Food restriction-induced myocardial dysfunction demonstrated by the combination of in vivo and in vitro studies

The aim of this study was to test the hypothesis that protein-calorie undernutrition decreases myocardial contractility jeopardizing ventricular function, and that ventricular dysfunction can be detected noninvasively. Five-month-old male Wistar-Kyoto rats were fed with regular rat chow ad libitum for 90 days (Control group, n = 14). A second group of rats received 50% of the amount of diet consumed by de control group (Food restricted group, n = 14). Global LV systolic function was evaluated in vivo, noninvasively, by transthoracic echocardiogram. After echocardiographic study, myocardial contractility was assessed in vitro in the isovolumetrically beating isolated heart in eight animals from each group (Langendorff preparation). The in vivo LV fractional shortening showed that food restriction depressed LV systolic function (p < 0.05). Myocardial contractility was impaired as assessed by the maximal rate of rise of LV pressure (+dP/dt), and developed pressure at diastolic pressure of 25 mmHg (p < 0.05). Furthermore, food restriction induced eccentric ventricular remodeling, and reduced myocardial elasticity and LV compliance (p < 0.05). In conclusion, food restriction causes systolic dysfunction probably due to myocardial contractility impairment and reduction of myocardial elasticity. © 2002 Elsevier B.V. All rights reserved.

Hepatic bleeding induced by streptokinase and heparin in a patient with acute myocardial infarction

Although rare, major bleeding is the most important side effect of thrombolytic therapy in acute myocardial infarction (AMI) (Levine et al., 1995). Spontaneous hepatic bleeding in normal liver after thrombolytic administration has rarely been reported in literature. To our knowledge, there are only three cases of hepatic bleeding related to thrombolytic therapy in AMI. In these, the used drugs were anisolylated plasminogen streptokinase activator complex (APSAC) (Garcia-Jiménez et al., 1997; Fox et al., 1991) and rt-PA (Garcia-Jiménez et al., 1997). We report a case of hepatic bleeding after streptokinase followed by units over 60 minutes). The next day, the patient developed third-degree atrioventricular block and a temporary pacemaker was inserted. Twenty-seven hours after streptokinase infusion, the patient complained of refractory chest pain that was interpreted as post-myocardial infarction angina; clotting screen was normal and intravenous heparin was started (80 U/kg followed by 18 U/kg/hour). After four hours of heparin administration, the patient presented abdominal pain and distension, and his blood pressure and hematocrit level dropped. Abdominal ultrasonography revealed free fluid in the peritoneal cavity (about 3,000 mL). A laparotomy disclosed blood in the abdominal cavity with bleeding from the right lateral hepatic segment, which was removed. The remaining abdominal viscera were normal and there was no other evidence of hemorrhage. The partial liver resection presented subcapsular hemorrhage with small parenchymal hemorrhage. Histopathological examination also revealed focal areas of ischemic centrilobular necrosis. The patient died of multiple organ system failure 21 days after admission. Copyright © 2002 By PJD Publications Limited.

Improved systolic ventricular function with normal myocardial mechanics in compensated cardiac hypertrophy

