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Objective: Elevated plasma levels of lipoprotein(a) [Lp(a)], referred to as lipoprotein(a)-hyperlipoproteinemia [Lp(a)-HLP], are an independent risk factor for atherosclerosis. Lipoprotein apheresis (LA) enables an effective reduction of Lp(a) plasma levels. The present study investigates the effects of LA in patients with Lp(a)-HLP and peripheral artery disease (PAD)., Methods: Ten patients with isolated Lp(a)-HLP and severe PAD and who had recently undergone a revascularization (index procedure) were prospectively included in this observational single center study. All patients received weekly LA. Ankle-brachial-index (ABI), transcutaneous partial oxygen pressure (tcpO 2 ), pain level, and walking distance were assessed at baseline and at the follow ups scheduled 1, 3, 6, 12, and 24 months after initiation of LA. The number of revascularizations within 12 months prior and within 24 months after the index procedure was determined., Results: As early as 1 month after initiation of LA, all investigated parameters had improved significantly compared to baseline. This improvement was further substantiated under LA throughout the entire follow-up period. Comparing baseline results with the 24-month follow-up, the average ABI increased from 0.53 ± 0.15 to 0.97 ± 0.08 (P < 0.001). The mean tcpO 2 also increased from 42.9 ± 2.3 mmHg to 61 ± 4.6 mmHg (P < 0.001). The improved perfusion led to a reduction of the mean pain level from 7.0 ± 1.5 to 1.1 ± 0.4 (P < 0.001) on a visual analogue scale (VAS) and an extension of the mean walking distance from 87 ± 60 m to 402 ± 119 m (P < 0.001). All patients suffered from severe PAD with a high number of revascularizations in the 12 months prior to the index procedure (35 procedures in 120 patient-months). Since initiation of LA, the number of revascularizations dropped significantly and remained very low during the entire follow-up period (2 procedures in 229 patient-months, P < 0.001)., Conclusion: In patients with Lp(a)-HLP and severe PAD, LA results in sustained improvement of circulation, pain level and walking distance. The number of repeat revascularizations is strongly reduced under LA treatment., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Objective: Hyperlipoproteinemia(a) [Lp(a)-HLP] is a major risk factor for severe atherosclerosis. The present investigation sought to assess the effect of lipoprotein apheresis (LA) in patients with peripheral artery disease (PAD) and Lp(a)-HLP., Methods: In January 2013, we started a registry for Lp(a)-HLP patients who receive weekly LA in our center. So far, ten patients with severe PAD and isolated Lp(a)-HLP who recently underwent revascularization (index procedure) have been included. Pain level, ankle-brachial-index (ABI), transcutaneous oxygen pressure (tcpO2) and walking distance were determined before, as well as 1, 3, 6 and 12 months after initiation of LA. Furthermore, the mean time interval between revascularizations within the 12 months prior to the index procedure and up to 12 months after the index procedure was assessed., Results: All analyzed parameters significantly improved under LA. When comparing the results before LA with the results after 12 months, the ankle-brachial-index increased from 0.5 ± 0.2 to 0.9 ± 0.1 (P < 0.001). The tcpO2 levels also increased from 42.9 ± 2.3 mmHg to 59.0 ± 8.9 mmHg (P < 0.001). The improved microcirculation was associated with a reduction of the mean pain level from 7.0 ± 1.5 to 2.0 ± 0.8 (P < 0.001) as determined using the visual analog scale. The walking distance increased from 87 ± 60 m to 313 ± 145 m (P < 0.001). Importantly, the frequency of revascularization procedures was strongly decreased under LA. All patients combined underwent 35 revascularizations within the 12 months prior to the index procedure (mean interval between two revascularizations: 104.3 days). Since the index procedure, only one revascularization was necessary within 79 patient-months under LA (mean interval: 2404.5 days, P < 0.001)., Conclusion: LA improves circulation, oxygen supply, level of pain and walking distance in patients with severe PAD and Lp(a)-HLP. The frequency of revascularization procedures is strongly reduced under LA treatment., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

The lateral habenular complex (LHb) is a key signal integrator between limbic forebrain regions and monoaminergic hindbrain nuclei. Major projections of LHb neurons target the dopaminergic ventral tegmental area (VTA) and the serotonergic dorsal (DR) and median raphe nuclei (MnR). Both monoaminergic neurotransmitter systems play a central role in reward processing and reward-related decision-making. Glutamatergic LHb efferents terminate on GABAergic neurons in the VTA, the rostromedial tegmental nucleus (RMTg), and the raphe nuclei, thereby suppressing monoamine release when required by the present behavioral context. Recent studies suggest that the LHb exerts a strong tonic inhibition on monoamine release when no reward is to be obtained. It is yet unknown whether this inhibition is the result of a continuous external activation by other brain areas, or if it is intrinsically generated by LHb projection neurons. To analyze whether the tonic inhibition may be the result of a hyperpolarization-activated cyclic nucleotid-gated cation channel (HCN)-mediated pacemaker activity of LHb projection neurons, we combined retrograde tracing in rats with in situ hybridization of HCN1 to HCN4 mRNAs. In fact, close to all LHb neurons targeting VTA or raphe nuclei are equipped with HCN subunit mRNAs. While HCN1 mRNA is scarce, most neurons display strong expression of HCN2 to HCN4 mRNAs, in line with the potential formation of heteromeric channels. These results are supported by quantitative PCR and immunocytochemical analyses. Thus, our data suggest that the tonic inhibition of monoamine release is intrinsically generated in LHb projection neurons and that their activity may only be modulated by synaptic inputs to the LHb., (Copyright © 2011 IBRO. Published by Elsevier Ltd. All rights reserved.)