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.

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.

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.

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.

[Myocardial remodeling in chronic pressure or volume overload in the rat heart]. / Remodelação miocárdica na sobrecarga crônica de pressão ou de volume no coração de ratos.

OBJECTIVE: To compare cardiac structural changes in experimental pressure and volume overload models. METHODS: The study analysis included renovascular hypertensive rats (RVH, n = 8), normotensive rats with volume overload caused by an aortocaval fistula (ACF, n = 10) and control rats (CONT, n = 8). After four weeks, tail cuff blood pressure (SBP) was recorded. Rats were killed, the hearts were excised and the right and left ventricles (RV&LV) were weighed (RVW&LVW). Using histological sections, myocyte cross sectional areas (MA). LV wall thickness (LVWT) LV cavity diameter (LVD), normalized LVWT (LVWT/LVD) and collagen volume fraction (CVF) were measured. The comparisons were made using the ANOVA and Tukey test for a significance level of 5%. RESULTS: Tail cuff blood pressure (mmHg) was higher in the RVH group (RVH = 187 +/- 22; CONT = 125 +/- 10; ACF = 122 +/- 6, p < 0.05). LV hypertrophy was observed in the RVH and ACF groups. The ACF group presented a significant increase in size of LVD, compared to CONT and RVH. The absolute and normalized ventricular wall thickness were similar among the groups. The RVH group presented a significant increase in CVF compared to CONT group and ACF group. CONCLUSION: Cardiac remodeling patterns following volume or pressure overload are distinct, suggesting that their implications on ventricular dysfunction are not interchangeable.

Diastolic function and functional capacity after a single session of continuous positive airway pressure in patients with compensated heart failure.

OBJECTIVE: The effects of acute continuous positive airway pressure therapy on left ventricular diastolic function and functional capacity in patients with compensated systolic heart failure remain unclear. METHODS: This randomized, double-blind, placebo-controlled clinical trial included 43 patients with heart failure and a left ventricular ejection fraction <0.50 who were in functional classes I-III according to the New York Heart Association criteria. Twenty-three patients were assigned to continuous positive airway pressure therapy (10 cmH2O), while 20 patients received placebo with null pressure for 30 minutes. All patients underwent a 6-minute walk test (6MWT) and Doppler echocardiography before and immediately after intervention. Clinicaltrials.gov: NCT01088854. RESULTS: The groups had similar clinical and echocardiographic baseline variables. Variation in the diastolic function index (e') after intervention was associated with differences in the distance walked in both groups. However, in the continuous positive airway pressure group, this difference was greater (continuous positive airway pressure group: Δ6MWT = 9.44+16.05×Δe', p = 0.002; sham group: Δ6MWT = 7.49+5.38×Δe'; p = 0.015). There was a statistically significant interaction between e' index variation and continuous positive airway pressure for the improvement of functional capacity (p = 0.020). CONCLUSIONS: Continuous positive airway pressure does not acurately change the echocardiographic indexes of left ventricle systolic or diastolic function in patients with compensated systolic heart failure. However, 30-minute continuous positive airway pressure therapy appears to have an effect on left ventricular diastolic function by increasing functional capacity.

Left ventricular sphericity index predicts systolic dysfunction in rats with experimental aortic regurgitation.

Although an increased left ventricular (LV) diastolic diameter (DD) and a decreased ejection fraction have been used as markers for the surgical replacement of an insufficient aortic valve, these signals may be observed when irreversible myocardium damage has already occurred. The aim of this study was to determine whether change in LV geometry predicts systolic dysfunction in experimental aortic regurgitation. Male Wistar rats underwent surgical acute aorta regurgitation (aorta regurgitation group; n = 23) or a sham operation (sham group; n = 12). After the procedure, serial transthoracic echocardiograms were performed at 1, 4, 8, and 16 wk. At the end of protocol, the LV, lungs, and liver were dissected and weighed. During the follow-up, no animal developed overt heart failure. There was a correlation between the LV sphericity index and reduced fractional shortening (P < 0.001) over time. A multiple regression model showed that the LVDD-sphericity index association at 8 wk was a better predictor of decreased fractional shortening at week 16 (R(2) = 0.50; P < 0.001) than was the LVDD alone (R(2) = 0.39; P = 0.001). LV geometry associated with increased LVDD improved the prediction of systolic dysfunction in experimental aortic regurgitation.

