bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 5010: Is Impact of Proton Pump Inhibitor on Platelet Reactivity to Clopidogrel A Class Effect?
Authors: Hokimoto Seiji , Ogawa Hisao , Yamamoto Koichiro , Kaikita Koichi , Ono Takamichi , Nakagawa Kazuko 
Published: April 2024

Background: Concomitant administration of clopidogrel and proton pump inhibitor (PPI) is associated with the reduced effect on platelet response to clopidogrel, and increased risk of adverse outcome after stent placement in patients with acute coronary syndrome. However, it remains unknown whether all PPIs may reduce platelet inhibitory effects of clopidogrel. The aim of this study was to examine the impact of rabeprazole, which is one of PPIs and mostly not metabolized by CYP2C19, on platelet response to clopidogrel.
Methods: Adenosine diphosphate (ADP) induced platelet aggregation (PA) using light transmission aggregometer (MCM HEMA TRACER 313) was measured as response to clopidogrel in 127 patients (male 64%, age68 years) with coronary artery disease (CAD), and CYP2C19 polymorphism, which is involved with metabolism of clopidogrel and PPI, is also examined using PCR.
Results: CYP2C19 genotypes were divided into 3 groups such as homozygous extensive metabolizer (homoEM, n=46, CYP2C19*1/*1), heterozygous EM (heteroEM, n=52, *1/*2, *1/*3), and poor metabolizer (PM, n=29, *2/*2, *2/*3, *3/*3). In contrast to distribution of CYP2C19 polymorphism in Caucasian, the rate of CYP2C19 loss of function was higher in Japanese. ADP induced PA decreased significantly in homoEM, subsequently heteroEM, and was not well inhibited in PM (PA; 3250+/−1800, 4250+/−1300, and 5010+/−1370, respectively). However, ADP induced PA was not significantly different between patients treated with (n=29; PA=4637 +/−1800) and without rabeprazole (n=98; PA=3980 +/−1159). Moreover, there were no differences in ADP induced PA between groups with and without rabeprazole, in each subgroup categorized according to the genotype of CYP2C19. As to clinical events, the intake of PPI was not associated with increased risk of mortality and stent thrombosis in patients treated with stent delivery.
Conclusion: In contrast to the reported negative PPI-clopidogrel drug interaction, the intake of rabeprazole is not associated with impaired response to clopidogrel and increased risk of mortality and stent thrombosis in patients with CAD.
Abstract 5033: Safety and Efficacy of Carotid Stenting in the Very Elderly
Authors: Grant Arthur , White Christopher , Ansel Gary , Bacharach Michael , Metzger Christopher , Velez Carlos 
Published: April 2024

Background: Carotid artery stenting (CAS) has emerged as an alternative to carotid endarterectomy (CEA) in patients at high-risk for complications from surgery. The very elderly (> 79 years old) are one subgroup of patients identified as being at increased risk for carotid surgery. However, there is concern that the very elderly are also at increased risk for complications of CAS. A stroke and death rate of 12% was reported in very elderly patients during the roll-in phase of Carotid Revascularization Endarterectomy versus Stent Trial (CREST). We are reporting on a large clinical series of CAS with independent neurological assessment in the very elderly.
Methods: Between 1994 and 2008, a consecutive series of 418 CAS patients (> 79 years old) were treated at four high-volume centers with extensive CAS experience. Independent neurologic assessment was performed after CAS procedures. Thirty-day follow-up information was available in 389 patients.
Results: The average age was 83.2±2.8 years. Most patients were male (63.2%) and the target lesion carotid stenosis was asymptomatic in two-thirds (68.2%) of patients. The majority of patients treated with CAS had a history of coronary artery disease (74.4%), hypertension (87.8%) and dyslipidemia (71.1%). One third (30.1%) were diabetic and more than half (56.5%) were current or former smokers. Embolic protection devices (EPD) were used in 78.7% of cases with the CAS procedure being performed prior to EPD availability being the most common reason for not using them. The 30-day incidence of stroke and death was 2.8% (11/389). The cumulative incidence of major cardiovascular events (stroke, death or myocardial infarction) during that time period was 3.3% (13/389).
Conclusion: This large series of CAS with independent neurologic assessment is convincing evidence that the very elderly (> 79 years old) can safely undergo CAS with stroke and death rates comparable to younger patients. The key to obtaining these excellent results is that CAS be performed by high-volume, experienced operators who exercise restraint regarding patient selection.
Abstract 5102: Patients Developing STEMI In-hospital Have Delayed Reperfusion and Increased 1-year Mortality Compared to STEMI Patients Presenting to the Emergency Department
Authors: Haryani Anand , Richmond Tyler , Haw Janet M , Melgoza Norma , Purim-Shem-Tov Yaninia , Calvin James E , Schaer Gary L 
Published: April 2024