There still controversy about the relation between changes in myocardial contractile function and global left ventricular (LV) performance during stable concentric hypertrophy. To clarify this, we analyzed LV function in vivo and myocardial mechanics in vitro in rats with pressure overload-induced cardiac hypertrophy. Male Wistar rats (70 g) underwent ascending aorta stenosis for 8 weeks (group AAS, n=9). LV performance was assessed by transthoracic echocardiography under light anesthesia. Myocardial function was studied in isolated papillary muscle preparation during isometric contraction. The data were compared with age- and sex-matched sham-operated rats (group C, n=9). LV weight-to-body weight ratio (C: 2.0 ± 0.5 mg/g; AAS: 3.3 ± 0.7 mg/g), LV relative wall thickness (C: 0.19 ± 0.02; AAS; 0.34 ± 0.10), and LV fractional shortening (C: 54 ± 5%; AAS: 70 ± 8%) were increased in the group AAS (p<0.05). Echocardiographic analysis also indicated a significant association (r=0.74; p<0.001) between percent fractional shortening and LV relative wall thickness. The performance of AAS isolated muscle revealed that active tension (C: 6.6 ± 1.7 g/mm 2; AAS: 6.5 ± 1.5 g/mm 2) and maximum rate of tension development (C: 69 ± 21 g/mm 2/s; AAS: 69 ± 18 g/mm 2) were not significantly different from group C (p>0.05). In conclusion: 1) Compensated pressure-overload myocardial hypertrophy is associated with preserved myocardial function and increased ventricular performance; 2) The improved LV function might be due to the ventricular remodeling characterized by an increased relative wall thickness. Copyright © 2002 By PJD Publications Limited.

Synergistic action of olive oil supplementation and dietary restriction on serum lipids and cardiac antioxidant defences

Caloric intake is higher than recommended in many populations. Therefore, enhancing olive oil intake alone may not be the most effective way to prevent cardiovascular diseases. The purpose of the present study was to analyse the association of olive oil and dietary restriction on lipid profile and myocardial antioxidant defences. Male Wistar rats (180-200 g, n = 6) were divided into 4 groups: control ad libitum diet (C), 50% restricted diet (DR), fed ad libitum and supplemented with olive oil (3 mL/(kg-day)) (OO), and 50% restricted diet and supplemented with olive oil (DROO). After 30 days of treatments, OO, DR, and DROO groups had increased total cholesterol and high-density lipoprotein cholesterol concentrations. DR and DROO animals showed decreased low-density lipoprotein cholesterol. DROO had the lowest low-density lipoprotein cholesterol concentration. Total lipids and triacylglycerols were raised by dietary restriction and diminished by olive oil. OO rats had higher myocardial Superoxide dismutase and lower catalase and glutathione peroxidase activities than C rats. DR and DROO showed enhanced cardiac Superoxide dismutase, catalase, and glutathione peroxidase activities from the control. Olive oil supplementation alone improved the lipid profile but was more effective when coupled with dietary restriction. There was a synergistic beneficial action of dietary restriction and olive oil on serum lipids and myocardial antioxidant defences.

β-carotene attenuates the paradoxical effect of tobacco smoke on the mortality of rats after experimental myocardial infarction

The objective of this study was to investigate the effects of exposure to tobacco smoke (ETS) in rats that were or were not supplemented with dietary β-carotene (BC), on ventricular remodeling and survival after myocardial infarction (Ml). Rats (n = 189) were allocated to 4 groups: the control group, n = 45; group BC administered 500 mg/kg diet, n = 49, BC supplemented rats; group ETS, n - 55, rats exposed to tobacco smoke; and group BC+ETS, n = 40. Wistar rats weighing 10O g were administered one of the treatments until they weighed 200 to 250 g (∼5 wk). The ETS rats were exposed to cigarette smoke for 30 min 4 times/d, in a chamber connected to a smoking device. After reaching a weight of 200-250 g, rats were subjected to experimental MI (coronary artery occlusion) and mortality rates were determined over the next 105 d. In addition, echocardiographic, isolated heart, morphometrical, and biochemical studies were performed. Mortality data were tested using Kaplan-Meyer curves and other data by 2-way ANOVA. Survival rates were greater in the ETS group (58.2%) than in the control (33.3%) (P = 0.001) and BC+ETS rats (30.0%) (P = 0.007). The groups did not differ in the other comparisons. Left ventricular end-diastolic diameter normalized to body weight was greater and maximal systolic pressures were lower in the ETS groups than in non-ETS groups. Previous exposure to tobacco smoke induced a process of cardiac remodeling after MI. There is a paradoxical protector effect with tobacco smoke exposure, characterized by lower mortality, which is offset by BC supplementation. © 2005 American Society for Nutritional Sciences.

