Exposure time and ventricular remodeling induced by tobacco smoke exposure in rats

Background: We investigated the effects of length of exposure to tobacco smoke on the cardiac remodeling process induced by exposure to cigarette smoke in rats.Material/Methods: Rats were separated into 4 groups: nonsmoking (NS) 2 (n=25; control animals not exposed to tobacco smoke for 2 months), smoking (S)2 (n=22; rats exposed to smoke from 40 cigarettes/d for 2 months), NS6 (n=18; control animals not exposed to tobacco smoke for 6 months), and S6 (n=25; rats exposed to smoke from 40 cigarettes/d for 6 months). All animals underwent echocardiographic, isolated heart, and morphometric studies. Data were analyzed with a 2-way analysis of variance.Results: No interaction among the variables was found; this suggests that length of exposure to tobacco smoke did not influence the effects of exposure to smoke. Values for left ventricular diastolic diameter/body weight and left atrium/body weight were higher (p=0.023 and p=0.001, respectively) in smoking (S2 and S6) than in nonsmoking animals (NS2 and NS6). Left ventricular mass index was higher (p=0.048) in smoking than in nonsmoking animals. In the isovolumetrically beating ventricle, peak systolic pressure was higher (p=0.034) in smoking than in nonsmoking animals. Significantly higher values were found for left ventricular weight (p=0.017) and right ventricular weight (p=0.001) adjusted for body weight in smoking as opposed to nonsmoking animals. Systolic pressure was higher (p=0.001) in smoking (128 +/- 14 mm Hg) than in nonsmoking animals (112 +/- 11 mm Hg).Conclusions: Length of exposure to cigarette smoke did not influence cardiac remodeling caused by exposure to sm oke in rats.

GROWTH HORMONE ATTENUATES MYOCARDIAL FIBROSIS IN RATS WITH CHRONIC PRESSURE OVERLOAD-INDUCED LEFT VENTRICULAR HYPERTROPHY

1. The role of growth hormone (GH) in cardiac remodelling and function in chronic and persistent pressure overload-induced left ventricular hypertrophy has not been defined. The aim of the present study was to assess short-term GH treatment on left ventricular function and remodelling in rats with chronic pressure overload-induced hypertrophy.2. Twenty-six weeks after induction of ascending aortic stenosis (AAS), rats were treated with daily subcutaneous injections of recombinant human GH (1 mg/kg per day; AAS-GH group) or saline (AAS-P group) for 14 days. Sham-operated animals served as controls. Left ventricular function was assessed by echocardiography before and after GH treatment. Myocardial fibrosis was evaluated by histological analysis.3. Before GH treatment, AAS rats presented similar left ventricular function and structure. Treatment of rats with GH after the AAS procedure did not change bodyweight or heart weight, both of which were higher in the AAS groups than in the controls. After GH treatment, posterior wall shortening velocity (PWSV) was lower in the AAS-P group than in the control group. However, in the AAS-GH group, PWSV was between that in the control and AAS-P groups and did not differ significantly from either group. Fractional collagen (% of total area) was significantly higher in the AAS-P and AAS-GH groups compared with control (10.34 +/- 1.29, 4.44 +/- 1.37 and 1.88 +/- 0.88%, respectively; P < 0.05) and was higher still in the AAS-P group compared with the AAS-GH group.4. The present study has shown that short-term administration of GH to rats with chronic pressure overload-induced left ventricular hypertrophy induces cardioprotection by attenuating myocardial fibrosis.

Tissue Vitamin A Insufficiency Results in Adverse Ventricular Remodeling after Experimental Myocardial Infarction

Background/Aims: The role of tissue vitamin-A insufficiency on post-infarction ventricular remodeling is unknown. We tested the hypothesis that cardiac vitamin A insufficiency on post-infarction is associated with adverse myocardial remodeling. Methods: After infarction, rats were allocated into two groups: C (controls, n=25); VA (dietary vitamin A restriction, n= 26). After 3 months, the animals were submitted to echocardiogram, morphometric and biochemical analysis. Results: Rats fed the vitamin-A-deficient diet had lower heart and liver retinol concentration and normal plasma retinol. There were no differences in infarct size between the groups. VA showed higher diastolic left ventricular area normalised by body weight (C= 1.81 +/- 0.4 cm2/kg, VA= 2.15 +/- 0.3 cm2/kg; p=0.03), left ventricular diameter (C= 9.4 +/- 1.4 mm, VA= 10.5 +/- 1.2 mm; p=0.04), but similar systolic ventricular fractional area change (C= 33.0 +/- 10.0 %, VA= 32.1 +/- 8.7 %; p=0.82). VA showed decreased isovolumetric relaxation time normalised by heart rate (C= 68.8 +/- 11.4 ms, VA= 56.3 +/- 16.8 ms; p=0.04). VA showed higher interstitial collagen fraction (C= 2.8 +/- 0.9 %, VA= 3.7 +/- 1.1 %; p=0.05). There were no differences in myosin heavy chain expression, metalloproteinase 2 and 9 activation, or IFN-gamma and TNF-alpha cardiac levels. Conclusion: Local tissue vitamin A insufficiency intensified ventricular remodeling after MI, worsening diastolic dysfunction. Copyright (C) 2010 S. Karger AG, Basel

