he sirolimus-eluting stent (SES) is a stent coated with sirolimus, and is reported to prevent neo-intimal proliferation and injury-induced arterial intimal thickening. 1 It is widely used to treat coronary stenotic lesions because of the associated very low rates of in-stent restenosis and need for target lesion revascularization compared with conventional bare metal stents (BMS). [2][3][4] Sirolimus is a macrolide antifungal agent with antiproliferative and immunosuppressant properties. It inhibits vascular smooth muscle cell proliferation via cell cycle arrest in the late G1 phase. 5 It also inhibits endothelial cell proliferation and smooth muscle progenitor cell circulation. 6 Experimental studies using sirolimus 7,8 have reported a decrease in endothelial function in vitro, but the effects of SES on endothelial vasomotor function in humans is not well known. 9 The present study aimed to evaluate the influence of SES implantation on endothelial vasomotor function 6 months following stent implantation, using a pharmacological acetylcholine test. To clarify whether endothelial dysfunction was already present before SES implantation, we examined vasomotor tone of the coronary segment before stenting in a subgroup study, and compared endothelium-dependent vasomotor function before and 6 months after SES implantation. Methods Study PopulationFrom August 2004 to June 2005, a total of 23 patients who had stable angina pectoris and underwent successful SES (Cypher, Cordis Corp, Miami Lakes, FL, USA) implantation were included in this study. The control group consisted of 12 patients who had significant coronary artery stenosis, and were successfully treated with BMS. Exclusion criteria were acute coronary syndrome, any coronary revascularization site, reperfused coronary arteries, stent restenosis, history of coronary spasm, symptomatic congestive heart failure, atrial fibrillation, severe valvular heart disease, previous coronary bypass graft surgery, and left main coronary artery or bifurcation lesions. Risk factors for endothelial dysfunction were assessed, and patients with insulin-dependent diabetes mellitus, hypertension (systolic blood pressure ≥140 mmHg), currently smoking, hypercholesterolemia (total cholesterol ≥240 mg/dl) were also excluded. Patients in a stable condition who returned for the 6-month angiographic follow-up formed the final study population. Study ProtocolAll participants gave written informed consent for coronary angiography and the endothelial function test. The Background Sirolimus inhibits endothelial cell proliferation in vitro, but although the sirolimus-eluting stent (SES) is widely used because of the very low rates of in-stent restenosis, the influence of SES on coronary endothelial vasomotor function in humans is not well known. Methods and ResultsThe present study included 21 patients treated with SES, and 12 patients treated with conventional bare metal stent (BMS). Endothelium-dependent vasomotor function was evaluated 6 months after stent implantation, using intracoronary ace...

A 40-year-old man with a recent anterior myocardial infarction but with no history of coronary spasm and no risk factors for endothelial dysfunction such as diabetes mellitus, hypertension, smoking, or hypercholesterolemia was admitted to our hospital. Coronary angiography showed diffuse 90% proximal left anterior descending artery stenosis ( Figure 1A). He received a sirolimus-eluting stent (Cypher, Cordis Corporation, Miami Lakes, Fla) to treat diffuse long left anterior descending stenosis on January 20, 2005 ( Figure 1B). After predilation, 3 Cypher stents (2.5ϫ28 mm, 2.5ϫ28 mm, and 3.0ϫ23 mm) were deployed, overlapping 3 mm at nominal pressure. Overlapped segments were postdilated at 18 atm. Finally, complete expansion was obtained, and the lesion was fully covered. The patient remained asymptomatic after stenting. Follow-up angiography at 6 months on June 9, 2005, showed 0% stenosis ( Figure 2A). To evaluate endothelium-dependent vasomotor response, we performed intracoronary infusion of acetylcholine at 0.14 g/min over a period of 2 minutes, yielding estimated intracoronary concentrations of 10 Ϫ8 mol/L. Angiography repeated immediately after acetylcholine infusion showed total occlusion at the middle portion of the stents ( Figure 2B) associated with chest pain and ST elevation. No vasoconstrictive response was observed in any other coronary artery. Intracoronary nitroglycerin (250 g, bolus) quickly and completely resolved this angiographic obstruction ( Figure 2C). In this case, severe vasoconstrictive response was produced by small-dose intracoronary acetylcholine infusion. This phenomenon indicated severe endothelial dysfunction in the sirolimus-eluting stent at 6 months after stenting, suggesting delayed reendothelialization with inadequate endothelial coverage in the long sirolimus-eluting stents. DisclosuresNone.From Cardiovascular Medicine, Okayama Red Cross General Hospital, Okayama, Japan. Correspondence to Kiyoaki Maekawa, MD, 2-1-1, Aoe, Okayama-City, Okayama 700-8607, Japan. E-mail maekawa@okayama-med.jrc.or.jp

Recent studies have shown that infraorbital nerve constriction (IoNC)-induced mechanical allodynia has been attenuated by administration of highly purified 150-kDa Botulinum neurotoxin type A (BoNT/A). Here, we extend these studies to determine whether BoNT/A could attenuate IoNC-induced symptoms of thermal hyperalgesia. Instead of testing head withdrawal thresholds, a thermal operant assay was used to evaluate cortical processing of sensory input following IoNC. In this assay, a fasted rat's desire to obtain a food reward (sweetened condensed milk) is coupled to its ability to tolerate facial contact with a warm (45 °C) thermode. Bilateral IoNC decreased the ratio of thermode contact duration/event, which is an indicative of thermal hyperalgesia. BoNT/A injection intradermally in the area of infraorbital nerve (IoN) innervation 7 days after IoNC resulted in decreased number of facial contacts and increased the ratio of contact duration/event (measured at 14 days after IoNC). The BoNT/A (2-200 pg) effects were dose dependent and statistically significant at 100 and 200 pg (P < 0·05). Complete reversal of thermal hyperalgesia symptoms was obtained with a 200-pg dose, without affecting sham rat behaviour. Off-site (neck) injection of BoNT/A did not relieve thermal hyperalgesia, while co-injection of BoNT/A with a neutralising antibody in the area of IoN innervation prevented relief of thermal hyperalgesia. Neither IoNC nor BoNT/A injection affected operant assay parameters with a 24 °C thermode, indicating selectivity of thermal hyperalgesia measurements. These results strongly suggest that intradermal injection of BoNT/A in the area of IoN innervation alleviates IoNC-induced thermal hyperalgesia in an operant assay.

SUMMARYWe report a rescued 37-year-old woman in her 30 th week of gestation with massive pulmonary thromboembolism who was admitted to our cardiac care unit with progressive dyspnea and 2 episodes of syncope. Helical chest CT showed massive pulmonary thromboembolism of both pulmonary arteries. Although 26,000 U/day of heparin was administered following insertion of a temporary filter, hemodynamic evaluation documented no improvement. Since pulmonary artery (PA) pressure increased from 62/22 mmHg to 80/ 24 mmHg just after an emergency cesarean section on day 2, an emergency transcatheter thrombectomy was performed and it showed decreased PA pressure following extensive thrombus aspiration. Mother and baby were discharged with no complications.(Int Heart J 2007; 48: [269][270][271][272][273][274][275][276]

The results suggest that oral theophylline may be beneficial for the treatment of patients with sick sinus syndrome.