The influence of temporal food restriction on the performance of isolated cardiac muscle

In this study we assessed the mechanical function of isolated left ventricular papillary muscles from 60 day-old male Wistar-Kyoto rats (WKY) subjected to different periods of food restriction (FR). The food-restricted animals (R) were fed 50% of the amount of diet consumed by the ad Libitum-fed rats (C). The cardiac muscles were studied after 30, 60, and 90 days (R-30, R-60 and R-90) of FR. The effect of FR on myocardial collagen concentration was also evaluated. The parameters from the three control groups that were statistically identical were combined and the control pool group (CP) was formed. The left ventricular weight-to-body weight ratio was lower in the R-30 and higher in the R-60 and R-90 in relation to their control groups. Hydroxyproline concentration was higher only in R-90 compared to CP and R-30. Myocardial mechanical function was the same in the C groups. The comparisons between CP and FR groups showed that: the muscles of R-30 presented increased resting tension and maximum rate of tension decline, and decreased velocity of shortening; the muscles of R-60 and R-90 groups showed a prolongation of the time to peak tension (TPT) and the time to peak shortening (TPS); and R-30 had an increased time from peak tension to 50% relaxation (RT1/2). Increases in TPT, TPS, and RT1/2 in groups R-60 and R-90 were significant in relation to R-30. In conclusion, while FR for 30 days produces disparate effects on myocardial performance, FR for 60 and 90 days prolongs the contraction period. The change of relaxation time in R-90 might be related to the increased myocardial collagen content. (C) 2001 Elsevier B.V. All rights reserved.

Direct effects of colchicine on myocardial function - Studies in hypertrophied and failing spontaneously hypertensive rats

The aging spontaneously hypertensive rat (SHR) is a model in which the transition from chronic stable left ventricular hypertrophy to overt heart failure can be observed. Although the mechanisms for impaired function in hypertrophied and failing cardiac muscle from the SHR have been studied, none accounts fully for the myocardial contractile abnormalities. The cardiac cytoskeleton has been implicated as a possible cause for myocardial dysfunction. If an increase in microtubules contributes to dysfunction, then myocardial microtubule disruption by colchicine should promote an improvement in cardiac performance. We studied the active and passive properties of isolated left ventricular papillary muscles from 18- to 24-month-old SHR with evidence of heart failure (SHR-F, n=6), age-matched SHR without heart failure (SHR-NF, n=6), and age-matched normotensive Wistar-Kyoto rats (WKY, n=5). Mechanical parameters were analyzed before and up to 90 minutes after the addition of colchicine (10(-5), 10(-4), and 10(-3) mol/L). In the baseline state, active tension (AT) developed by papillary muscles from the WKY group was greater than for SHR-NF and SHR-F groups (WKY 5.69+/-1.47 g/mm(2) [mean+/-SD], SHR-NF 3.41+/-1.05, SHR-F 2.87+/-0.26; SHR-NF and SHR-F P<0.05 versus WKY rats). The passive stiffness was greater in SHR-F than in the WKY and SHR-NF groups (central segment exponential stiffness constant, K-cs: SHR-F 70+/-25, SHR-NF 44+/-17, WKY 41+/-13 [mean+/-SD]; SHR-F P<0.05 versus; SHR-NF and WKY rats). AT did not improve after 10, 20, and 30 minutes of exposure to colchicine (10(-5), 10(-4), and 10(-3) mol/L) in any group. In the SHR-F group, AT and passive stiffness did not change after 30 to 90 minutes of colchicine exposure (10(-4) mol/L). In summary, the data in this study fail to demonstrate improvement of intrinsic muscle function in SHR with heart failure after colchicine. Thus, in the SHR there is no evidence that colchicine-induced cardiac microtubular depolymerization affects the active or passive properties of hypertrophied or failing left ventricular myocardium.