Heart failure with normal ejection fraction.

Heart failure with normal ejection fraction (HFNEF) is a complex syndrome that has been broadly studied since the last decade. It is caused by diastolic ventricular dysfunction demonstrated by complementary methods, such as hemodynamic study or echocardiogram, in the presence of a normal ejection fraction (EF). It affects primarily elderly individuals with comorbidities, such as systemic arterial hypertension, coronary failure and obesity. The physiopathological mechanisms are complex and multifactorial, involving the myocardial passive stiffness, the ventricular geometry, the pericardial restraint and the interaction between the ventricles. The main objectives of the treatment were to decrease the pulmonary venous congestion and the heart rate and control the comorbidities. There is no strong evidence that the use of specific medications, such as the angiotensin-converting enzyme inhibitors or beta-blockers can influence mortality. The poorer prognostic factors include advanced age, presence of kidney dysfunction, diabetes, functional class III and IV (NYHA) and advanced-stage diastolic dysfunction, with a restrictive pattern of ventricular filling. Another aspect that has been increasingly cited in the literature is the analysis of the role of the systolic function in HFNEF cases. All these aspects are analyzed in detail in the present review.

Quality of life in patients with severe and stable coronary atherosclerotic disease.

BACKGROUND: There are few data on the factors decreasing quality of life (QoL) in patients with coronary artery disease (CAD) before a percutaneous coronary intervention (PCI). OBJECTIVE: To associate clinical variables with QoL scores in patients with stable CAD before the PCI and with unfavorable outcomes, 12 months after the procedure. METHODS: The present is a longitudinal study of 78 patients (43 men and 35 women), before an elective PCI. The associations between the QoL scores (SF-36 questionnaire) and age, sex, weight, body mass index, diabetes mellitus (DM), arterial hypertension, dyslipidemia, current smoking, previous cardiovascular event or PCI, glycemia control and blood pressure (BP) were analyzed by multivariate logistic regression. We also analyzed the associations between the clinical features and the unfavorable outcomes (death due to any cause, heart failure or nonfatal infarction). The level of significance was set at p < 0.05. RESULTS: The medians of the QoL scores were < 70 percentage in all domains. Female sex, age < 60 years, previous cardiovascular event or PCI, BMI ≥ 25 kg/m², DM and high BP were associated with a higher degree of impairment of at least one QoL score. Female sex (OR: 7.19; 95%CI: 1.55 - 33.36; p = 0.012), previous cardiovascular event (OR: 3.97; 95%CI: 1.01 - 15.66; p = 0.049) and PCI failure (OR: 10.60; 95%CI: 1.83 - 61.46; p = 0.008) were associated with increased risk of combined outcome. CONCLUSION: In the presence of CAD, women and patients with comorbidities present a higher degree of QoL impairment. The unfavorable outcomes 12 months after the PCI are associated with the female sex, previous event or procedure failure.

Diastolic function and functional capacity after a single session of continuous positive airway pressure in patients with compensated heart failure

