Vonoprazan and amoxicillin dual therapy as the first-line treatment of Helicobacter pylori infection: A systematic review and meta-analysis.

BACKGROUND: Recent clinical trials have evaluated the efficacy of vonoprazan-amoxicillin (VA) dual therapy as the first-line treatment for Helicobacter pylori infection in different regions with inconsistent results reported. In this systematic review and meta-analysis, we aimed to evaluate the efficacy of VA dual therapy compared to the currently recommended therapy for eradicating H. pylori. MATERIALS AND METHODS: A comprehensive search of the PubMed, Cochrane, and Embase databases was performed using the following search terms: ("Helicobacter" OR "H. pylori" OR "Hp") AND ("vonoprazan" OR "potassium-competitive acid blocker" OR "P-CAB") AND ("amoxicillin" OR "penicillin") AND ("dual"). The primary outcome was to evaluate the eradication rate according to intention-to-treat and per-protocol analysis. The secondary outcomes were adverse events and compliance. RESULTS: A total of 15 studies involving 4, 568 patients were included. The pooled eradication rate of VA dual therapy was 85.0% and 90.0% by intention-to-treat and per-protocol analysis, respectively. The adverse events rate and compliance of VA dual therapy were 17.5% and 96%, respectively. The efficacy of VA dual therapy was superior to proton pump inhibitors-based triple therapy (82.0% vs. 71.4%, p < 0.01) but lower than vonoprazan-containing quadruple therapy (83.1% vs. 93.3%, p = 0.02). 7-day VA dual therapy showed lower eradication rates than 10-day (χ2 = 24.09, p < 0.01) and 14-day VA dual therapy (χ2 = 11.87, p < 0.01). The adverse events rate of VA dual therapy was lower than vonoprazan triple therapy (24.6% vs. 30.9%, p = 0.01) and bismuth-containing quadruple therapy (20.5% vs. 47.9%, p < 0.01). No significant difference of compliance was observed between VA dual therapy and each subgroup. CONCLUSION: VA dual therapy, a novel regimen, showed high efficacy as the first-line treatment for H. pylori eradication, which should be optimized before application in different regions.

Placental growth factor increases regional myocardial blood flow and contractile function in chronic myocardial ischemia.

Placental growth factor (PlGF) has a distinct biological phenotype with a predominant proangiogenic role in disease without affecting quiescent vessels in healthy organs. We tested whether systemic administration of recombinant human (rh)PlGF improves regional myocardial blood flow (MBF) and systolic function recovery in a porcine chronic myocardial ischemia model. We implanted a flow-limiting stent in the proximal left anterior descending coronary artery and measured systemic hemodynamics, regional myocardial function using MRI, and blood flow using colored microspheres 4 wk later. Animals were then randomized in a blinded way to receive an infusion of rhPlGF (15 µg·kg(-1)·day(-1), n = 9) or PBS (control; n = 10) for 2 wk. At 8 wk, myocardial perfusion and function were reassessed. Infusion of rhPlGF transiently increased PlGF serum levels >30-fold (1,153 ± 180 vs. 33 ± 18 pg/ml at baseline, P < 0.001) without affecting systemic hemodynamics. From 4 to 8 wk, rhPlGF increased regional MBF from 0.46 ± 0.11 to 0.85 ± 0.16 ml·min(-1)·g(-1), with a concomitant increase in systolic wall thickening from 11 ± 3% to 26 ± 5% in the ischemic area. In control animals, no significant changes from 4 to 8 wk were observed (MBF: 0.45 ± 0.07 to 0.49 ± 0.08 ml·min(-1)·g(-1) and systolic wall thickening: 14 ± 4% to 18 ± 1%). rhPlGF-induced functional improvement was accompanied by increased myocardial neovascularization, enhanced glycogen utilization, and reduced oxidative stress and cardiomyocyte apoptosis in the ischemic zone. In conclusion, systemic rhPlGF infusion significantly enhances regional blood flow and contractile function of the chronic ischemic myocardium without adverse effects. PlGF protein infusion may represent an attractive therapeutic strategy to increase myocardial perfusion and energetics in chronic ischemic cardiomyopathy.

Fourteen-day vonoprazan and low- or high-dose amoxicillin dual therapy for eradicating Helicobacter pylori infection: A prospective, open-labeled, randomized non-inferiority clinical study.

