High-dose adenosine-induced asystole assisting accurate deployment of thoracic stent grafts in conscious patients.

Adenosine has been used to induce asystole and assist deployment of endoluminal grafts. However, application of high-dose adenosine in conscious patients has not been described. In this prospective study, we administered high-dose adenosine in patients undergoing thoracic stent grafting. Asystole duration in relationship to the dosage of adenosine, safety, and side effect profiles was investigated. All patients who underwent thoracic stent grafting between 1998 and 2006 were the potential study subjects. They received monitored anesthesia care and local anesthesia unless contraindicated. Adenosine was given via rapid intravenous bolus immediately prior to the deployment of the stent graft. Every patient received a dose of 36 mg. If needed, a second dose of 18 mg was given. Duration of asystole was recorded after each administration. Patients' vital signs before and after administration were also documented. Side effect profiles were collected intra- and postoperatively. A total of 46 patients received adenosine (34 men, 12 women). Mean age was 60.4 +/- 17.5 years. American Society of Anesthesiologists scores were II in one patient (2%), III in six patients (13%), and IV in 39 patients (85%). Eighteen patients received a single dose of 36 mg adenosine, 15 were given a second dose of 18 mg, and 13 received nonstandard dosages. Asystole durations were 18.8 +/- 8.8 and 11.6 +/- 5.5 sec for 36 and 18 mg, respectively. Technical success was achieved in all cases. The differences achieved statistical significance (p = 0.0009). There were no severe cardiac or pulmonary complications. High-dose adenosine can be given safely in conscious patients. The dose-response was predictable and reproducible. The dosages used in our study induce sufficient duration of asystole, which ensured accurate deployment of thoracic stent grafts.

High-dose retinoic acid modulates rat calvarial osteoblast biology.

Retinoic acid has been shown to adversely affect craniofacial development. Cleft palate and craniosynostosis are two examples of craniofacial defects associated with prenatal exposure to this agent. Although the effects of retinoic acid on cephalic neural crest-derived tissues have previously been studied, the specific effects of retinoic acid on the cellular biology of osteoblasts remain unclear. The purpose of this study was to analyze in detail the effects of pharmacologic doses of retinoic acid on the differentiation and proliferation of osteoblasts derived from an intramembranous source. Primary rat calvarial osteoblasts were established in culture and treated with 1 or 10 microM all-trans-retinoic acid. Retinoic acid treatment markedly increased expression of osteopontin up to 48 h after stimulation. Consistent with this early stage of differentiation, both mRNA and protein analysis of FGF receptor isoforms demonstrated a switch in predominance from fibroblast growth factor receptor 2 (fgfr2) to fgfr1. Analysis of PCNA protein confirmed inhibition of proliferation by retinoic acid. To determine whether these alterations in osteoblast biology would lead to increased differentiation, we examined short term [alkaline phosphatase (AP) activity] and long term (von Kossa staining) surrogates of bone formation in vitro. These assays confirmed that retinoic acid increased osteogenesis, with a 4-fold increase in bone nodule formation in cells treated with 10 microM retinoic acid after 28 days. Overall, our results demonstrated that pharmacologic doses of all-trans-retinoic acid decreased osteoblast proliferation and increased differentiation, suggesting that retinoic acid may effect craniofacial development by pathologically enhancing osteogenesis.