OBJECTIVE: The effects of acute continuous positive airway pressure therapy on left ventricular diastolic function and functional capacity in patients with compensated systolic heart failure remain unclear. METHODS: This randomized, double-blind, placebo-controlled clinical trial included 43 patients with heart failure and a left ventricular ejection fraction <0.50 who were in functional classes I-III according to the New York Heart Association criteria. Twenty-three patients were assigned to continuous positive airway pressure therapy (10 cmH2O), while 20 patients received placebo with null pressure for 30 minutes. All patients underwent a 6-minute walk test (6MWT) and Doppler echocardiography before and immediately after intervention. Clinicaltrials.gov: NCT01088854. RESULTS: The groups had similar clinical and echocardiographic baseline variables. Variation in the diastolic function index (e′) after intervention was associated with differences in the distance walked in both groups. However, in the continuous positive airway pressure group, this difference was greater (continuous positive airway pressure group: Δ6MWT = 9.44+16.05×Δe′, p = 0.002; sham group: Δ6MWT = 7.49+5.38×Δe′; p = 0.015). There was a statistically significant interaction between e′ index variation and continuous positive airway pressure for the improvement of functional capacity (p = 0.020). CONCLUSIONS: Continuous positive airway pressure does not acurately change the echocardiographic indexes of left ventricle systolic or diastolic function in patients with compensated systolic heart failure. However, 30-minute continuous positive airway pressure therapy appears to have an effect on left ventricular diastolic function by increasing functional capacity. .

Unmeasured anions as predictors of mortality in medical intensive care unit / Ânions não mensuráveis podem predizer mortalidade em unidade de terapia intensiva clínica

BACKGROUND AND OBJECTIVE: The present study aimed to evaluate the utility of variables that represent unmeasured anions (anion gap, anion gap corrected for albumin, anion gap corrected for albumin and lactate, base excess and modified base excess) to predict mortality in medical intensive care unit patients. METHODS: This prospective study included 156 con secutive patients admitted to a medical intensive care unit in a Medical school hospital between August 2006 and June 2007. Serum levels of potassium, sodium, chloride, C-reactive protein, albumin, and lactate were measured. Variables that re- present unmeasured anions and APACHE II score were calcula- ted. RESULTS: Among the studied patients, 60.9% were male, and mean age was 59.2±17.2 years. Mortality rate was 31.4%. Spearman?s test showed correlation among unmeasured anions and lactate. Comparison between survivors and non-survivors showed differences in length of intensive care unit stay, APACHE II score, albumin, C-reactive protein, lactate, anion gap corrected for albumin, base excess, and modified base excess. Anion gap corrected for albumin, base excess, and modified base excess are predictors of medical intensive care unit mortality; however, theirs areas under the ROC curves are smaller than APACHE II score and C-reactive protein. CONCLUSION: Variables that estimate unmeasured anions, such as anion gap corrected for albumin, base excess, and modified base excess, can be used to predict mortality in medical intensive care unit patients.(AU)

JUSTIFICATIVA E OBJETIVO: O presente estudo teve como objetivo avaliar a utilidade de variáveis que representam ânions não mensuráveis (ânion gap, ânion gap corrigido para a al- bumina, ânion gap corrigido para a albumina e lactato, excesso de base e excesso de base modificado) para prever a mortalidade em pacientes de unidade de terapia intensiva. MÉTODOS: Foram incluídos 156 pacientes consecutivos admitidos na unidade de terapia intensiva em um hospital escola de Medicina entre agosto de 2006 e junho de 2007. Os níveis séricos de potássio, sódio, cloreto, proteina C-reativa, albumina e lactato fo ram medidos. Foram calculadas variáveis que representaram os ânions não mensuráveis e APACHE II. RESULTADOS: Entre os pacientes estudados, 60,9% eram do sexo masculino, e a idade média foi de 59,2±17,2 anos. A taxa de mortalidade foi de 31,4%. O teste de Spearman mostrou correlação entre ânions não mensuráveis e lactato. A comparação entre sobreviventes e não sobreviventes mostrou diferenças no tempo de permanência na unidade de terapia intensiva, APACHE II, albumina, proteína C-reativa, lactato, ânion gap corrigido para a albumina, excesso de base e excesso de base modificado. Ânion gap corrigido para a albumina, excesso de base e excesso de base modificado foram preditores de mortalidade na unidade de terapia intensiva médica, mas as áreas sob as curvas ROC foram menores do que o escore APACHE II e a proteína C-reativa. CONCLUSÃO: Variáveis que estimam ânions não mensuráveis, como o ânion gap corrigido para a albumina, o excesso de base e o excesso de base modificado, podem ser usados para prever a mortalidade em pacientes em unidade de terapia intensiva clínica.(AU)

