Surgical Removal of a Detached Mitral Valve Repair Clip to Resolve Cardiogenic Shock.

Transcatheter edge-to-edge mitral valve repair (TEER) with a clip device relieves symptoms and improves outcomes in patients not suitable for open heart surgery. Here, we present a patient in whom ventricular arrhythmias developed as a result of clip embolization shortly after TEER. He underwent successful emergent surgical clip removal and mitral valve replacement. (Level of Difficulty: Advanced.).

Nicotine increases alcohol self-administration in male rats via a µ-opioid mechanism within the mesolimbic pathway.

BACKGROUND AND PURPOSE: Alcohol and nicotine use disorders are commonly comorbid. Both alcohol and nicotine can activate opioid systems in reward-related brain regions, leading to adaptive changes in opioid signalling upon chronic exposure. The potential role of these adaptations for comorbidity is presently unknown. Here, we examined the contribution of µ and κ-opioid receptors to nicotine-induced escalation of alcohol self-administration in rats. EXPERIMENTAL APPROACH: Chronic nicotine was tested on alcohol self-administration and motivation to obtain alcohol. We then tested the effect of the κ antagonist CERC-501 and the preferential µ receptor antagonist naltrexone on basal and nicotine-escalated alcohol self-administration. To probe µ or κ receptor adaptations, receptor binding and G-protein coupling assays were performed in reward-related brain regions. Finally, dopaminergic activity in response to alcohol was examined, using phosphorylation of DARPP-32 in nucleus accumbens as a biomarker. KEY RESULTS: Nicotine robustly induced escalation of alcohol self-administration and motivation to obtain alcohol. This was blocked by naltrexone but not by CERC-501. Escalation of alcohol self-administration was associated with decreased DAMGO-stimulated µ receptor signalling in the ventral tegmental area (VTA) and decreased pDARPP-32 in the nucleus accumbens shell in response to alcohol. CONCLUSIONS AND IMPLICATIONS: Collectively, these results suggest that nicotine contributes to escalate alcohol self-administration through a dysregulation of µ receptor activity in the VTA. These data imply that targeting µ rather than κ receptors may be the preferred pharmacotherapeutic approach for the treatment of alcohol use disorder when nicotine use contributes to alcohol consumption.

Acute effects on brain cholecystokinin-like concentration and anxiety-like behaviour in the female rat upon a single injection of 17ß-estradiol.

BACKGROUND: The neuropeptide cholecystokinin (CCK) has been implicated in the neurobiology of anxiety and panic disorders, as well as in dopamine-related behaviours. Anxiety and panic-disorders are twice as common in females compared to males, but studies of females are rare, although increasing in number. Limited studies have found that CCK fluctuates in limbic regions during the estrous cycle, and that CCK and its receptors are sensitive to estrogen. AIM/PURPOSE: The aim of the present work was to study the acute effects of 17ß-estradiol on anxiety-like behaviour and on CCK-like immunoreactivity (LI) in the female rat brain (amygdala, hippocampus, nucleus accumbens, and cingulate cortex). METHODS: Four groups of female Sprague-Dawley rats were used: ovariectomized, ovariectomized+17ß-estradiol-replacement, sham, and sham+17ß-estradiol-replacement. The effect of 17ß-estradiol-replacement on anxiety-related behaviour was measured in all animals on the elevated plus maze 2-24 h after injection. CCK-LI concentration was measured in punch biopsies by means of radioimmunoassay. RESULTS: 17ß-estradiol decreased anxiety-like behaviour 2 h after administration in ovariectomized and sham-operated animals, as demonstrated by increased exploration of the open arms compared to respective sesame oil-treated controls. This effect was not present when testing occurred 24 h post-treatment. The rapid behavioural effect of 17ß-estradiol was accompanied by changes in CCK-LI concentrations in regions of the limbic system including cingulate cortex, hippocampus, amygdala and nucleus accumbens. CONCLUSION: Although the interpretation of these data requires caution since the data were collected from two different experiments, our results suggest that estrogen-induced anxiolytic effects may be associated with changes of the CCK-system in brain regions controlling anxiety-like behaviour.

