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 Langendorffs 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 min Hg s(-1) vs. 1361 +/- 217 mm Hg s(-1), P < 0.001) in the AVF group, which presented increased ventricular compliance (Delta V-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. (c) 2006 European Society of Cardiology. Published by Elsevier B.V. All rights reserved.

Myocardial contractile dysfunction contributes to the development of heart failure in rats with aortic stenosis

Objectives: To analyze the potential contribution of contractility state and ventricular geometry to the development of heart failure in rats with aortic stenosis.Methods: Rats were divided into three groups: compensated aortic stenosis (AS, n = 11), heart failure AS (n = 12) and control rats (C, n = 13).Results: After 21 weeks, failing AS rats presented higher systolic (C = 36.6 +/- 3.1, AS-78.6 +/- 4.8*, failing AS = 104.6 +/- 7.8*) and diastolic meridian stress (C = 6.9 +/- 0.4, AS = 20.1 +/- 1.1*, failing AS = 43.2 +/- 3.2*(dagger)), hydroxyproline (C = 3.6 +/- 0.7 mg/g, AS = 6.6 +/- 0.6* mg/g, failing AS = 9.2 +/- 1.4*(dagger) mg/g) and cross-sectional area (C = 338 +/- 25 mu m(2), AS = 451 +/- 32* mu m(2), failing AS = 508 +/- 36*(dagger) mu m(2)), in comparison with control and compensated AS animals (*p < 0.05 vs. control, (dagger)p < 0.05 vs. AS). In the isometric contraction study, considering the time from peak tension to 50% relaxation (RT50), the relative variation responses, following post-rest contraction and increase in Ca2+ concentration, were higher in failing AS than compensated AS animals. In contrast, following post-rest contraction, compensated AS group presented higher values of the peak developed tension (DT) than failing AS group. Following beta-adrenergic stimulation, control animals presented higher values of +dT/dt and -dT/dt than AS animals. In addition, failing AS animals presented higher TPT values than compensated AS animals.Conclusion: Myocardial contractile dysfunction contributes to the development of heart failure in rats with aortic stenosis. (c) 2006 Elsevier B.V.. All rights reserved.

Dysautonomia and ventricular dysfunction in the indeterminate form of Chagas disease

Background: the associations between autonomic function and biventricular function in patients with the indeterminate form of Chagas disease remains to be elucidated.Methods: In 42 asymptornatic patients and 19 healthy volunteers, the autonomic function was assessed by time domain indices of heart rate variability (HRV), analyzed for 24 h; the right ventricular function was assessed by fraction area change, right ventricle shortening, and systolic excursion of the tricuspid valve; and the left ventricular function was assessed by ejection fraction and transmittal flow velocities. Data were expressed as mean SD or medians (including the lower quartile and upper quartile). Groups were compared by Student's t or Mann-Whitney U test. Autonomic and ventricular function were correlated by Pearson's or Spearman's correlation coefficient. The level of significance was 5%.Results: Right and left ventricular systolic function indexes were comparable between groups. Transmittal flow velocities were decreased in the Chagas disease group (p < 0.05). The patients presented impaired HRV as indicated by the values of SDNN-day (80 (64-99) ms vs. 98 (78-127) ms; p = 0.045), SDNNI-24 It (54 (43-71) vs. 65 (54-105) ms; p = 0.027), SDNNI-day (49 (42-64) vs. 67 (48-76) ms; p = 0.045), pNN50-day (2.2 (0.7-5)% vs. 10 (3-11)%; p = 0.033); and pNN50-24 It (3 (1-7)% vs. 12 (8-19)%; p = 0.013). There were no correlations between the left ventricular diastolic indices and autonomic dysfunctional indices (p > 0.05).Conclusion: Patients with the indeterminate form of Chagas disease have both dysautonomia, and left ventricular diastolic dysfunction. However, the right ventricular function is preserved. Importantly, ventricular diastolic dysfunction and dysautonomia. are independent phenomena. (c) 2005 Elsevier B.V.. All rights reserved.