Insuficiência cardíaca com fração de ejeção normal / Heart failure with normal ejection fraction

A insuficiência cardíaca com fração de ejeção normal (ICFEN) é uma síndrome complexa que vem sendo largamente estudada, desde a última década. É causada por disfunção ventricular diastólica evidenciada por métodos complementares, como estudo hemodinâmico ou ecocardiograma, na presença de fração de ejeção preservada. Acomete preferencialmente indivíduos mais idosos e com comorbidades, como hipertensão arterial sistêmica, insuficiência coronariana e obesidade. Os mecanismos fisiopatológicos são complexos e multifatoriais, envolvendo a rigidez passiva do miocárdio, a geometria ventricular, a força de contenção do pericárdio e a interação entre os ventrículos. Os objetivos principais do tratamento são reduzir a congestão venosa pulmonar, a frequência cardíaca e controlar as comorbidades. Ainda não há evidências fortes de que o uso de medicações específicas, como inibidores de enzima de conversão ou betabloqueadores, interfiram na mortalidade. Os fatores de pior prognóstico incluem a idade avançada, presença de disfunção renal, diabete, classe funcional III e IV (NYHA) e estágio avançado de disfunção diastólica, com padrão restritivo ao enchimento ventricular. Outro aspecto que vem ganhando espaço na literatura é o questionamento do papel da disfunção sistólica nos quadros de ICFEN. Todos esses aspectos são abordados detalhadamente na presente revisão.

Heart failure with normal ejection fraction (HFNEF) is a complex syndrome that has been broadly studied since the last decade. It is caused by diastolic ventricular dysfunction demonstrated by complementary methods, such as hemodynamic study or echocardiogram, in the presence of a normal ejection fraction (EF). It affects primarily elderly individuals with comorbidities, such as systemic arterial hypertension, coronary failure and obesity. The physiopathological mechanisms are complex and multifactorial, involving the myocardial passive stiffness, the ventricular geometry, the pericardial restraint and the interaction between the ventricles. The main objectives of the treatment were to decrease the pulmonary venous congestion and the heart rate and control the comorbidities. There is no strong evidence that the use of specific medications, such as the angiotensin-converting enzyme inhibitors or beta-blockers can influence mortality. The poorer prognostic factors include advanced age, presence of kidney dysfunction, diabetes, functional class III and IV (NYHA) and advanced-stage diastolic dysfunction, with a restrictive pattern of ventricular filling. Another aspect that has been increasingly cited in the literature is the analysis of the role of the systolic function in HFNEF cases. All these aspects are analyzed in detail in the present review.

Qualidade de vida em pacientes com doença ateroclerótica coronariana grave e estável / Quality of life in patients with severe and stable coronary atherosclerotic disease / Calidad de vida en pacientes con enfermedad aterosclerótica coronaria severa y estable

