The Role of Extracellular Matrix in the Experimental Acute Aortic Regurgitation Model in Rats.

BACKGROUND: Mechanisms involved in cardiac remodelling by aortic regurgitation (AR) and the moment when cardiac dysfunction begins are largely unknown. This study aimed to investigate cardiac morphology and function after 1, 4, 8, and 12 weeks of experimental AR in Wistar rats. Extracellular matrix was also investigated as the potential mechanism that underlies the AR remodelling process. METHODS: Male Wistar rats underwent surgical acute AR (AR group, n=51) or a sham surgery (sham group, n=32). After the procedure, serial transthoracic echocardiograms were performed at 1, 4, 8, and 12 weeks. Morphometry of cardiac tissue and the activities of metalloproteinase 2 (MMP-2) and tissue metalloproteinase inhibitor-1 (TIMP-1) were analysed. Statistical analysis was performed by two-way ANOVA. Significance level was 5%. RESULTS: The AR group presented an increase in the sphericity index (week 1); an increase in the left atrium, left ventricular mass index, TIMP-1 and MMP-2 activities, and collagen fraction (week 4); an increase in myocyte area (week 8); and a reduction in fraction shortening (week 12). First, the chamber became more spherical; second, MMP-2 and TIMP-1 were activated and this may have contributed to hypertrophy and atrial enlargement, until systolic dysfunction occurred. CONCLUSIONS: This study showed a sequence of abnormalities that preceded myocardial dysfunction in an experimental model of AR. First, haemodynamic volume overload led to a more spherical left ventricle chamber. Second, MMP-2 and TIMP-1 transitorily increased and may have contributed to atrial enlargement, eccentric hypertrophy, and systolic dysfunction.

Acute doxorubicin-induced cardiotoxicity is associated with matrix metalloproteinase-2 alterations in rats.

BACKGROUND: Doxorubicin can cause cardiotoxicity. Matrix metalloproteinases (MMP) are responsible for degrading extracellular matrix components which play a role in ventricular dilation. Increased MMP activity occurs after chronic doxorubicin treatment. In this study we evaluated in vivo and in vitro cardiac function in rats with acute doxorubicin treatment, and examined myocardial MMP and inflammatory activation, and gene expression of proteins involved in myocyte calcium transients. METHODS: Wistar rats were injected with doxorubicin (Doxo, 20 mg/kg) or saline (Control). Echocardiogram was performed 48 h after treatment. Myocardial function was assessed in vitro in Langendorff preparation. RESULTS: In left ventricle, doxorubicin impaired fractional shortening (Control 0.59 ± 0.07; Doxo 0.51 ± 0.05; p < 0.001), and increased isovolumetric relaxation time (Control 20.3 ± 4.3; Doxo 24.7 ± 4.2 ms; p = 0.007) and myocardial passive stiffness. MMP-2 activity, evaluated by zymography, was increased in Doxo (Control 141338 ± 8924; Doxo 188874 ± 7652 arbitrary units; p < 0.001). There were no changes in TNF-α, INF-γ, IL-10, and ICAM-1 myocardial levels. Expression of phospholamban, Serca-2a, and ryanodine receptor did not differ between groups. CONCLUSION: Acute doxorubicin administration induces in vivo left ventricular dysfunction and in vitro increased myocardial passive stiffness in rats. Cardiac dysfunction is related to myocardial MMP-2 activation. Increased inflammatory stimulation or changed expression of the proteins involved in intracellular calcium transients is not involved in acute cardiac dysfunction.

Influence of N- acetylcysteine on oxidative stress in slow-twitch soleus muscle of heart failure rats.