Diet-induced obesity causes metabolic, endocrine and cardiac alterations in spontaneously hypertensive rats

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Atrophic Cardiac Remodeling Induced by Taurine Deficiency in Wistar Rats

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Influence of Taurine on Cardiac Remodeling Induced by Tobacco Smoke Exposure

Background/Aims: To investigate the effect of taurine on cardiac remodeling induced by smoking. Methods: In the first step, rats were allocated into two groups: Group C (n=14): control; Group T (n=14): treated with taurine (3% in drinking water), for three months. In the second step, rats were allocated into two groups: Group ETS (n=9): rats exposed to tobacco smoke; Group ETS-T (n=9): rats exposed to tobacco smoke and treated with taurine for two months. Results: After three months, taurine presented no effects on morphological or functional variables of normal rats assessed by echocardiogram. on the other hand, after two months, ETS-T group presented higher LV wall thickness (ETS=1.30 (1.20-1.42); ETS-T=1.50 (1.40-1.50); p=0.029), E/A ratio (ETS=1.13 +/- 0.13; ETS-T=1.37 +/- 0.26; p=0.028), and isovolumetric relaxation time normalized for heart rate (ETS=53.9 +/- 4.33; ETS-T=72.5 +/- 12.0; p<0.001). The cardiac activity of the lactate dehydrogenase was higher in the ETS-T group (ETS=204 +/- 14 nmol/mg protein; ETS-T=232 +/- 12 nmol/mg protein; p<0.001). ETS-T group presented lower levels of phospholamban (ETS=1.00 +/- 0.13; ETS-T=0.82 +/- 0.06; p=0.026), phosphorylated phospholamban at Ser16 (ETS=1.00 +/- 0.14;ETS-T=0.63 +/- 0.10;p=0.003), and phosphorylated phosfolamban/phospholamban ratio (ETS=1.01 +/- 0.17; ETS-T=0.77 +/- 0.11; p=0.050). Conclusion: In normal rats, taurine produces no effects on cardiac morphological or functional variables. on the other hand, in rats exposed to cigarette smoke, taurine supplementation increases wall thickness and worsens diastolic function, associated with alterations in calcium handling protein and cardiac energy metabolism. Copyright (C) 2011 S. Karger AG, Basel

Influence of different doses of retinoic acid on cardiac remodeling

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

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 28degreesC 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 (RT1/2) was similar in these animals. ACE did not change any parameters ill 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, RT1/2 increased significantly ill the SHR-ACF in relation to the WKY-controls. In conclusion, the data lead LIS to infer that volume-overload for 30 days promotes more mechanical functional changes in hypertrophied muscle than in normal cardiac muscle.

Energy Expenditure and Oxygen Consumption as Novel Biomarkers of Obesity-induced Cardiac Disease in Rats

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Dietary restriction: Metabolic shifting for cardiac health

Purpose: To determine the effect of dietary restriction on metabolic pathways and the relationship of the metabolic shifting on antioxidant enzymes in cardiac tissue. Design: Randomized, controlled study. Male rats at 60 days old were randomly divided into four groups. Materials and Methods: The rats of control groups C30 and C60 were given free access to the diet over 30 and 60 days. The rats of the DR30 group were fed 60% of the chow consumed by the control groups over 30 days. The animals of the DR60 group ate 60% of the amount consumed by the C60 group over 60 days. Serum was used for total protein, lactate dehydrogenase (LDH), alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Protein, glycogen, total lipids, superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), LDH, AST and ALT were determined in cardiac tissue. Results: Dietary restriction induced diminished serum and cardiac LDH activities. AST activities were lower in the serum and cardiac muscle of the DR60 animals. Dietary restriction induced elevated total lipid concentrations in cardiac muscle. No significant differences were observed in total protein and glycogen content among the groups. Antioxidant enzyme determinations demonstrated increased cardiac GSH-Px activities in the DR60 animals and increased SOD activities in the cardiac tissue of both feed-restricted groups. Conclusions: Dietary restriction was protective against oxidative stress in the heart by improving cardiac endogenous antioxidant defences and shifting the metabolic pathway for energy production.

