Graciela Ottaviano

Lipid profile and plasma antioxidant status in sweet carbonated beverage-induced metabolic syndrome in rat

There is little information in the literature regarding the clinical significance of SVT on the prognosis of patients with severe PAH. A previous study by Tongers et al. analyzed SVT inpatientswith PHand [3] in contrast to our study, these authors included patients with chronic thromboembolic pulmonary hypertension, selecting a population not as homogeneous as the one in our study. It is noteworthy that the global incidence of atrial flutter and INRT was higher than described in left ventricular dysfunction, which could be related to morphological and functional changes that occur in both the atrium and the RV along with the modulation of autonomic activity. Moreover, there was a long interval between the diagnosis of PAH and the onset of SVT, with an average of five years which suggests that these arrhythmias would be a manifestation of long-standing PH and chronic heart failure [4]. Most episodes of SVT produced an important clinical deterioration. This could be related to the deleterious hemodynamic effects that the loss of atrial support produce on right ventricular filling in the presence of ventricular dysfunction. Thus, wemight consider that the initiation of these arrhythmias (AF or atrial flutter) could be a warning for the need for increasing specific therapy for PAH or to consider lung transplantation. Nevertheless, in short-term our patients with AF or atrial flutter showed a significant clinical improvement after restoration of SR, suggesting a role of TSV in the exacerbation of RV failure and that the maintenance of a stable SR could be an important goal in the treatment. According to our results EPS was a safe and effective procedure to diagnose the typeof SVTand to restore stable SR. Thehigh rate of success of radiofrequency ablation in the general population in common flutter (95%), and in INRT (100%), with recurrence rates of 5% per year is comparable to the rate of success obtained in our patients [5]. The authors of this manuscript have certified that they comply with the Principles of Ethical Publishing in the International Journal of Cardiology [6].

Rate of atherosclerosis progression in ApoE-/- mice long after discontinuation of cola beverage drinking.

This study was conducted in order to evaluate the effect of cola beverages drinking on atherosclerosisand test the hypothesis whether cola beverages consumption at early life stages might affect the development and progression of atherosclerosis later in life. ApoE−/− C57BL/6J mice (8 week-old) were randomized in 3 groups (n = 20 each) according to free accessto water (W), sucrose sweetened carbonated cola drink(C) or aspartame-acesulfame K sweetened carbonated ‘light’ cola drink (L)for the next 8 weeks. Drinking treatment was ended by switching C and L groups to drinking water. Four mice per group and time were sequentially euthanized: before treatment (8weeks-old), at the end of treatment (16 weeks-old) and after treatment discontinuation (20 weeks-old, 24 weeks-old, 30 week-old mice). Aortic roots and livers were harvested, processed for histology and serial cross-sections were stained. Aortic plaque area was analyzed and plaque/media-ratio was calculated. Early consumption of cola drinks accelerated atherosclerotic plaque progression favoring the interaction between macrophages and myofibroblasts, without the participation of either T lymphocytes or proliferative activity. Plaque/media-ratio varied according to drink treatment (F2,54 = 3.433, p<0.04) and mice age (F4,54 = 5.009, p<0.03) and was higher in C and L groups compared with age-matched W group (p<0.05 at 16 weeks and 20 weeks, p<0.01 at 24 weeks and 30 weeks). Natural evolution of atherosclerosis in ApoE−/− mice (W group) evidenced atherosclerosis acceleration in parallel with a rapid increase in liver inflammation around the 20 weeks of age. Cola drinking within the 8–16 weeks of age accelerated atherosclerosis progression in ApoE−/− mice favoring aortic plaque enlargement (inward remodeling) over media thinning all over the study time. Data suggest that cola drinking at early life stages may predispose to atherosclerosis progression later in life in ApoE−/− mice.