BACKGROUND: Chronic heart failure is characterized by decreased exercise capacity with early exacerbation of fatigue and dyspnea. Intrinsic skeletal muscle abnormalities can play a role in exercise intolerance. Causal or contributing factors responsible for muscle alterations have not been completely defined. This study evaluated skeletal muscle oxidative stress and NADPH oxidase activity in rats with myocardial infarction (MI) induced heart failure. METHODS AND RESULTS: Four months after MI, rats were assigned to Sham, MI-C (without treatment), and MI-NAC (treated with N-acetylcysteine) groups. Two months later, echocardiogram showed left ventricular dysfunction in MI-C; NAC attenuated diastolic dysfunction. In soleus muscle, glutathione peroxidase and superoxide dismutase activity was decreased in MI-C and unchanged by NAC. 3-nitrotyrosine was similar in MI-C and Sham, and lower in MI-NAC than MI-C. Total reactive oxygen species (ROS) production was assessed by HPLC analysis of dihydroethidium (DHE) oxidation fluorescent products. The 2-hydroxyethidium (EOH)/DHE ratio did not differ between Sham and MI-C and was higher in MI-NAC. The ethidium/DHE ratio was higher in MI-C than Sham and unchanged by NAC. NADPH oxidase activity was similar in Sham and MI-C and lower in MI-NAC. Gene expression of p47(phox) was lower in MI-C than Sham. NAC decreased NOX4 and p22(phox) expression. CONCLUSIONS: We corroborate the case that oxidative stress is increased in skeletal muscle of heart failure rats and show for the first time that oxidative stress is not related to increased NADPH oxidase activity.

Higher salt preference in heart failure patients.

Heart failure (HF) is a complex syndrome that involves changes in behavioral, neural and endocrine regulatory systems. Dietary salt restriction along with pharmacotherapy is considered an essential component in the effective management of symptomatic HF patients. However, it is well recognized that HF patients typically have great difficulty in restricting sodium intake. We hypothesized that under HF altered activity in systems that normally function to regulate body fluid and cardiovascular homeostasis could produce an increased preference for the taste of salt. Therefore, this study was conducted to evaluate the perceived palatability (defined as salt preference) of food with different concentrations of added salt in compensated chronically medicated HF patients and comparable control subjects. Healthy volunteers (n=25) and medicated, clinically stable HF patients (n=38, NYHA functional class II or III) were interviewed and given an evaluation to assess their preferences for different amounts of saltiness. Three salt concentrations (0.58, 0.82, and 1.16 g/100 g) of bean soup were presented to the subjects. Salt preference for each concentration was quantified using an adjective scale (unpleasant, fair or delicious). Healthy volunteers preferred the soup with medium salt concentration (p=0.042), HF patients disliked the low concentration (p<0.001) and preferred the high concentration of salted bean soup (p<0.001). When compared to healthy volunteers, HF patients demonstrated a significantly greater preference for the soup with a high salt concentration (p=0.038). It is concluded that medicated, compensated patients under chronic treatment for HF have an increased preference for salt.

Influence of taurine on cardiac remodeling induced by tobacco smoke exposure.

BACKGROUND/AIMS: To investigate the effect of taurine on cardiac remodeling induced by smoking. METHODS: In the first step, rats were allocated into two groups: Group C (n = 14): control; Group T (n = 14): treated with taurine (3% in drinking water), for three months. In the second step, rats were allocated into two groups: Group ETS (n = 9): rats exposed to tobacco smoke; Group ETS-T (n = 9): rats exposed to tobacco smoke and treated with taurine for two months. RESULTS: After three months, taurine presented no effects on morphological or functional variables of normal rats assessed by echocardiogram. On the other hand, after two months, ETS-T group presented higher LV wall thickness (ETS = 1.30 (1.20-1.42); ETS-T = 1.50 (1.40-1.50); p = 0.029), E/A ratio (ETS = 1.13 ± 0.13; ETS-T = 1.37 ± 0.26; p = 0.028), and isovolumetric relaxation time normalized for heart rate (ETS = 53.9 ± 4.33; ETS-T = 72.5 ± 12.0; p < 0.001). The cardiac activity of the lactate dehydrogenase was higher in the ETS-T group (ETS = 204 ± 14 nmol/mg protein; ETS-T = 232 ± 12 nmol/mg protein; p < 0.001). ETS-T group presented lower levels of phospholamban (ETS = 1.00 ± 0.13; ETS-T = 0.82 ± 0.06; p = 0.026), phosphorylated phospholamban at Ser16 (ETS = 1.00 ± 0.14;ETS-T = 0.63 ± 0.10;p = 0.003), and phosphorylated phosfolamban/phospholamban ratio (ETS = 1.01 ± 0.17; ETS-T = 0.77 ± 0.11; p = 0.050). CONCLUSION: In normal rats, taurine produces no effects on cardiac morphological or functional variables. On the other hand, in rats exposed to cigarette smoke, taurine supplementation increases wall thickness and worsens diastolic function, associated with alterations in calcium handling protein and cardiac energy metabolism.