Background and aim: We previously reported that vonoprazan-amoxicillin (VA) dual therapy for 7 or 10 days is not satisfactorily efficacious for Helicobacter pylori (H. pylori) eradication. We aimed to explore the efficacy of VA dual therapy for 14 days as a first-line treatment for H. pylori infection. Methods: This was a single center, prospective, open-labeled, randomized non-inferiority clinical study conducted in China. Treatment naïve H. pylori infected patients were randomized into two groups: 20 mg vonoprazan (VPZ) b.i.d. in combination with low-dose (1000 mg b.i.d.) or high-dose (1000 mg t.i.d) amoxicillin for 14 days. 13C-urea breath tests were used to access the cure rate at least 4 weeks after treatment. Results: A total of 154 patients were assessed and 110 subjects were randomized. The eradication rate of VPZ with b.i.d. amoxicillin or t.i.d. amoxicillin for 14 days was 89.1% and 87.3% by intention-to-treat analysis, respectively, and 94.1% and 95.9% by per-protocol analysis, respectively. The eradication rate and incidence of adverse events were not different between the two groups. Conclusion: VPZ with b.i.d. or t.i.d. amoxicillin for 14 days provides satisfactory efficacy as a first-line treatment for H. pylori infection in China.

Ventricular phosphodiesterase-5 expression is increased in patients with advanced heart failure and contributes to adverse ventricular remodeling after myocardial infarction in mice.

BACKGROUND: Ventricular expression of phosphodiesterase-5 (PDE5), an enzyme responsible for cGMP catabolism, is increased in human right ventricular hypertrophy, but its role in left ventricular (LV) failure remains incompletely understood. We therefore measured LV PDE5 expression in patients with advanced systolic heart failure and characterized LV remodeling after myocardial infarction in transgenic mice with cardiomyocyte-specific overexpression of PDE5 (PDE5-TG). METHODS AND RESULTS: Immunoblot and immunohistochemistry techniques revealed that PDE5 expression was greater in explanted LVs from patients with dilated and ischemic cardiomyopathy than in control hearts. To evaluate the impact of increased ventricular PDE5 levels on cardiac function, PDE5-TG mice were generated. Confocal and immunoelectron microscopy revealed increased PDE5 expression in cardiomyocytes, predominantly localized to Z-bands. At baseline, myocardial cGMP levels, cell shortening, and calcium handling in isolated cardiomyocytes and LV hemodynamic measurements were similar in PDE5-TG and wild-type littermates. Ten days after myocardial infarction, LV cGMP levels had increased to a greater extent in wild-type mice than in PDE5-TG mice (P<0.05). Ten weeks after myocardial infarction, LV end-systolic and end-diastolic volumes were larger in PDE5-TG than in wild-type mice (57+/-5 versus 39+/-4 and 65+/-6 versus 48+/-4 muL, respectively; P<0.01 for both). LV systolic dysfunction and diastolic dysfunction were more marked in PDE5-TG than in wild-type mice, associated with enhanced hypertrophy and reduced contractile function in isolated cardiomyocytes from remote myocardium. CONCLUSIONS: Increased PDE5 expression predisposes mice to adverse LV remodeling after myocardial infarction. Increased myocardial PDE5 expression in patients with advanced cardiomyopathy may contribute to the development of heart failure and represents an important therapeutic target.

Cardioselective nitric oxide synthase 3 gene transfer protects against myocardial reperfusion injury.

Nitric oxide modulates the severity of myocardial ischemia-reperfusion (I/R) injury. We investigated whether cardioselective nitric oxide synthase 3 (NOS3) gene transfer could confer myocardial protection against I/R injury in pigs and examined potential molecular mechanisms. I/R injury was induced by balloon occlusion of the left anterior descending artery for 45 min followed by 4 or 72 h reperfusion. Hemodynamic and pathological changes were measured in pigs in the absence (n = 11) or presence of prior intracoronary retroinfusion of human NOS3 (AdNOS3, 5 x 10(10) PFU, n = 13) or control vector (AdRR5, 5 x 10(10) PFU, n = 11). Retrograde NOS3 gene transfer selectively increased NOS3 expression and NO bioavailability in the area at risk (AAR) without changing endogenous NOS isoform expression. At 4 h R, LV systolic (dP/dt(max)) and diastolic (dP/dt(min)) function was better preserved in AdNOS3- than in AdRR5-injected pigs (2,539 +/- 165 vs. 1,829 +/- 156 mmHg/s, and -2,781 +/- 340 vs. -2,062 +/- 292 mmHg/s, respectively, P < 0.05 for both). Myocardial infarct size (% AAR) was significantly smaller in AdNOS3 than in control and AdRR5 and associated with a significantly greater reduction in cardiac myeloperoxidase activity, a marker of neutrophil infiltration. The latter effects were sustained at 72 h R in a subset of pigs (n = 7). In the AAR, intercellular endothelial adhesion molecule-1 expression and cardiomyocyte apoptosis were significantly lower in AdNOS3. In conclusion, single myocardial NOS3 retroinfusion attenuates I/R injury, and causes a sustained reduction in myocardial infarct size and inflammatory cell infiltration. Gene-based strategies to increase NO bioavailability may have therapeutic potential in myocardial I/R.