FUNDAMENTO: Existem poucas informações sobre fatores agravantes da qualidade de vida em pacientes com doença arterial coronariana (DAC), antes da intervenção coronária percutânea (ICP). OBJETIVO: Associar variáveis clínicas com escores de qualidade de vida (EQV) em pacientes com DAC estável, antes da ICP e com desfechos desfavoráveis, 12 meses após o procedimento. MÉTODOS: Trata-se de estudo longitudinal incluindo 78 pacientes (43 homens e 35 mulheres), antes da ICP eletiva. As associações entre EQV (questionário SF-36) e idade, sexo, peso, índice de massa corpórea, diabete melito (DM), hipertensão arterial, dislipidemia, tabagismo atual, evento cardiovascular ou ICP prévios, controle da glicemia e da pressão arterial foram analisadas por meio de regressão logística multivariada. Também se analisaram as associações entre esses atributos clínicos e os desfechos desfavoráveis (morte por qualquer causa, insuficiência cardíaca ou infarto não fatal). O nível de significância foi p < 0,05. RESULTADOS: As medianas dos EQV estiveram abaixo de 70 percentuais em todos os domínios. Sexo feminino, idade < 60 anos, evento cardiovascular ou ICP prévios, IMC > 25 kg/m², DM e pressão arterial elevada foram associados a maior prejuízo de, pelo menos, um dos EQV. Sexo feminino (OR: 7,19; IC95 por cento: 1,55 - 33,36; p = 0,012), evento cardiovascular prévio (OR: 3,97; IC95 por cento: 1,01 - 15,66; p = 0,049) e insucesso na ICP (OR: 10,60; IC95 por cento: 1,83 - 61,46; p = 0,008) foram associados com risco aumentado de desfecho combinado. CONCLUSÃO: Na presença de DAC, mulheres e pacientes com comorbidades têm maior prejuízo da qualidade de vida. Os desfechos desfavoráveis após 12 meses da ICP estão associados com o sexo feminino, evento prévio ou insucesso do procedimento.

BACKGROUND: There are few data on the factors decreasing quality of life (QoL) in patients with coronary artery disease (CAD) before a percutaneous coronary intervention (PCI). OBJECTIVE: To associate clinical variables with QoL scores in patients with stable CAD before the PCI and with unfavorable outcomes, 12 months after the procedure. METHODS: The present is a longitudinal study of 78 patients (43 men and 35 women), before an elective PCI. The associations between the QoL scores (SF-36 questionnaire) and age, sex, weight, body mass index, diabetes mellitus (DM), arterial hypertension, dyslipidemia, current smoking, previous cardiovascular event or PCI, glycemia control and blood pressure (BP) were analyzed by multivariate logistic regression. We also analyzed the associations between the clinical features and the unfavorable outcomes (death due to any cause, heart failure or nonfatal infarction). The level of significance was set at p < 0.05. RESULTS: The medians of the QoL scores were < 70 percentage in all domains. Female sex, age < 60 years, previous cardiovascular event or PCI, BMI > 25 kg/m², DM and high BP were associated with a higher degree of impairment of at least one QoL score. Female sex (OR: 7.19; 95 percentCI: 1.55 - 33.36; p = 0.012), previous cardiovascular event (OR: 3.97; 95 percentCI: 1.01 - 15.66; p = 0.049) and PCI failure (OR: 10.60; 95 percentCI: 1.83 - 61.46; p = 0.008) were associated with increased risk of combined outcome. CONCLUSION: In the presence of CAD, women and patients with comorbidities present a higher degree of QoL impairment. The unfavorable outcomes 12 months after the PCI are associated with the female sex, previous event or procedure failure.

FUNDAMENTO: Hay pocas informaciones sobre factores agravantes de la calidad de vida en pacientes con enfermedad arterial coronaria (EAC), antes de la intervención coronaria percutánea (ICP). OBJETIVOS: Asociar variables clínicas con scores de calidad de vida (ECV) en pacientes con CAC estable, antes de la ICP y con desenlaces desfavorables, 12 meses tras el procedimiento. MÉTODOS: Se trata de estudio longitudinal incluyendo a 78 pacientes (43 varones y 35 mujeres), antes de la ICP electiva. Las asociaciones entre ECV (cuestionario SF-36) y edad, sexo, peso, índice de masa corpórea, diabetes melito (DM), hipertensión arterial, dislipidemia, tabaquismo actual, evento cardiovascular o ICP previos, control de glucemia y de la presión arterial se analizaron por medio de regresión logística multivariada. También se analizaron las asociaciones entre estos atributos clínicos y los desenlaces desfavorables (muerte por cualquier causa, insuficiencia cardiaca o infarto no fatal). El nivel de significancia fue p < 0,05. RESULTADOS: Las medianas de los ECV estuvieran abajo de 70 en todos los dominios. Sexo femenino, edad < 60 años, evento cardiovascular o ICP previos, IMC > 25 kg/m², DM y presión arterial elevada se asociaron a mayor perjuicio de, al menos uno de los ECV. Sexo femenino (OR: 7,19; IC95 por ciento: 1,55 - 33,36; p = 0,012), evento cardiovascular previo (OR: 3,97; IC95 por ciento: 1,01 - 15,66; p = 0,049) y sin éxito en la ICP (OR: 10,60; IC95 por ciento: 1,83 - 61,46; p = 0,008) se asociaron con riesgo aumentado de desenlace combinado. CONCLUSIÓN: En la presencia de EAC, mujeres y pacientes con comorbidades tiene mayor perjuicio de la calidad de vida. Los desenlaces desfavorables tras 12 meses de la ICP están asociados con el sexo femenino, evento previo o sin éxito del procedimiento.