Tobacco smoke induces ventricular remodeling associated with an increase in NADPH oxidase activity.

BACKGROUND: Recent studies have assessed the direct effects of smoking on cardiac remodeling and function. However, the mechanisms of these alterations remain unknown. The aim of this study was to investigate de role of cardiac NADPH oxidase and antioxidant enzyme system on ventricular remodeling induced by tobacco smoke. METHODS: Male Wistar rats that weighed 200-230 g were divided into a control group (C) and an experimental group that was exposed to tobacco smoke for a period of two months (ETS). After the two-month exposure period, morphological, biochemical and functional analyses were performed. RESULTS: The myocyte cross-sectional area and left ventricle end-diastolic dimension was increased 16.2% and 33.7%, respectively, in the ETS group. The interstitial collagen volume fraction was also higher in ETS group compared to the controls. In addition to these morphological changes, the ejection fraction and fractional shortening were decreased in the ETS group. Importantly, these alterations were related to augmented heart oxidative stress, which was characterized by an increase in NADPH oxidase activity, increased levels of lipid hydroperoxide and depletion of antioxidant enzymes (e.g., catalase, superoxide dismutase and glutathione peroxidase). In addition, cardiac levels of IFN-γ, TNF-α and IL-10 were not different between the groups. CONCLUSION: Cardiac alterations that are induced by smoking are associated with increased NADPH oxidase activity, suggesting that this pathway plays a role in the ventricular remodeling induced by exposure to tobacco smoke.

Retinoic acid prevents ventricular remodelling induced by tobacco smoke exposure in rats.

OBJECTIVE: Our objective was to test the hypothesis that retinoic acid supplementation could attenuate ventricular remodelling induced by tobacco smoke exposure in rats. METHODS AND RESULTS: Wistar rats were allocated into three groups: control (C, n = 8); exposed to tobacco smoke (ETS, n = 9); exposed to tobacco smoke and all-trans-retinoic acid (ETS-RA, n = 9). After two months, cardiac function and geometry were assessed by echocardiography, and geometry changes were confirmed by morphometric analysis. Data are expressed as mean +/- SD or medians (including the lower quartile and upper quartile). ETS showed higher normalized left ventricular diastolic diameters than groups C and ETS-RA (C = 18.4 +/- 3.57 mm/kg, ETS = 23.0 +/- 1.8, ETS-RA = 19.5 +/- 0.99; P <0.05) and systolic diameters (C = 8.25 +/- 2.16 mm/kg, ETS = 11.5 +/- 1.31, ETS-RA = 8.25 +/- 0.71 mm/kg; P < 0.05). ETS showed reduced ejection fraction (C= 91 +/- 2.0, ETS = 87 +/- 3.0, ETS-RA = 92 +/- 3.0; P < 0.05) and fractional shortening (C = 55.8 +/- 4.41%, ETS = 49.7 +/- 4.43%, ETS-RA = 57.6 +/- 5.15 %; P= 0.01) compared to C and ETS-RA. ETS had increased myocyte cross-sectional area (C = 294 +/- 21 mm2, ETS = 352 +/-44, ETS-RA = 310 +/- 35; P < 0.05) compared to C and ETS-RA. Considering all variables, there were no differences between groups C and ETS-RA. CONCLUSION: Retinoic acid prevented ventricular remodelling induced by tobacco smoke exposure.