Effects of losartan on ventricular remodeling in experimental infarction in rats

OBJECTIVE: To evaluate the effects of losartan on ventricular remodeling and on survival after myocardial infarction in rats. METHODS: After surgical occlusion of left coronary artery, 84 surviving male Wistar rats were divided into two groups: LO treated with losartan (20mg/kg/day, n=33) and NT (n=51), without medication. After 3 months, we analyzed mortality; ventricular to body mass ratio (VM /BM); myocardial hydroxyproline concentration (HOP); isovolumetric pressure, +dp/dt, -dp/dt, and diastolic volume/left ventricle mass ratio (VO/LV). RESULTS: Mortality was: LO = 22%, and NT = 47% (p<0.05). Ventricular mass,(VM/BM, mg/g) was 4.14 ± 0.76 and 3.54±0.48, in the NT and LO groups, respectively (p<0.05). HOP (median) was 4.92 upsilong/mg in the LO and 5.54 upsilong/g in the NT group (p>0.05). The V0/LV values (median) were 0.24 mL/g in group LO and 0.31 mL/g in group NT (p<0.05) compared to NT group. There were no differences between the groups for +dp/dt and -dp/dt parameters. CONCLUSION: 1- The use of losartan myocardial infarction causes an attenuation of ventricular remodeling, bringing about an increased survival, an attenuation of ventricular hypertrophy and dilation, and an improvement of the isovolumetric pressure; 2- the treatment does not modify the myocardial collagen concentration.

Efeitos da inibição prolongada da enzima de conversão da angiotensina sobre as características morfológicas e funcionais da hipertrofia ventricular esquerda em ratos com sobrecarga pressórica persistente

OBJETIVO: Avaliar os efeitos do lisinopril (L) sobre as taxas de mortes (M), insuficiência cardíaca (ICC), características da remodelação miocárdica, geométrica e funcional do ventrículo esquerdo (VE), em ratos com estenose aórtica supravalvar (EAS). MÉTODOS: Ratos foram submetidos a EAS ou cirurgia simulada (GC:n=10). Randomizados após 6 semanas para receber L (GL:n=30) ou nenhum tratamento (GE:n=73) sendo avaliados 6s e 21s por estudos ecocardiográfico, hemodinâmico e morfológico concomitantes. RESULTADOS: As taxas de M (GE: 53,9% vs GL: 16,7% e ICC GE: 44,8% vs GL: 20% p<0,05). No final do experimento, os valores da pressão sistólica do VE dos grupos GE e GL foram equivalentes e significantemente mais elevados do que no grupo GC; (p<0,05) não diferindo dos observados 6 semanas após os procedimentos cirúrgicos. Os valores da pressão diastólica do VE no grupo GE foram maiores do que os do grupo GL (p<0,05) sendo ambos maiores do que os do grupo GC (4 ± 2 mmHg, p<0,05). O mesmo comportamento foi observado com as variáveis: razão E/A; índice de massa, área seccional dos miócitos e conteúdo de hidroxiprolina do VE. A porcentagem de encurtamento do VE foi semelhante nos grupos GC e GL (p>0,05) sendo ambos maiores que os verificados no grupo GE. Comportamento semelhante foram obtidos com os valores da primeira derivada positiva e negativa da pressão do VE. CONCLUSÃO: em ratos com EAS o L reduziu as taxas de M e ICC e exerceu efeitos benéficos sobre a remodelação e a função do VE.

Ventricular remodeling and diastolic myocardial dysfunction in rats submitted to protein-calorie malnutrition

The effects of protein-calorie malnutrition (PCM) on heart structure and function are not completely understood. We studied heart morphometric, functional, and biochemical characteristics in undernourished young Wistar rats. They were submitted to PCM from birth (undernourished group, UG). After 10 wk, left ventricle function was studied using a Langendorff preparation. The results were compared with age-matched rats fed ad libitum (control group, CG). The UG rats achieved 47% of the body weight and 44% of the left ventricular weight (LVW) of the CG. LVW-to-ventricular volume ratio was smaller and myocardial hydroxyproline concentration was higher in the UG. Left ventricular systolic function was not affected by the PCM protocol. The myocardial stiffness constant was greater in the UG, whereas the end-diastolic pressure-volume relationship was not altered. In conclusion, the heart is not spared from the adverse effects of PCM. There is a geometric alteration in the left ventricle with preserved ventricular compliance despite the increased passive myocardial stiffness. The systolic function is preserved.