BACKGROUND: Despite recent advances in ST-elevation myocardial infarction (STEMI) systems of care, there has been little focus on patients who develop STEMI in-hospital. We hypothesized that inpatients who develop STEMI receive less timely care and have worse clinical outcome compared to patients who present to the emergency department (ED) with STEMI.
METHODS: One hundred and twenty-six consecutive cases of STEMI treated with primary percutaneous coronary intervention (PCI) from May 2004 to May 2009 were included in the analysis. A retrospective medical record review was utilized to identify ECG to balloon times, intraaortic balloon pump (IABP) utilization, pre-discharge left ventricular ejection fraction, and duration of hospital stay following STEMI. In-hospital, 30-day, and 1-year mortality data was collected using the National Death Registry.
RESULTS: Twenty-nine inpatients and 97 ED patients diagnosed with STEMI and undergoing PCI were included in this analysis. ECG to balloon time (357±419 min vs 163±188 min, p <0.001), one-year mortality (24.1% vs 5%, p <0.006), and duration of hospital stay (9±12.6 d vs 4.1±4.5 d, p <0.001) were significantly increased in inpatients compared to patients admitted through the ED. Inpatients trended toward increased need for IABP (28% vs. 14.4%, p =0.09) and increased 30-day mortality (13.8% vs 5%, p=0.12). There were no differences in LVEF (45% vs 50%, p=0.22) or in-hospital mortality (10% vs 5%, p=0.27) between the two cohorts.
CONCLUSION: Inpatients who develop STEMI have delayed reperfusion, increased length of stay, and greater 1-year mortality compared to STEMI patients admitted through the ED. Further study is needed to determine if improved identification and more rapid PCI could improve the clinical outcome of patients who develop STEMI in-hospital.
Abstract 5110: The Inhibition of Poly(ADP-ribose) Polymerase-1 (PARP-1) Significantly Accelerates the Vasculogenesis in a Model of Hind Limb Ischemia
Authors: Elmageed Zakaria Y Abd , Amin Ali H , Nair Devika , Megan Partyka , Belmadani Souad , Matrougui Khalid 
Published: April 2024