Ventricular remodeling induced by tissue vitamin A deficiency in rats.

BACKGROUND/AIMS: Experimental studies suggest that vitamin A plays a role in regulating cardiac structure and function. We tested the hypothesis that cardiac vitamin A deficiency is associated with adverse myocardial remodeling in young adult rats. METHODS: Two groups of young female rats, control (C - n = 29) and tissue vitamin A deficient (RVA - n = 31), were subjected to transthoracic echocardiography exam, isolated rat heart study and biochemical study. RESULTS: The RVA rats showed a reduced total vitamin A concentration in both the liver and heart [vitamin A in heart, micromol/kg (C = 0.95 +/- 0.44 and RVA = 0.24 +/- 0.16, p = 0.01)] with the same serum retinol levels (C = 0.73 +/- 0.29 micromol/L e RVA = 0.62 +/- 0.17 micromol/L, p = 0.34). The RVA rats showed higher left ventricular diameters and reduced systolic function. The RVA rats also demonstrated increased lipid hydroperoxide/total antioxidant capacity ratio and cardiac levels of IFN-gamma and TNF-alpha but not of metalloproteinase (MMP)-2 and -9 activity. On the other hand, the RVA rats had decreased levels of beta-hydroxyacylcoenzyme A dehydrogenase and lactate dehydrogenase. CONCLUSIONS: Tissue vitamin A deficiency stimulated cardiac remodeling and ventricular dysfunction. Additionally, the data support the involvement of oxidative stress, energy metabolism, and cytokine production in this remodeling process.

Tissue vitamin A insufficiency results in adverse ventricular remodeling after experimental myocardial infarction.

BACKGROUND/AIMS: The role of tissue vitamin-A insufficiency on post-infarction ventricular remodeling is unknown. We tested the hypothesis that cardiac vitamin A insufficiency on post-infarction is associated with adverse myocardial remodeling. METHODS: After infarction, rats were allocated into two groups: C (controls, n=25); VA (dietary vitamin A restriction, n= 26). After 3 months, the animals were submitted to echocardiogram, morphometric and biochemical analysis. RESULTS: Rats fed the vitamin-A-deficient diet had lower heart and liver retinol concentration and normal plasma retinol. There were no differences in infarct size between the groups. VA showed higher diastolic left ventricular area normalised by body weight (C= 1.81 ± 0.4 cm2/kg, VA= 2.15 ± 0.3 cm2/kg; p=0.03), left ventricular diameter (C= 9.4 ± 1.4 mm, VA= 10.5 ± 1.2 mm; p=0.04), but similar systolic ventricular fractional area change (C= 33.0 ± 10.0 %, VA= 32.1 ± 8.7 %; p=0.82). VA showed decreased isovolumetric relaxation time normalised by heart rate (C= 68.8 ± 11.4 ms, VA= 56.3 ± 16.8 ms; p=0.04). VA showed higher interstitial collagen fraction (C= 2.8 ± 0.9 %, VA= 3.7 ± 1.1 %; p=0.05). There were no differences in myosin heavy chain expression, metalloproteinase 2 and 9 activation, or IFN-γ and TNF-α cardiac levels. CONCLUSION: Local tissue vitamin A insufficiency intensified ventricular remodeling after MI, worsening diastolic dysfunction.

Protective effects of carvedilol on systemic vascular damage induced by angiotensin II: organ-specific effects independent of antihypertensive effects.

BACKGROUND: The protective effect of carvedilol on multiple organ damage induced by angiotensin II (Ang II) remains unclear. The aim of this study was to evaluate the protective effect of carvedilol on the heart, liver, and kidney in rats infused with Ang II. MATERIAL/METHODS: Wistar rats were randomly distributed into three groups: control (no treatment), continuously infused with Ang II (150 etag/min for 72 hr), and treated with Ang II + carvedilol (90 mg/kg/d). Histological sections of the myocardium, kidney, and liver were analyzed for the presence of necrosis. RESULTS: Ang II induced arterial hypertension which was not affected by carvedilol treatment (tail-cuff blood pressures, control: 125+/-13.6, Ang II: 163+/-27.3, Ang II + CV: 178+/-39.8 mmHg, p<0.05). Also, there were perivascular inflammation and necrosis in the myocardium, kidney, and hepatocytes necrosis around the terminal vein. Carvedilol treatment fully prevented damage to the heart and kidney and attenuated liver lesions induced by the Ang II infusion. CONCLUSIONS: The protective effect of carvedilol on perivascular damage induced by Ang II infusion depended on the target organ. The prevention of heart damage occurred independently of the antihypertensive effects of carvedilol.

