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Evolution of atheroma usually take many years and this process is stimulated by a high dietary intake of cholesterol and both, saturated and trans fatty acids, added to accelerating factors such as tobacco, stress, diabetes, arterial hypertension, sedentary life style and obesity. Histopathology of the plaque reveals recruitment of Th 1 helper lymphocytes which destabilizes the atheroma, making it vulnerable to occlusion because of erosions and fissures; then adhering platelets and blood cells to its surface ensuing a myocardial infarction. On the contrary, plaque stabilization avoids its rupture, a result that can be achieved through reduction of the inflammatory activity in the plaque with medications that reduce its lipid content or by impairing macrophage activity inside the plaque. The former objectives can be obtained by 1) stoping LDL-c deposit 2) increasing reverse cholesterol transport with HDL-c 3) promoting foam cells death or macrophage migration or 4) remotion of the necrotic core of the atheroma. Studies of pharmacological regression of the atheromatous plaque in humans started several years ago with niacin; then with simvastatin (a HMG CoA reductase inhibitor) combined to niacin that increased by 26% HDL-c and reduced 42% LDL-c, a finding associated to 0,4% reduction of angiographically demonstrated coronary stenosis and surprisingly to 87% lowering of acute coronary risk events. On the other hand, recombinant apoA-I Milano, intravenously injected, also induce 4,2% regression of the atheroma volume in comparison to 0,14% decreased volume reduction with placebo. It is worth to consider renin-angiotensin-aldosterone system actively participate in atheroma development because olmesartan, an angiotensin II antagonist molecule (ARA II), reduce in 5,4% coronary atheroma volume, compared to 0,6% reduction obtained with a control treatment; this change was associated to a longer survival of patients without major cardiovascular events in comparison to the control group. This result points to an important cardiovascular protecting effect of ARA II agents. [ABSTRACT FROM AUTHOR]

Fructose-enriched diet administered to rodents is a useful experimental model for reproducing the human changes observed the metabolic syndrome; and the changes this diet induce in plasma non-esterified fatty acids (NEFA) has not been studied, considering those changes have been related to cardiac sudden death caused by heart arrhytmias in humans. Sprague-Daweley, male albino rats, 250 g body weight, received 60% fructose in food pellets for 3 months. Control rats were fed on conventional diet. Routine plasma biochemical assays were glucose, insuline, triglicerydes, cholesterol and intravenous glucose tolerance test. Nefa assay was done by gas chromatography. Glucose increased from 51.3 ± 3.1 mg/dL in controls, to 111.8 ± 9.2 mg/dL in fructose-fed ones and insulin increased from 18.3 ± 7.4 uU/mL up to 42.9 ± 8.3 uU/mL (p< .05). Glucose tolerance test, after 60 min glucose in i.v. injection, showed 2.5 timeshigher glucose values, compared to control (p< .05). NEFA assays: fructose diet significantly (p <.01) increased palmitoleic acid (+98.8%) and decreased linoleic acid (-40.1%) and arachidonic acid (-84.0 %). Plasma triglycerides increased 2.7 times and cholesterol 2.6 times over control plasma levels. In conclusion, long-term administered fructose-enriched diet promote NEFA plasma changes that may facilitate heart arrhytmias and arterial atheromas. [ABSTRACT FROM AUTHOR]

Hypertensive retinopathy is related to the time of exposure of the arteries to increased blood pressure, and its pattern is useful to estimate hypertensive disease evolution. The retinal arterial changes start with an initial acute vasoconstrictor phase, followed by a chronic sclerotic stage. Clinical studies have demonstrated a relationship between hypertension and left ventricle diastolic dysfunction. On the other hand, urinary albumin excretion is linked to subclinical organs damage, such as left ventricle hypertrophy and thickening of carotid artery wall; microalbuminuria is considered as a marker of morbidity and mortality in hypertensive patients. This study included 45 male hypertensive patients (blood pressure > 140/90 mm Hg, systolic/diastolic), age range 18-65 years old. Eye funduscopy and retinography was found normal in 19 (42.2%) patients hypertensive retinopathy was found in 2 (57.8%) of patients. Stage I retinopathy was found in 1 (35.5%)patients; Stage II in 9 (20.0 %) patients and Stage III in 1 (2.2%) patient. No patients showed Stage IV retinopathy. Left ventricle (LV) mass was found normal in 25 (55.6%) patients and left ventricle hypertrophy in 20 (44.4 %) of them. LV diastolic dysfunction (DD) was found in 21 (46.6%) patients; Type I DD was observed in 20 (44.4%) patients and Type II DD in only one (2.2%) case. No patients showed Type III DD. Microalbuminuria was found in 12 (26.7%) patients. When hypertensive retinopathy was matched to microalbuminuria, 19 (73.07 %) of patients did not have microalbuminuria and only 7 (26.9%) patients presented this disorder (Cramer coefficient of association= 0.007, p= 0.96). In conclusion, our findings do not demonstrate association between hypertensive retinopathy and microalbuminuria, as it has been shown in other clinical studies. [ABSTRACT FROM AUTHOR]

