Participação do Estado Contrátil e do Relaxamento Miocárdico na Disfunção Ventricular durante a Transição Hipertrofia-Falência Cardíaca

Purpose - To investigate the participation of contractile state and relaxation in cardiac muscle dysfunction during the transition from stable hypertrophy to cardiac decompensation in aging spontaneously hypertensive rats (SHR). Methods - isolated left ventricular papillary muscle function was studied in SHR with heart failure (SHR-F), in age-matched SHR without evidence of heart failure (SHR-NF), and in nonhypertensive controls Wistar-Kyoto rats (WKY). Muscles were analised in isometric and isotonic contractions in Krebs-Henseleit solution with calcium concentration of 1.25mM at 28°C. Results - Papillary muscles from SHR-F and SHR-NF demonstrated decreased active tension development and shortening velocity relative to normotensive WKY (p<0.05). SHR-F and SHR-NF did not differ. Compared with SHR-NF and WKY, muscle passive stiffness was increased in the failing SHR (p<0.05 versus WKY and SHR-NF). This parameter did not differ between SHR-NF and WKY (p> 0.05). Conclusion - These data suggest that the progression from stable hypertrophy to heart failure is associated with changes in the passive stiffness and is not related to depression of myocardial contractile function.

Metabolic Disturbances in Male Broilers of Different Strains. 1. Performance, Mortality, and Right Ventricular Hypertrophy

Two trials were carried out to test the susceptibility for metabolic disturbances of different strains of male broilers. In Trial 1, 1,890 male chickens were allotted in a randomized block design with seven treatments (Arbor Acres, Avian Farms, Cobb-500, Hubbard-Peterson, ISA, Naked Neck, and Ross) and six blocks of 45 chickens. Trial 2 involved 2,184 male chickens of six strains (Arbor Acres, Avian Farms, Cobb 500, Hubbard-Peterson, ISA Naked Neck, and Ross) allotted in seven complete blocks of 52 birds. The same management system was adopted for all birds, reared up to 42 d in an open house during late winter (Trial 1) or late autumn (Trial 2). The most marked differences observed among the strains tested was the lower BW and higher feed conversion of Naked Neck broilers. Total percentage mortalities were high among the most productive broilers, being more than 50% due to sudden death (SDS) and ascites syndrome (AS). No Naked Neck birds died as a consequence of these disturbances and the total mortalities were significantly lower (P ≤ 0.05) than the other strains. The ratio of right ventricle weight to total ventricle weight of the dead birds was over 0.25, except for Naked Neck birds, which presented a nonhypertrophic ratio. The two trials confirmed the relationship between high productivity and high incidence of SDS and AS and indicated that Naked Neck male broilers are resistant to these metabolic disturbances.

Reduction of diameter of the left ventricle of dogs by plication of the left ventricular free wall

Objective - To determine effects of reducing the diameter of the left ventricle of dogs by plication of the left ventricular free wall. Animals - 8 healthy adult mixed-breed dogs. Procedure - Left lateral thoracotomy and a T-shaped pericardiotomy were performed. The free wall of the left ventricle was imbricated with 3 interrupted transfixing sutures applied in a horizontal mattress pattern, using 3-0 polypropylene suture assembled on a straight cutting needle. Surgeons were careful to avoid the coronary vessels. Echocardiography was performed 24 hours before and 48 hours after surgery. Electrocardiography was performed before and 1, 2, 7, 15, 21, 30, and 60 days after surgery. Results - Echocardiographic measurements revealed that the diameter of the left ventricle was reduced by a mean of 23.5%. Electrocardiography revealed ventricular premature complexes 24 hours after surgery that regressed without treatment during the first week after surgery. Conclusions and Clinical Relevance - Plication of the left ventricular free wall of dogs can reduce end-diastolic and end-systolic dimensions of the left ventricle. The technique is simple and does not require cardiopulmonary bypass. According to Laplace's law, the reduction of cardiac diameter leads to reduction on free-wall tension and may improve left ventricular function in dilatated hearts. Thus, additional studies involving dogs with dilated cardiomyopathy should be conducted.

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.

