Andrew W. Owens

Bisulfite-containing Propofol: Is it a Cost-effective Alternative to Diprivan™ for Induction of Anesthesia?

Propofol (Diprivan™; AstraZeneca, Wilmington, DE) is a commonly used drug for the induction of general anesthesia in the ambulatory setting. With the availability of a new bisulfite-containing generic formulation of propofol, questions have arisen regarding its cost effectiveness and safety compared with Diprivan™. Two hundred healthy outpatients were randomly assigned, according to a double-blinded protocol, to receive either Diprivan™ or bisulfite-containing propofol 1.5 mg/kg IV as part of a standardized induction sequence. Maintenance of anesthesia consisted of either desflurane (4%–8% end-tidal) or sevoflurane (1%–2% end-tidal) in combination with a remifentanil infusion (0.125 &mgr;g · kg−1 · min−1 IV). Patient assessments included pain on injection, induction time, hemodynamic and bispectral electroencephalographic changes during induction, emergence time, and incidence of postoperative nausea and vomiting. The two propofol groups were comparable demographically, and the induction times and bispectral index values during the induction were also similar. However, the bisulfite-containing formulation was associated with less severe pain on injection (5% vs 11%), with fewer patients recalling pain on injection after surgery (38% vs 51%, P < 0.05). None of the patients manifested allergic-type reactions after the induction of anesthesia. The acquisition cost (average wholesale price in US dollars) of a 20-mL ampoule of Diprivan™ was

Differential Associations Between Soluble Cellular Adhesion Molecules and Atherosclerosis in the Dallas Heart Study: A Distinct Role for Soluble Endothelial Cell-Selective Adhesion Molecule

15 compared with

Associations of four circulating chemokines with multiple atherosclerosis phenotypes in a large population-based sample: Results from the Dallas heart study

13 for the bisulfite-containing propofol formulation. Therefore, we concluded that the bisulfite-containing formulation of propofol is a cost-effective alternative to Diprivan™ for the induction of outpatient anesthesia. Implications Bisulfite-containing propofol and Diprivan™ (AstraZeneca, Wilmington, DE) were similar with respect to their induction characteristics; however, the generic formulation was associated with a smaller incidence of injection pain. Assuming that the drug costs are similar, these data suggest that the bisulfite-containing formulation of propofol is a cost-effective alternative to Diprivan™.

Circulating lymphotoxin β receptor and atherosclerosis: Observations from the Dallas Heart Study☆☆☆

Objective—Endothelial cell–selective adhesion molecule (ESAM) is a junctional-type cellular adhesion molecule (CAM) that is uniquely expressed in vascular endothelium and activated platelets and mediates neutrophil and monocyte diapedesis across the endothelium. Given its role in endothelial pathobiology, we hypothesized that soluble ESAM (sESAM) would be independently associated with atherosclerosis and vascular stiffness. Methods and Results—We measured sESAM, soluble intercellular adhesion molecule (sICAM)-1, and soluble vascular cell adhesion molecule (sVCAM)-1 in 3222 subjects participating in the Dallas Heart Study, a probability-based population sample. Coronary artery calcium (CAC) was measured by electron beam computed tomography, and abdominal aortic wall thickness (AWT), aortic plaque burden (APB), and aortic compliance (AC) by MRI. Increasing levels of sESAM were associated with all major cardiovascular risk factors as well as with inflammatory markers such as monocyte chemoattractant protein-1, but only weakly correlated with sICAM-1 and sVCAM-1. In multivariate analyses, sESAM was independently associated with prevalent CAC (OR 1.2 per SD increase, 95% CI 1.1 to 1.3; P=0.005), AWT (P=0.035), and AC (P=0.006), but not APB (P=0.15). In contrast, no independent associations were observed between sICAM-1 or sVCAM-1 and any of the atherosclerosis phenotypes. Conclusions—In this first reported clinical study of sESAM in humans, sESAM levels were independently associated with CAC, AWT, and AC, whereas sICAM-1 and sVCAM-1 were not. These findings support a unique role of this cellular adhesion molecule in atherosclerosis and suggest the need for further exploration of sESAM as a predictive biomarker and potential mediator of atherosclerosis.

Discordant effects of rosiglitazone on novel inflammatory biomarkers.

Specific chemokines contribute to vascular inflammation and may be useful biomarkers to detect atherosclerosis. The chemokines CXCL1 and CCL11 have previously been studied in animal or human models of atherosclerosis, while CXCL2 and CCL23 have not. Among 2,454 subjects enrolled in the Dallas Heart Study, a multi-ethnic population-based sample, we measured plasma CCL11, CCL23, CXCL1, and CXCL2, and associated levels with coronary artery calcium (CAC) by computed tomography, and aortic wall thickness, plaque burden, and compliance by magnetic resonance imaging. Elevated chemokine levels were defined as greater than or equal to the median for CCL11 and CCL23 and greater than or equal to the upper detection limit for CXCL1 and CXCL2. Elevated CCL23 (P < 0.01) and CXCL1 (P = 0.01), but not CCL11 and CXCL2, associated with CAC in univariable analyses. After adjustment for traditional risk factors, elevated CCL23 remained associated with CAC (OR 1.3, 95% CI 1.0-1.7; P = 0.02), while the association with CXCL1 was modestly attenuated (OR 1.4, 95% CI 1.0-2.1; P = 0.06). CCL23 also associated with aortic wall thickness, plaque, and compliance in univariable analyses (P < 0.05 for each), but these associations were attenuated after multivariable adjustment. The novel chemotactic protein, CCL23, which has not been previously studied in atherosclerosis, is independently associated with coronary atherosclerosis, suggesting that this chemokine merits further study in animal and human models.

