Leonardo Antonio Mamede Zornoff

Heart failure after myocardial infarction: clinical implications and treatment.

Heart failure is a frequent complication of myocardial infarction. Several factors, such as recurrent myocardial ischemia, infarct size, ventricular remodeling, stunned myocardium, mechanical complications, and hibernating myocardium influence the appearance of left ventricular systolic dysfunction after myocardial infarction. Importantly, its presence increases the risk of death by at least 3‐ to 4‐fold. The knowledge of the mechanisms and clinical features are essential for the diagnosis and treatment of left ventricular dysfunction and heart failure after myocardial infarction. Therefore, this review will focus on the clinical implications and treatment of heart failure after myocardial infarction.

Ventricular remodeling after myocardial infarction: concepts and clinical implications

Correspondencia: Leonardo Antonio Mamede Zornoff • Faculdade de Medicina de Botucatu / Departamento de Clinica Medica Distrito de Rubiao Jr, s/n, Botucatu, SP Brasil E-mail: lzornoff@cardiol.br, lzornoff@fmb.unesp.br Artigo enviado em 14/08/2007; revisado enviado em 14/01/2008; aceito em 26/02/2008. Apos infarto agudo do miocardio, o processo de remodelacao se caracteriza, clinicamente, por aumento da cavidade ventricular. Na fase aguda, a dilatacao ventricular e consequencia do processo de expansao do infarto, enquanto a dilatacao cavitaria tardia e consequencia do processo de hipertrofia excentrica.

Early rather than delayed administration of lisinopril protects the heart after myocardial infarction in rats

AbstractBackground:ACE inhibitors have shown beneficial results in several studies after myocardial infarction (MI). However, this studies have shown conflicting results about the ideal starting time of the ACE inhibitors administration after MI and the importance of infarct size. Objectives: This study was designed to assess the long-term effects of lisinopril on mortality, cardiac function, and ventricular fibrosis after MI, in rats. Methods: Lisinopril (20 mg/kg/day) was given on day 1 or 21 days after coronary occlusion in small or large infarctions. Results: The mortality rate was reduced by 39% in early treatment and 30% in delayed treatment in comparison to the untreated rats. Early treatment reduced cardiac dysfunction in small MIs; however, delayed treatment did not. No statistical difference was observed among the groups for large MIs. No statistical difference was observed among the groups with large or small MIs on myocardial hydroxyproline concentration. Conclusions: Both early and delayed treatments with lisinopril increased survival. Treatment exerts no marked effects on fibrosis; early treatment has exerted beneficial influences on cardiac function whereas delayed treatment had no consistent effects. The protective effect of lisinopril is detectable only in small (< 40% of LV) MIs.

Left ventricular adaptation to chronic pressure overload induced by inhibition of nitric oxide synthase in rats

Summary Recent studies have indicated that chronic inhibition of nitric oxide synthase induces arterial hypertension without myocardial hypertrophy. We investigated the mechanisms of left ventricular (LV) adaptation to this condition, Also, we analyzed the effect of the angiotensin-converting enzyme inhibitor (ACEI), lisinopril, in this experimental model of ventricular pressure overload. Fiftyeight Wistar rats received eight weeks of treatment with either Nw-nitro-L-arginine-methyl ester (L-NAME group, n=19), lisinopril (LISINOPRIL group, n=19) or the combination of both drugs (LNAMELIS group, n=20). All results were compared to age and sex matched untreated rats (CONTROL group, n=18). Tail-cuff blood pressure rose significantly in L-NAME treated rats (195±29 mm Hg) compared to the CONTROL (141±12 mm Hg), LISINOPRIL (97±13 mm Hg), and LNAMELIS (113±16 mm Hg) groups. There was no myocardial hypertrophy in the chronically hypertensive rats. The ventricular unstressed volume was significantly reduced in the L-NAME group (0.119±0.027 mL) compared to the CONTROL (0.158±0.026 mL) indicating a disproportional reduction in ventricular volume related to the myocardial mass. The chamber size modification resulted in a systolic stress which was comparable to the CONTROL even though the isovolumetric systolic pressure was higher. The systolic functional data indicated preserved myocardial contractility in L-NAME. LV compliance was increased in the LISINOPRIL group and myocardial passive stiffness was lower in all treated rats compared to CONTROL. We conclude that LV adaptation to chronic pressure overload without hypertrophy involves changes in chamber geometry and myocardial diastolic mechanical properties. Also, ACEI fully prevents L-NAME induced hypertension, reduces myocyte cross-sectional area, and myocardial passive stiffness. The combination of L-NAME plus lisinopril decreases the load independent index of myocardial contractility.

