alpha 1- and alpha 2-adrenoceptors, or application of 5-HT in all conditions, induced a 1-3 mV slow depolarization which was associated with a pronounced increase in apparent input conductance. This response to NA and 5-HT persisted during blocked synaptic transmission and was present in both the guinea-pig and cat medial and lateral geniculate nuclei. 3. The increase in membrane conductance elicited by NA was mimicked by the beta-specific agonist isoprenaline and blocked by the beta-antagonists propranolol and atenolol, indicating that it is mediated by beta-adrenoceptors. The response to 5-HT was blocked by the 5-HT1 and 5-HT2 antagonist methysergide, but not by the 5-HT2 antagonist ritanserin. Applications of either the 5-HT1A agonist ipsapirone or the partial agonist 8-hydroxy-dipropylaminotetralin (8-OHDPAT) were without effect. 4. Current versus voltage relationships obtained under voltage clamp revealed NA and 5-HT to cause a voltage-dependent inward shift at membrane potentials negative to approximately -60 mV. This response appeared to be shared by NA and 5-HT since maximal application of 5-HT greatly reduced or abolished the response to NA. 5. Application of NA and/or 5-HT during hyperpolarizing voltage steps in voltage clamp resulted in a marked increase in amplitude of the hyperpolarization-activated cation current, Ih. In addition, the rate of activation of Ih was strongly increased during activation of beta-adrenoceptors. 6. The activation curve of the conductance underlying Ih (Gh) was shifted by 4-6 mV on the voltage axis with NA and/or 5-HT. The positive shift of Gh activation in the voltage domain resulted in an increase in the amplitude of Gh which is active at resting, and more hyperpolarized, membrane potentials. The subsequent increase in resting membrane conductance decreased the responsiveness of thalamic neurones to hyperpolarizations of all durations. 7. Local or bath application of caesium blocked both Ih and the increase in membrane conductance in response to NA and 5-HT. By contrast, barium blocked neither Ih nor the responses to NA and 5-HT.(ABSTRACT TRUNCATED AT 400 WORDS)

Action Potentials↗
PubMed1989

Noradrenaline and serotonin selectively modulate thalamic burst firing by enhancing a hyperpolarization-activated cation current.

Neurons in many regions of the mammalian nervous system generate action potentials in two distinct modes: rhythmic oscillations in which spikes cluster together in a cyclical manner, and single spike firing in which action potentials occur relatively independently of one another. Which mode of action potential generation a neuron displays often varies with the behavioural state of the animal. For example, the shift from slow-wave sleep to waking and attentiveness is associated with a change in thalamic neurons from rhythmic burst firing to repetitive single spike activity, and a greatly increased responsiveness to excitatory synaptic inputs. This marked change in firing pattern and excitability is controlled in part by ascending noradrenergic and serotonergic inputs from the brainstem, although the cellular mechanisms of this effect have remained largely unknown. Here we report that noradrenaline and serotonin enhance a mixed Na+/K+ current which is activated by hyperpolarization (Ih) and that this enhancement may be mediated by increases in intracellular concentration of cyclic AMP. This novel action of noradrenaline and serotonin reduces the ability of thalamic neurons to generate rhythmic burst firing and promotes a state of excitability that is conducive to the thalamocortical synaptic processing associated with cognition.

Action Potentials↗
PubMed1989

Identification of two calcium currents in acutely dissociated neurons from the rat lateral geniculate nucleus.

1. Intracellular recording in the in vitro slice preparation and whole-cell, patch-clamp recording of acutely dissociated neurons from the rat lateral geniculate nucleus (LGN) were combined to study the Ca currents underlying their electrical responses. In slices from young animals (postnatal days 13-16), we found that dorsal LGN neurons have responses similar to those of adult preparations, including the presence of a low-threshold Ca spike (LTS). After enzymatic isolation of LGN neurons from the same animals, the firing properties appeared well preserved, as indicated by whole-cell, current-clamp recordings from dissociated multipolar cells (presumably geniculocortical relay neurons). 2. Two types of Ca currents were identified in voltage-clamped, isolated LGN neurons on the basis of their voltage dependency, pharmacology, and selectivity properties. These two currents resemble the low-voltage-activated (LVA) and high-voltage-activated (HVA) Ca channels found in rat sensory neurons (9). 3. The LVA current component required negative potentials (less than -80 mV) to deinactivate completely, started to activate around -60 mV and reached a plateau level around -25 mV. It peaked within 30-6 ms and decayed with a single time constant of approximately 24 ms at -20 mV. Its inactivation curve ranged from -100 to -40 mV, with a half-inactivation near -60 mV. The HVA current component could be isolated by holding the membrane potential positive to -60 mV, activated at potentials positive to -30 mV and peaked around +5 mV. The time-to-peak ranged from 30 to 6 ms in the voltage range from -30 to +35 mV and decayed very slowly with sustained depolarizing pulses (time constant ranged between 1,600 and 40 ms over the same voltage range). 4. The inactivation of LVA Ca current during depolarizing voltage steps was consistent with a voltage-dependent process. The recovery from inactivation after short (100 ms), inactivating prepulses displayed two exponential phases. The slower phase was predominant under conditions that induce large current flow through the membrane, suggesting a Ca-mediated mechanism. 5. The LVA current was preferentially blocked by 50 microM Ni2+, leaving the HVA currents almost unaltered. Fifty micromolars Cd2+, in contrast, seemed more effective in blocking the HVA component of the Ca current.(ABSTRACT TRUNCATED AT 400 WORDS)

Action Potentials↗