Retinoic acid supplementation attenuates ventricular remodeling after myocardial infarction in rats

The objective of this study was to evaluate the role of retinoic acid in experimental postinfarction myocardial remodeling. Wistar rats were subjected to myocardial infarction (MI) and treated with retinoic acid (RA), 0.3 mg/(kg · d) (MI-RA, n = 29), or fed a control diet (MI, n = 34). After 6 mo, the surviving rats (MI-RA = 18 and MI = 22) underwent echocardiograms, and isolated hearts were tested for function in vitro. The cross-sectional area of the myocyte (CSA) and interstitial collagen fraction (IC) were measured in a cross section of the heart stained by hematoxylin-eosin and picrosirius red, respectively. The CSA was smaller in the MI-RA group [229 (220, 234) μm 2] [medians (lower quartile, upper quartile)] than in the MI group [238 (232, 241) μm 2] (P = 0.01) and IC was smaller in the MI-RA group [2.4 (1.7, 3.1)%] than in the MI group [3.5 (2.6, 3.9)%] (P = 0.05). The infarct size did not differ between the groups [MI = 44.6 (40.8, 48.4)%, MI-RA = 45 (38.6, 47.2)%]. Maximum rate of rise of left ventricular pressure (+dp/dt) was greater in the MI-RA group (2645 ± 886 mm Hg/s) than in the MI group (2081 ± 617 mm Hg/s) (P = 0.05). The other variables tested did not differ between groups. Retinoic acid supplementation of rats for 6 mo attenuates the ventricular remodeling process after MI. © 2005 American Society for Nutrition.

β-Carotene supplementation results in adverse ventricular remodeling after acute myocardial infarction

Objective: We studied the effects of β-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. © 2006 Elsevier Inc. All rights reserved.

Tele-education environment and didactic iconography in sexual transmitted diseases

The field of advertising has developed techniques of mass communication and rapid transmission of information. Among these techniques are slogans and iconographies. This work used such tools for educational purposes and was divided into three modules. Module 1 evaluated the use of simplified textual communication (slogans) about the subject Sexually Transmitted Diseases. It was applied to third-year medical students, which had not taken the course on this theme. To evaluate the impact of the textual communication form (slogans), long phrases were elaborated in scientific language containing 15 topics. From these long phrases, compact phrases were developed using techniques of the advertising area for elaboration of slogans. Three forms of didactic material about that theme were developed. The first form consisted of long phrases in descriptive topics, using scientific language. The second was constituted exclusively of compact phrases in the form of slogans, and the third was composed of the combination of the two previous forms. Then, 10 multiple-choice questions were elaborated and applied in two phases. In the first phase, application occurred immediately after the reading of didactic texts; in the second phase, it happened 60 days after the reading. For statistical analysis, Snedcor's F test was used for analysis of variance, at 5% significance level. There was an increase in memorization by students who read the material containing the association between long phrases and slogans, which indicates that the latter, when used as an auxiliary model of learning, can bring significant benefits for education. Module 2 consisted of analyzing the elaboration of educational videos produced in graphic computing (called iconographies) for development of dynamic communication means. The theme Hair Cycle was utilized. Viability of high quantities of information in few minutes of animation could be demonstrated together with the advantage of presenting the process in a dynamic form without wasting scientific details. Module 3 presented the inclusion of slogans in educational videos produced in graphic computing about the Hair Cycle, showing a new tool for rapid and efficient transference of data. Slogans and iconographies, when utilized in educational material, can bring significant benefits for the student's learning.