Background: Cardiovascular and metabolic diseases are associated with impaired vasculogenesis in response to ischemia. PARP-1, an abundant nuclear enzyme involved in DNA repair and transcriptional regulation and recognized as a key regulator of cell survival and cell death in response to noxious stimuli in various forms of cardiovascular and metabolic disease. Our hypothesis is to determine whether PARP-1 has a key role in vasculogensis in response to ischemia.
Methods and Results: Hind limb ischemia was performed in C57/Bl6 mice for 15 days with and without PARP-1 inhibition using TIQ (PARP-1 inhibitor) or local injection of lentivirus-PARP-1-siRNA. We also used microvascular cultured endothelial cells stimulated with hypoxia with and without PARP-1 inhibition (TIQ and lentivirus-PARP-1-siRNA) and determined the expression of VEGF. Mice treated with TIQ significantly accelerated the recovery of blood flow, as determined with MoorLDI-Laser and X-ray, by 50 – 60% the first week and complete recovery at the second week compared to control. Interestingly, mice locally injected with lentivirus-PARP-1-siRNA significantly accelerated blood flow recovery compared to control. Western blot analysis revealed an increase in VEGF level in muscle from mice treated with TIQ or injected with lentivirus-PARP-1-siRNA compared to control. VEGF release in the conditioned media was increased when cultured endothelial cells were stimulated with hypoxia. In addition, endothelial cells pre-treated with TIQ or transfected with lentivirus-PARP-1-siRNA and then stimulated with hypoxia significantly increased VEGF release in the conditioned media compared control and to cells stimulated with hypoxia.
Conclusion: Our novel data provide evidence that PARP-1 plays a key role in the regulation of vasculogenesis in response to ischemia. We demonstrated that the inhibition of PARP-1 enhances earlier the formation of new vessels in response to ischemia through the increase of VEGF release. The inhibition of PARP-1 would be interesting in model of altered vasculogenesis such cardiovascular and metabolic diseases.
Abstract 5113: Ablation of Lectin-like Receptor for Oxidized Low-density Lipoproteins (LOX-1) Resulted in Suppression of Ischemia-Induced Angiogenesis
Authors: Shiraki Takeru , Aoyama Takuma , Yokoyama Chiharu , Kazuhiko Nishigaki , Takemura Genzou , Fujiwara Takako , Fujiwara Hisayoshi , Sawamura Tatsuya , Minatoguchi Shinya 
Published: April 2024

Background: We previously identified LOX-1 as a receptor for oxidized low-density lipoproteins. Recent studies show LOX-1 contributes to capillary formation induced by Angiotensin II or oxLDL, suggesting the potential effects of LOX-1 on angiogenesis. Therefore, we elucidated whether LOX-1 might be involved in angiogenesis in ischemic hindlimb tissue.
Methods and Results: Ischemia was surgically produced by femoral artery ligature in both wild-type mice (WT) and LOX-1 deletion mice (LOX-1 KO). The ratio of ischemic/nonischemic leg blood flow measured by laser Doppler perfusion imaging was significantly smaller in LOX-1 KO than WT on Day 14, 21 and 28 (p<0.01). In agreement, histological capillary density (vWF immunostaining) was significantly lower in LOX-1 KO than in WT on Day 28 (115±28 vs. 177±19/HPF, p<0.01). Next, we analyzed phosphorylation of p38 involved in LOX-1 signaling. Phosphorylation of p38 was suppressed in ischemic hindlimb tissue of LOX-1 KO mice compared with WT mice. Western blot analyses also showed remarkable induction of VEGF in hindlimb of WT on Day 3 after ischemia. On the other hand, ischemic tissues of LOX-1 KO contained very low VEGF, resulting in suppressed phospholylation of Akt and eNOS, which are downstream signaling of VEGFR2. Considering the fact that inflammation is important for ischemia-induced angiogenesis, we examined whether infiltrated macrophages (F4/80 immunochemistry) release VEGF in ischemic hindlimb using two-color immunofluorescence histochemical staining. Fewer numbers of macrophages infiltrated into the ischemic tissues in LOX-1 KO than in WT (64±24 vs. 118±25/HPF, p<0.01), and immunohistochemical analysis revealed the number of infiltrated macrophages expressing VEGF was also decreased in LOX-1 KO (LOX-1: 34±19 vs. WT: 50±14/HPF, p<0.01).
Conclusions: This study demonstrates that LOX-1 deletion negatively modulates ischemia-induced angiogenesis through impairment of early inflammatory mononuclear cell infiltration, which releases VEGF. LOX-1 would become a novel target molecule for modulating angiogenesis in ischemic tissue.
Abstract 5169: Endovascular Injury Induces Rapid Phenotypic Changes in Perivascular Adipose Tissue
Authors: Takaoka Minoru , Nagai Ryozo , Sata Masataka 
Published: April 2024