Sustained endothelial progenitor cell dysfunction after chronic hypoxia-induced pulmonary hypertension.

Circulating endothelial progenitor cells (EPCs) contribute to neovascularization of ischemic tissues and repair of injured endothelium. The role of bone marrow-derived progenitor cells in hypoxia-induced pulmonary vascular remodeling and their tissue-engineering potential in pulmonary hypertension (PH) remain largely unknown. We studied endogenous mobilization and homing of EPCs in green fluorescent protein bone marrow chimeric mice exposed to chronic hypoxia, a common hallmark of PH. Despite increased peripheral mobilization, as shown by flow cytometry and EPC culture, bone marrow-derived endothelial cell recruitment in remodeling lung vessels was limited. Moreover, transfer of vascular endothelial growth factor receptor-2+/Sca-1+/CXCR-4+-cultured early-outgrowth EPCs failed to reverse PH, suggesting hypoxia-induced functional impairment of transferred EPCs. Chronic hypoxia decreased migration to stromal cell-derived factor-1alpha, adhesion to fibronectin, incorporation into a vascular network, and nitric oxide production (-41%, -29%, -30%, and -32%, respectively, vs. normoxic EPCs; p < .05 for all). The dysfunctional phenotype of hypoxic EPCs significantly impaired their neovascularization capacity in chronic hind limb ischemia, contrary to normoxic EPCs cultured in identical conditions. Mechanisms contributing to EPC dysfunction include reduced integrin alphav and beta1 expression, decreased mitochondrial membrane potential, and enhanced senescence. Novel insights from chronic hypoxia-induced EPC dysfunction may provide important cues for improved future cell repair strategies.

Use of a tacrolimus-eluting stent to inhibit neointimal hyperplasia in a porcine coronary model.

In-stent restenosis remains an unresolved problem which occurs in 5-20% of patients undergoing coronary stenting within the first 3-6 months. Neointimal formation is the main contributor to in-stent restenosis. Stent-induced arterial injury and peri-strut inflammation are involved in the process of neointimal formation by activating cytokines and growth factors which induce smooth muscle cell dedifferentiation, migration, and proliferation. Histopathological studies found that neointimal hyperplasia is principally composed of smooth muscle cells, inflammatory cells, and extracellular matrix. Stent-based delivery of anti-proliferative and/or anti-inflammatory agents have shown beneficial effects on neointimal hyperplasia in experimental studies and clinical trials. Tacrolimus (FK506) is a water-insoluble macrolide immunosuppressant discovered in 1984. It has been widely used in reducing the incidence and severity of allograft rejection after organ transplantation. It has also been used to treat other inflammatory conditions such as atopic dermatitis. In this study, we evaluated the efficacy of stent-based delivery of tacrolimus on inflammation and neointimal formation in an overstretched coronary stent model.

Long-term biocompatibility evaluation of a novel polymer-coated stent in a porcine coronary stent model.

