1. The mechanism of post-ischaemic ectopic impulse generation in nerve is not known, and previous measurements of excitability changes in human motor axons have appeared to conflict. We have used automatic threshold tracking and different stimulus-response combinations to follow the effects on excitability of brief (5-10 min) periods of ischaemia, too short to induce motor fasciculations. Excitability changes have been compared at different sites in axons innervating hand, arm and foot muscles. 2. Threshold was determined as the percutaneous stimulus current required to excite a single motor unit, or to evoke a constant multiunit response, after rectifying and integrating the electromyogram (EMG). Three different waveforms of stimulus current were compared: short (less than or equal to 2 ms) pulses, long (100-200 ms) pulses to measure rheobase, and 100 ms current ramps. We also measured accommodation by recording the effects of subthreshold depolarizing currents on excitability. 3. Ischaemic and post-ischaemic excitability changes were greatest in the proximal parts of the longest motor axons, and greater if the sphygmomanometer cuff was inflated over, rather than proximal to, the stimulating site. 4. Using integrated EMG responses from abductor digiti minimi, the ulnar nerve stimulated above the elbow became rapidly much less excitable after ischaemia when tested with short pulses, but more excitable when tested with current ramps. The rheobase rose briefly, but then fell, often below resting level, always staying below the pulse and ramp thresholds. 5. The latency of the response to a rheobasic stimulus altered in parallel with the threshold to short current pulses, and increased dramatically after ischaemia. This latency increase was associated with a prolonged phase of 'negative accommodation', i.e. the continued increase in excitability to a maintained subthreshold depolarizing current. 6. Changes in excitability and accommodation similar to those occurring after ischaemia were recorded following high frequency trains of stimuli. They were attributed primarily to hyperpolarization by the electrogenic sodium pump, since comparable changes could be induced by passing a steady hyperpolarizing current through the stimulating electrode. 7. Threshold and latency recordings from single motor units during and after ischaemia resembled in most respects the multiunit responses, but single unit rheobase did not show a post-ischaemic fall below the resting level. Repetitive firing contributed to the low multiunit thresholds recorded with long current pulses during the post-ischaemic period. 8. We conclude that human motor nerves become simultaneously both more and less excitable than normal after 10 min of ischaemia, depending on the choice of stimulus and response.

The inositol 1,4,5-trisphosphate (IP3)-induced Ca2+ release was studied using streptolysin O-permeabilized bovine adrenal chromaffin cells. The IP3-induced Ca2+ release was followed by Ca2+ reuptake into intracellular compartments. The IP3-induced Ca2+ release diminished after sequential applications of the same amount of IP3. Addition of 20 μM GTP fully restored the sensitivity to IP3. Guanosine 5'-O-(3-thio)triphosphate (GTPγS) could not replace GTP but prevented the action of GTP. The effects of GTP and GTPγS were reversible. Neither GTP nor GTPγS induced release of Ca2+ in the absence of IP3. The amount of Ca2+ whose release was induced by IP3 depended on the free Ca2+ concentration of the medium. At 0.3 μM free Ca2+, a half-maximal Ca2+ release was elicited with ∼0.1 μM IP3. At 1 μM free Ca2+, no Ca2+ release was observed with 0.1 μM IP3; at this Ca2+ concentration, higher concentrations of IP3 (0.25 μM) were required to evoke Ca2+ release. At 8 μM free Ca2+, even 0.25 μM IP3 failed to induce release of Ca2+ from the store. The IP3-induced Ca2+ release at constant low (0.2 μM) free Ca2+ concentrations correlated directly with the amount of stored Ca2+. Depending on the filling state of the intracellular compartment, 1 mol of IP3 induced release of between 5 and 30 mol of Ca2+.

Objective: To determine whether regional hypoperfusion of the interventricular septum occurs during ventilation with positive end-expiratory pressure. Design: Animal study. Animals: Anesthetized, closed chest dogs (n = 8). Interventions: Induction of experimental adult respiratory distress syndrome (ARDS) and then ventilation with 10,15, and 20 cm H2O of positive end-expiratory pressure. Measurements and Main Results: Cardiac output and regional interventricular septum blood flow 'were assessed at control, at induction of experimental ARDS, and at each level of positive end-expiratory pressure. Ventilation with 20 cm H2O of positive end-expiratory pressure decreased cardiac output (-32% vs. control, p <.05), and did not change absolute, but increased relative (to cardiac output) interventricular septum blood flow. During experimental ARDS and ventilation at 20 cm H2O end-expiratory pressure, there was a redistribution of flow toward the right ventricular free wall (+93%, p < .001) and the right ventricular part of the interventricular septum (+68%, p < .01), while flow to the left ventricular interventricular septum and to the left ventricular free wall remained unchanged. Locally hypoperfused interventricular septum areas or findings indicative of interventricular septum ischemia were not observed during positive end-expiratory pressure. Conclusions: The decrease in cardiac output during positive end-expiratory pressure is not caused by impaired interventricular septum blood supply. The preferential perfusion of the right ventricular interventricular septum indicates increased local right ventricular interventricular septum oxygen-demand and suggests that during positive end-expiratory pressure, this part of the interventricular septum functionally dissociates from the left ventricular interventricular septum and the left ventricular free wall to support the stressed right ventricle.

ICRP hat 1977 zum ersten Mal Risikokoeffizienten für strahlcninduzierte Krebsmortalität angegeben. Diese Zahlen stützen sich vor allem auf die Beobachtungen an den Atombomben-Überlebenden. Durch die Revision der Atombombcn-Dosimetric und die Weiterführung der Beobachtungen bis zum Jahr 1985 ergaben sich erhöhte Risikoschätzungen. Ihre Zahlenwerte und die Ursachen für die Änderung werden diskutiert. Die Risikoschätzungen für die in jungem Alter Bestrahlten sind noch unsicher. Die neuen Empfehlungen der ICRP basieren auf Berechnungen, die sich aus dem Modell des relativen Risikos ergeben, das im Widerspruch steht zu dem beobachteten Trend abnehmender Proportionalitätsfaktoren des Exzeßrisikos mit zunehmender Zeit nach Bestrahlung. Ein modifiziertes Modell des relativen Risikos, bei dem die Proportionalitätsfaktoren nur vom erreichten Alter abhängen, führt für Bestrahlungen im Alter von weniger als 30 Jahren zu deutlich geringeren Projektionen in die Zukunft. Gcmittclt über alle Altersstufen erhält man Risikowertc, die etwa halb so hoch sind wie die Schätzungen der ICRP. Mit dem modifizierten Modell erhält man ohne den hypothetischen Reduktionsfaktor zur Extrapolation auf kleine Dosen etwa die gleichen Risikokoeffizienten, wie sie von ICRP angegeben werden.