Intraoperative thrombosis of right coronary artery drug-eluting stent after 2 years of dual antiplatelet therapy.

This study presents the case of intraoperative thrombosis of a right coronary drug-eluting stent and subsequent right heart ischemia more than 2 years poststent placement and after recent withdrawal of clopidogrel therapy. Dual antiplatelet therapy had been continued uninterrupted since placement until 7 days prior to surgery when clopidogrel was stopped. This case highlights the emerging evidence that drug-eluting stents are susceptible to late occlusive thrombosis on acute withdrawal of antiplatelet therapy. Right heart ischemia resolved with rapid intraoperative management and emergent cardiac catheterization. This emphasizes the necessity of immediate availability to cardiac interventional facilities, which can influence outcomes.

Differential agonist-mediated internalization of the human 5-hydroxytryptamine 7 receptor isoforms.

The human 5-hydroxytryptamine 7 (5-HT(7)) serotonin receptor is a class A G-protein coupled receptor that has three isoforms, 5-HT(7(a)), 5-HT(7(b)), and 5-HT(7(d)), which are produced by alternative splicing. The 5-HT(7) receptors are expressed in discrete areas of the brain and in both vascular and gastrointestinal smooth muscle. Central nervous system 5-HT(7) receptors may play a role in mood and sleep disorders. 5-HT(7) receptors show high affinity for a number of antidepressants and typical and atypical antipsychotics. We report here that the human 5-HT(7(d)) isoform expressed in human embryonic kidney (HEK) 293 cells exhibits a pattern of receptor trafficking in response to agonist that differ from 5-HT(7(a)) or 5-HT(7(b)) isoforms. We employed a modification of a live cell-labeling technique to demonstrate that surface 5-HT(7(d)) receptors are constitutively internalized in the absence of agonist. This is in contrast to 5-HT(7(a)) and 5-HT(7(b)) isoforms, which do not show this profound agonist-independent internalization. Indeed, the 5-HT(7(d)) isoform displays this internalization in the presence of a 5-HT(7) -specific antagonist. In addition, the human 5-HT(7) isoform shows a diminished efficacy in stimulation of cAMP-responsive reporter gene activity in transfected cells compared with 5-HT(7(a)) or 5-HT(7(b)) receptors expressed at comparable levels. Thus, the carboxy-terminal tail of 5-HT(7(d)), which is the longest among known human 5-HT(7) isoforms, may contain a motif that interacts with cellular transport mechanisms that is distinct from 5-HT(7(a)) and 5-HT(7(b)).