BACKGROUND: Polymer coatings have been used to modify the surface of stents and to serve as a matrix for local drug delivery. METHODS: Bare stainless steel stents or poly-bis-trifluorethoxy phosphazene (PTFEP) dip-coated stents (Coroflex, Germany) were randomly implanted into porcine coronary arteries with a balloon-to-artery ratio of 1.1-1.2 : 1. Scanning electron microscopy (SEM), repeat quantitative coronary angiography (QCA) and histomorphometric analysis were performed at 5 days, 6 weeks and 6 months. RESULTS: At 5 days, complete endothelial cell coverage with fibrin strands was detected in both the bare and the coated stents with SEM. Late loss, determined by QCA, of coated and bare stents was identical at all time points. Histomorphometric analysis showed that coated and bare stents elicited a similar tissue response at 5 days. At 6 weeks, the coated stents showed a moderate peri-strut inflammatory response, resulting in increased neointimal hyperplasia. Compared to the bare stents, however, no significant differences were observed. At 6 months, peri-strut inflammation was minimal and similar in the coated and the bare stent groups. Neointimal hyperplasia of the coated and bare stent groups was also comparable (1.37+/-0.44 compared with 1.15+/-0.40 mm2, P=0.213) and decreased compared to the 6-week response. CONCLUSION: This PTFEP stent coating showed a long-term biocompatibility in a porcine coronary stent model. Because no increased proliferative response was observed up to 6 months, this phosphazene coating may serve as a vehicle for local drug delivery.

Addition of cytochalasin D to a biocompatible oil stent coating inhibits intimal hyperplasia in a porcine coronary model.

BACKGROUND: Polymer-based, drug-eluting stents, are currently under extensive investigation in the conquest against in-stent restenosis. Concern remains, however, about potential long-term lack of biocompatibility of the polymers used in these studies. Therefore, this study aimed to evaluate in porcine coronary arteries (1) the in vivo biocompatibility of a new natural, eicosapentaenoic acid oil stent-coating and (2) the efficacy of this coating in preventing in-stent restenosis when cytochalasin D--an inhibitor of actin filament formation, that interferes with cell proliferation and migration--was added. METHODS AND RESULTS: To assess in vivo biocompatibility of the oil coating, 15 bare and 15 oil-coated stents were randomly deployed in coronary arteries of 15 pigs. No difference in tissue response, regarding inflammation or proliferation, was seen between both groups at five days or at four weeks follow-up. To evaluate the efficacy of the coating in preventing in-stent restenosis by adding a potential anti-restenotic drug, stents were dip-coated in 20 mg cytochalasin D/ml oil solution, resulting in 93 +/- 18 microg cytochalasin D/stent load (n = 3). In vitro drug release studies showed sustained release up to four weeks. Next, 11 oil-coated and 11 cytochalasin D-loaded stents were randomly implanted in coronary arteries of 11 pigs. At four weeks, a 39% decrease in neointimal hyperplasia (p < 0.05, ANCOVA, with injury as covariate) was found in cytochalasin D-loaded stents compared to oil-coated stents. CONCLUSIONS: This new natural oil stent-coating shows excellent biocompatibility to vascular tissue. Local cytochalasin D delivery from this stent-platform significantly inhibits neointimal hyperplasia in a porcine coronary model.

Dexamethasone-eluting stent: an anti-inflammatory approach to inhibit coronary restenosis.

The long-term efficacy of percutaneous coronary interventions is still hampered by restenosis. Restenosis is the result of a complex pathophysiological process, which is thought to be caused by an exaggerated healing response induced by the vascular injury caused by the percutaneous coronary interventions and the implantation of a foreign body (the stent). There is increasing evidence that inflammation plays an important role in the initiation and development of neointimal hyperplasia and subsequent restenosis. Dexamethasone (Decadron, Merck Sharpe and Dohme Ltd) is a glucocorticoid with well-known potent anti-inflammatory and antiproliferative properties. Early studies using either systemic or local delivery of dexamethasone have shown limited beneficial effects on restenosis. The dexamethasone-eluting stent (Dexamet, Abbott Vascular Devices Ltd) is one of the first generation of drug-eluting stents for local drug delivery to prevent restenosis. Preclinical studies demonstrated that implantation of dexamethasone-loaded coronary stents was safe and had a beneficial effect on stent implantation-related inflammation. A pilot trial suggested a beneficial effect on restenosis. Large randomized trials are underway to confirm these findings. This article reviews the potential role of inflammation in the pathogenesis of restenosis and the efficacy of dexamethasone in the prevention of restenosis.

Optimization of local methylprednisolone delivery to inhibit inflammatory reaction and neointimal hyperplasia of coated coronary stents.