Chorismate synthase: An attractive target for drug development against orphan diseases

The increase in incidence of infectious diseases worldwide, particularly in developing countries, is worrying. Each year, 14 million people are killed by infectious diseases, mainly HIV/AIDS, respiratory infections, malaria and tuberculosis. Despite the great burden in the poor countries, drug discovery to treat tropical diseases has come to a standstill. There is no interest by the pharmaceutical industry in drug development against the major diseases of the poor countries, since the financial return cannot be guaranteed. This has created an urgent need for new therapeutics to neglected diseases. A possible approach has been the exploitation of the inhibition of unique targets, vital to the pathogen such as the shikimate pathway enzymes, which are present in bacteria, fungi and apicomplexan parasites but are absent in mammals. The chorismate synthase (CS) catalyses the seventh step in this pathway, the conversion of 5-enolpyruvylshikimate-3-phosphate to chorismate. The strict requirement for a reduced flavin mononucleotide and the anti 1,4 elimination are both unusual aspects which make CS reaction unique among flavin-dependent enzymes, representing an important target for the chemotherapeutic agents development. In this review we present the main biochemical features of CS from bacterial and fungal sources and their difference from the apicomplexan CS. The CS mechanisms proposed are discussed and compared with structural data. The CS structures of some organisms are compared and their distinct features analyzed. Some known CS inhibitors are presented and the main characteristics are discussed. The structural and kinetics data reviewed here can be useful for the design of inhibitors. © 2007 Bentham Science Publishers Ltd.

A clinical decision support system for cancer diseases

The second main cause of death in Brazil is cancer, and according to statistics disclosed by National Cancer Institute from Brazil (INCA) 466,730 new cases of cancer are forecast for 2008. The analysis of tumour tissues of various types and patients' clinical data, genetic profiles, characteristics of diseases and epidemiological data may lead to more precise diagnoses, providing more effective treatments. In this work we present a clinical decision support system for cancer diseases, which manages a relational database containing information relating to the tumour tissue and their location in freezers, patients and medical forms. Furthermore, it is also discussed some problems encountered, as database integration and the adoption of a standard to describe topography and morphology. It is also discussed the dynamic report generation functionality, that shows data in table and graph format, according to the user's configuration. © ACM 2008.

Profile of cardiovascular risk factors and mortality in patients with symptomatic peripheral arterial disease

Introduction: The present study examines cardiovascular risk factor profiles and 24-month mortality in patients with symptomatic peripheral arterial disease. Design Study: Prospective observational study including 75 consecutive patients with PAD (67 ± 9.7 years of age; 52 men and 23 women) hospitalized for planned peripheral vascular reconstruction. Doppler echocardiograms were performed before surgery in 54 cases. Univariate analyses were performed using Student's t-test or Fisher's exact test. Survival analysis at 24-month follow-up was performed using the Cox regression model and Kaplan-Meier method including age and chronic use of aspirin as covariates. Survival curves were compared using the log-rank test. Results: Hypertension and smoking were the most frequent risk factors (52 cases and 51 cases, respectively), followed by diabetes (32 cases). Undertreated dyslipidemia was found in 26 cases. Fasting glycine levels (131 ± 69.1 mg/dl) were elevated in 29 cases. Myocardial hypertrophy was found in 18 out of 54 patients. Thirty-four patients had been treated with aspirin. Overall mortality over 24 months was 24% and was associated with age (HR: 0.064; CI95: 0.014-0.115; p=0.013) and lack of use of aspirin, as no deaths occurred among those using this drug (p<0.001). No association was found between cardiovascular death (11 cases) and the other risk factors. Conclusion: There is a high prevalence of uncontrolled (treated or untreated) cardiovascular risk factors in patients undergoing planned peripheral vascular reconstruction, and chronic use of aspirin is associated with reduced all-cause mortality in these patients.