A administração precoce de hormônio de crescimento resulta em efeitos deletérios na remodelação ventricular após o infarto agudo do miocárdio

Objective: To assess the effect of growth hormone (GH) on myocardial remodeling in infarcted rats. Methods: This study comprised 24 Wistar rats divided into 3 groups as follows: 1) AMI-GH group - comprising 8 rats that underwent infarction and were treated with GH; 2) AMI group - comprising 8 rats that underwent infarction and received only the diluent of the GH solution; and 3) control group (C group) - comprising 8 rats that underwent simulated infarction. After 30 days, the animals underwent functional study through echocardiography, and the changes in myocardial contractility of the isolated left ventricular (LV) papillary muscle were studied. Results: The echocardiography identified an increase in the diastolic (C=7.32±0.49; AMI=8.50±0.73; AMI-GH=9.34±0.73; P<0.05) and systolic (C=3.38±0.47, AMI=5.16±1.24; AMI-GH=5.96±1.54; P<0.05) diameters (mm) in the LV of the infarcted animals. The AMI-GH group animals had a lower ejection fraction (%) (C=0.9±0.03; AMI=0.76±0.12; AMI-GH=0.72± 0.14; P<0.05 for C vs AMI-GH) compared with those in controls. The study of the isolated left ventricular papillary muscle showed that the AMI-GH group had changes (C=1.50±0.59; AMI= 1.28±0.38; AMI-GH=1.98±0.41; P<0.05 for C vs AMI-GH) only in the tension at rest (TR - g/mm2) and in the time delta for a 50% decrease in the tension developed (TR50, ms) after stimulation with calcium (C=23.75±9.16; AMI=-16.56±14.82; AMI-GH=-4.69±8.39; P<0.05 for C vs AMI-GH) and in the delta of tension developed (TD, g/mm2) after stimulation with isoproterenol (C=0.99±0.17; AMI=0.54±0.62; AMI-GH=0.08±0.75; P<0.05 for C vs AMI-GH) compared with those in control animals. Conclusion: The early administration of GH in the experimental infarction model in rats may result in adverse effects on the process of ventricular remodeling.

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.

Ventricular Systolic Reserve in Asymptomatic Children Previously Treated With Low Doses of Anthracyclines

Doppler echocardiography has been used for the diagnosis of anthracycline-induced cardiotoxicity. However, few data are available that include asymptomatic children previously treated with a low cumulative dose of this drug and therefore have a low risk of cardiac dysfunction. The aim of this study was to evaluate after-exercise cardiac function in asymptomatic children previously treated with a low cumulative dose of anthracycline and no clinical or laboratory evidence of cardiotoxicity. Doppler echocardiography was performed before and immediately after physical exercise in 29 children aged 5 to 17 years (anthracycline [ADRIA] group). All had finished cancer treatment with anthracycline derivatives for ≥1 year (cumulative dose 100 mg/m2). Results were compared with those from age- and gender-matched healthy children (control group; n = 26) using the Mann-Whitney rank test. Exercise-induced cardiac function changes within groups were analyzed using Wilcoxon's signed-rank test. Exercise induced significant increases in left ventricular systolic function indexes in both groups. However, the ADRIA group had significantly lower changes in left ventricular ejection fraction (ADRIA group 0.71 ± 0.02 vs 0.80 ± 0.04 and control group 0.71 ± 0.02 vs 0.89 ± 0.05, p = 0.0017) and end-systolic stress-volume index (ADRIA group 4.59 ± 0.69 vs 6.4 ± 2.0 g.cm-2/ml.m-2 and control group 5.49 ± 0.98 vs 11.54 ± 2.86 g.cm-2/ml.m-2; p <0.0001), indicating decreased functional systolic reserve. In conclusion, asymptomatic children previously treated with low cumulative doses of anthracycline had decreased functional systolic reserve evidenced by exercise, suggesting a nonclinically manifested cardiotoxicity. © 2007 Elsevier Inc. All rights reserved.

Treatment of pulmonary thromboembolism in patients with systemic blood pressure stability and right ventricular dysfunction

Pulmonary thromboembolism (PTE) ranges from incidental, clinically unimportant thromboembolism to massive embolism with sudden death. Its treatment is well established in two groups of patients: heparin for those with normal systemic blood pressure without right ventricular dysfunction (RVD) and thrombolysis for those with RVD and circulatory shock. In an intermediate group of patients with systemic blood pressure stability combined with RVD, which is usually associated with worse outcome, the treatment is controversial. There are authors who strongly suggest thrombolysis while others contraindicate this procedure and recommend anticoagulation with heparin. This is a narrative review that includes clinical trials comparing thrombolysis and heparin for the treatment of PTE patients with systemic blood pressure stability and RVD published since 1973. The results show that there are only four trials on this subject with less than 500 patients. Many PTE patients with systemic blood pressure stability and RVD might benefit from thrombolysis but, on the other hand, the risk for hemorrhagic events may be increased. Large randomized clinical trials are required to clarify this. © 2008 Bentham Science Publishers Ltd.

