In vivo actions of aripiprazole on serotonergic and dopaminergic systems in rodent brain.

RATIONALE: Aripiprazole is an atypical antipsychotic drug with high in vitro affinity for 5-HT(1A), 5-HT(2A) and dopamine (DA) D2 receptors. However, its in vivo actions in the brain are still poorly characterized. OBJECTIVE: The aim was to study the in vivo actions of aripiprazole in the rat and mouse brain. METHODS: Brain microdialysis and single-unit extracellular recordings were performed. RESULTS: The systemic administration of aripiprazole reduced 5-HT output in the medial prefrontal cortex (mPFC) and dorsal raphe nucleus of the rat. Aripiprazole also reduced extracellular 5-HT in the mPFC of wild-type (WT) but not of 5-HT(1A) (-/-) knockout (KO) mice. Aripiprazole reversed the elevation in extracellular 5-HT output produced by the local application of the 5-HT(2A/2C) receptor agonist DOI in mPFC. Aripiprazole also increased the DA output in mPFC of WT but not of 5-HT(1A) KO mice, as observed for atypical antipsychotic drugs, in contrast to haloperidol. Contrary to haloperidol, which increases the firing rate of DA neurons in the ventral tegmental area (VTA), aripiprazole induced a very moderate reduction in dopaminergic activity. Haloperidol fully reversed the inhibition in dopaminergic firing rate induced by apomorphine, whereas aripiprazole evoked a partial reversal that was significantly different from that evoked by haloperidol and from the spontaneous reversal of dopaminergic activity in rats treated with apomorphine. CONCLUSIONS: These results indicate that aripiprazole modulates the in vivo 5-HT and DA release in mPFC through the activation of 5-HT(1A) receptors. Moreover, aripiprazole behaves as a partial agonist at DA D2 autoreceptors in vivo, an action which clearly distinguishes it from haloperidol.

Isovolumic contraction time by pulsed-wave Doppler tissue imaging in aortic stenosis.

BACKGROUND: Doppler Tissue Imaging (DTI) has been evaluated in ischaemic heart disease and some cardiomyopathies. In patients with aortic stenosis (AS), left ventricular contraction is slowered. This study aimed to evaluate the possible role of the measurement of isovolumic contraction time (ICT) by DTI in the evaluation of AS severity. METHODS: The study population constitutes 30 patients: 15 with AS (nine severe and six non-severe) and 15 control subjects. All of them had normal systolic function, sinus rhythm, and absence of ischaemic heart disease of conduction abnormalities. ICT was defined as the time from the onset of the QRS complex to the beginning of the DTI systolic wave. The correlation between ICT and aortic area obtained by continuity equation, as well as the diagnostic value of ICT in the identification of severe AS were studied. RESULTS: ICT was significantly increased in patients with severe AS (98+/-27 versus 65+/-21 ms, p=0.024). There was a significant correlation between ICT and aortic area (r=-0.56; p=0.035). The receiver operator characteristic curve of ICT in the identification of severe AS yielded an area under the curve of 0.852 (95% confidence interval: 0.665-1.0). The two best cut-points were >73 ms (88% sensitivity, 77% specificity) and >85 ms (78% sensitivity, 83% specificity). A value of >41 ms had a 100% sensitivity, but only a 17% specificity, and >91 ms showed a 100% specificity, but only a 44% sensitivity. CONCLUSIONS: ICT measured by pulsed-wave DTI is increased in patients with aortic stenosis.

Weak concordance between wall motion and microvasculature status after acute myocardial infarction: study with myocardial contrast echocardiography in real time with power modulation.

AIMS: The microvasculature damage after myocardial infarction has important implications. The hypothesis of the study was that wall motion abnormalities and microcirculation status do not necessarily match after myocardial infarction, and therefore the study of only myocardial wall motion could offer an incomplete evaluation in these patients. METHODS: Wall motion and myocardial perfusion assessed by contrast echocardiography were evaluated by two different blinded investigators in 29 patients with recent (<1 week) myocardial infarction. Myocardial perfusion was assessed in real-time using power modulation after Optison (1.5-3.0 ml) intravenous administration. RESULTS: One hundred and ninety-nine segments could be adequately evaluated. Of these, 54 (27%) were akinetic. Regarding contrast opacification, 134 segments (67%) had a normal perfusion, whereas the remaining 65 (33%) had an impaired (n=37, 19%) or absent (n= 28, 14.1%) perfusion. Concordance between presence of akinesia and abnormal contrast opacification was only moderate (kappa index 0.42) and agreement only occurred in 116 segments (58%). Fourteen per cent of normoquinetic segments had an impaired perfusion, whereas 35% of akinetic segments had a preserved perfusion. Correlation between the proportion of segments with akinesia and the proportion of segments with impaired perfusion was moderate (r=0.41), and there was no correlation between the proportion of segments with akinesia and the percentage of segments with absent perfusion. CONCLUSION: There is a weak association between regional systolic function and myocardial perfusion after myocardial infarction, as assessed by real-time contrast myocardial echocardiography using power modulation.