Overexpression of endothelial nitric oxide synthase increases skeletal muscle blood flow and oxygenation in severe rat hind limb ischemia

AbstractObjectiveAlthough nitric oxide (NO) has a critical role in angiogenesis, the therapeutic potential of NO synthase overexpression in severe ischemia remains undefined. We tested the hypothesis that overexpression of endothelial NO synthase (eNOS) would improve tissue perfusion in severe hind limb ischemia.MethodsSevere hind limb ischemia was induced in 122 adult male Sprague-Dawley rats. Ten days after the induction of hind limb ischemia, vascular isolation and intraarterial delivery of an adenoviral vector encoding eNOS (AdeNOS), a control adenoviral vector (AdE1), or phosphate-buffered saline solution (PBS) was performed. Skeletal muscle blood flow, muscle oxygen tension, angiography, and immunohistochemistry for capillary counts were measured.ResultsGene transfer of AdeNOS increased eNOS protein expression and enzyme activity. Two weeks after gene transfer, skeletal muscle blood flow was fourfold higher in eNOS-transduced than in AdE1-transduced or PBS treated rats and was similar to exercise-induced maximal flow in nonischemic muscle. eNOS overexpression increased muscle oxygen tension in a titer-dependent fashion. This increase persisted 1 month after transduction, even though eNOS enzyme activity had declined to normal levels. Angiography and capillary counts showed that eNOS overexpression increased the size and number of collateral arteries, but did not significantly increase the capillary–muscle fiber ratio.ConclusionseNOS overexpression in an ischemic rat hind limb significantly increased skeletal muscle blood flow, muscle oxygen tension, and collateral arteries (arteriogenesis). Furthermore, eNOS overexpression did not result in capillary angiogenesis above control levels. These studies demonstrate the potential for eNOS overexpression as treatment for severe limb ischemia in human beings

Cerebral embolic lesions detected with diffusion-weighted magnetic resonance imaging following carotid artery stenting: a meta-analysis of 8 studies comparing filter cerebral protection and proximal balloon occlusion.

OBJECTIVES: The aim of this meta-analysis was to evaluate and compare the efficacy of the 2 different neuroprotection systems in preventing embolization during carotid artery stenting (CAS), as detected by diffusion-weighted magnetic resonance imaging (DW-MRI). BACKGROUND: Data from randomized and nonrandomized studies comparing both types of embolic protection devices revealed contrasting evidence about their efficacy in neuroprotection, as assessed by the incidence of new ischemic lesions detected by DW-MRI. METHODS: Eight studies, enrolling 357 patients, were included in the meta-analysis. Our study analyzed the incidence of new ischemic lesions/patient, comparing filter cerebral protection and proximal balloon occlusion. RESULTS: Following CAS, the incidence of new ischemic lesions/patient detected by DW-MRI was significantly lower in the proximal balloon occlusion group (effect size [ES]: -0.43; 95% confidence interval [CI]: -0.84 to -0.02, I(2) = 70.08, Q = 23.40). Furthermore, following CAS, the incidence of lesions at the contralateral site was significantly lower in the proximal protection group (ES: -0.50; 95% CI: -0.72 to -0.27, I(2) = 0.00, Q = 3.80). CONCLUSIONS: Our meta-analysis supports the concept that the use of proximal balloon occlusion compared with filter cerebral protection is associated with a reduction of the amount of CAS-related brain embolization. The data should be confirmed by a randomized clinical tria

Non-invasive vulnerable plaque imaging: how do we know that treatment works?

Atherosclerosis is an inflammatory disorder that can evolve into an acute clinical event by plaque development, rupture, and thrombosis. Plaque vulnerability represents the susceptibility of a plaque to rupture and to result in an acute cardiovascular event. Nevertheless, plaque vulnerability is not an established medical diagnosis, but rather an evolving concept that has gained attention to improve risk prediction. The availability of high-resolution imaging modalities has significantly facilitated the possibility of performing in vivo regression studies and documenting serial changes in plaque stability. This review summarizes the currently available non-invasive methods to identify vulnerable plaques and to evaluate the effects of the current cardiovascular treatments on plaque evolution

Use of statins in lower extremity artery disease: a review

BACKGROUND: Lower extremity artery disease (LE-PAD) is one of the most common manifestations of atherosclerosis, particularly in elderly patients, and it is related to a high cardiovascular risk. DESCRIPTION: It is well established that statin therapy is characterized by crucial benefits on cardiovascular system by limiting atherosclerotic progression and reducing cardiovascular events and mortality. A growing body of evidence support efficacy of statins in LE-PAD due to the ability of both reducing cardiovascular risk and improving walking distance and, hence, quality of life. Consequently, statin therapy should be considered in all LE-PAD patients and new LDL-cholesterol targets should be reached. CONCLUSIONS: Our opinion is that statin therapy remains still underutilized or with inadequate dosage, so therapy of LE-PAD patients should be improved to obtain all the demonstrated benefits of statin

Predictors of carotid occlusion intolerance?during proximal protected?carotid artery?stenting.

