Intestinal lipoprotein overproduction, a newly recognized component of insulin resistance, is ameliorated by the insulin sensitizer rosiglitazone: studies in the fructose-fed Syrian golden hamster

We investigated whether intestinal lipoprotein overproduction in a fructose-fed, insulin-resistant hamster model is prevented with insulin sensitization. Syrian Golden hamsters were fed either chow, 60% fructose for 5 wk, chow for 5 wk with the insulin sensitizer rosiglitazone added for the last 3 wk, or 60% fructose plus rosiglitazone. In vivo Triton studies showed a 2- to 3-fold increase in the large (Svedberg unit > 400) and smaller (Sf 100-400) triglyceride-rich lipoprotein particle apolipoprotein B48 (apoB48) but not triglyceride secretion with fructose feeding in the fasted state (P < 0.01) and partial normalization with rosiglitazone in fructose-fed hamsters. Ex vivo pulse-chase labeling of enterocytes confirmed the oversecretion of apoB48 lipoproteins with fructose feeding. Intestinal lipoprotein oversecretion was associated with increased expression of microsomal triglyceride transfer protein expression. With rosiglitazone treatment of fructose-fed hamsters, there was approximately 50% reduction in apoB48 secretion from primary cultured enterocytes and amelioration of the elevated microsomal triglyceride transfer protein mass and activity in fructose-fed hamsters. In contrast, in the postprandial state, the major differences between nutritional and drug intervention protocols were evident in triglyceride-rich lipoprotein triglyceride and not apoB48 secretion rates. The data suggest that intestinal lipoprotein overproduction can be ameliorated with the insulin sensitizer rosiglitazone.     

Outcomes of paclitaxel-eluting stent implantation in patients with stenosis of the left anterior descending coronary artery

OBJECTIVES: We sought to examine the efficacy of paclitaxel-eluting stent implantation in the left anterior descending coronary artery (LAD). BACKGROUND: Restenosis and recurrent cardiac events after percutaneous intervention are more common for lesions in the LAD than other native coronary arteries, and often necessitate bypass surgery. Drug-eluting stents may improve the long-term prognosis of this high-risk group. METHODS: In the TAXUS-IV trial, 1,314 patients with single de novo coronary lesions were assigned to implantation of the slow-release, polymer-based, paclitaxel-eluting TAXUS stent or an identical bare-metal stent; 536 (41%) randomized patients had LAD lesions. RESULTS: Baseline characteristics of patients with LAD lesions were well-matched between the randomized groups. Late lumen loss at nine months after paclitaxel-eluting and control stent implantation were 0.28 +/- 0.51 mm and 0.54 +/- 0.57 mm, respectively (p = 0.0004), and binary restenosis rates were 11.3% and 26.9%, respectively (p = 0.004). At one year, major adverse cardiac events (MACE) occurred in 13.5% of TAXUS-treated patients versus 21.2% treated with the control stent (p = 0.01). The need for bypass surgery at one year was reduced among patients randomized to the TAXUS stent (2.6% vs. 6.3%, p = 0.02). In the proximal LAD subgroup (n = 126), the one-year target vessel revascularization rate was 7.9% with the TAXUS stent and 18.6% with the bare-metal stent (p = 0.009). CONCLUSIONS: Compared to bare-metal stents, implantation of polymer-based, paclitaxel-eluting stents in LAD lesions is safe, and reduces angiographic restenosis and MACE one year. Notably, the need for bypass graft surgery due to restenosis is reduced after TAXUS stent implantation in LAD lesions.     

Impact of coronary culprit lesion calcium in patients undergoing paclitaxel-eluting stent implantation (a TAXUS-IV sub study)

Randomized clinical trials have shown that paclitaxel-eluting stents significantly reduce restenosis after percutaneous coronary intervention. The impact of lesion calcification on the efficacy of paclitaxel-eluting stents is unknown. In the TAXUS-IV trial, 1,314 patients who underwent percutaneous coronary intervention were randomly assigned to a bare-metal or paclitaxel-eluting stent. By core laboratory analysis, 247 lesions (19%) were moderately or severely calcified. At the 9-month angiographic follow-up examination, the paclitaxel-eluting stent had significantly reduced the amount of late loss compared with the control stent (0.26 +/- 0.56 vs 0.51 +/- 0.48 mm, p = 0.015) within the analysis segment in the calcific lesions. The analysis segment restenosis rate was similar in patients with calcified and noncalcified lesions after paclitaxel-eluting stent implantation (7.5% vs 8.0%, respectively; p = 1.0). The rate of ischemia-driven target lesion revascularization (TLR) at 1 year was reduced by 56% in patients with calcified lesions (11.9% vs 5.1%, p = 0.09) and by 75% in noncalcified lesions (15.7% vs 4.3%, p <0.0001). By interaction testing, the efficacy of the paclitaxel-eluting stent in reducing TLR at 1 year was similar in the calcified and noncalcified lesions (p = 0.30). Moreover, by multivariate analysis, implantation of the paclitaxel-eluting stent was a powerful independent predictor of freedom from TLR, with similar hazard ratios for efficacy in calcified and noncalcified lesions (0.30 and 0.26, respectively). In conclusion, implantation of paclitaxel-eluting stents in patients with de novo coronary lesions significantly reduced restenosis in patients with and without calcified lesions.     

