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.

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.

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.

Waist circumference, but not body mass index, is a predictor of ventricular remodeling after anterior myocardial infarction

Objective: The impact of obesity on ventricular remodeling after myocardial infarction (MI) is still poorly understood. Therefore, the aim of this study was to evaluate the role of waist circumference (WC) and body mass index as predictors of cardiac remodeling in patients after an anterior MI. Methods: Eighty-three consecutive patients with anterior MI were prospectively evaluated. Clinical characteristics and echocardiographic data were analyzed at admission and at a 6-mo follow-up. Ventricular remodeling was defined as a 10% increase in left ventricular end-systolic or end-diastolic diameter at the 6-mo follow-up. Results: In our study, 83 consecutive patients were evaluated (72% men). Ventricular remodeling was present in 31% of the patients (77% men). Patients with remodeling had higher creatine phosphokinase and creatine phosphokinase-MB peak values, a higher resting heart rate, a larger left atrial diameter, and a larger interventricular septum diastolic thickness. In addition, patients with remodeling had lower peak velocity of early ventricular filling deceleration time and ejection fraction. Patients with remodeling presented higher WC values (with remodeling, 99.2 ± 10.4 cm; without remodeling, 93.9 ± 10.8 cm, P = 0.04), but there were no differences in the body mass index values. In the logistic regression analysis, WC, adjusted by age, gender, ejection fraction, and creatine phosphokinase levels, was an independent predictor of left ventricular remodeling (odds ratio 1.067, 95% confidence interval 1.001-1.129, P = 0.02). Conclusion: Waist circumference, but not body mass index, is a predictor of ventricular remodeling after an anterior MI. Therefore, the WC of these patients should be measured in clinical practice. © 2013 Elsevier Inc.

Disproportionate pregnancy-induced myocardial hypertrophy in women with essential hypertension

BACKGROUND Pregnancy and arterial hypertension (AH) have a prohypertrophic effect on the heart. It is suspected that the 2 conditions combined cause disproportionate myocardial hypertrophy. We sought to evaluate myocardial hypertrophy (LVH) and left ventricular function in normotensive and hypertensive women in the presence or absence of pregnancy.METHODS This prospective cross-sectional study included 193 women divided into 4 groups: hypertensive pregnant (HTP; n = 57), normotensive pregnant (NTP; n = 47), hypertensive nonpregnant (HTNP; n = 41), and normotensive nonpregnant (NTNP; n = 48). After clinical and echocardiographic evaluation, the variables were analyzed using 2-way analysis of variance with pregnancy and hypertension as factors. Left ventricular mass (LVM) was compared using nonparametric analysis of variance and Dunn′s test. Predictors of LVH and diastolic dysfunction were analyzed using logistic regression (significance level, P < 0.05).RESULTS Myocardial hypertrophy was independently associated with hypertension (odds ratio (OR) = 11.1, 95% confidence interval (CI) = 3.2-38.5; P < 0.001) and pregnancy (OR = 6.1, 95% CI = 2.6-14.3; P < 0.001) in a model adjusted for age and body mass index. Nonpregnant women were at greater risk of LVH in the presence of AH (OR = 25.3, 95% CI = 3.15-203.5; P = 0.002). The risk was additionally increased in hypertensive women during pregnancy (OR = 4.3, 95% CI = 1.7-10.9; P = 0.002) in the model adjusted for stroke volume and antihypertensive medication. Although none of the NTNP women presented with diastolic dysfunction, it was observed in 2% of the NTP women, 29% of the HTNP women, and 42% of the HTP women (P < 0.05).CONCLUSIONS Hypertension and pregnancy have a synergistic effect on ventricular remodeling, which elevates a woman's risk of myocardial hypertrophy. © 2013 © American Journal of Hypertension, Ltd 2013. All rights reserved.

Serotonergic neurons in the nucleus raphé obscurus are not involved in the ventilatory and thermoregulatory responses to hypoxia in adult rats

The medullary raphé is an important component of the central respiratory network, playing a key role in CO2 central chemoreception. However, its participation in hypoxic ventilatory responses is less understood. In the present study, we assessed the role of nucleus raphé obscurus (ROb), and specifically 5-HT neurons confined in the ROb, on ventilatory and thermoregulatory responses to hypoxia. Chemical lesions of the ROb were performed using either ibotenic acid (non-specific lesion; control animals received PBS) or anti-SERT-SAP (5-HT specific lesion; control animals received IgG-SAP). Ventilation (VE; whole body plethysmograph) and body temperature (Tb; data loggers) were measured during normoxia (21% O2, N2 balance) and hypoxia exposure (7% O2, N2 balance, 1h) in conscious adult rats. Ibotenic acid or anti-SERT-SAP-induced lesions did not affect baseline values of VE and Tb. Similarly, both lesion procedures did not alter the ventilatory or thermoregulatory responses to hypoxia. Although evidence in the literature suggests a role of the rostral medullary raphé in hypoxic ventilatory responses, under the present experimental conditions our data indicate that caudal medullary raphé (ROb) and its 5-HT neurons neither participate in the tonic maintenance of breathing nor in the ventilatory and thermal responses to hypoxia. © 2013 Elsevier B.V.