Functional and Morphological Changes in Endocrine Pancreas following Cola Drink Consumption in Rats

Aim We report the effects of long-term cola beverage drinking on glucose homeostasis, endocrine pancreas function and morphology in rats. Methods Wistar rats drank: water (group W), regular cola beverage (group C, sucrose sweetened) or “light” cola beverage (group L, artificially sweetened). After 6 months, 50% of the animals in each group were euthanized and the remaining animals consumed water for the next 6 months when euthanasia was performed. Biochemical assays, insulinemia determination, estimation of insulin resistance (HOMA-IR), morphometry and immunohistochemistry evaluations were performed in pancreas. Results Hyperglycemia (16%, p<0.05), CoQ10 (coenzyme-Q10) decrease (−52%,p<0.01), strong hypertriglyceridemia (2.8-fold, p<0.01), hyperinsulinemia (2.4 fold, p<0.005) and HOMA-IR increase (2.7 fold, p<0.01) were observed in C. Group C showed a decrease in number of α cells (−42%, p<0.01) and β cells (−58%, p<0.001) and a moderate increase in α cells’ size after wash-out (+14%, p<0.001). Group L showed reduction in β cells’ size (−9%, p<0.001) and only after wash-out (L12) a 19% increase in size (p<0.0001) with 35% decrease in number of α cells (p<0.01). Groups C and L showed increase in α/β-cell ratio which was irreversible only in C (α/β = +38% in C6,+30% in C12, p<0.001vs.W6). Regular cola induced a striking increase in the cytoplasmic expression of Trx1 (Thioredoxin-1) (2.25-fold in C6 vs. W6; 2.7-fold in C12 vs. W12, p<0.0001) and Prx2 (Peroxiredoxin-2) (3-fold in C6 vs. W6; 2-fold in C12 vs. W12, p<0.0001). Light cola induced increase in Trx1 (3-fold) and Prx2 (2-fold) after wash-out (p<0.0001, L12 vs. W12). Conclusion Glucotoxicity may contribute to the loss of β cell function with depletion of insulin content. Oxidative stress, suggested by increased expression of thioredoxins and low circulating levels of CoQ10, may follow sustained hyperglycemia. A likely similar panorama may result from the effects of artificially sweetened cola though via other downstream routes.

Cardiorenal Involvement in Metabolic Syndrome Induced by Cola Drinking in Rats: Proinflammatory Cytokines and Impaired Antioxidative Protection.

We report experimental evidence confirming renal histopathology, proinflammatory mediators, and oxidative metabolism induced by cola drinking. Male Wistar rats drank ad libitum regular cola (C, n = 12) or tap water (W, n = 12). Measures. Body weight, nutritional data, plasma glucose, cholesterol fractions, TG, urea, creatinine, coenzyme Q10, SBP, and echocardiograms (0 mo and 6 mo). At 6 months euthanasia was performed. Kidneys were processed for histopathology and immunohistochemistry (semiquantitative). Compared with W, C rats showed (I) overweight (+8%, p < 0.05), hyperglycemia (+11%, p < 0.05), hypertriglyceridemia (2-fold, p < 0.001), higher AIP (2-fold, p < 0.01), and lower Q10 level (−55%, p < 0.05); (II) increased LV diastolic diameter (+9%, p < 0.05) and volume (systolic +24%, p < 0.05), posterior wall thinning (−8%, p < 0.05), and larger cardiac output (+24%, p < 0.05); (III) glomerulosclerosis (+21%, p < 0.05), histopathology (+13%, p < 0.05), higher tubular expression of IL-6 (7-fold, p < 0.001), and TNFα (4-fold, p < 0.001). (IV) Correlations were found for LV dimensions with IL-6 (74%, p < 0.001) and TNFα (52%, p < 0.001) and fully abolished after TG and Q10 control. Chronic cola drinking induced cardiac remodeling associated with increase in proinflammatory cytokines and renal damage. Hypertriglyceridemia and oxidative stress were key factors. Hypertriglyceridemic lipotoxicity in the context of defective antioxidant/anti-inflammatory protection due to low Q10 level might play a key role in cardiorenal disorder induced by chronic cola drinking in rats.

Rosuvastatin increases myocardial microvessels in SHR rats. Role of thioredoxin-1 and peroxiredoxin-2 expression

Fil: Cao, Gabriel Fernando. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Oficina de Coordinacion Administrativa Houssay. Instituto de Investigaciones Cardiologicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Cardiologicas; Argentina

Exercise Ameliorates Endocrine Pancreas Damage Induced by Chronic Cola Drinking in Rats.