Respiratory chemoreceptor function in vertebrates - Comparative and evolutionary aspects

The sensing of blood gas tensions and/or pH is an evolutionarily conserved, homeostatic mechanism, observable in almost all species studied from invertebrates to man. In vertebrates, a shift from the peripheral O2-oriented sensing in fish, to the central CO2/pH sensing in most tetrapods reflects the specific behavioral requirements of these two groups whereby, in teleost fish, a highly O2-oriented control of breathing matches the ever-changing and low oxygen levels in water, whilst the transition to air-breathing increased the importance of acid-base regulation and O2-related drive, although retained, became relatively less important. The South American lungfish and tetrapods are probably sister groups, a conclusion backed up by many similar features of respiratory control. For example, the relative roles of peripheral and central chemoreceptors are present both in the lungfish and in land vertebrates. In both groups, the central CO2/pH receptors dominate the ventilatory response to hypercarbia (60-80), while the peripheral CO2/pH receptors account for 20-30. Some basic components of respiratory control have changed little during evolution. This review presents studies that reflect the current trends in the field of chemoreceptor function, and several laboratories are involved. An exhaustive review on the previous literature, however, is beyond the intended scope of the article. Rather, we present examples of current trends in respiratory function in vertebrates, ranging from fish to humans, and focus on both O2 sensing and CO2 sensing. As well, we consider the impact of chronic levels of hypoxia - a physiological condition in fish and in land vertebrates resident at high elevations or suffering from one of the many cardiorespiratory disease states that predispose an animal to impaired ventilation or cardiac output. This provides a basis for a comparative physiology that is informative about the evolution of respiratory functions in vertebrates and about human disease. Currently, most detail is known for mammals, for which molecular biology and respiratory physiology have combined in the discovery of the mechanisms underlying the responses of respiratory chemoreceptors. Our review includes new data on nonmammalian vertebrates, which stresses that some chemoreceptor sites are of ancient origin.

Cardiac baroreflex is already blunted in eight weeks old spontaneously hypertensive rats

Background. The literature did not evidence yet with which age spontaneously hypertensive rats (SHR) start to present baroreflex reduction. We endeavored to evaluate the baroreflex function in eight-week-old SHR. Methods. Male Wistar Kyoto (WKY) normotensive rats and SHR aged eight weeks were studied. Baroreflex was calculated as the variation of heart rate (HR) divided by the mean arterial pressure (MAP) variation (HR/MAP) tested with a depressor dose of sodium nitroprusside (SNP, 50 g/kg) and with a pressor dose of phenylephrine (PHE, 8 g/kg) in the right femoral venous approach through an inserted cannula in the animals. Significant differences for p < 0.05. Results. Baseline MAP (p < 0.0001) and HR (p = 0.0028) was higher in SHR. Bradycardic peak was attenuated in SHR (p < 0.0001), baroreflex gain tested with PHE was also reduced in the SHR group (p = 0.0012). PHE-induced increase in MAP was increased in WKY compared to SHR (p = 0.039). Bradycardic reflex responses to intravenous PHE was decreased in SHR (p < 0.0001). Conclusion. Eight weeks old SHR already presents impairment of the parasympathetic component of baroreflex. © 2010 Cisternas et al; licensee BioMed Central Ltd.

Influence of lisinopril on cardiac remodeling induced by tobacco smoke exposure

Background: To investigate the effect of lisinopril on cardiac remodeling induced by smoking. Material/Methods: Rats were allocated into 3 groups: group CON (n=8): control; group CSE (n=8): cigarette smoke exposure; group CSE-LIS (n=8): exposed to tobacco smoke and treated with lisinopril. Results: After 2 months, the tail systolic pressure was lower in CSE-LIS (CON=116 ±27 mm Hg, CSE=126±16, CSE-LIS=89±12; P<.001). CSE animals showed higher left ventricular systolic diameter (CON=8.25±2.16 mm/kg, CSE=11.5±1.3, CSE-LIS=9.27±2.00; P=.009) and myocyte cross-sectional area (CON=245±8 μm2, CSE=260±17, CSE-LIS=238±12; P=.01) than CON and CSE-LIS. The ejection fraction (CON =0.91±0.02, CSE=0.86±0.02, CSE-LIS=0.92±0.03; P=.002) and fractional shortening (CON=55.7±4.41%, CSE=48.7±3.43, CSE-LI=58.2±7.63; P=.006) were lower in CSE group than CON and CSE-LIS. CSE and CSE-LIS animals showed higher collagen amounts (CON=3.49±0.95%, CSE= 5.01±1.58, CSE-LIS=5.27±0.62; P=.009) than CON. CON group showed a higher connexin 43 amount in the intercalated disc (CON=3.70±0.38, CSE=2.13±0.53; CSE-LIS=2.17±0.73; P=.004) than CSE and CSE-LIS. There were no differences in IFN-g or TNF-a cardiac levels among the groups. Conclusions: Lisinopril attenuated both morphologic and functional abnormalities induced by exposure to tobacco smoke. In addition, this effect was associated with diminished blood pressure, but not alterations in connexin 43 distribution, cytokine production or collagen amount. © Med Sci Monit, 2010.