OBJECTIVES: The aim of this study was to identify predictors of occlusion intolerance (OI) developing during proximal protected carotid artery stenting (CAS). BACKGROUND: The use of proximal embolic protection devices, such as endovascular occlusion, during CAS has been demonstrated to be particularly safe and effective. However, endovascular occlusion can expose the ipsilateral hemisphere to hypoperfusion and produce transient neurological symptoms (OI). METHODS: From March 2010 to March 2012, 605 consecutive patients underwent proximal protected CAS at our institution. To identify independent predictors of OI, a multivariate logistic regression model was developed that included all patients' clinical/angiographic and procedural characteristics. RESULTS: OI developed in a total of 184 patients (30.4%). Compared with patients in whom OI did not develop, those who experienced OI had lower occlusion pressure (OP) (42.3 ± 12.7 mm Hg vs. 61.9 ± 15.4 mm Hg, p < 0.001). Receiver-operating characteristic curve analysis demonstrated that OP was the most consistent predictor of OI with a C-statistic of 0.85 (95% confidence interval [CI]: 0.82 to 0.88) with best cutoff being ≤40 mm Hg (sensitivity, 68.5%; specificity, 93.3%). By logistic regression analysis, the most powerful independent predictor of OI developing was an OP ≤40 mm Hg (odds ratio: 33.2, 95% CI: 19.1 to 57.7) and the most powerful clinical predictor of such OP was the presence of contralateral internal carotid artery occlusion (odds ratio: 3.1, 95% CI: 1.5 to 6.2). CONCLUSIONS: OI may occur in as many as one-third of the patients undergoing proximal protected CAS. This event is more common in those patients with an OP ≤40 mm Hg. Patients presenting with concomitant occlusion of the contralateral internal carotid artery more frequently have an OP ≤40 mm Hg

Endovascular treatment of lower extremity arteries is associated with an improved outcome in diabetic patients affected by intermittent claudication

BACKGROUND: Lower extremity peripheral arterial disease (LE-PAD) is a highly prevalent condition among diabetic patients, associated with reduced walking capacity and a high incidence of cardiovascular events. Endovascular revascularization of lower extremities arteries improves walking performance and quality of life of diabetic patients affected by intermittent claudication, but few studies evaluated the impact of revascularization on cardiovascular outcome in this high-risk population. Accordingly, in the present study we evaluated if leg-ischemia resolution by effective lower limbs percutaneous revascularization can also impact cardiovascular outcome in a homogeneous group of diabetic patients affected by intermittent claudication. METHODS: 236 diabetic patients affected by LE-PAD at stage II of Fontaine's classification, with ankle/brachial index ≤ 0.90 and one or more hemodynamically significant stenosis in at least one artery of the ileo-femoro-popliteal axis were enrolled in the study. According to the Trans-Atlantic Inter Society Consensus II recommendations, 123 (52.1%) underwent percutaneous transluminal angioplasty (PTA group), while 113 (47.9%) underwent conservative medical therapy only (MT group). The incidence of major cardiovascular events (cardiovascular death, myocardial infarction, ischemic stroke, coronary or carotid revascularization) was prospectively analyzed with Kaplan-Meier curves and the risk of developing a cardiovascular event calculated by Cox analyses. RESULTS: No baseline difference in cardiovascular risk factors were observed between the PTA and MT groups, except for a lower prevalence of males in PTA group (74.8% vs. 85.8%, p=0.034). Furthermore, patients in the PTA group showed a worse walking capacity as expressed by maximum walking distance (108.7 ± 300.9 vs 378.4 ± 552.3 meters, p<0.001). During a median follow-up of 20 months (12.0-29.0), the incidence of cardiovascular events was markedly lower in patients in the PTA group with respect to patients in the MT group (7.3% vs. 22.1%, p=0.001), and patients of the MT group had at Cox analysis a 3.9 increased risk with respect to PTA group, after adjustment for potential confounding factors (95% CI 1.1-15.3, p=0.049). CONCLUSIONS: The present study shows that lower limbs revascularization of diabetic patients affected by intermittent claudication, in addition to improve walking performance, is associated with a reduction in the incidence of future major cardiovascular events

