Effect of physiological overload on pregnancy in women with mitral regurgitation

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

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.

Curvas de percentis de valores normais de medidas ecocardiográficas em crianças eutróficas procedentes da região centro-sul do Estado de São Paulo

OBJETIVO: Avaliar os valores de medidas ecocardiográficas em crianças eutróficas sem cardiopatia, relacionando-os com a superfície corporal (SC, m²), e construir curvas de percentis que relacionem as variáveis ecocardiográficas estudadas com a SC. MÉTODOS: Foram analisadas medidas ecocardiográficas unidimensionais de crianças entre 1 e 144 meses de idade. Avaliaram-se: diâmetros diastólicos dos ventrículos direito (VDd, mm) e esquerdo (VEd, mm), sistólico do VE (VEs, mm), da via de saída do VD (VSVD, mm), da aorta (DAo, mm) e do átrio esquerdo (DAE, mm); fração de ejeção do VE (FEVE, %); porcentagem da variação do diâmetro ventricular esquerdo (deltaVE, %); espessura diastólica do septo interventricular (ESIV, mm) e da parede posterior do VE (EPPVE, mm); massa (MVE, g) e índice de massa muscular do VE (IMVE, g/m²). RESULTADOS: Ao final do estudo, 595 crianças (326 do sexo masculino) foram avaliadas. Os valores das medidas ecocardiográficas apresentaram boa correlação com a SC e possibilitaram a construção de curvas de percentis (3%, 25%, 50%, 75% e 97%). Diferenças estatisticamente significantes, entre os sexos, foram evidenciadas para as variáveis VEs, VEd, VSVD, DAo, MVE e IMVE, sendo os maiores valores observados em crianças do sexo masculino. CONCLUSÃO: As curvas de percentis dos valores obtidas podem ser utilizadas como referência para a avaliação de crianças com suspeita de cardiopatia ou para o acompanhamento daquelas já diagnosticadas como cardiopatas ou em tratamento com agentes potencialmente cardiotóxicos.

Hemodynamic effects of butorphanol in desflurane-anesthetized dogs

Objective To evaluate the effects of butorphanol on cardiopulmonary parameters in dogs anesthetized with desflurane and breathing spontaneously.Study design Prospective, randomized experimental trial.Animals Twenty dogs weighing 12 +/- 3 kg.Methods Animals were distributed into two groups: a control group (CG) and butorphanol group (BG). Propofol was used for induction and anesthesia was maintained with desflurane (10%). Forty minutes after induction, the dogs in the CG received sodium chloride 0.9% (0.05 mL kg(-1) IM), and dogs in the BG received butorphanol (0.4 mg kg(-1) IM). The first measurements of body temperature (BT), heart rate (HR), arterial pressures (AP), cardiac output (CO), cardiac index (CI), central venous pressure (CVP), stroke volume index (SVI), pulmonary arterial occlusion pressure (PAOP), mean pulmonary arterial pressure (mPAP), left ventricular stroke work (LVSW), systemic (SVR) and pulmonary (PVR) vascular resistances, respiratory rate (fR), and arterial oxygen (PaO(2)) and carbon dioxide (PaCO(2)) partial pressures were taken immediately before the administration of butorphanol or sodium chloride solution (T0) and then at 15-minute intervals (T15-T75).Results In the BG, HR, AP, mPAP and SVR decreased significantly from T15 to T75 compared to baseline. fR was lower at T30 than at T0 in the BG. AP and fR were significantly lower than in the CG from T15 to T75. PVR was lower in the BG than in the CG at T30, while PaCO(2) was higher compared with T0 from T30 to T75 in the BG and significantly higher than in the CG at T30 to T75.Conclusions and clinical relevance At the studied dose, butorphanol caused hypotension and decreased ventilation during desflurane anesthesia in dogs. The hypotension (from 86 +/- 10 to 64 +/- 10 mmHg) is clinically relevant, despite the maintenance of cardiac index.

Myocardial dysfunction induced by food restriction is related to morphological damage in normotensive middle-aged rats

Previous works from our laboratory have revealed that food restriction (FR) promotes discrete myocardial dysfunction in young rats. We examined the effects of FR on cardiac function, in vivo and in vitro, and ultrastructural changes in the heart of middle-aged rats. Twelve-month-old Wistar- Kyoto rats were fed a control (C) or restricted diet (daily intake reduced to 50% of the control group) for 90 days. Cardiac performance was studied by echocardiogram and in isolated left ventricular (LV) papillary muscle by isometric contraction in basal condition, after calcium chloride (5.2 mM) and beta- adrenergic stimulation with isoproterenol (10(-6) M). FR did not change left ventricular function, but increased time to peak tension, and decreased maximum rate of papillary muscle tension development. Inotropic maneuvers promoted similar effects in both groups. Ultrastructural alterations were seen in most FR rat muscle fibers and included, absence and/or disorganization of myofilaments and Z line, hyper-contracted myofibrils, polymorphic and swollen mitochondria with disorganized cristae, and a great quantity of collagen fibrils. In conclusion, cardiac muscle sensitivity to isoproterenol and elevation of extracellular calcium concentration is preserved in middle-aged FR rats. The intrinsic muscle performance depression might be related to morphological damage.