Myocardial remodeling and dysfunction are induced by chronic food restriction in spontaneously hypertensive rats

Several studies have shown alterations in hearts from animals subjected to food restriction (FR). However, few experiments in hearts evaluating pressure overload have been reported. We examined the effects of chronic FR on myocardial function and morphology in spontaneously hypertensive rats (SHR). Sixty-day-old SHR were fed a control (C) or a restricted diet (daily intake reduced to 50% of amount of food consumed by the control group) for 90 days. Myocardial performance was studied in isolated left ventricular (LV) papillary muscle. Food restriction decreased body weight and LV weight; LV weight/body-weight ratio was lower in the food-restricted group (SHR-C, 2.84 +/- 0.21 mg/g; SHR-FR, 2.56 +/- 0.24 mg/g; P <.05). Food restriction did not change arterial systolic blood pressure. Myocyte surface area was lower in the food-restricted group (P <.01). Food restriction induced myocardial ultrastructural alterations including reduced sarcoplasm content, reduced and disorganized myofilaments, disorganized Z line, dilated sarcoplasmic reticulum, and deep infoldings of plasma membrane. Myocardial hydroxyproline concentration was increased in the restricted rats. Peak developed tension (P <.05) and maximum rate of tension development (P <.01) were decreased in the SHR-FR group. In conclusion, myocardium of SHR subjected to chronic FR presents attenuation of hypertrophy development, ultrastructural changes, increased collagen content, and systolic dysfunction. (c) 2006 Elsevier B.V. All rights reserved.

Myocardial fibrosis rather than hypertrophy induces diastolic dysfunction in renovascular hypertensive rats

The aim of the present study was to evaluate the-effect of interstitial fibrosis alone or associated with hypertrophy. on diastolic myocardial function in renovascular hypertensive rats. Myocardial function was evaluated in isolated papillary muscle from renovascular hypertensive Wistar rats (RHT, n = 14), renovascular hypertensive rats treated with the angiotensin converting enzyme inhibitor (ACEI) ramipril, 20 mg.kg(-1).day(-1) (RHT RAM, n = 14), and age-matched unoperated and untreated Wistar rats (CONT, n = 12). The ACEI treatment for 3 weeks allowed the regression of myocyte mass and the maintenance of interstitial fibrosis. Myocardial passive stiffness was analyzed by the resting tension - length relationship. The myocardial fibrosis was evaluated by measuring myocardial hydroxyproline (Hyp) concentration and by histological studies of the myocardium stained with hematoxylin and eosin or picrosirius red. Left ventricular weight was significantly higher in RHT (0.97 +/- 0.12 g) compared with CONT (0.66 +/- 0.06 g) and RHT RAM (0.69 +/- 0.14 g). The Hyp levels were 2.9 +/- 0.4, 3.4 +/- 0.3, and 3.8 +/- 0.4 mu g/mg of dry tissue for the CONT, RHT, and RHT RAM, respectively. Perivascular and interstitial fibrosis were observed in RHT and RHT RAM groups. There were lymphomononuclear inflammatory exudate and edema around arteries, involving adjacent myocytes in the RHT group. There was an increased passive stiffness in RHT and RHT RAM groups compared with the CONT group. In conclusion, our results indicate that the Impaired diastolic function in the renovascular hypertensive rats is related to interstitial fibrosis rather than to myocardial hypertrophy.

Food restriction induces in vivo ventricular dysfunction in spontaneously hypertensive rats without impairment of in vitro myocardial contractility

Cardiac structures, function, and myocardial contractility are affected by food restriction (FR). There are few experiments associating undernutrition with hypertension. The aim of the present study was to analyze the effects of FR on the cardiac response to hypertension in a genetic model of hypertension, the spontaneously hypertensive rat (SHR). Five-month-old SHR were fed a control or a calorie-restricted diet for 90 days. Global left ventricle (LV) systolic function was evaluated in vivo by transthoracic echocardiogram and myocardial contractility and diastolic function were assessed in vitro in an isovolumetrically beating isolated heart (Langendorff preparation). FR reduced LV systolic function (control (mean ± SD): 58.9 ± 8.2; FR: 50.8 ± 4.8%, N = 14, P < 0.05). Myocardial contractility was preserved when assessed by the +dP/dt (control: 3493 ± 379; FR: 3555 ± 211 mmHg/s, P > 0.05), and developed pressure (in vitro) at diastolic pressure of zero (control: 152 ± 16; FR: 149 ± 15 mmHg, N = 9, P > 0.05) and 25 mmHg (control: 155 ± 9; FR: 150 ± 10 mmHg, N = 9, P > 0.05). FR also induced eccentric ventricular remodeling, and reduced myocardial elasticity (control: 10.9 ± 1.6; FR: 9.2 ± 0.9%, N = 9, P < 0.05) and LV compliance (control: 82.6 ± 16.5; FR: 68.2 ± 9.1%, N = 9, P < 0.05). We conclude that FR causes systolic ventricular dysfunction without in vitro change in myocardial contractility and diastolic dysfunction probably due to a reduction in myocardial elasticity.