Background: It was reported that the serum levels of circulating proinflammatory cytokines are increased in overweight people with enhanced accumulation of visceral fat. In contrast to visceral fat, little attention has been paid to the role of perivascular fat in the pathogenesis of obesity-associated diseases. Here, we investigated the effect of endovascular injury on the phenotype of perivascular fat.
Methods and Results: First, endovascular injury significantly down-regulated adiponectin and up-regulated proinflammatory adipocytokines, TNF-alpha, IL-6, PAI-1 and MCP-1 within perivascular fat tissue in models of murine femoral artery wire injury and rat iliac artery balloon injury (p<0.05). Second, diet-induced obesity augmented endovascular injury-induced up-regulation of proinflammatory adipocytokines within perivascular fat tissue (p<0.05) and neointimal hyperplasia (p<0.05) compared with standard chow diet in wild-type mice. Third, up-regulation of proinflammatory adipocytokines within perivascular fat by endovascular injury was significantly blunted in TNF-alpha deficient mice (p<0.05). Neointima formation was attenuated in TNF-alpha deficient mice compared with wild-type mice (p<0.05). Furthermore, perivascular delivery of TNF-alpha to the femoral artery using osmotic minipump enhanced endovascular injury-induced up-regulation of proinflammatory adipocy-tokines within perivascular fat (p<0.05) and neointimal hyperplasia (p<0.05) compared with contralateral PBS delivered artery in TNF-alpha deficient mice. Fourth, conditioned medium from the coculture of 3T3L1-derived adipocyte and RAW264 macrophage stimulated rat vascular smooth muscle cells proliferation relative to the control medium from 3T3L1-derived adipocyte (p<0.05). Blockade of TNF-alpha in the co-culture using an anti-TNF-alpha neutralizing antibody reduced the stimulatory activity of the condition medium (p<0.05).
Conclusions: Our findings indicate that endovascular injury induces rapid and marked changes in perivascular adipose tissue, mainly mediated by TNF-alpha. It is suggested that the phenotypic changes in perivascular adipose tissue may have a role in the pathogenesis of neointimal hyperplasia after angioplasty.
Abstract 5263: Renin Angiotensin System Plays a Crucial Role in the Development of Myocardial Ischemia/Reperfusion Injury With a Condition of Renal Failure in Mice
Authors: Suzuki Jun-ichi , Ogawa Masahito , Hirata Yasunobu , Nagai Ryozo , Isobe Mitsuaki 
Published: April 2024

Background: The clinical relationship between the heart and renal diseases has been clarified. Although renin angiotensin system (RAS) mediates the development of cardio-renal syndrome, little is known about the etiology obtained from experimental models with myocardial ischemia and renal failure.
Methods: To test the hypothesis that RAS plays a pivotal role in cardio-renal syndrome, we developed a novel murine cardio-renal disease model using both the 5/6 subtotal nephrectomy (NTX) and the myocardial ischemia/reperfusion injury (I/R) techniques. Four weeks after the subtotal nephrectomy, the left coronary artery was occluded for 60 minutes followed by 24 hour reperfusion.
Results: Serum creatinine levels on day 28 were higher in the NTX group (0.28±0.04 mg/dl, n=8) compared to those in the non-NTX group (0.13±0.01 mg/dl, n=5, p<0.05). The infarction area/area at risk ratio significantly increased in NTX+I/R mice (50.7±5.9 %, n=7) compared to the non-NTX+I/R mice (20.8±3.1 %, n=8, p<0.05), while ischemic area/whole myocardial area was comparable between the two groups. The NTX+I/R hearts had significantly larger left ventricular diameters compared with that of the non-NTX+I/R mice. The number of infiltrating cells was enhanced by the NTX+I/R, while they were limited in non-NTX+I/R. Interstitial fibrosis also increased in NTX+I/R, while non-NTX+I/R suppressed this change. The hearts isolated from NTX+I/R mice increased the mRNA expression ratios (the NTX-IR group per the native group) of angiotensin-converting enzyme (1.57±1.26) and angiotensin II receptor type 1 levels (1.21±0.07) measured by quantitative RT-PCR.
Conclusion: RAS deeply involves the development of cardio-renal syndrome and it may have a clinical usefulness in the treatment of myocardial ischemia with renal dysfunction.
Abstract 5268: A Critical Role of Bradykinin in the Murine Model of Contrast Media-Induced Nephropathy
Authors: Suzuki Jun-ichi , Ogawa Masahito , Hirata Yasunobu , Nagai Ryozo , Isobe Mitsuaki 
Published: April 2024

