Clusterin (CLU) is a multifunctional 75- to 80-kDa glycoprotein that is upregulated during cellular stress and might represent a defense mechanism during local cellular damage. Mechanisms discussed are antiapoptotic, antioxidative, and anticomplement properties as well as chaperone-like features protecting stressed proteins. The aim of this study was to investigate potential protective effects of CLU on pulmonary vasculature after in situ PMN activation in isolated rabbit lungs. The experiments were performed on 24 isolated and ventilated rabbit lungs that were perfused with 200 mL of Krebs-Henseleit-10% blood buffer with a constant flow of 150 mL/min in a recirculating system. It was tested whether pretreatment with CLU (2.5 microg/ml; n = 8) or catalase (CAT, 5000 U/ml; n = 8) before N-formyl-Met-Leu-Phe (fMLP; 10(-8) M) injection influenced pulmonary artery pressure (PAP) peak airway pressures (PAW) and edema formation as compared with controls (n = 8). Baseline values of PAP were 9-11 mmHg and PAW 11-13 cm H2O. Application of fMLP resulted in an acute significant (P < 0.01) increase of PAP (48 +/- 29 mmHg) within 2 min in the control group and PAW increased to 35 +/- 7 cm H2O within 30 min. Pretreatment with CLU completely suppressed the PAP and PAW response as a result of the fMLP challenge (P < 0.001), whereas a transient PAW increase up to 27 +/- 15 mmHg was observed after CAT. Complement factor C3a release was suppressed by CAT, whereas CLU blocked the complement cascade at the level of C5b-9 formation. Moreover, generation of thromboxane A(2) was reduced after CLU and CAT. Lung edema occurred in the fMLP group but was absent (P < 0.001) after CLU and CAT treatment. Both CLU and CAT prevented fMLP-induced lung injury. Stabilizing effects of CLU, point towards complement regulating features at the level of the terminal complement sequence. Elevated levels of CLU during inflammation could reflect a compensatory organ protective mechanism. Further studies are required to elucidate the clinical impact of the observed organ-protective properties of CLU.

Peripheral magnetic stimulation is a promising technique for several applications like rehabilitation or diagnose of neuronal pathways. However, most available magnetic stimulation devices are designed for transcranial stimulation and require high-power, expensive hardware. Modern technology such as rectangular pulses allows to adapt parameters like pulse shape and duration in order to reduce the required energy. Nevertheless, the effect of different temporal electromagnetic field shapes on neuronal structures is not yet fully understood. We created a simulation environment to find out how peripheral nerves are affected by induced magnetic fields and what pulse shapes have the lowest energy requirements. Using the electric field distribution of a Figure-of-8 coil together with an axon model in saline solution, we calculated the potential along the axon and determined the required threshold current to elicit an action potential. Further, for the purpose of selective stimulation, we investigated different axon diameters. Our results show that rectangular pulses have the lowest thresholds at a pulse duration of 20 μs. For sinusoidal coil currents, the optimal pulse duration was found to be 40 μs. Most importantly, with an asymmetric rectangular pulse, the coil current could be reduced from 2.3 kA (cosine shaped pulse) to 600 A. In summary, our results indicate that for magnetic nerve stimulation the use of rectangular pulse shapes holds the potential to reduce the required coil current by a factor of 4, which would be a massive improvement.

Magnetic stimulation of peripheral nerves is evoked by electric field gradients caused by high-intensity, pulsed magnetic fields created from a coil. Currents required for stimulation are very high, therefore devices are large, expensive, and often too complex for many applications like rehabilitation therapy. For repetitive stimulation, coil heating due to power loss poses a further limitation. The geometry of the magnetic coil determines field depth and focality, making it the most important factor that determines the current required for neuronal excitation. However, the comparison between different coil geometries is difficult and depends on the specific application. Especially the distance between nerve and coil plays a crucial role. In this investigation, the electric field distribution of 14 different coil geometries was calculated for a typical peripheral nerve stimulation with a 27 mm distance between axon and coil. Coil parameters like field strength and focality were determined with electromagnetic field simulations. In a second analysis, the activating function along the axon was calculated, which quantifies the efficiency of neuronal stimulation. Moreover, coil designs were evaluated concerning power efficacy based on ohmic losses. Our results indicate that power efficacy of magnetic neurostimulation can be improved significantly by up to 40 % with optimized coil designs.

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