A exposição crônica à fumaça do cigarro resulta em remodelação cardíaca e prejuízo da função ventricular em ratos

OBJECTIVE: To determine the cardiac structural and functional alterations caused by cigarette smoke exposure in rats. METHODS: The animals were randomly distributed into the following 2 groups: 1) smokers (S), comprising 10 animals exposed to cigarette smoke at a rate of 40 cigarettes/day; and 2) control (C), comprising 10 animals not exposed to cigarette smoke. After 4 months, the animals underwent morphological and functional study with echocardiography. The variables studied were analyzed by use of the t test or the Mann-Whitney test. RESULTS: The smoking rats had a greater left atrium (S=4.2±0.7mm; C=3.5±0.6mm; P<0.05), and greater left ventricular diastolic (S=7.9±0.7mm; C=7.2±0.5mm; P<0.05) and systolic (S=4.1±0.5; C=3.4±0.5; P<0.05) diameters. The left ventricular mass index was greater in the smoking animals (S=1.5mg/kg±0.2; C=1.3mg/kg±0.2; P<0.05), and the ejection fraction (S=0.85±0.03; C=0.89±0.03; P<0.05) and the shortening fraction (S=47.8%±3.7; C=52.7%±4.6; P<0.05) were greater in the control group. No differences were observed in the diastolic transmitral flow variables (E wave, A wave, and E/A ratio). CONCLUSION: Chronic cigarette smoke exposure results in cardiac remodeling with a decrease in ventricular functional capacity.

Mini Nutritional Assessment predicts gait status and mortality 6 months after hip fracture.

The aim of the present study was to evaluate the Mini Nutritional Assessment (MNA), the Nutritional Risk Screening (NRS) 2002 and the American Society of Anesthesiologists Physical Status Score (ASA) as predictors of gait status and mortality 6 months after hip fracture. A total of eighty-eight consecutive patients over the age of 65 years with hip fracture admitted to an orthopaedic unit were prospectively evaluated. Within the first 72 h of admission, each patients characteristics were recorded, and the MNA, the NRS 2002 and the ASA were performed. Gait status and mortality were evaluated 6 months after hip fracture. Of the total patients, two were excluded because of pathological fractures. The remaining eighty-six patients (aged 80·2 (sd 7·3) years) were studied. Among these patients 76·7 % were female, 69·8 % walked with or without support and 12·8 % died 6 months after the fracture. In a multivariate analysis, only the MNA was associated with gait status 6 months after hip fracture (OR 0·773, 95 % CI 0·663, 0·901; P= 0·001). In the Cox regression model, only the MNA was associated with mortality 6 months after hip fracture (hazard ratio 0·869, 95 % CI 0·757, 0·998; P= 0·04). In conclusion, the MNA best predicts gait status and mortality 6 months after hip fracture. These results suggest that the MNA should be included in the clinical stratification of patients with hip fracture to identify and treat malnutrition in order to improve the outcomes.