Objective: To assess the association between epicardial adipose tissue thickness (EAT) and plasma adrenomedullin plasma levels in patients with metabolic syndrome (MS)., Methods: Twenty-one patients (12 females and 9 males) with MS according to the International Diabetes Federation guidelines, aged 22-58 years, were enrolled into the study and compared to 19 age-matched control subjects without MS. Plasma glucose, lipid, and adrenomedullin levels were assessed. EAT, left ventricular mass, and carotid intima-media thickness were evaluated by transthoracic two-dimensional echocardiography., Results: No statistically significant differences were found between the groups in age, sex, and height. Body weight, abdominal circumference (AC), body mass index (BMI), systolic blood pressure (SBP), and diastolic blood pressure (DBP) were significantly higher (p=0.0001) in MS patients; this group also showed significantly higher glucose (p=0.001), total cholesterol (p=0.01), LDL-C (p=0.03), VLDL-C (p=0.005), triglyceride (p=0.002), Tg/HDL ratio (p=0.0001), and plasma adrenomedullin (3.49±1.21 vs 1.69±0.92 ng/mL; p=0.0001) levels and lower HDL-C (p=0.02) levels as compared to the control group. EAT was significantly thicker in MS patients compared to the control group (8.45±3.14 vs 5.43±0.96; p=0.0001), showed a positive correlation to BMI (r=0.347; p=0.02), AC (r=0.350; p=0.02), DBP (r=0.346; p=0.02), and adrenomedullin levels (r=0.741; p=0.0001). In multiple linear regression analysis, adrenomedullin was the only parameter associated to EAT (R(2)=0.550; p=0.0001)., Conclusion: In this small patient group, a statistically significant association was found between EAT and plasma adrenomedullin levels, which may be considered as a potential biomarker of MS., (Copyright © 2011 SEEN. Published by Elsevier Espana. All rights reserved.)

Endothelial dysfunction (ED) is observed in patients with hypercholesterolemia, arterial hypertension, obesity and diabetes mellitus. Recent evidences suggest the involvement of glycosaminoglycans (GSG) in ED. We evaluated the effect of sulodexide (SLD), a natural GSG used in albuminuria and ischemic diabetes treatment, on arterial relaxation and vascular morphological changes in a diabetic type I model. Diabetes was induced, in Sprague-Dawley rats by streptozotocine (STZ) administration, 60 mg, i.v. Rats were divided into four groups; I: control, II: diabetics, III: control + SLD, IV: diabetics treated with SLD (15 mg/day). After three months, phenylephrine precontracted aortic rings were used to evaluate acetylcholine (ACh) and sodium nitroprusside (NPS) relaxation capacities. Light microscopy of aorta was done with several staining procedures. In vitro, SLD did not change smooth muscle tone in resting or phenylephrine precontracted aortic rings. In diabetic rats, ACh relaxation was 28.8-35.1% lower than in control rats. Diabetic rats treated with SLD showed aortic ACh relaxation similar to control rats. No significative statistical difference was found in endothelium-independent NPS relaxation, between the different groups. Light microscopy histological studies revealed important morphological alterations, particularly in intima and adventitia layers of aortic artery; those changes were dramatically reversed in SLD treated rats. Our experiments support the conclusion that SLD is a potential drug for improving endothelial dysfunction in diabetes.

Introduction and Objectives: To investigate the hemodynamic sympathetic response evoked by NaCI microinjection into the third ventricle anteroventral brain area (AV3V) in rats long-term fed with high fructose diet., Methods: Twelve male rats received 60% fructose enriched diet for 6 months. Control rats (n=12) received regular diet., Results: Fructose diet increased (P< .01) body weight; plasma glucose, triglycerides; cholesterol, insulin; systolic (SBP) and diastolic blood pressure (DBP). Basal heart rate (HR) did not change. AV3V microinjection of 2 microL of hypertonic 1.5 M NaCI in fructose fed rats increased SBP 44.64(3.6) mm Hg, DBP 19.9(2.4) mm Hg and HR 66.2(8.4) beats/min over basal values (P< .01). In control rats, smaller responses were observed, SBP increased 28.33(3.10) mm Hg, DBP 13.0(1.9) mm Hg and HR 23.0(5.0) beats/min over basal values (P< .01)., Conclusions: Long-term fructose diet in rats induces cardiovascular hyperactivity of AV3V neurons to sodium chloride, and is associated to hypertension and insulin-resistance.

LDL interaction with arterial proteoglycans and its oxidative modification is closely related to atherosclerosis. The objective of the present study was to examine the effect of the individual administration of vitamin E and a combination of vitamin E and C on LDL affinity for arterial proteoglycans in smokers and non-smokers subjects. Twenty smokers and ten non-smokers healthy subjects received by the oral route placebos of vitamins E and C for 15 days; then vitamin E (400 mg/d) for 30 days and finally vitamin E plus vitamin C (1000 mg/d) during the following 30 days. During the vitamin E supplementation period, the affinity of LDL for arterial proteoglycans decreased 19.3% in smokers and 25.2% in non-smokers. When the subjects received vitamin E plus vitamin C, the affinity of LDL for arterial proteoglycans decreased 25.6% and 30.1% in smokers and non-smokers respectively. In conclusion, simultaneous administration of vitamins E and C showed a synergistic effect to diminish the affinity of the LDL by arterial proteoglycans, that was greater than caused by the administration of vitamin E alone. These finding suggest a potential antiatherogenic effect of both antioxidant vitamins.