Influence of lisinopril on cardiac remodeling induced by tobacco smoke exposure.

BACKGROUND: To investigate the effect of lisinopril on cardiac remodeling induced by smoking. MATERIAL/METHODS: Rats were allocated into 3 groups: group CON (n=8): control; group CSE (n=8): cigarette smoke exposure; group CSE-LIS (n=8): exposed to tobacco smoke and treated with lisinopril. RESULTS: After 2 months, the tail systolic pressure was lower in CSE-LIS (CON=116 +/-27 mm Hg, CSE=126+/-16, CSE-LIS=89+/-12; P<.001). CSE animals showed higher left ventricular systolic diameter (CON=8.25+/-2.16 mm/kg, CSE=11.5+/-1.3, CSE-LIS=9.27+/-2.00; P=.009) and myocyte cross-sectional area (CON=245+/-8 microm2, CSE=260+/-17, CSE-LIS=238+/-12; P=.01) than CON and CSE-LIS. The ejection fraction (CON =0.91+/-0.02, CSE=0.86+/-0.02, CSE-LIS=0.92+/-0.03; P=.002) and fractional shortening (CON=55.7+/-4.41%, CSE=48.7+/-3.43, CSE-LI=58.2+/-7.63; P=.006) were lower in CSE group than CON and CSE-LIS. CSE and CSE-LIS animals showed higher collagen amounts (CON=3.49+/-0.95%, CSE= 5.01+/-1.58, CSE-LIS=5.27+/-0.62; P=.009) than CON. CON group showed a higher connexin 43 amount in the intercalated disc (CON=3.70+/-0.38, CSE=2.13+/-0.53; CSE-LIS=2.17+/-0.73; P=.004) than CSE and CSE-LIS. There were no differences in IFN-gamma or TNF-alpha cardiac levels among the groups. CONCLUSIONS: Lisinopril attenuated both morphologic and functional abnormalities induced by exposure to tobacco smoke. In addition, this effect was associated with diminished blood pressure, but not alterations in connexin 43 distribution, cytokine production or collagen amount.

Doxorubicin as an antioxidant: maintenance of myocardial levels of lycopene under doxorubicin treatment.

The mechanism of doxorubicin-induced cardiotoxicity remains controversial. Wistar rats (n=96) were randomly assigned to a control (C), lycopene (L), doxorubicin (D), or doxorubicin+lycopene (DL) group. The L and DL groups received lycopene (5 mg/kg body wt/day by gavage) for 7 weeks. The D and DL groups received doxorubicin (4 mg/kg body wt intraperitoneally) at 3, 4, 5, and 6 weeks and were killed at 7 weeks for analyses. Myocardial tissue lycopene levels and total antioxidant performance (TAP) were analyzed by HPLC and fluorometry, respectively. Lycopene metabolism was determined by incubating (2)H(10)-lycopene with intestinal mucosa postmitochondrial fraction and lipoxygenase and analyzed with HPLC and APCI mass spectroscopy. Myocardial tissue lycopene levels in DL and L were similar. TAP adjusted for tissue protein were higher in myocardium of D than those of C (P=0.002). Lycopene metabolism study identified a lower oxidative cleavage of lycopene in D as compared to those of C. Our results showed that lycopene was not depleted in myocardium of lycopene-supplemented rats treated with doxorubicin and that higher antioxidant capacity in myocardium and less oxidative cleavage of lycopene in intestinal mucosa of doxorubicin-treated rats suggest an antioxidant role of doxorubicin rather than acting as a prooxidant.