Exercise training increases myocardial inotropic response in food restricted rats

This study evaluated the effects of exercise training on myocardial function and ultrastructure of rats submitted to different levels of food restriction (FR). Male Wistar-Kyoto rats, 60 days old, were submitted to free access to food, light FR (20%), severe FR (50%) and/or to swimming training (one hour per day with 5% of load, five days per week for 90 days). Myocardial function was evaluated by left ventricular papillary muscle under basal condition (calcium 1.25 mM), and after extracellular calcium elevation to 5.2 mM and isoproterenol (I PM) addition. The ultrastructure of the myocardium was examined in the papillary muscle. The training effectiveness was verified by improvement of myocardial metabolic enzyme activities. Both 20% and 50% food restriction protocols presented minor body and ventricular weights gain. The 20%-FR, in sedentary or trained rats, did not alter myocardial function or ultrastructure. The 50%-FR, in sedentary rats, caused myocardial dysfunction under basal condition, decreased response to inotropic stimulation, and promoted myocardial ultrastructural damage. The 50%-FR, in exercised rats, increased myocardial dysfunction under basal condition but increased response to inotropic stimulation although there was myocardial ultrastructural damage. In conclusion, the exercise training in severe restriction caused marked myocardial dysfunction at basal condition but increased myocardial response to inotropic stimulation. (c) 2005 Elsevier B.V.. All rights reserved.

Myocardial dysfunction induced by food restriction is related to calcium cycling and beta-adrenergic system changes

Food restriction (FR) has been shown to promote myocardial dysfunction in rats. The aim of this study was to verify the participation of calcium and beta-adrenergic system on myocardial mechanical alteration in rats submitted to FR. Myocardial performance was studied in isolated left ventricular papillar muscle from young Wistar-Kyoto rats (WKY) submitted to FR or to control diet. The groups subjected to FR were fed 50% less food than the control group for 90 days. Mechanical function was studied in isometric contraction at post-rest contraction of 30 seconds (PRC), calcium chloride concentration 5.20 mM, and beta-adrenergic stimulation with isoproterenol 10(-6) M. FR decreased the body weight, and left and right ventricular weight. In basal condition (1.25 MM of calcium) time to peak tension (TPT) and time from peak tension to 50% relaxation (RT50) were greater in the FR group. Muscle function was. The same in both PRC groups. TPT decrease in both high calcium groups, more in FR rats; RT50 dropped only in FR animals. TPT decreased in both Isoproterenol groups, more intensely in the FR group. This result suggests that food restriction impairs myocardial performance and these changes may be attributed to alterations in the intracellular calcium cycling and beta-adrenergic system. (C) 2003 Elsevier B.V. All rights reserved.

Chronic heart failure-induced skeletal muscle atrophy, necrosis, and changes in myogenic regulatiory factors

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Food restriction impairs myocardial inotropic response to calcium and beta-adrenergic stimulation in spontaneously hypertensive rats

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Echocardiographic detection of congestive heart failure in postinfarction rats

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Cardiac remodeling in a rat model of diet-induced obesity

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Severe food restriction induces myocardial dysfunction related to SERCA2 activity

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Growth hormone attenuates skeletal muscle changes in experimental chronic heart failure

Objective: This study evaluated the effects of growth hormone (GH) on morphology and myogenic regulatory factors (MRF) gene expression in skeletal muscle of rats with ascending aortic stenosis (AAS) induced chronic heart failure.Design: Male 90-100 g Wistar rats were subjected to thoracotomy. AAS was created by placing a stainless-steel clip on the ascending aorta. Twenty five weeks after surgery, rats were treated with daily subcutaneous injections of recombinant human GH (2 mg/kg/day; AAS-GH group) or saline (AAS group) for 14 days. Sham-operated animals served as controls. Left ventricular (LV) function was assessed before and after treatment. IGF-1 serum levels were measured by ELISA. After anesthesia, soleus muscle was frozen in liquid nitrogen. Histological sections were stained with HE and picrosirius red to calculate muscle fiber cross-sectional area and collagen fractional area, respectively. MRF myogenin and MyoD expression was analyzed by reverse transcription PCR.Results: Body weight was similar between groups. AAS and AAS-GH groups presented dilated left atrium, left ventricular (LV) hypertrophy (LV mass index: Control 1.90 +/- 0.15; AAS 3.11 +/- 0.44; AAS-GH 2.94 +/- 0.47 g/kg; p < 0.05 AAS and AAS-GH vs. Control), and reduced LV posterior wall shortening velocity. Soleus muscle fiber area was significantly lower in AAS than in Control and AAS-GH groups; there was no difference between AAS-GH and Control groups. Collagen fractional area was significantly higher in MS than Control; AAS-GH did not differ from both Control and AAS groups. Serum IGF-1 levels decreased in AAS compared to Control. MyoD mRNA was significantly higher in AAS-GH than AAS; there was no difference between AAS-GH and Control groups. Myogenin mRNA levels were similar between groups.Conclusion: In rats with aortic stenosis-induced heart failure, growth hormone administration increases MyoD gene expression above non-treated animal levels, preserves muscular trophism and attenuates interstitial fibrosis. These results suggest that growth hormone may have a potential role as an adjuvant therapy for chronic heart failure. (C) 2009 Elsevier Ltd. All rights reserved.

Influence of different doses of retinoic acid on cardiac remodeling

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)