LDL-lipids peroxidation is an important step in LDL atherogenicity. Tobacco smoke, promotes oxidative stress and reduces LDL-alfa tocoferol content and plasmatic vitamin C concentration. The objective of this double-blind randomized study was to assess the effect of vitamins E and C combined administration, on oxidative susceptibility of LDL isolated from 20 smokers and 10 non-smokers healthy volunteers who received placebo for 15 days and then concomitantly received 400 mg/d vitamin E and 1000 mg/d vitamin C for 30 days. At the end of placebo administration of and vitamins E and C combination; plasma total cholesterol, LDL-C and HDL-C values did not change significantly (p>0.05), plasma triglycerides increased significantly within a normal accepted range (p<0.05) and LDL oxidation susceptibility in smokers decreased by 41,3% and in non-smokers by 54,4% (p<0.05 vs placebo). In conclusion, simultaneous administration of vitamins E and C exerts an important antioxidant effect on LDL-lipids peroxidation. This effect could operate as an attenuating factor of the increased atherogenesis commonly observed in smoker subjects.

Impedance pletismography is based on the evaluation of the voltage change that occur as a consequence of blood flow variations in a particular tissue section. Current applied for the procedure should be alternating, weak and of high frequency to avoid electrically excitable cells stimulation, such as muscles and nerves. Blood volume changes can be measured by this method and has been applied in the diagnosis of deep venous thrombosis of limbs. An impedance meter was designed and built to be used in the forearm of patients. It consists of a voltage stabilizer TPS 76150 with simultaneous ECG recording (DII lead). Injected signal had 50 KHz (Wien's bridge) and registered through two operational amplifiers LM 3080 (1 mA). Signal was demodulated and amplified. Electrodes used were made of silver strips with conductance improved by conductivity gel, fixed by elastic rubber strips. Circuit wiring and equisition software was developed at the Bioengineering Department of Simón Bolívar University. Fifteen healthy subjects, age range 18-30 years old, were submitted to noninvasive forearm blood flow evaluation with the already described electronic device. Brachial artery occlusions were made with a cuff at subdiastolic, supradiastolic and suprasystolic blood pressures, for 60 and 90 seconds and then this occlusion was abruptly released. The curve was displayed and recorded in a portable PC (laptop). During suprasystolic occlusion the impedance observed curve showed a progressive increased until stabilization. When occlusion was released a sudden peak appeared which corresponds to reactive hyperemia of the forearm. This peak has been associated to the secretion of endothelial vasodilatory substances. In conclusion, this device is suitable to be used in clinical settings for the evaluation of reactive hyperemia and potentially useful in diagnosis of deep veins occlusions.

Cocaine as a drug of abuse can cause many cardiovascular toxic effects. The objective of this work was to study the mechanism of the negative inotropic effect of cocaine on isolated right ventricle strips and its relationship with myocardial catecholamines desensitization after long- term cocaine administration. Right ventricle strips were incubated in oxygenated Krebs solution at 37 degrees C, and driven with 2 ms, 15 mA, 1.8 Hz electric square pulses. Beat tension force was recorded with a force-displacement transducer. In control long-term saline (0.9% NaCl) treated rats (0.1 mL/Kg x 15 days, s.c.), in vitro 0.1-30 microM cocaine progressively increased the ventricle strip force up to 53% over baseline value. On the contrary, a negative inotropic effect of cocaine was observed in strips obtained from long-term cocaine treated rats (3 mg/Kg x 15 days, s.c.). The contractile force change ("Bowditch" phenomenon) induced by short (30s) rising of myocardial stimulating frequency to 2.7, 3.5 and 4.3 Hz respectively, was completely reversed in ventricular strips obtained from long-term cocaine treated rats. Myocardial desensitization to isoproterenol (saline 4.67 nM Vs cocaine 13.17 nM DE50) and to phenylephrine (saline 5.44 nM Vs cocaine 8.6 nM DE50) was observed in long term cocaine treated rats when compared to the control group. Aorta desensitization to phenylephrine-induced constriction in long-term cocaine treated rats was also observed; phenylephrine DE50 increased from 1.9 nmol/l in control rats to 15.5 nmol/l in long-term cocaine treated ones. Cocaine metabolites, benzoylecgonine and ecgonine methyl ester were excreted (121.6 micrograms/ml) in urine samples from all cocaine treated rats and not in the saline treated group. Long-term cocaine treatment seems to interfere with the cytosolic calcium increase that normally occurs during systole; this could explain its negative inotropic effect observed during in vitro cocaine reexposure. The adrenergic receptor desensitization induced by chronic cocaine administration could lead to a full expression of the negative inotropic effect of this drug. Extrapolated to clinical grounds, this mechanism could explain some clinical cases of heart failure reported in cocaine overdosed addicts.