Tobacco smoke-induced left ventricular remodelling is not associated with metalloproteinase-2 or -9 activation.

AIM: To investigate the role of MMP-2 and MMP-9 in cardiac remodelling induced by tobacco smoke exposure in rats. METHODS: Rats were allocated into two groups: C (n=9): control animals; ETS (n=9): exposed to tobacco smoke. After 4months, the animals underwent echocardiography, morphometric study and determination of MMP-2 and MMP-9 activity. RESULTS: ETS rats had larger diastolic (C=15.6 +/-1.2 mm/kg, ETS=18.0+/-0.9 mm/kg; p < 0.001) and systolic (C=7.3+/-1.2 mm/kg, ETS=9.2+/-0.9 mm/kg; p=0.001) ventricular diameters adjusted for body weight. Fractional shortening (C=53+/-4.8%, ETS=48+/- 3.3%; p=0.031) and ejection fraction (C=0.89+/-0.03, ETS=0.86+/-0.02; p=0.030) were smaller in the ETS group. Myocyte cross-sectional area (C=245+/-8 microm2, ETS=253+/-8 microm2; p=0.028) was higher in ETS rats. There were no differences in MMP-2 (C=50+/-14%; ETS=43+/-11%, p=0.228) or MMP-9 (C=0.36+/-0.3%; ETS=0.62+/-0.3%, p=0.630) activity between the groups. CONCLUSION: MMP-2 and MMP-9 did not participate in the remodelling process induced by tobacco smoke exposure.

Tomato-oleoresin supplement prevents doxorubicin-induced cardiac myocyte oxidative DNA damage in rats.

Doxorubicin (DOX) is an efficient chemotherapeutic agent used against several types of tumors; however, its use is limited due to severe cardiotoxicity. Since it is accepted that reactive oxygen species are involved in DOX-induced cardiotoxicity, antioxidant agents have been used to attenuate its side effects. To determine tomato-oleoresin protection against cardiac oxidative DNA damage induced by DOX, we distributed Wistar male rats in control (C), lycopene (L), DOX (D) and DOX+lycopene (DL) groups. They received corn oil (C, D) or tomato-oleoresin (5mg/kg body wt. day) (L, DL) by gavage for a 7-week period. They also received saline (C, L) or DOX (4mg/kg body wt.) (D, DL) intraperitoneally at the 3rd, 4th, 5th, and at 6th week. Lycopene absorption was checked by HPLC. Cardiac oxidative DNA damage was evaluated by the alkaline Comet assay using formamidopyrimidine-DNA glycosylase (FPG) and endonuclease III (endo III). Cardiomyocyte levels of SBs, SBs FPG and SBs Endo III were higher in rats from D when compared to other groups. DNA damage levels in cardiomyocytes from DL were not different when compared to C and L groups. The viability of cardiomyocytes from D or DL was lower than C or L groups (p<0.01). Lycopene levels (mean+/-S.D.nmol/kg) in saponified hearts were similar between L (47.43+/-11.78) and DL (49.85+/-16.24) groups. Our results showed: (1) lycopene absorption was confirmed by its cardiac levels; (2) DOX-induced oxidative DNA damage in cardiomyocyte; (3) tomato-oleoresin supplementation protected against cardiomyocyte oxidative DNA damage.

Chorea-ballism as a manifestation of decompensated type 2 diabetes mellitus.

Chorea and ballism are movement disorders that result from a variety of conditions. Hyperglycemia is an unusual recognized cause of these movement disorders. We report 3 cases of new-onset chorea-ballism induced by nonketotic hyperglycemia in elderly patients, highlighting that chorea may be the first manifestation of undiagnosed decompensated diabetes mellitus.

Effect of lycopene on doxorubicin-induced cardiotoxicity: an echocardiographic, histological and morphometrical assessment.