Different methods for administering 17beta-estradiol to ovariectomized rats result in opposite effects on ischemic brain damage.

BACKGROUND: Numerous stroke studies have controversially shown estrogens to be either neuroprotective or neurodamaging. The discordant results observed in rat brain ischemia models may be a consequence of discrepancies in estrogen administration modes resulting in plasma concentration profiles far from those intended. To test this hypothesis we reproduced in detail and extended an earlier study from our lab using a different mode of 17beta-estradiol administration; home-made silastic capsules instead of commercial slow-release 17beta-estradiol pellets. Four groups of female rats (n = 12) were ovariectomized and administered 17beta-estradiol or placebo via silastic capsules. All animals underwent MCAo fourteen days after ovariectomy and were sacrificed three days later. RESULTS: In contrast to our earlier results using the commercial pellets, the group receiving 17beta-estradiol during the entire experiment had significantly smaller lesions than the group receiving placebo (mean +/- SEM: 3.85 +/- 0.70% versus 7.15 +/- 0.27% of total slice area, respectively; p = 0.015). No significant neuroprotection was found when the 17beta-estradiol was administered only during the two weeks before or the three days immediately after MCAo. CONCLUSIONS: The results indicate that different estrogen treatment regimens result in diametrically different effects on cerebral ischemia. Thus the effects of estrogens on ischemic damage seem to be concentration-related, with a biphasic, or even more complex, dose-response relation. These findings have implications for the design of animal experiments and also have a bearing on the estrogen doses used for peri-menopausal hormone replacement therapy.

Rapid change of neuropeptide Y levels and gene-expression in the brain of ovariectomized mice after administration of 17beta-estradiol.

Estrogen alters excitability and changes synaptic morphology in the rat hippocampal formation. We have compared, by means of radioimmunoassay and in situ hybridization, the effects of short-term treatment with 17beta-estradiol on neuropeptide Y (NPY) in the brain of ovariectomized mice. A highly significant reduction in concentrations of NPY-like immunoreactivity (LI) was observed in the hippocampal formation, some cortical areas and the caudate nucleus 1h after administration of 17beta-estradiol as compared to the control group. In contrast, NPY transcript levels increased in the hippocampal formation (dentate gyrus) and the caudate nucleus, possibly representing a compensatory increase of NPY synthesis following increased estradiol-induced NPY release. These data suggest that 17beta-estradiol, via membrane-related mechanisms, increases NPY release and synthesis in forebrain areas involved in cognition, mood and motor functions.

Estrogen induces a rapid increase in galanin levels in female rat hippocampal formation--possibly a nongenomic/indirect effect.

Administration of 17beta-estradiol to ovariectomized rats increased the concentrations of galanin-like immunoreactivity (LI) in the hippocampal formation by 215% (P < 0.001) within 1 h. An increase of 125% (P < 0.05) was observed in the same brain region in the proestrous phase of a normal estrous cycle. Tamoxifen did not block the 17beta-estradiol-induced increase in the concentration of galanin-LI but resulted in a 62% decrease in the hypothalamus within 1 h. In vivo microdialysis in the dorsal hippocampal formation showed a decrease of extracellular galanin-LI (P < 0.001) 1-2 h after treatment with 17beta-estradiol, indicating a decreased release of galanin. For comparison, we studied the concentrations of neuropeptide Y, which were not influenced significantly in any of the regions studied. Taken together our results suggest that 17beta-estradiol inhibits galanin release, presumably from noradrenergic nerve terminals, and primarily via a nongenomic/indirect action, not necessarily involving the classical nuclear receptors ER-alpha or ER-beta. These rapid estrogen-induced changes in galanin release could influence transmitter signalling and plasticity in the hippocampal formation.