Branchial O2 chemoreceptors in Nile tilapia Oreochromis niloticus: Control of cardiorespiratory function in response to hypoxia

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

Glucose homoeostasis in rats exposed to acute intermittent hypoxia

Aim: Chronic exposure to intermittent hypoxia commonly induces the activation of sympathetic tonus and the disruption of glucose homoeostasis. However, the effects of exposure to acute intermittent hypoxia (AIH) on glucose homoeostasis are not yet fully elucidated. Herein, we evaluated parameters related to glucose metabolism in rats exposed to AIH. Methods: Male adult rats were submitted to 10 episodes of hypoxia (6% O2, for 45 s) interspersed with 5-min intervals of normoxia (21%), while the control (CTL) group was kept in normoxia. Results: Acute intermittent hypoxia rats presented higher fasting glycaemia, normal insulinaemia, increased lactataemia and similar serum lipid levels, compared to controls (n = 10, P < 0.05). Additionally, AIH rats exhibited increased glucose tolerance (GT) (n = 10, P < 0.05) and augmented insulin sensitivity (IS) (n = 10, P < 0.05). The p-Akt/Akt protein ratio was increased in the muscle, but not in the liver and adipose tissue of AIH rats (n = 6, P < 0.05). The elevated glycaemia in AIH rats was associated with a reduction in the hepatic glycogen content (n = 10, P < 0.05). Moreover, the AIH-induced increase in blood glucose concentration, as well as reduced hepatic glycogen content, was prevented by prior systemic administration of the β-adrenergic antagonist (P < 0.05). The effects of AIH on glycaemia and Akt phosphorylation were transient and not observed after 60 min. Conclusions: We suggest that AIH induces an increase in blood glucose concentration as a result of hepatic glycogenolysis recruitment through sympathetic activation. The augmentation of GT and IS might be attributed, at least in part, to increased β-adrenergic sympathetic stimulation and Akt protein activation in skeletal muscles, leading to a higher glucose availability and utilization. © 2013 Scandinavian Physiological Society.

Mechanisms Involved in the Beneficial Effects of Spironolactone after Myocardial Infarction

Introduction:Our objective was to analyze the effect of spironolactone on cardiac remodeling after experimental myocardial infarction (MI), assessed by matricellular proteins levels, cardiac collagen amount and distribution, myocardial tissue metalloproteinase inhibitor-1(TIMP-1) concentration, myocyte hypertrophy, left ventricular architecture, and in vitro and in vivo cardiac function.Methods:Wistar rats were assigned to 4 groups: control group, in which animals were submitted to simulated surgery (SHAM group; n=9); group that received spironolactone and in which animals were submitted to simulated surgery (SHAM-S group, n=9); myocardial infarction group, in which animals were submitted to coronary artery ligation (MI group, n=15); and myocardial infarction group with spironolactone supplementation (MI-S group, n=15). The rats were observed for 3 months.Results:The MI group had higher values of left cardiac chambers and mass index and lower relative wall thicknesses compared with the SHAM group. In addition, diastolic and systolic functions were worse in the MI groups. However, spironolactone did not influence any of these variables. The MI-S group had a lower myocardial hydroxyproline concentration and myocyte cross-sectional area compared with the MI group. Myocardial periostin and collagen type III were lower in the MI-S group compared with the MI-group. In addition, TIMP-1 concentration in myocardium was higher in the MI-S group compared with the MI group.Conclusions:The predominant consequence of spironolactone supplementation after MI is related to reductions in collagens, with discrete attenuation of other remodeling variables. Importantly, this effect may be modulated by periostin and TIMP-1 levels. © 2013 Minicucci et al.