Background: Iodinated contrast media (CM) has been broadly used for diagnostic procedures; CM-induced nephropathy (CIN) affects morbidity and mortality of patients. Although CIN is known to be mediated by several factors, including the renin-angiotensin system (RAS), little is known about the evidence obtained from experimental models. Thus, we developed a murine CIN model to evaluate the mechanism.

Methods: We performed 5/6 subtotal nephrectomy (NTX) and administered CM (iopamidol, 500
μ
l/25 g mice) intravenously into the mice 4 weeks after NTX. We administered an angiotensin converting enzyme inhibitor (ACEI, imidapril, 1 mg/kg/day, n=6), an angiotensin II receptor blocker (ARB, TA606, 1 mg/kg/day, n=4), or ACEI plus a bradykinin B2 receptor antagonist (Hoe-140, 0.25 mg/kg, n=5) into the mice daily.

Results: Serum creatinine levels on day 28 were significantly elevated in the NTX group (0.26±0.01 mg/dl) compared to those in the non-NTX group (0.13±0.01 mg/dl). A day after CM injection, creatinine levels were significantly elevated in the non-treated group (0.41±0.01 mg/dl). While ACEI treatment significantly suppressed the increase in creatinine levels (0.34±0.04 mg/dl, p<0.05 vs. CIN group), ARB treatment did not suppress (0.47±0.06 mg/dl). A bradykinin antagoninst Hoe-140 negated (0.43±0.07 mg/dl, p<0.05 vs. CIN+ACEI) ACEI’s ability to suppress renal damage. We examined renal AT1R, COX-2, MCP-1 and MMP-9 mRNA levels using quantitative RT-PCR. AT1R mRNA levels were enhanced in the NTX and CIN groups compared to those in the native group. COX-2, MCP-1 and MMP-9 mRNA levels were enhanced in the CIN+ACEI group compared to the native and CIN groups. ACEI+Hoe-140 treatment suppressed the mRNA expression. Both treatments did not reduce their blood pressure compared to those of the vehicle treatment, statistically.
Conclusion: ACEI treatment is useful for the prevention of CM-induced nephropathycompared to that of ARB treatment in the murine model of CIN because bradykinin pathway is critical in regulating CIN development.
Abstract 5336: Presence of Ischemia and Non-Sustained Ventricular Tachycardia is Strongly Associated With the Risk of Cardiovascular Outcomes: Observations From the MERLIN-TIMI 36 Trial
Authors: Harkness James R , Morrow David A , Braunwald Eugene , Qin Jie , Belardinelli Luiz , Wang Whedy , Karwatowska-Prokopczuk Ewa , Lopez-Sendon Jose , Bode Christophe , Scirica Benjamin M 
Published: April 2024

Background: Among pts with NSTEACS, recurrent ischemia and ventricular arrhythmias detected on continuous ECG (cECG) remain common clinical events with uncertain clinical significance.
Methods: We determined the risk associated with the presence of ischemia (> 1mm ST depression lasting > 1min) and NSVT (> 4beats) alone or combined on 7-day cEKG in 6355 pts with NSTEACS. Pts were categorized into 4 groups:

No ischemia or NSVT,

NSVT alone,

Ischemia alone or

Both ischemia and NSVT.

Median clinical follow-up was 348 days.