Insights into pathophysiology of smoke-related cardiovascular disease

cardiovascular morbidity and mortality are well established. Both active and passive smoking represent a major health hazard for both men and women. The great concerns related to the deleterious effects of CS on cardiovascular disease have been translated into various kinds of social interventions and targeted health policies since ever. The high health impact of cigarette smoking has driven a huge number of researches at the epidemiological, clinical and biological level. Nevertheless, even though many progresses have been made in understanding the mechanisms underlying the high disease burden associated to cigarette smoke, the exact components and the mechanisms by means of which it exerts its effects remain to be completely clarified as yet. The present paper reviews the main observations on the pathophysiology of smoke-related cardiovascular diseases, providing an up-to-date perspective about one of the main cardiovascular killers of our days

Common carotid intima media thickness and ankle-brachial pressure index correlate with local but not global atheroma burden:a cross sectional study using whole body magnetic resonance angiography

Common carotid intima media thickness (CIMT) and ankle brachial pressure index (ABPI) are used as surrogate marker of atherosclerosis, and have been shown to correlate with arterial stiffness, however their correlation with global atherosclerotic burden has not been previously assessed. We compare CIMT and ABPI with atheroma burden as measured by whole body magnetic resonance angiography (WB-MRA).50 patients with symptomatic peripheral arterial disease were recruited. CIMT was measured using ultrasound while rest and exercise ABPI were performed. WB-MRA was performed in a 1.5T MRI scanner using 4 volume acquisitions with a divided dose of intravenous gadolinium gadoterate meglumine (Dotarem, Guerbet, FR). The WB-MRA data was divided into 31 anatomical arterial segments with each scored according to degree of luminal narrowing: 0 = normal, 1 = <50%, 2 = 50-70%, 3 = 70-99%, 4 = vessel occlusion. The segment scores were summed and from this a standardized atheroma score was calculated.The atherosclerotic burden was high with a standardised atheroma score of 39.5±11. Common CIMT showed a positive correlation with the whole body atheroma score (β 0.32, p = 0.045), however this was due to its strong correlation with the neck and thoracic segments (β 0.42 p = 0.01) with no correlation with the rest of the body. ABPI correlated with the whole body atheroma score (β -0.39, p = 0.012), which was due to a strong correlation with the ilio-femoral vessels with no correlation with the thoracic or neck vessels. On multiple linear regression, no correlation between CIMT and global atheroma burden was present (β 0.13 p = 0.45), while the correlation between ABPI and atheroma burden persisted (β -0.45 p = 0.005).ABPI but not CIMT correlates with global atheroma burden as measured by whole body contrast enhanced magnetic resonance angiography in a population with symptomatic peripheral arterial disease. However this is primarily due to a strong correlation with ilio-femoral atheroma burden

Prevalence of peripheral arterial disease in subjects with moderate cardiovascular risk: Italian results from the PANDORA study Data from PANDORA (Prevalence of peripheral Arterial disease in subjects with moderate CVD risk, with No overt vascular Diseases nor Diabetes mellitus)

<p>Abstract</p> <p>Background</p> <p>The PANDORA study has recently examined the prevalence of low ankle brachial index (ABI) in subjects with moderate risk of cardiovascular disease. This sub-analysis of the PANDORA study examines the prevalence of asymptomatic peripheral arterial disease (PAD), as determined by ABI, in Italian subjects presenting with moderate cardiovascular risk, in the absence of diabetes or overt vascular disease.</p> <p>Methods</p> <p>PANDORA is a non-interventional, cross-sectional study that was performed in 6 European countries, involving subjects with at least one cardiovascular (CV) risk factor. The primary objective was to evaluate the prevalence of asymptomatic PAD using ABI. For this post-hoc sub-analysis, data were extracted for subjects enrolled in Italy, comprising 51.5% (n = 5298) of subjects from the original PANDORA study. Secondary objectives were to establish the prevalence and treatment of CV risk factors.</p> <p>Results</p> <p>The mean age was 63.9 years and 22.9% (95% CI 21.7-24.0) of subjects presented with asymptomatic PAD. A range of risk factors comprising smoking, hypertension, low HDL-cholesterol, family history of coronary heart disease and habit of moderate-high alcohol intake were significantly associated with asymptomatic PAD (p < 0.0001). Statin treatment had the lowest incidence in Italian subjects. Furthermore, patients treated with statins were significantly less likely to have asymptomatic PAD than those who were not (p = 0.0001).</p> <p>Conclusions</p> <p>Asymptomatic PAD was highly prevalent in Italian subjects, the majority of whom were not candidates for ABI assessment according to current guidelines. Findings from this study suggest that these patients should be carefully examined in clinical practice and ABI measured so that therapeutic interventions known to decrease their CV risk may be offered.</p> <p>Trial registration number</p> <p>ClinicalTrials.gov: <a href="http://www.clinicaltrials.gov/ct2/show/NCT00689377">NCT00689377</a></p