Antitachycardia pacing as both therapy and diagnostic tool: What is the diagnosis?

OBJECTIVE Lymphotoxin β receptor (LTβR), a member of the tumor necrosis factor superfamily, binds ligands expressed by activated lymphocytes. Interruption of LTβR signaling improves autoimmune diseases and alters lipid homeostasis. We assayed circulating LTβR and examined its association with atherosclerosis phenotypes in a population-based sample. METHODS AND RESULTS Plasma LTβR was measured by ELISA in 3215 subjects enrolled in the Dallas Heart Study. Atherosclerosis was assessed using CT measurements of coronary calcium (CAC) and abdominal MRI measurements of aortic plaque (AP) (n=2252) and aortic wall thickness (AWT) (n=2265). We analyzed associations between LTβR and atherosclerosis using multivariable logistic and linear regression methods. Higher levels of LTβR associated with most traditional cardiovascular risk factors, multiple inflammatory markers, and markers of cardiac injury. Univariable analyses demonstrated significant associations of LTβR with CAC, AP, and AWT (p<0.0001 for each). In multivariable models adjusted for traditional risk factors, the 4th vs. the 1st quartile of LTβR remained associated with prevalent CAC, AP, and increased AWT (all p<0.05). Similar associations were observed when LTβR was modeled as a log-transformed continuous variable. CONCLUSION LTβR levels are independently associated with atherosclerosis in multiple vascular beds. These findings support further investigation of the lymphotoxin/LTβR pathway in atherosclerosis.

ATRIAL LEAD IMPLANTATION IS ASSOCIATED WITH CONVERSION TO SINUS RHYTHM AND MAINTENANCE OF SINUS RHYTHM IN PATIENTS WITH LONG-STANDING ATRIAL FIBRILLATION UNDERGOING ATRIOVENTRICULAR NODE ABLATION AND BIVENTRICULAR PACEMAKER IMPLANTATION

BACKGROUND Although rosiglitazone favorably affects myriad intermediate markers of atherosclerosis, it appears to increase myocardial infarction (MI) risk. We analyzed the effects of rosiglitazone on a panel of 8 novel circulating biomarkers, 4 of which are independently associated with atherosclerosis: lymphotoxin β receptor, peptidoglycan recognition protein 1, chemokine ligand 23, and soluble receptor for advanced glycation end products (sRAGE) as well as on high-sensitivity C-reactive protein (hs-CRP). METHODS Blood samples were analyzed at baseline and after 6 months of study treatment from subjects with type 2 diabetes with or at high risk for coronary artery disease in a randomized trial comparing rosiglitazone versus placebo. RESULTS Data from 111 subjects (rosiglitazone 55, placebo 56) were analyzed. Mean age was 56 years, 41% were women, and 66% were nonwhite. Compared with baseline values, rosiglitazone adversely affected levels of lymphotoxin β receptor (1.7 vs 2.4 ng/mL, P = .002), peptidoglycan recognition protein 1 (29.0 vs 30.1 ng/mL, P = .01), and chemokine ligand 23 (0.76 vs 0.84 ng/mL, P = .02) and favorably affected levels of sRAGE (inversely associated with atherosclerosis, 1.1 vs 1.4 ng/mL, P = .003) and hs-CRP (0.42 vs 0.31 ng/mL, P = .02); no changes were observed with rosiglitazone in the other biomarkers. In the placebo group, change was observed only for sRAGE (1.0 vs 1.1 ng/mL, P = .046). CONCLUSION Rosiglitazone adversely affected 3 novel biomarkers and favorably affected a fourth previously associated with atherosclerosis while improving hs-CRP, as has previously been shown. Whether these complex effects on circulating inflammatory biomarkers contribute to the signal of increased MI risk with rosiglitazone and whether pioglitazone has similar effects warrant further investigation.

The association between plasma caspase-3, atherosclerosis, and vascular function in the Dallas Heart Study

Case presentation A 53-year-old man presented for routine follow-up of his dualchamber implantable cardioverter-defibrillator (ICD; Medtronic, Secura DR), which had been implanted 1 year earlier for primary prevention of sudden cardiac death. His history included coronary artery disease with remote coronary artery bypass grafting, moderately depressed left ventricular ejection fraction, and New York Heart Association class II heart failure symptoms. A ventricular fibrillation (VF) zone had been programmed at 300 ms ( 200 pm) and a ventricular tachycardia (VT) zone at 340 ms (176– 00 bpm). ICD interrogation revealed multiple antitachycardia acing (ATP) therapies occurring in the VF zone. Stored data rom one of these therapies are shown, including the interval plot Figure 1) and intracardiac electrograms (EGMs; Figure 2). All tored episodes showed a similar initiation and termination of rrhythmia. What is the diagnosis?

Abstract 9852: T Lymphocyte Depletion Following Primary Percutaneous Coronary Intervention Predicts Infarct Size and Ischemia Reperfusion Injury

Background: Patients with heart failure (HF) and long-standing atrial fibrillation (AF) who undergo atrioventricular node ablation with biventricular pacing (AVN+BiV) generally do not receive atrial leads (A-leads) since the atrium is refractory to pacing during AF. We have noted spontaneous conversion to sinus rhythm (SR) following AVN+BiV in a number of such patients and have therefore been implanting A-leads in some. We examined the rates of conversion to and maintenance of SR in such patients with particular reference to the presence of an A-lead.