Sudden cardiac death athletes: a systematic review

Previous events evidence that sudden cardiac death (SCD) in athletes is still a reality and it keeps challenging cardiologists. Considering the importance of SCD in athletes and the requisite for an update of this matter, we endeavored to describe SCD in athletes. The Medline (via PubMed) and SciELO databases were searched using the subject keywords sudden death, athletes and mortality. The incidence of SCD is expected at one case for each 200,000 young athletes per year. Overall it is resulted of complex dealings of factors such as arrhythmogenic substrate, regulator and triggers factors. In great part of deaths caused by heart disease in athletes younger than 35 years old investigations evidence cardiac congenital abnormalities. Athletes above 35 years old possibly die due to impairments of coronary heart disease, frequently caused by atherosclerosis. Myocardial ischemia and myocardial infarction are responsible for the most cases of SCD above this age (80%). Pre-participatory athletes' evaluation helps to recognize situations that may put the athlete's life in risk including cardiovascular diseases. In summary, cardiologic examinations of athletes' pre-competition routine is an important way to minimize the risk of SCD. © 2010 Ferreira et al; licensee BioMed Central Ltd.

A comparative study of myocardial function and morphology during fasting/refeeding and food restriction in rats

Background: This study compared the influence of fasting/refeeding cycles and food restriction on rat myocardial performance and morphology. Methods: Sixty-day-old male Wistar rats were submitted to food ad libitum (C), 50% food restriction (R50), and fasting/refeeding cycles (RF) for 12 weeks. Myocardial function was evaluated under baseline conditions and after progressive increase in calcium and isoproterenol. Myocardium ultrastructure was examined in the papillary muscle. Results: Fasting/refeeding cycles maintained rat body weight and left ventricle weight between control and food-restricted rats. Under baseline conditions, the time to peak tension (TPT) was more prolonged in R50 than in RF and C rats. Furthermore, the maximum tension decline rate (-dT/dt) increased less in R50 than in RF with calcium elevation. While the R50 group showed focal changes in many muscle fibers, such as the disorganization or loss of myofilaments, polymorphic mitochondria with disrupted cristae, and irregular appearance or infolding of the plasma membrane, the RF rats displayed few alterations such as loss or disorganization of myofibrils. Conclusion: Food restriction promotes myocardial dysfunction, not observed in RF rats, and higher morphological damage than with fasting/refeeding. The increase in TPT may be attributed possibly to the disorganization and loss of myofibrils; however, the mechanisms responsible for the alteration in -dT/dt in R50 needs to be further clarified. © 2010 Elsevier Inc. All rights reserved.

Partial external mitral annuloplasty in dogs with myxomatous mitral valve degeneration and congestive heart failure: Outcome in 9 cases

Objective: To report the outcome of partial external mitral annuloplasty in dogs with congestive heart failure (CHF) due to mitral regurgitation caused by myxomatous mitral valve degeneration (MMVD). Animals, materials and methods: Nine client-owned dogs with CHF due to mitral regurgitation caused by MMVD. Surgery consisted of a double row of pledget-butressed continuous suture lines placed into the left ventricle parallel and just ventral to the atrioventricular groove between the subsinuosal branch of the left circumflex coronary artery and the paraconal branch of the left coronary artery. Results: Two dogs died during surgery because of severe hemorrhage. Two dogs died 12 and 36 h after surgery because of acute myocardial infarction. Three dogs were euthanized 2 and 4 weeks after surgery because of progression of CHF, 1 was euthanized 30 days after surgery for non-cardiac disease, and 1 survived for 48 months. In the 5 dogs that survived to discharge there was no significant change in the left atrium to aortic ratio with surgery (3.6 ± 0.56 before surgery; 3.1 ± 0.4 after surgery; p = 0.182), and no significant change in mitral regurgitant fraction in 4 dogs in which this measurement was made (78.7 ± 2.0% before surgery; 68.7 ± 7.5% after surgery; p = 0.09). Conclusions: Partial external mitral annuloplasty in dogs with CHF due to MMVD was associated with high perioperative mortality and most dogs that survived to discharge failed to show clinically relevant palliation from this procedure. Consequently, partial external mitral annuloplasty is not a viable option for dogs with mitral regurgitation due to MMVD that has progressed to the stage of CHF. © 2011 Elsevier B.V. All rights reserved.