AT1-receptor mediated vascular damage in myocardium, kidneys and liver in rats / Lesão vascular mediada pelo receptor AT1 esses efeitos em miocárdio, rins e fígado de ratos

The systemic aspect of vascular damage induced by angiotensin II (ANG II) has been poorly explored in the literature. Considering the presence of ANG II and its specific receptor AT1, in several organs, all tissues might be potentially affected by its effects. The aims of this study were: To evaluate the early histological changes in the heart, liver and kidneys, produced by ANG II infusion, to evaluate the protective effect of losartan. Wistar rats were distributed into three groups: control (no treatment), treated with ANG II, and treated with ANG II + losartan. ANG II was continuously infused over 72 hours by subcutaneous osmotic pumps. Histological sections of the myocardium, kidneys and liver were stained and observed for the presence of necrosis. There were ANG II-induced perivascular inflammation and necrosis of the arteriolar wall in the myocardium, kidney, and liver by, which were partially prevented by losartan. There was no significant correlation between heart and kidney damage. Tissue lesion severity was lower than that of vascular lesions, without statistical difference between groups. ANG II causes vascular injury in the heart, kidneys and liver, indicating a systemic vasculotoxic effect; the mechanisms of damage/protection vary depending on the target organ; perivascular lesions may occur even when anti-hypertensive doses of losartan are used.

O aspecto sistêmico da lesão vascular induzida pela angiotensina II (ANG II) tem sido pouco explorada na literatura. Considerando a presença de ANG II e de seu receptor AT1 em diversos órgãos, todos os tecidos poderiam ser potencialmente afetados por esses efeitos. Os objetivos deste estudo foram: avaliar as alterações histológicas iniciais no coração, fígado e rins, produzidas pela infusão de ANG II, e avaliar o efeito protetor do losartan. Ratos Wistar foram divididos em três grupos: controle (sem tratamento), tratados com ANG II, e tratados com ANG II + losartan. A ANG II foi infundida continuamente por 72 horas por meio de mini-bombas osmóticas. Foram realizados cortes histológicos de miocárdio, rim e fígado para coloração e observação para a presença de necrose. Observou-se a presença de inflamação perivascular e necrose de parede arteriolar em miocárdio, rins e fígado, que foram parcialmente prevenidas pelo losartan. Não houve correlação significante entre as lesões observadas no coração e nos rins. A severidade da lesão tissular foi menor quando comparada às lesões vasculares, sem diferença estatística entre os grupos. A ANG II causa injúria vascular no coração, rins e fígado, sugerindo um efeito vasculotóxico sistêmico; os mecanismos de lesão/proteção variam dependendo do órgão afetado; as lesões perivasculares podem ocorrer mesmo quando doses antihipertensivas de losartan forem utilizadas.