Predictors of Right Ventricle Dysfunction After Anterior Myocardial Infarction

Background: Regardless significant therapeutic advances, mortality and morbidity after myocardial infarction (MI) are still high. For a long time, the importance of right ventricle (RV) function has been neglected. Recently, RV dysfunction has also been associated with poor outcomes in the setting of heart failure. The shape, location, and contraction conditions make the RV chamber assessment technically challenging.Methods: Our study identified clinical characteristics and left ventricle (LV) echocardiographic data performed 3-5 days after MI that could be associated with RV dysfunction (RV fractional area change [FAC] < 35%) 6 months after MI.Results: The RV dysfunction group consisted of 11 patients (RV FAC 29.4% +/- 5.2) and the no RV dysfunction group of 71 patients (RV FAC 43.7% +/- 5.1); (P < 0.001). Both groups presented the same baseline clinical characteristics. Left atrium (LA), interventricular septum (IVS), and left ventricular posterior wall (LVPW) were larger in RV dysfunction than in no RV dysfunction. Conversely, E wave deceleration time (EDT) was lower in RV dysfunction when compared with no RV dysfunction. Left atrium(adj) (adjusted by gender, age, infarct size, and body mass index) (odds ratio [OR], 1.22; confidence interval [CI], 1.016-1.47; P = 0.032), interventricular septum(adj) (OR, 1.49; CI, 1.01-2.23; P = 0.044), and E wave deceleration time(adj) (OR, 0.98; CI, 0.97-0.98; P = 0.029) assessed soon after MI predicted RV failure after 6-months.Conclusions: LV diastolic dysfunction, resulting from anterior MI and assessed 3-5 days after the event, may play an important role in predicting RV dysfunction 6 months later.

Involvement of L-Type Calcium Channel and SERCA2a in Myocardial Dysfunction Induced by Obesity

Obesity has been shown to impair myocardial performance. Nevertheless, the mechanisms underlying the participation of calcium (Ca2+) handling on cardiac dysfunction in obesity models remain unknown. L-type Ca2+ channels and sarcoplasmic reticulum (SR) Ca2+-ATPase (SERCA2a), may contribute to the cardiac dysfunction induced by obesity. The purpose of this study was to investigate whether myocardial dysfunction in obese rats is related to decreased activity and/or expression of L-type Ca2+ channels and SERCA2a. Male 30-day-old Wistar rats were fed standard (C) and alternately four palatable high-fat diets (Ob) for 15 weeks. Obesity was determined by adiposity index and comorbidities were evaluated. Myocardial function was evaluated in isolated left ventricle papillary muscles under basal conditions and after inotropic and lusitropic maneuvers. L-type Ca2+ channels and SERCA2a activity were determined using specific blockers, while changes in the amount of channels were evaluated by Western blot analysis. Phospholamban (PLB) protein expression and the SERCA2a/PLB ratio were also determined. Compared with C rats, the Ob rats had increased body fat, adiposity index and several comorbidities. The Ob muscles developed similar baseline data, but myocardial responsiveness to post-rest contraction stimulus and increased extracellular Ca2+ was compromised. The diltiazem promoted higher inhibition on developed tension in obese rats. In addition, there were no changes in the L-type Ca2+ channel protein content and SERCA2a behavior (activity and expression). In conclusion, the myocardial dysfunction caused by obesity is related to L-type Ca2+ channel activity impairment without significant changes in SERCA2a expression and function as well as L-type Ca2+ protein levels. J. Cell. Physiol. 226: 2934-2942, 2011. (C) 2011 Wiley-Liss, Inc.