Results: A total of 43.6% pts had no VT or ischemia; 31.2% had NSVT alone; 18.5% had ischemia alone; and 6.8% had both NSVT and ischemia. Pts with either NSVT or ischemia on cECG were at increased risk of CV outcomes (Table

). In a MV analysis, recurrent ischemia alone increased the risk of all CV outcomes while NSVT alone increased the risk of CVD, SCD, and subsequent heart failure. Pts with both ischemia and NSVT were at high-risk for CVD (10.1 v 3.0%, p<0.001), SCD (7.8 v 0.9%, p<0.001), recurrent MI (15.4 v 6.2%, p<0.001) and heart failure (13.0 v 3.0%, p<0.001) compared to pts with neither. In pts with both ischemia and NSVT, 47.1% of SCD occurred within 90d (Figure

).

Conclusion: In more than 6300 pts with NSTEACS, the presence of either ischemia or NSVT alone or particularly in combination was independently associated with poor CV outcomes, including a particularly high risk for early SCD. These findings raise the question whether such pts should be considered for ICD implantation.

Sudden Cardiac Death

1-yr Clinical Outcomes(%) by NSVT or Ischemia detected on cECG monitoring
Abstract 5337: Morphological Characteristics of the Culprit Lesion Correlate With the Angiographic Flow Grade Following Thrombolysis in Myocardial Infarction. An Optical Coherence Tomography Study
Authors: Karanasos Antonis , Toutouzas Konstantinos , Drakopoulou Maria , Synetos Andreas , Riga Maria , Tsiamis Eleftherios , Klettas Dimitrios , Tentolouris Costas , Stefanadi Elli , Stefanadis Christodoulos 
Published: April 2024

Background: Intravenous thrombolysis fails to restore blood flow in a significant percentage of patients with ST-elevation myocardial infarction (STEMI). It remains unknown, whether certain morphological characteristics of the culprit lesion (CL) can predict the success of thrombolysis. We hypothesized that the thickness of the fibrous cap and the incidence of plaque rupture at the CL, as measured by Optical Coherence Tomography (OCT), may correlate with the outcome of thrombolysis.
Methods: We prospectively enrolled 55 consecutive patients with STEMI that were treated with thrombolysis 6 hours from symptom onset. All patients underwent coronary angiography within 24 hours from thrombolysis. We estimated TIMI flow grade and the corrected TIMI frame count (CTFC) for patients with TIMI flow II or III. In target vessels with TIMI flow grade ≤1 aspiration thrombectomy was performed. We then acquired OCT images from the CL. We measured the fibrous cap thickness (FCT) at the thinnest part overlying a lipid pool, the lipid content (in quadrants) and the incidence of plaque rupture, which was defined as the presence of fibrous-cap discontinuity.

Results: Of the total study population, 15 patients had TIMI flow 0 or I, 15 had TIMI flow II, and 25 had TIMI flow III. The number of lipid quadrants was greater in patients with TIMI flow 0-I than in patients with TIMI flow II and III (median 4, (range 1) vs. median 3 (range 2) vs. median 2 (range 1), p<0.001). The culprit lesion of the patients with TIMI flow 0 or I was more often characterized by a ruptured plaque compared to those with TIMI flow II and III (n=13 (86.67%) for TIMI 0–1, n=8 (53.33%) for TIMI II and n=6 (24%) for TIMI III, p<0.001). For patients with TIMI 0 and I, minimum FCT was 41±7
μ
m, for patients with TIMI II 55±23
μ
m and for those with TIMI III 87±26
μ
m (p<0.001). In patients with TIMI flow II or III, a correlation was found between CTFC and the minimal cap thickness (r=−0.423, p=0.006).

Conclusion: In patients with STEMI, TIMI flow III following thrombolysis is associated with greater fibrous cap thickness, reduced lipid content and reduced incidence of plaque rupture in the CL. This study suggests that specific morphological features of the CL correlate with the flow grade following thrombolytic therapy in patients with STEMI.