AT1-receptor mediated vascular damage in myocardium, kidneys and liver in rats / Lesão vascular mediada pelo receptor AT1 esses efeitos em miocárdio, rins e fígado de ratos

The systemic aspect of vascular damage induced by angiotensin II (ANG II) has been poorly explored in the literature. Considering the presence of ANG II and its specific receptor AT1, in several organs, all tissues might be potentially affected by its effects. The aims of this study were: To evaluate the early histological changes in the heart, liver and kidneys, produced by ANG II infusion, to evaluate the protective effect of losartan. Wistar rats were distributed into three groups: control (no treatment), treated with ANG II, and treated with ANG II + losartan. ANG II was continuously infused over 72 hours by subcutaneous osmotic pumps. Histological sections of the myocardium, kidneys and liver were stained and observed for the presence of necrosis. There were ANG II-induced perivascular inflammation and necrosis of the arteriolar wall in the myocardium, kidney, and liver by, which were partially prevented by losartan. There was no significant correlation between heart and kidney damage. Tissue lesion severity was lower than that of vascular lesions, without statistical difference between groups. ANG II causes vascular injury in the heart, kidneys and liver, indicating a systemic vasculotoxic effect; the mechanisms of damage/protection vary depending on the target organ; perivascular lesions may occur even when anti-hypertensive doses of losartan are used.

O aspecto sistêmico da lesão vascular induzida pela angiotensina II (ANG II) tem sido pouco explorada na literatura. Considerando a presença de ANG II e de seu receptor AT1 em diversos órgãos, todos os tecidos poderiam ser potencialmente afetados por esses efeitos. Os objetivos deste estudo foram: avaliar as alterações histológicas iniciais no coração, fígado e rins, produzidas pela infusão de ANG II, e avaliar o efeito protetor do losartan. Ratos Wistar foram divididos em três grupos: controle (sem tratamento), tratados com ANG II, e tratados com ANG II + losartan. A ANG II foi infundida continuamente por 72 horas por meio de mini-bombas osmóticas. Foram realizados cortes histológicos de miocárdio, rim e fígado para coloração e observação para a presença de necrose. Observou-se a presença de inflamação perivascular e necrose de parede arteriolar em miocárdio, rins e fígado, que foram parcialmente prevenidas pelo losartan. Não houve correlação significante entre as lesões observadas no coração e nos rins. A severidade da lesão tissular foi menor quando comparada às lesões vasculares, sem diferença estatística entre os grupos. A ANG II causa injúria vascular no coração, rins e fígado, sugerindo um efeito vasculotóxico sistêmico; os mecanismos de lesão/proteção variam dependendo do órgão afetado; as lesões perivasculares podem ocorrer mesmo quando doses antihipertensivas de losartan forem utilizadas.

Volume overload influence on hypertrophied myocardium function.

The aim of this study was to demonstrate that hypertrophied cardiac muscle is more sensitive to volume-overload than normal cardiac muscle. We assessed the mechanical function of isolated left ventricular papillary muscle from male spontaneously hypertensive rats (SHR) and age-matched normotensive Wistar-Kyoto rats (WKY) submitted to volume overload caused by aortocaval fistula (ACF) for 30 days. Muscles were perfused with Krebs-Henseleit solution at 28 degrees C and studied isometrically at a stimulation rate of 0.2 Hz. The ACF increased the right and left ventricular weight-to-body weight ratio in WKY rats; it also promoted right ventricular hypertrophy and further increased the basal hypertrophy in the left ventricle from SHR. The arterial systolic pressure was greater in SHR than in WKY rats, and decreased with ACF in both groups. Developed tension (DT) and maximum rate of DT (+dT/dt) were greater in the SHR-control than in the WKY-control (P < 0.05); the time from peak tension to 50% relaxation (RT 1/2) was similar in these animals. ACF did not change any parameters in the SHR group and increased the resting tension in the WKY group. However, the significant difference observed between myocardial contraction performance in WKY-controls and SHR-controls disappeared when the SHR-ACF and WKY-controls were compared. Furthermore, RT 1/2 increased significantly in the SHR-ACF in relation to the WKY-controls. In conclusion, the data lead us to infer that volume-overload for 30 days promotes more mechanical functional changes in hypertrophied muscle than in normal cardiac muscle.