Doxorubicin is an excellent chemotherapeutic agent utilized for several types of cancer but the irreversible doxorubicin-induced cardiac damage is the major limitation for its use. Oxidative stress seems to be associated with some phase of the toxicity mechanism process. To determine if lycopene protects against doxorubicin-induced cardiotoxicity, male Wistar rats were randomly assigned either to control, lycopene, doxorubicin or doxorubicin + lycopene groups. They received corn oil (control, doxorubicin) or lycopene (5 mg/kg body weight a day) (lycopene, doxorubicin + lycopene) by gavage for a 7-week period. They also received saline (control, lycopene) or doxorubicin (4 mg/kg) (doxorubicin, doxorubin + lycopene) intraperitoneally by week 3, 4, 5 and 6. Animals underwent echocardiogram and were killed for tissue analyses by week 7. Mean lycopene levels (nmol/kg) in liver were higher in the doxorubicin + lycopene group (5822.59) than in the lycopene group (2496.73), but no differences in lycopene were found in heart or plasma of these two groups. Lycopene did not prevent left ventricular systolic dysfunction induced by doxorubicin. However, morphologic examination revealed that doxorubicin-induced myocyte damage was significantly suppressed in rats treated with lycopene. Doxorubicin treatment was followed by increase of myocardium interstitial collagen volume fraction. Our results show that: (i) doxorubicin-induced cardiotoxicity was confirmed by echocardiogram and morphological evaluations; (ii) lycopene absorption was confirmed by its levels in heart, liver and plasma; (iii) lycopene supplementation provided myocyte protection without preventing interstitial collagen accumulation increase; (iv) doxorubicin-induced cardiac dysfunction was not prevented by lycopene supplementation; and (v) lycopene depletion was not observed in plasma and tissues from animals treated with doxorubicin.

Myocardial dysfunction with increased ventricular compliance in volume overload hypertrophy.

The aim this study was to evaluate systolic and diastolic function in volume overload induced myocardial hypertrophy in rats. Volume overload myocardial hypertrophy was induced in thirteen male Wistar rats by creating infrarenal arteriovenous fistula (AVF). The results were compared with a SHAM operated group (n=11). Eight weeks after surgery, tail-cuff blood pressure was recorded, then rats were sacrificed for isolated heart studies using Langendorff's preparation. AVF rats presented increased left and right ventricular weights, compared to controls. The increased normalized ventricular volume (V0/LVW, 0.141+/-0.035 mL/g vs. 0.267+/-0.071 mL/g, P<0.001) in the AVF group indicated chamber dilation. Myocardial hydroxyproline concentration remained unchanged. There was a significant decrease in +dP/dt (3318+/-352 mm Hg s(-1) vs. 2769+/-399 mm Hg s(-1); P=0,002), end-systolic pressure-volume relation (246+/-56 mm Hg mL(-1) vs. 114+/-63 mm Hg mL(-1); P<0,001), and -dP/dt (1746+/-240 mm Hg s(-1) vs. 1361+/-217 mm Hg s(-1), P<0.001) in the AVF group, which presented increased ventricular compliance (DeltaV(25): SHAM=0.172+/-0.05 mL vs. AVF=0.321+/-0.072 mL, P<0.001) with preserved myocardial passive stiffness (Strain(25): SHAM=13.5+/-3.0% vs. AVF=12.3+/-1.9%, P>0.05). We conclude that volume-overload induced hypertrophy causes myocardial systolic and diastolic dysfunction with increased ventricular compliance. These haemodynamic features help to explain the long-term compensatory phase of chronic volume overload before transition to overt congestive heart failure.

Beta-carotene supplementation attenuates cardiac remodeling induced by one-month tobacco-smoke exposure in rats.