Purpose This study evaluates whether the daily practice of an exercise routine might protect from endocrine pancreas damage in cola drinking rats. Methods Forty-eight Wistar rats were randomly assigned to 4 groups depending on a) beverage consumption ad libitum, water (W) or cola beverage (C), and b) physical activity, sedentary (S) or treadmill running (R). Accordingly, 4 groups were studied: WS (water sedentary), WR (water runner), CS (cola sedentary) and CR (cola runner). Body weight, nutritional data, plasma levels of glucose, creatinine, total cholesterol and cholesterol fractions, and triglycerides (enzymocolorimetry), and systolic blood pressure (plethysmography) were measured. After 6 months, euthanasia was performed (overdose sodium thiopental). Pancreatic tissue was immediately excised and conventionally processed for morphometrical and immunohistochemical determinations. Results The effects of running and chronic cola drinking on pancreas morphology showed interaction (p<0.001) rather than simple summation. Cola drinking (CS vs WS) reduced median pancreatic islet area (-30%, 1.8 104 μm2 vs 2.58 104 μm2, p<0.0001) and median β-cell mass (-43%, 3.81 mg vs 6.73 mg, p<0.0001), and increased median α/β ratio (+49%, 0.64 vs 0.43, p< 0.001). In water drinking rats (WR vs WS), running reduced median α-cell mass (-48%, 1.48 mg vs 2.82 mg, p<0.001) and α/β ratio (-56%, 0.19 vs 0.43, p<0.0001). Differently, in cola drinking rats (CR vs CS), running partially restored median islet area (+15%, 2.06 104 μm2 vs 1.79 104 μm2, p<0.05), increased median β-cell mass (+47%, 5.59 mg vs 3.81 mg, p <0.0001) and reduced median α/β ratio (-6%, 0.60 vs 0.64, p<0.05). Conclusion This study is likely the first reporting experimental evidence of the beneficial effect of exercise on pancreatic morphology in cola-drinking rats. Presently, the increase of nearly 50% in β cells mass by running in cola drinking rats is by far the most relevant finding. Moderate running, advisably indicated in cola consumers and patients at risk of diabetes, finds here experimental support.

Carvedilol protects the peritubular capillaries and kidney structure in spontaneously hypertensive rats

Fil: Cao, Gabriel Fernando. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Oficina de Coordinacion Administrativa Houssay. Instituto de Investigaciones Cardiologicas (i); Argentina

Left ventricular hypertrophy does not prevent heart failure in experimental hypertension

BACKGROUND Left ventricular hypertrophy (LVH) secondary to hypertension has been accepted to prevent heart failure (HF) while paradoxically increasing cardiovascular morbi-mortality. OBJECTIVES To evaluate whether antihypertensive treatment inhibits LVH, restores beta-adrenergic response and affects myocardial oxidative metabolism. METHODS Ninety spontaneously hypertensive rats (SHR) were distributed into groups and treated (mg/kg, p.o.) with: losartan 30 (L), hydralazine 11 (H), rosuvastatin 10 (R), carvedilol 20 (C). Hypertension control group comprised 18 normotensive rats (Wistar-Kyoto, WKY). Following euthanasia at 16months, contractility was measured in 50% of rats (Langendorff system) before and after isoproterenol (Iso) 10-9M, 10-7M and 10-5M stimulation. Left ventricular weight (LVW) was measured in the remaining hearts, and normalized by BW. Expression of thioredoxin 1 (Trx-1), peroxyredoxin 2 (Prx-2), glutaredoxin 3 (Grx-3), caspase-3 and brain natriuretic peptide (BNP) was determined. RESULTS Systolic blood pressure (mmHg): 154±3 (L), 137±1 (H), 190±3 (R)*, 206±3 (SHR)*, 183±1 (C)**, and 141±1 (WKY) (*p<0.05 vs. L, H, WKY, **p<0.05 vs. L, H, WKY, SHR). LVW/BW was higher in SHR and R (p<0.05). Groups SHR, R and C evidenced baseline contractile depression. Response to Iso 10-5M was similar in WKY and L. Expression of Trx-1, Prx-2 and Grx-3 increased in C, H, R and L (p<0.01). CONCLUSIONS Present findings argue against the traditional idea and support that LVH might not be required to prevent HF. Increased expression of thioredoxins by antihypertensive treatment might be involved in protection from HF.