Impact of the Length of Vitamin D Deficiency on Cardiac Remodeling

Background—This study was aimed to evaluate the influence of vitamin D (VD) deficiency on cardiac metabolism, morphology, and function. Thus, we investigated the relationship of these changes with the length of the nutrient restriction. Methods and Results—Male weanling Wistar rats were allocated into 4 groups: C2 (n=24), animals were fed an AIN-93G diet with 1000 IU VD/kg of chow and were kept under fluorescent light for 2 months; D2 (n=22), animals were fed a VD-deficient AIN-93G diet and were kept under incandescent light for 2 months; C4 (n=21) animals were kept in the same conditions of C2 for 4 months; and D4 (n=23) animals were kept in the same conditions of D2 for 4 months. Biochemical analyses showed lower &bgr;-hydroxyacyl coenzyme-A dehydrogenase activity and higher lactate dehydrogenase activity in VD-deficient animals. Furthermore, VD deficiency was related to increased cytokines release, oxidative stress, apoptosis, and fibrosis. Echocardiographic data showed left ventricular hypertrophy and lower fractional shortening and ejection fraction in VD-deficient animals. Difference became evident in the lactate dehydrogenase activity, left ventricular weight, right ventricle weight, and left ventricular mass after 4 months of VD deficiency. Conclusions—Our data indicate that VD deficiency is associated with energetic metabolic changes, cardiac inflammation, oxidative stress, fibrosis and apoptosis, cardiac hypertrophy, left chambers alterations, and systolic dysfunction. Furthermore, length of the restriction influenced these cardiac changes.

Behavior of cardiac variables in animals exposed to cigarette smoke

OBJECTIVE To assess the behavior of cardiac variables in animals exposed to cigarette smoke. METHODS Two groups of Wistar rats were studied as follows: control group (C), comprising 28 animals; and smoking group (S), comprising 23 animals exposed to cigarette smoke for 30 days. Left ventricular cardiac function was assessed in vivo with transthoracic echocardiography, and myocardial performance was analyzed in vitro in preparations of isolated left ventricular papillary muscle. The cardiac muscle was assessed in isometric contractions with an extracellular calcium concentration of 2.5 mmol/L. RESULTS No statistical difference was observed in the values of the body variables of the rats and in the mechanical data obtained from the papillary muscle between the control and smoking groups. The values of left ventricular systolic diameter were significantly greater in the smoking animals than in the control animals (C=3.39 +/- 0.4 mm and S=3.71 +/- 0.51 mm, P=0.02). A significant reduction was observed in systolic shortening fraction (C=56.7 +/- 4.2% and S=53.5 +/- 5.3%, P=0.02) and in ejection fraction (C=0.92 +/- 0.02 and S=0.89 +/- 0.04, P=0.01). CONCLUSION The rats exposed to cigarette smoke had a reduction in left ventricular systolic function, although their myocardial function was preserved.

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

To investigate the role of MMP‐2 and MMP‐9 in cardiac remodelling induced by tobacco smoke exposure in rats.

A exposição à fumaça de cigarro intensifica a remodelação ventricular após o infarto agudo do miocárdio

OBJECTIVE: To evaluate the role of cigarette smoke exposure (CSE) on ventricular remodeling following acute myocardial infarction (AMI). METHODS: Rats were submitted to myocardial infarction and divided into two groups: C (control, n = 31) and F (CSE: 40 cigarettes/day, n = 22). After 6 months, the survivors were submitted to echocardiogram, functional study with isolated heart, and morphometric analysis. For comparison purposes, we used the t test (mean ± standard deviation) or the Mann-Whitney test (with median and 25th and 75th percentiles). RESULTS: The CSE animals tended to have larger diastolic (C = 1.5 ± 0.4 mm2, F = 1.9 ± 0.4 mm2; p = 0.08) and systolic (C = 1.05 ± 0.3 mm2, F = 1.32 ± 0.4 mm2; p = 0.08) left ventricular(LV) areas. The systolic function of the LV, assessed according to the fractional area change, tended to be impaired in CSE animals (C = 31.9 ± 9.3%, F = 25.5 ± 7.6%; p = 0.08). The - dp/dt values for CSE animals were statistically lower (C = 1474 ± 397 mmHg, F = 916 ± 261 mmHg; p = 0.02) than for control animals. The CSE animals presented higher right ventricle (RV) weight adjusted for body weight (C = 0.8 ± 0.3 mg/g, F = 1.3 ± 0.4 mg/g; p = 0.01), higher content of water in lungs (C = 4.8 (4.3-4.8)%, F = 5.4 (5.1-5.5); p = 0.03), and larger LV myocyte cross-sectional areas (C = 239.8 ± 5.8 µm2, F = 253.9 ± 7.9 µm2; p = 0.01). CONCLUSION: Cigarette smoke exposure intensifies ventricular remodeling following acute myocardial infarction.