Polymer coating can optimize the surface characteristics of metallic coronary stents and serve as a vehicle for local drug delivery. Major problems, however, include the lack of biocompatibility of the polymers used and the limited amount of drug that can be loaded onto the stent. Stainless-steel stents were spray-coated or spray-coated combined with a barrier coating using a fluorinated polymethacrylate PFM-P75 impregnated with different methylprednisolone concentrations. When spray-coated with highly concentrated methylprednisolone ( 33%) fluorinated polymethacrylate PFM-P75, the surface became progressively more rough. Adding a barrier coating, however, could decrease these surface irregularities of methylprednisolone-loaded PFM-P75 spray-coated stents. In vitro, most of the methylprednisolone was released in the first 48 hours. A barrier coating could dramatically slow down the drug release from 80% to 13% during the first 48 hours. Histomorphometric analysis showed that the inflammatory response and neointimal hyperplasia of methylprednisolone-loaded stents were lower than in control stents. Neointimal hyperplasia of methylprednisolone-loaded PFM-P75 stents spray-coated with a barrier coating was decreased compared to the non-barrier-coated methylprednisolone-loaded stents. In conclusion, spray coating enables the use of high methylprednisolone concentrations. A barrier coating could significantly slow down the methylprednisolone release. Methylprednisolone-loaded PFM-P75-coated stents could significantly inhibit the inflammatory response and neointimal hyperplasia. The response to methylprednisolone was related to the dose used and the release time of the drug.

Differential effects of progenitor cell populations on left ventricular remodeling and myocardial neovascularization after myocardial infarction.

OBJECTIVES: We compared biological repair after acute myocardial infarction (AMI) with selected porcine progenitor cell populations. BACKGROUND: Cell types and mechanisms responsible for myocardial repair after AMI remain uncertain. METHODS: In a blinded, randomized study, we infused autologous late-outgrowth endothelial progenitor cells (EPC) (n = 10, 34 +/- 22 x 10(6) CD29-31-positive, capable of tube formation), allogeneic green fluorescent peptide-labeled mesenchymal stem cells (MSC) (n = 11, 10 +/- 2 x 10(6) CD29-44-90-positive, capable of adipogenic and osteogenic differentiation), or vehicle (CON) (n = 12) in the circumflex artery 1 week after AMI. Systolic function (ejection fraction), left ventricular (LV) end-diastolic and end-systolic volumes, and infarct size were assessed with magnetic resonance imaging at 1 week and 7 weeks. Cell engraftment and vascular density were evaluated on postmortem sections. RESULTS: Recovery of LV ejection fraction from 1 to 7 weeks was similar between groups, but LV remodeling markedly differed with a greater increase of LV end-systolic volume in MSC and CON (+11 +/- 12 ml/m(2) and +7 +/- 8 ml/m(2) vs. -3 +/- 11 ml/m(2) in EPC, respectively, p = 0.04), and a similar trend was noted for LV end-diastolic volume (p = 0.09). After EPC, infarct size decreased more in segments with >50% infarct transmurality (p = 0.02 vs. MSC and CON) and was associated with a greater vascular density (p = 0.01). Late outgrowth EPCs secrete higher levels of the pro-angiogenic placental growth factor (733 [277 to 1,214] pg/10(6) vs. 59 [34 to 88] pg/10(6) cells in MSC, p = 0.03) and incorporate in neovessels in vivo. CONCLUSIONS: Infusion of late-outgrowth EPCs after AMI improves myocardial infarction remodeling via enhanced neovascularization but does not mediate cardiomyogenesis. Endothelial progenitor cell transfer might hold promise for heart failure prevention via pro-angiogenic or paracrine matrix-modulating effects.

Nitric oxide inhalation improves microvascular flow and decreases infarction size after myocardial ischemia and reperfusion.