Effect of a Contrast Modulation System on Contrast Media Use and the Rate of Acute Kidney Injury After Coronary Angiography

Objectives

The aim of the AVERT (AVERT Clinical Trial for Contrast Media Volume Reduction and Incidence of CIN) trial was to test the efficacy of the AVERT system to reduce the contrast media volume (CMV) used during coronary angiographic procedures without impairing image quality and to prevent contrast-induced acute kidney injury (CI-AKI) in patients at risk for CI-AKI.

Intra-arterial reteplase for the treatment of acute limb ischemia

The removal of urokinase from the market has created a dilemma for interventionists and vascular surgeons treating patients with acute limb threatening ischemia due to arterial thrombosis or embolization. Reteplase is a newer, fibrin-specific thrombolytic agent with properties that make it an attractive alternative to urokinase. We report two cases of successful treatment of acute, limb threatening ischemia with intra-arterial Reteplase therapy.     

Estrogen-eluting, phosphorylcholine-coated stent implantation is associated with reduced neointimal formation but no delay in vascular repair in a porcine coronary model.

Estrogen can inhibit intimal proliferation and accelerate endothelial regeneration after angioplasty. This suggests that estrogen may prevent in-stent restenosis. Unlike other therapies to prevent restenosis, estrogen may also not delay endothelial regrowth, thereby avoiding the risk of late stent thrombosis. The purpose of this work was to determine the effect of a 17beta-estradiol-eluting stent on neointimal formation in a porcine model. Each artery of six pigs was randomized to either a control, low-dose, or high-dose 17beta-estradiol-eluting stent. All animals were sacrificed at 30 days for histopathological analysis. There was a 40% reduction in intimal area in the high-dose stents compared with control stents (2.54 +/- 1.0 vs. 4.13 +/- 1.1 mm(2), for high dose vs. control, respectively; P < 0.05). There was complete endothelial regeneration at 30 days and similar inflammatory response to stenting on histopathology in all the stent groups. This is the first study to show that 17beta-estradiol-eluting stents are associated with reduced neointimal formation without affecting endothelial regeneration in the pig model of in-stent restenosis. Estrogen-coated stents may have a potential benefit in the prevention and treatment of in-stent restenosis.     

Dedicated two-stent technique in complex bifurcation percutaneous coronary intervention with use of everolimus-eluting stents: The EES-bifurcation study

Objectives

To compare the outcomes of initial one-stent (1S) versus dedicated two-stent (2S) strategies in complex bifurcation percutaneous coronary intervention (PCI) using everolimus-eluting stents (EES).

Background

PCI of true bifurcation lesions is technically challenging and historically associated with reduced procedural success and increased restenosis. Prior studies comparing initial one-stent (1S) versus dedicated two-stent (2S) strategies using first-generation drug-eluting stents have shown no reduction in ischemic events and more complications with a 2S strategy.

Methods

We performed a retrospective study of 319 consecutive patients undergoing PCI at a single referral center with EES for true bifurcation lesions, defined by involvement of both the main vessel (MV) and side branch (SB). Baseline, procedural characteristics, quantitative coronary angiography and clinical outcomes in-hospital and at one year were compared for patients undergoing 1S (n = 175) and 2S (n = 144) strategies.

Results

Baseline characteristics were well-matched. 2S strategy was associated with greater SB acute gain (0.65 ± 0.41 mm vs. 1.11 ± 0.47 mm, p < 0.0001). In-hospital serious adverse events were similar (9% with 2S vs. 8% with 1S, p = 0.58). At one year, patients treated by 2S strategy had non-significantly lower rates of target vessel revascularization (5.8% vs. 7.4%, p = 0.31), myocardial infarction (7.8% vs. 12.2%, p = 0.31) and major adverse cardiovascular events (16.6% vs. 21.8%, p = 0.21).

Conclusion

In this study of patients undergoing PCI for true coronary bifurcation lesions using EES, 2S strategy was associated with superior SB angiographic outcomes without excess complications or ischemic events at one year.