Pollution-induced metabolic responses in hypoxia-tolerant freshwater turtles

The physiological control to support the absence of O2 for long periods of diving, and oxidative damage impact caused by the whole process of hypoxia/reperfusion in freshwater turtles is well known. However, effects of contaminants may act as co-varying stressors and cause biological damage, disrupting the hypoxia/reperfusion oxidative damage control. In order to investigate the action of environmental stressors present in domestic or industrial wastewater effluent, we performed a biochemical analysis of biotransformation enzymes, oxidative stress, as well as neuromuscular, physiological and morphological parameters in Phrynops geoffroanus, an hypoxic-tolerant freshwater turtle endemic of South America, using animals sampled in urban area, contaminated by sewage and industrial effluents and animals sampled in control area. Here we demonstrate the physiological and biochemical impact caused by pollution, and the effect that these changes cause in antioxidant activity. Animals from the urban area exhibited higher EROD (ethoxyresorufin-O-deethylase, CYP1A1), GST (glutathione S-transferase), G6PDH (glucose-6-phosphate deshydrogenase), AChE (acetilcholinesterase) activities and also TEAC (trolox-equivalent antioxidant capacity) and TBARS (thiobarbituric acid reactive substances) values. We examined whether two morphometric indices (K - condition factor and HIS - hepatosomatic index) which help in assessing the general condition and possible liver disease, respectively, were modified. The K of the urban animals was significantly decreased compared to the control animals, but the HIS value was increased in animals from the urban area, supporting the idea of an impact in physiology and life quality in the urban freshwater turtles. We propose that this freshwater turtle specie have the ability to enhance its antioxidants defenses in order to protect from tissue damage caused by hypoxia and reperfusion, but also that caused by environmental contamination and that the oxidative damage control in hypoxic conditions has resulted in an adaptive condition in hypoxic-tolerant freshwater turtle species, in order to better tolerate the release of contaminated effluents resulting from human activity. © 2013 Elsevier Inc.

Periostin as a modulator of chronic cardiac remodeling after myocardial infarction

OBJECTIVE: After acute myocardial infarction, during the cardiac repair phase, periostin is released into the infarct and activates signaling pathways that are essential for the reparative process. However, the role of periostin in chronic cardiac remodeling after myocardial infarction remains to be elucidated. Therefore, the objective of this study was to investigate the relationship between tissue periostin and cardiac variables in the chronic cardiac remodeling induced by myocardial infarction. METHODS: Male Wistar rats were assigned to 2 groups: a simulated surgery group (SHAM; n = 8) and a myocardial infarction group (myocardial infarction; n = 13). After 3 months, morphological, functional and biochemical analyses were performed. The data are expressed as means±SD or medians (including the lower and upper quartiles). RESULTS: Myocardial infarctions induced increased left ventricular diastolic and systolic areas associated with a decreased fractional area change and a posterior wall shortening velocity. With regard to the extracellular matrix variables, the myocardial infarction group presented with higher values of periostin and types I and III collagen and higher interstitial collagen volume fractions and myocardial hydroxyproline concentrations. In addition, periostin was positively correlated with type III collagen levels (r = 0.673, p = 0.029) and diastolic (r = 0.678, p = 0.036) and systolic (r = 0.795, p = 0.006) left ventricular areas. Considering the relationship between periostin and the cardiac function variables, periostin was inversely correlated with both the fractional area change (r = -0.783, p = 0.008) and the posterior wall shortening velocity (r = -0.767, p = 0.012). CONCLUSIONS: Periostin might be a modulator of deleterious cardiac remodeling in the chronic phase after myocardial infarction in rats.

Is hypoxia a stressor to American bullfrog tadpoles?

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

Infarct Size as Predictor of Systolic Functional Recovery after Myocardial Infarction

Background: The effects of modern therapy on functional recovery after acute myocardial infarction (AMI) are unknown.Objectives: To evaluate the predictors of systolic functional recovery after anterior AMI in patients undergoing modern therapy (reperfusion, aggressive platelet antiaggregant therapy, angiotensin-converting enzyme inhibitors and beta-blockers).Methods: A total of 94 consecutive patients with AMI with ST-segment elevation were enrolled. Echocardiograms were performed during the in-hospital phase and after 6 months. Systolic dysfunction was defined as ejection fraction value < 50%.Results: In the initial echocardiogram, 64% of patients had systolic dysfunction. Patients with ventricular dysfunction had greater infarct size, assessed by the measurement of total and isoenzyme MB creatine kinase enzymes, than patients without dysfunction. Additionally, 24.5% of patients that initially had systolic dysfunction showed recovery within 6 months after AMI. Patients who recovered ventricular function had smaller infarct sizes, but larger values of ejection fraction and E-wave deceleration time than patients without recovery. At the multivariate analysis, it can be observed that infarct size was the only independent predictor of functional recovery after 6 months of AMI when adjusted for age, gender, ejection fraction and E-wave deceleration time.Conclusion: In spite of aggressive treatment, systolic ventricular dysfunction remains a frequent event after the anterior myocardial infarction. Additionally, 25% of patients show functional recovery. Finally, infarct size was the only significant predictor of functional recovery after six months of acute myocardial infarction.