OBJECTIVES: The purpose of this study was to test if nitric oxide (NO) could improve microvascular perfusion and decrease tissue injury in a porcine model of myocardial ischemia and reperfusion (I/R). BACKGROUND: Inhaled NO is a selective pulmonary vasodilator with biologic effects in remote vascular beds. METHODS: In 37 pigs, the midportion of the left anterior descending coronary artery was occluded for 50 min followed by 4 h of reperfusion. Pigs were treated with a saline infusion (control; n = 14), intravenous nitroglycerin (IV-NTG) at 2 microg/kg/min (n = 11), or inhaled nitric oxide (iNO) at 80 parts per million (n = 12) beginning 10 min before balloon deflation and continuing throughout reperfusion. RESULTS: Total myocardial oxidized NO species in the infarct core was greater in the iNO pigs than in the control or IV-NTG pigs (0.60 +/- 0.05 nmol/mg tissue vs. 0.40 +/- 0.03 nmol/mg tissue and 0.40 +/- 0.02 nmol/mg tissue, respectively; p < 0.01 for both). Infarct size, expressed as percentage of left ventricle area at risk (AAR), was smaller in the iNO pigs than in the control or IV-NTG pigs (31 +/- 6% AAR vs. 58 +/- 7% AAR and 46 +/- 7% AAR, respectively; p < 0.05 for both) and was associated with less creatine phosphokinase-MB release. Inhaled NO improved endocardial and epicardial blood flow in the infarct zone, as measured using colored microspheres (p < 0.001 vs. control and IV-NTG). Moreover, NO inhalation reduced leukocyte infiltration, as reflected by decreased cardiac myeloperoxidase activity (0.8 +/- 0.2 U/mg tissue vs. 2.3 +/- 0.8 U/mg tissue in control and 1.4 +/- 0.4 U/mg tissue in IV-NTG; p < 0.05 for both) and decreased cardiomyocyte apoptosis in the infarct border zone. CONCLUSIONS: Inhalation of NO just before and during coronary reperfusion significantly improves microvascular perfusion, reduces infarct size, and may offer an attractive and novel treatment of myocardial infarction.

Stent-based tempamine delivery on neointimal formation in a porcine coronary model.

BACKGROUND: Tempamine is one of new class of antioxidant agents, the nitroxides, which have shown a wide range of biological effects like suppressing free radical driven reactions to maintain cell functions. The objectives of this study were to evaluate the effect of a biodegradable polymer coated stent loaded with tempamine on in-stent neointimal formation. METHODS: Stainless steel stents were dip coated in biodegradable elastomeric poly (ester-amide) (co-PEA) or in polymer solution mixed with 50% (wt%) and 100% (wt%) tempamine. One group 100% (wt%) tempamine loaded stents were further dip coated in co-PEA polymer to form a top layer. Stainless steel bare, polymer-only, and different doses tempanine coated stents were implanted into porcine coronary arteries with a stent to artery ratio 1.2:1. Histomorphometric analysis was performed at 5 days and 6 weeks respectively. RESULTS: Histomorphometric analysis showed that the bare, polymer-only and tempamine-coated stents elicited a similar tissue response at 5 days. At 6 weeks, the peri-strut inflammation and neointimal hyperplasia of polymer-only stents were comparable to the bare stents. Compared to the bare stents, 50% tempanine coated stents had a trend to decrease the arterial injury (0.62 +/- 0.41 versus 0.34 +/- 0.18, P = 0.075) and neointimal hyperplasia (1.80 +/- 0.77 versus 1.27 +/- 0.39 mm2, P = 0.085). However, 100% tempanine coated showed significantly increased inflammatory response and neointimal formation. CONCLUSION: These co-PEA polymer coatings showed a biocompatible performance. Loaded with 50% tempamine had a trend to decrease neointimal hyperplasia. The 100% tempamine for stent-based delivery may have potential cytotoxic effects to arterial wall. Using a co-PEA polymer topcoat could effectively abolish these side effects.

Local methylprednisolone delivery using a BiodivYsio phosphorylcholine-coated drug-delivery stent reduces inflammation and neointimal hyperplasia in a porcine coronary stent model.

Phosphorylcholine (PC)-coated stents have shown excellent blood and tissue biocompatibility in porcine coronary arteries. The purpose of this study was to determine the efficacy of local methylprednisolone (MP) delivery using PC-coated stents to inhibit inflammatory response and in-stent neointimal hyperplasia in an overstretched porcine coronary model. BiodivYsio (Biocompatibles, Farnham, Surrey, UK) PC-coated drug delivery (DD) stents and DD stents loaded with a high dose of MP (269 microg) were implanted in the coronary arteries of 20 pigs with a balloon/artery ratio of 1.2 : 1. At five days the peri-strut inflammatory response score and thrombus score of the MP-loaded DD stents were lower than in the control stents. The neointimal hyperplasia of MP-loaded DD stents was significantly reduced (0.80 +/- 0.10 versus 0.48 +/- 0.10 mm(2), p < 0.01). At four-week follow-up, the inflammatory response of MP-loaded stents was lower than the control stents, but without significant difference. The MP-loaded stents showed decreased peri-strut arterial injury and in-stent neointimal hyperplasia (2.42 +/- 0.87 versus 1.62 +/- 0.71 mm(2), p < 0.05). It is concluded that local vascular delivery of a high dose of MP from PC-coated DD stents could effectively decrease inflammatory response and thrombus formation after oversized stent deployment and result in a significant reduction of neointimal hyperplasia.