OBJECTIVE: The objectives were to analyze the cardiac effects of exposure to tobacco smoke (ETS), for a period of 30 days, alone and in combination with beta-carotene supplementation (BC). RESEARCH METHODS AND PROCEDURES: Rats were allocated into: Air (control, n = 13); Air + BC (n = 11); ETS (n = 11); and BC + ETS (n = 9). In Air + BC and BC + ETS, 500 mg of BC were added to the diet. After three months of randomization, cardiac structure and function were assessed by echocardiogram. After that, animals were euthanized and morphological data were analyzed post-mortem. One-way and two-way ANOVA were used to assess the effects of ETS, BC and the interaction between ETS and BC on the variables. RESULTS: ETS presented smaller cardiac output (0.087 +/- 0.001 vs. 0.105 +/- 0.004 l/min; p = 0.007), higher left ventricular diastolic diameter (19.6 +/- 0.5 vs. 18.0 +/- 0.5 mm/kg; p = 0.024), higher left ventricular (2.02 +/- 0.05 vs. 1.70 +/- 0.03 g/kg; p < 0.001) and atrium (0.24 +/- 0.01 vs. 0.19 +/- 0.01 g/kg; p = 0.003) weight, adjusted to body weight of animals, and higher values of hepatic lipid hydroperoxide (5.32 +/- 0.1 vs. 4.84 +/- 0.1 nmol/g tissue; p = 0.031) than Air. However, considering those variables, there were no differences between Air and BC + ETS (0.099 +/- 0.004 l/min; 19.0 +/- 0.5 mm/kg; 1.83 +/- 0.04 g/kg; 0.19 +/- 0.01 g/kg; 4.88 +/- 0.1 nmol/g tissue, respectively; p > 0.05). Ultrastructural alterations were found in ETS: disorganization or loss of myofilaments, plasmatic membrane infolding, sarcoplasm reticulum dilatation, polymorphic mitochondria with swelling and decreased cristae. In BC + ETS, most fibers showed normal morphological aspects. CONCLUSION: One-month tobacco-smoke exposure induces functional and morphological cardiac alterations and BC supplementation attenuates this ventricular remodeling process.

Beta-carotene supplementation results in adverse ventricular remodeling after acute myocardial infarction.

OBJECTIVE: We studied the effects of beta-carotene (BC) on ventricular remodeling after myocardial infarction. METHODS: Myocardial infarction was induced in Wistar rats that were then treated with a BC diet (500 mg/kg of diet per day; MI-BC; n = 27) or a regular diet (MI; n = 27). Hearts were analyzed in vivo and in vitro after 6 mo. RESULTS: BC caused decreased left ventricular wall thickness (MI = 1.49 +/- 0.3 mm, MI-BC = 1.23 +/- 0.2 mm, P = 0.027) and increased diastolic (MI = 0.83 +/- 0.15 cm2, MI-BC = 0.98 +/- 0.14 cm2, P = 0.020) and systolic (MI = 0.56 +/- 0.12 cm2, MI-BC = 0.75 +/- 0.13 cm2, P = 0.002) left ventricular chamber areas. With respect to systolic function, the BC group presented less change in fractional area than did controls (MI = 32.35 +/- 6.67, MI-BC = 23.77 +/- 6.06, P = 0.004). There was no difference in transmitral diastolic flow velocities between groups. In vitro results showed decreased maximal isovolumetric systolic pressure (MI = 125.5 +/- 24.1 mmHg, MI-BC = 95.2 +/- 28.4 mmHg, P = 0.019) and increased interstitial myocardial collagen concentration (MI = 3.3 +/- 1.2%, MI-BC = 5.8 +/- 1.7%, P = 0.004) in BC-treated animals. Infarct sizes were similar between groups (MI = 45.0 +/- 6.6%, MI-BC = 48.0 +/- 5.8%, P = 0.246). CONCLUSION: Taken together, these data suggest that BC has adverse effects on ventricular remodeling after myocardial infarction.

Myxedema ascites with elevated serum CA 125 concentration.

We report a case of myxedema ascites and markedly elevated serum CA 125 concentration. The cause of ascites and elevated tumor markers in hypothyroidism remains unknown. Diagnosis was characterized by no evidence of malignancy seen by transvaginal ultrasonography or abdominal computed tomography and ascites resolution with serum CA 125 normalization after adequate hormonal treatment. Our data suggest that hypothyroidism should be considered in patients with ascites and elevated serum CA 125.