Hypertrophied myocardium is more dependent on extracellular calcium than the normal cardiac muscle

Background: The aim of this study was to analyze stable hypertrophied myocardial function and its response to inotropic maneuvers in rats submitted to renovascular hypertension for a 10-week period (RHT group, n=10). Material/Methods: Myocardial performance was studied in isolated left ventricle papillary muscles in isometric contraction under the following conditions: at postrest contraction of 30 seconds (PRC), at extracellular calcium (ECa 2+) chloride concentration of 1.25 and 5.20 mM, and after beta-adrenergic stimulation with 10 -6 M isoproterenol (ISOP). Results: The results were compared with normotensive Wistar controls rats (C group, n=10). In basal condition, resting tension, and contraction time (TPT) were greater, while relaxation time (RT 50) tended to be longer in RHT than C group. PRC and ISOP promoted a similar change in muscle function response intensity (Δ) in both groups. ECa 2+ shift did not change TPT in the C group and decreased TPT in the RHT animals; Δ was different between these groups. RT 50 increased in C and decreased in RHT, both without statistical significance; however, Δ was different. Conclusions: These results suggest that hypertrophied myocardial dysfunction may be attibuted to changes in intracellular calcium cycling. © Med Sci Monit, 2010.

Cardiac remodeling induced by smoking: Concepts, relevance, and potential mechanisms

Cardiac or ventricular remodeling is characterized by molecular, cellular, and interstitial alterations that lead to changes in heart size, mass, geometry and function in response to a given insult. Currently, tobacco smoke exposure is recognized as one of these insults. Indeed, tobacco smoke exposure induces the enlargement of the left-sided cardiac chambers, myocardial hypertrophy, and ventricular dysfunction. Potential mechanisms for these alterations include hemodynamic and neurohormonal changes, oxidative stress, inflammation, nitric oxide bioavailability, matrix metalloproteinases and mitogen-activated protein kinase activation. This review will focus on the concepts, relevance, and potential mechanisms of cardiac remodeling induced by tobacco smoke. © 2012 Bentham Science Publishers.

Cardiac remodeling induced by 13-cis retinoic acid treatment in acne patients

Background: Currently, 13-cis-retinoic acid (13-cis-RA) is the most effective therapy for acne. Isotretinoin, a first-generation synthetic 13-cis-RA compound, is associated with numerous adverse effects. To investigate the cardiac effects of 13-cis-RA, acne patients receiving 13-cis-RA were studied. Methods: Twenty male patients with acne were enrolled in the study. Patients were treated with a dose of 0.5 mg/kg/d of isotretinoin. All participants were assessed prior to treatment and after 10 weeks of therapy with Doppler-echocardiogram. Results: Patients showed reductions in right atrium vertical diameter, left atrium longitudinal diameter, left atrium volume and left ventricular diastolic diameter over the course of treatment. Significant increases in interventricular septum diastolic thickness, posterior wall diastolic thickness, relative wall relative thickness and left ventricle (LV) mass were observed. The LV mass index showed an increase in ventricular mass and a decrease in the cavity size. Examining LV systolic function, a decrease was observed for the cardiac index. Conclusion: In this study, 10 weeks of 13-cis-RA therapy at a dose of 0.5 mg/kg/d was found to promote concentric-type heart remodeling due to the occurrence of two associated events: heart hypertrophy and hypovolemia. © 2011 Elsevier B.V. All rights reserved.