Study of antirestenosis with the BiodivYsio dexamethasone-eluting stent (STRIDE): a first-in-human multicenter pilot trial.

The aim of this multicenter pilot study was to evaluate the acute safety and efficacy of the dexamethasone-eluting stent (0.5 microg/mm(2) of stent) implanted in patients with de novo single-vessel disease. This study included 71 patients, 42% of whom had unstable angina pectoris. An appropriately sized BiodivYsio Matrix Lo stent loaded with a total dexamethasone dose of 0.5 microg/mm(2) of stent was used. Technical device success rate was 95%. Six-month MACE occurred in two patients (3.3%). Binary restenosis rate was 13.3%. Late loss was 0.45. Late loss and percent diameter stenosis were lower in the unstable angina pectoris patients compared to the stable patients (0.32 +/- 0.39 vs. 0.60 +/- 0.55 mm, P < 0.07, and 26.86 +/- 14 vs. 38.40 +/- 16%, P < 0.02). This study demonstrated the feasibility and safety of the implantation of a dexamethasone-eluting stent and its effect on in-stent neointimal hyperplasia.

The effect of reduced blood-flow on the coronary wall temperature. Are significant lesions suitable for intravascular thermography?

AIMS: The purpose of this study was to investigate the relation between acute coronary flow reduction and arterial wall temperature. METHODS AND RESULTS: Five pigs with normal coronary arteries were catheterized. Arterial wall temperature was studied with a thermographic system that uses a 4-thermistor sensor tip. Flow velocity was studied at the same time and place with the temperature measurements, using a Doppler wire. In order to modify the coronary flow, a balloon was gradually inflated proximally to the thermographic sensors. Temperature differences and flow velocities were simultaneously recorded. Flow velocities above an average peak velocity (APV) of 9 cm/s were associated with unaffected temperature measurements. At flow velocities around 4 cm/s, the wall temperature was increased (deltaT=0.015+/-0.005 degrees C, P approximately 0.05), following the heart-rate. When flow velocity dropped further below this value, the local wall temperature was logarithmically increased to a maximum value observed at total vessel occlusion (deltaT=0.188+/-0.023 degrees C, P<0.001). CONCLUSION: The reduction of coronary flow has an effect on the arterial wall temperature. This effect however, appears only below a critical threshold of APV and in a logarithmic fashion. Above this threshold, temperature measurements should be unaffected from flow reductions and related to the regional temperature heterogeneity.

A nonsurgical porcine model of left ventricular dysfunction. Validation of myocardial viability using dobutamine stress echocardiography and positron emission tomography.

BACKGROUND: Although several short-term animal models of stunning and hibernation have been studied extensively, it has been difficult to produce a consistent animal model of chronic hibernation. The aim of the present study was to develop a nonsurgical porcine stent model of coronary stenosis in order to investigate the relationship between chronic dysfunctional myocardium and viability using 2D-echo, dobutamine stress echo (DSE) and positron emission tomography (PET). METHODS AND RESULTS: Focal progressive coronary stenosis was induced by implantation of an oversized stent in the left anterior descending (LAD) and/or circumflex (LCX) coronary artery in a total of 115 pigs, according to various experimental protocols: copper stent in the LAD (group I, n = 5); noncoated stainless steel stent in the LAD combined with balloon overstretch (group II, n = 7); poly(organo)phosphazene-coated stent in the LAD (group III, n = 77); and poly(organo)phosphazene-coated stent in both the LAD and the LCX (group IV, n = 26). Occurrence of left ventricular dysfunction was evaluated weekly by 2D-echo. At the time of left ventricular dysfunction the presence of viable myocardium within the dysfunctional region was investigated with DSE and PET, and confirmed by histology. The degree of coronary artery stenosis was measured by quantitative coronary angiography and morphometry. Severe coronary artery stenosis in the presence of dysfunctional, but viable, myocardium was induced in groups III and IV (47% and 11% of the animals, respectively). CONCLUSIONS: The authors developed a nonsurgical porcine stent model of progressive coronary stenosis using an oversized polymer-coated stent resulting in chronically decreased myocardial function, with residual inotropic reserve and viable myocardium. This condition may arise from repetitive periods of ischemia, or from sustained hypoperfusion, or a combination of these processes eventually leading to myocardial hibernation.