Efectos de la administración de betabloqueante en la remodelación ventricular inducida por el tabaquismo en ratas

Background: The role of the adrenergic system on ventricular remodeling induced by cigarette smoking is unknown. Objective: To investigate the influence of propranolol on ventricular remodeling induced by exposure to tobacco smoke. Methods: Rats were divided into three groups: 1) C, n=10 - control group; 2) F, n=10 - animals exposed to tobacco smoke; 3) BB, n=10 - animals receiving propranolol and exposed to tobacco smoke (40 mg/kg/day). After 2 months, the animals underwent echocardiographic and morphometric analyses. One-way ANOVA (mean ± standard deviation) or the Kruskal-Wallis test (median and interquartile interval) was used. Results: Group BB showed a lower heart rate than group F (C = 358 ± 74 bpm, F = 374 ± 53 bpm, BB = 297± 30; P = 0.02). Group F showed greater end-diastolic diameters (C = 18.6 ± 3.4 mm/kg, F = 22.8 ± 1.8 mm/kg, BB = 21.7 ± 1.8 mm/kg; P = 0.003) and left ventricular (LV) end-systolic diameters (C = 8.6 ± 2.1 mm/kg, F = 11.3 ± 1.3 mm/kg, BB = 9.9 ± 1.2 mm/kg; P = 0.004), adjusted for body weight (BW) and a tendency towards a lower ejection fraction (C = 0.90 ± 0.03, F = 0.87 ± 0.03, BB =0.90 ± 0.02; P = 0.07) than group C. Group BB showed a tendency towards a lower LV/BW ratio than group F (C = 1.94 (1.87 - 1.97), F = 2.03 (1.9-2.1) mg/g, BB = 1.89 (1.86-1.94); P = 0.09). Conclusion: Administration of propranolol attenuated some of the variables of ventricular remodeling induced by the exposure to tobacco smoke in rats.

Relevãncia do padrão de remodelamento ventricular no modelo de infarto do miocárdio em ratos

Background: The relevance of the remodeling pattern in the model of infarcted rats is not known. Objective: To analyze the presence of different patterns of remodeling in this model and its functional implications. Methods: Infarcted rats (n=47) have been divided according to the geometry pattern, analyzed by echocardiogram: normal (normal mass index and normal relative thickness), concentric remodeling (normal mass index and increased relative thickness), concentric hypertrophy (increased mass index and increased relative thickness) and eccentric hypertrophy (increased mass index and normal relative thickness). Data are median and interquartile range. Results: Infarcted rats showed only two of the four geometric patterns: normal pattern (15%) and eccentric hypertrophy - EH (85%). Groups of normal pattern and EH showed no differences in the values of fractional area change (Normal = 32.1-28.8 to 50.7; EH = 31.3-26.5 to 36.7; p = 0.343). Out of the infarcted animals, 34 (74%) had systolic dysfunction, detected by fractional area change. Considering these two geometry patterns, 77% of animals with eccentric hypertrophy and 57% with normal geometry presented systolic dysfunction (p=0.355). The relative wall thickness, the geometric patterns and the body mass index were not predictors of ventricular dysfunction (p>0.05). On the other hand, infarct size was a predictive factor for ventricular dysfunction in univariate analysis (p<0.001) and multivariate analysis (p = 0.004). Conclusion: Rats that underwent coronary occlusion showed two different patterns of remodeling, which do not constitute a predictor of ventricular dysfunction.

Echocardiographic predictors of ventricular remodeling after acute myocardial infarction in rats

Background: The prediction of the ventricular remodeling process after acute myocardial infarction (AMI) may have important clinical implications. Objetive: To analyze echocardiographic variables predictors of remodeling in the infarction model in rats. Methods: The animals underwent echocardiography in two moments, five days and three months after infarction (AMI group) or sham surgery (control group). Linear regression was used to identify the echocardiographic variables on the fifth day after the infarction, which were predictive of remodeling after three months of coronary occlusion. We considered as a criterion of remodeling in this study, the values of left ventricular diastolic diameter (LVDD) after three months of infarction. Results: The infarction induced increase in the left chambers, associated with changes in systolic and diastolic functions. The variables body weight, left ventricular wall stress index (LVWSI), systolic area (SA), diastolic area (DA), LVDD, left ventricular systolic diameter (LVSD), fractional area change (FAC), ejection fraction (EF), fractional shortening (%Short), posterior wall shortening velocity (PWSV) and infarct size assessed five days after infarction were predictors of LVDD after three months. At the multivariate regression analysis, we included the size of infarction, the LVWSI and PWSV. The LVWSI (coefficient: 4.402, standard error: 2.221, p = 0.05), but not the size of infarction and PWSV, was a predictor of remodeling after three months of infarction. Conclusion: LVPSI was an independent predictor of remodeling three months after the myocardial infarction and could be included in the clinical stratification after the coronary occlusion.