KIR genes and their human leukocyte antigen ligands in the progression to cirrhosis in patients with chronic hepatitis C

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Cervical Lactobacillus and leukocyte infiltration in preterm premature rupture of membranes

Objectives: To evaluate the possible association between microorganisms present in the cervical secretions and amniotic fluid of pregnant women with preterm premature rupture of membranes (PPROM), and histologic chorioamnionitis. Methods: Thirty-seven pregnant women with PPROM and 21 healthy pregnant women were studied. Secretions from the cervical canal and amniotic fluid were collected to isolate microorganisms present in the genital tract. Cervical smears were Gram stained and evaluated microscopically. At delivery, chorioamniotic membranes were collected for histopathologic analysis. Results: Microscopic examination of the cervical secretion smears obtained from the PPROM group showed a low rate of Lactobacillus species, large numbers of leukocytes, and a wide diversity of microorganisms compared with the control group. The PPROM group presented an 80% rate of chorioamnionitis. Staphylococcus aureus isolation in cervical secretion was associated with intense inflammatory infiltrate in the membranes and might play a role in the pathogenesis of PPROM. Conclusions: the low colonization of cervical flora by Lactobacillus species associated with an intense leukocyte infiltrate detected in Gram-stained cervical smears can be considered a rapid method of detecting chorioamnionitis in pregnant women with PPROM. (C) 2003 International Federation of Gynecology and Obstetrics. Published by Elsevier B.V. Ireland Ltd. All rights reserved.

Levels of DNA damage in blood leukocyte samples from non-diabetic and diabetic female rats and their fetuses exposed to air or cigarette smoke

dThe objective of the present study was to evaluate DNA damage level in blood leukocytes from diabetic and non-diabetic female Wistar rats exposed to air or to cigarette smoke, and to correlate the findings with levels of DNA damage detected in blood leukocyte samples from their fetuses. A total of 20 rats were distributed into four experimental groups: non-diabetic (control; G1) and diabetic exposed to filtered air (G2): non-diabetic (G3) and diabetic (G4) exposed to cigarette smoke. Rats placed into whole-body exposure chambers were exposed for 30 min to filtered air (control) or to tobacco smoke generated from 10 cigarettes, twice a day, for 2 months. Diabetes was induced by a pancreatic beta-cytotoxic agent, streptozotocin (40 mg/kg b.w.). At day 21 of pregnancy, each rat was anesthetized and humanely killed to obtain maternal and fetal blood samples for genotoxicity analysis using the alkaline comet assay. G2, G3 and G4 dams presented higher DNA damage values in tail moment and tail length as compared to G1 group. There was a significant positive correlation between DNA damage levels in blood leukocyte samples from G2 and G3 groups (tail moment); G3 and G4 groups (tail length) and G3 group (tail intensity) and their fetuses. Thus, this study showed the association of severe diabetes and tobacco cigarette smoke exposure did not exacerbate levels of maternal and fetal DNA damages related with only diabetes or cigarette smoke exposure. Based on the results obtained and taking into account other published data, maternal diabetes requires rigid clinical control and public health and education campaigns should be increased to encourage individuals, especially pregnant women, to stop smoking. (C) 2008 Elsevier B.V. All rights reserved.

Menstrual irregularity: a possible clinical marker of metabolic dysfunction in women with class III obesity

Purpose. To evaluate whether menstrual irregularity in morbidly obese women is indicative of metabolic dysfunction.Patients and Methods. Fifty-seven women with morbid obesity were evaluated. They were divided into two groups: one comprising women without menstrual dysfunctions or hirsutism (Group 1), and another obese women showing menstrual dysfunction with or without hirsutism (Group 2). The following were evaluated: age, colour, childbirth, marital status, profession, socio-economic level, education, age at menarche, body weight, height, body mass index, presence of hirsutism (Ferriman Gallwey Index), abdominal circumference, hip circumference, waist-to-hip ratio, menstrual cycle, blood pressure, presence of acanthosis nigricans, insulin resistance (IR), fasting glycaemia, total cholesterol, HDL-C, LDL-C, triglycerides, thyroid-stimulating hormone, free T4, luteinising hormone (LH), follicle-stimulating hormone, prolactin, total testosterone, dehydroepiandrosterone sulfate, insulin and the Homeostasis Model Assessment (HOMA test).Results. Clinical and epidemiological aspects did not present statistical differences. Clinical and laboratory parameters did not show statistically significant alterations; however, HOMA test values for Group 2 were significantly higher than those for Group 1.Conclusions. The presence of IR in class III obese women can cause menstrual dysfunctions such as amenorrhoea or oligomenorrhoea even in the absence of hyperandrogenism, suggesting that IR plays an important role in the ovarian mechanisms involved in the menstrual cycle control.