Influência da elevaçáo transitória e da elevaçáo sustentada da pressáo arterial sobre a primeira derivada temporal da pressáo ventricular.

PURPOSE--To analyze the influence of transient and sustained elevations of arterial pressure (AP) on the rate of rise of the left ventricular pressure (dp/dt). METHODS--Thirteen anesthetized, thoracotomized and mechanically ventilated dogs, submitted to pharmacological autonomic block (oxprenolol-3 mg/kg plus atropine-0.5 mg/kg). The AP elevation was obtained by mechanical constriction of the descending thoracic aorta. Two protocols were applied to all animals: Transient Arterial Hypertension (TAH) and Sustained Arterial Hypertension (SAH) and the following variables were evaluated: heart rate (HR), systolic (LVSP) and end diastolic (LVEDP) left ventricular pressure and dp/dt. In TAH the variables were analyzed in the basal condition (To) and at the maximal value of AP attained during the transient pressure elevation (TM). In the protocol SAH the variables were evaluated in the conditions: Control (Ho), hypertension 1 (H1) and hypertension 2 (H2). RESULTS--Considering all conditions, there were no significant differences among the values of HR. In the protocol TAH, the LVSP varied from 133 +/- 22 mmHg to 180 +/- 27 mmHg, whereas in SAH the values of LVSP were as follow: HO = 129 +/- 25 mmHg; H1 = 152 = 23 mmHg; H2 = 182 +/- 24 mmHg. LVEDP changed in both protocols: To = 7 +/- 2 mmHg; TM = 13 +/- 2 mmHg (p < 0.05); Ho = 7 +/- 2 mmHg; H1 = 10 +/- 2 mmHg; H2 = 14 +/- 3 mmHg (p < 0.05). During TAH there was no difference between the values of dp/dt (To = 3.303 +/- 598 mmHg/s; TM = 3.350 +/- 653 mmHg/s; p > 0.05), however, there were increases of the dp/dt during SAH (Ho = 3.233 +/- 576 mmHg/s; H1 = 3.831 +/- 667 mmHg/s; H1 = 4.594 +/- 833 mmHg/2; p < 0.05). CONCLUSION--The values of dp/dt are not influenced by transient elevation of AP. Sustained increase of AP activates cardiac adjustments, which results in elevation of dp/dt, by stimulation of contractile state. Probably, the inotropic intervention mechanism is the length dependent activation due to the Frank-Starling mechanism.

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.

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: A longitudinal, prospective exercise echocardiography study

Background: The time course of mild cardiotoxicity induced by anthracycline remains unknown. The aim of this study was to evaluate the long-term evolution of decreased myocardial reserve in children previously treated with a cumulative dose of anthracycline up to 100mg/m 2. Patients and Methods: Twenty-seven asymptomatic cancer survival patients (25 with lymphoblastic leukemia), in continuous remission and off treatment for >12 months with no alterations in conventional echocardiograms were evaluated by exercise echocardiography at 37±15.4 months (T1) and 101±24 months (T2) after finishing treatment (ADRIA group). This group was compared with 25 healthy individuals (control group) similar to the ADRIA group with respect to age and body surface area (BSA). All individuals underwent treadmill exercise testing according to Bruce protocol. Echocardiograms were performed before and immediately after exercise. Results: The groups were similar regarding cardiac structure and left ventricular (LV) systolic function at rest at T1 and T2. The growth of LV posterior wall thickness related to BSA was lower in the ADRIA group at T2. Post exercise, smaller LV ejection indexes and attenuated changes in the afterload in ADRIA group were observed at T1 and T2. Conclusion: The decreased systolic reserve induced by a low dose of anthracycline in asymptomatic children and adolescents remains unaffected over a 5-year period, suggesting that positive outcomes in chronic cardiotoxicity would be expected in patients with mild impairment after anthracycline treatment. © 2011 Wiley Periodicals, Inc.

Efeito agudo de CPAP na funçao diastólica ventricular e na capacidade funcional de pacientes com insuficiência cardíaca

Pós-graduação em Fisiopatologia em Clínica Médica - FMB

Alterações histológicas do miocárdio, rim e fígado de ratos (Rattus novergicus) Wistar submetidos à infusão de angiotensina II: influência na função ventricular esquerda e resposta ao tratamento com losartan e carvedilol

Pós-graduação em Fisiopatologia em Clínica Médica - FMB