Probiotic administration attenuates myocardial hypertrophy and heart failure following myocardial infarction in the rat

Background—Probiotics are extensively used to promote gastrointestinal health and emerging evidence suggests that their beneficial properties can extend beyond the local environment of the gut. Here, we determined whether oral probiotic administration can alter the progression of post-infarction heart failure. Methods and Results—Rats were subjected to six weeks of sustained coronary artery occlusion and administered the probiotic Lactobacillus rhamnosus GR-1 or placebo in the drinking water ad libitum. Culture and 16s rRNA sequencing showed no evidence of GR-1 colonization or a significant shift in the composition of the cecal microbiome. However, animals administered GR-1 exhibited a significant attenuation of left ventricular hypertrophy based on tissue weight assessment as well as gene expression of atrial natriuretic peptide. Moreover, these animals demonstrated improved hemodynamic parameters reflecting both improved systolic and diastolic left ventricular function. Serial echocardiography revealed significantly improved left ventricular parameters throughout the six week follow-up period including a marked preservation of left ventricular ejection fraction as well as fractional shortening. Beneficial effects of GR-1 were still evident in those animals in which GR-1 was withdrawn at four weeks suggesting persistence of the GR-1 effects following cessation of therapy. Investigation of mechanisms showed a significant increase in the leptin to adiponectin plasma concentration ratio in rats subjected to coronary ligation which was abrogated by GR-1. Metabonomic analysis showed differences between sham control and coronary artery ligated hearts particularly with respect to preservation of myocardial taurine levels. Conclusions—The study suggests that probiotics offer promise as a potential therapy for the attenuation of heart failure.

Autonomic impairment after myocardial infarction: Role in cardiac remodelling and mortality

P>1. Impairmant of baroreflex sensitivity (BRS) has been implicated in the reduction of heart rate variability (HRV) and in the increased risk of death after myocardial infarction (MI). In the present study, we investigated whether the additional impairment in BRS induced by sinoaortic baroreceptor denervation (SAD) in MI rats is associated with changes in the low-frequency (LF) component of HRV and increased mortality rate. 2. Rats were randomly divided into four groups: control, MI, denervated (SAD) and SAD + MI rats. Left ventricular (LV) function was evaluated by echocardiography. Autonomic components were assessed by power spectral analysis and BRS. 3. Myocardial infarction (90 days) reduced ejection fraction (by similar to 42%) in both the MI and SAD + MI groups; however, an increase in LV mass and diastolic dysfunction were observed only in the SAD + MI group. Furthermore, BRS, HRV and the LF power of HRV were reduced after MI, with an exacerbated reduction seen in SAD + MI rats. The LF component of blood pressure variability (BPV) was increased in the MI, SAD and SAD + MI groups compared with the control group. Mortality was higher in the MI groups compared with the non-infarcted groups, with an additional increase in mortality in the SAD + MI group compared with the MI group. Correlations were obtained between BRS and the LF component of HRV and between LV mass and the LF component of BPV. 4. Together, the results indicate that the abolishment of BRS induced by SAD in MI rats further reduces the LF band of HRV, resulting in a worse cardiac remodelling and increased mortality in these rats. These data highlight the importance of this mechanism in the prognosis of patients after an ischaemic event.

Resposta anormal da função sistólica do ventrículo esquerdo ao exercício submáximo em pacientes submetidos à ventriculectomia parcial esquerda

Introdução. Pacientes com insuficiência cardíaca submetidos à ventriculectomia parcial esquerda apresentam melhora na função sistólica do ventrículo esquerdo em repouso, porém continuam apresentando limitação funcional. Objetivo. Para melhor compreender os mecanismos desta limitação funcional, estudamos a função sistólica e diastólica do ventrículo esquerdo em repouso e durante exercício submáximo em pacientes submetidos a ventriculectomia parcial esquerda e em pacientes com insuficiência cardíaca não operados, pareados para capacidade funcional máxima e submáxima. Métodos. Foram estudados 9 pacientes submetidos previamente a ventriculografia parcial esquerda (VPE) e 9 pacientes com insuficiência cardíaca não operados previamente (IC). Todos os pacientes foram submetidos inicialmente a um teste cardiopulmonar para determinação do consumo de oxigênio no limiar anaeróbio (LA) e de pico (VO2 pico). Após, foram estudados através da ventriculografia radioisotópica e analisadas a fração de ejeção (FE) e a taxa máxima de enchimento (TME) do ventrículo esquerdo, em repouso e exercício na intensidade do LA. Resultados. Os grupos apresentaram capacidade funcional semelhante avaliada pelo VO2 pico (VPE: [média ± DP] 13,1 ± 3,3 ml/kg.min; IC: 14,1 ± 3,6 ml/kg.min; P > 0,05) e LA (VPE: 7,9 ± 1.3 ml/kg.min; IC: 8,5 ± 1,6 ml/kg.min; P > 0,05). A frequência cardíaca máxima foi maior no grupo IC em comparação ao grupo da VPE (VPE: 119 ± 20 bpm; IC: 149 ± 21 bpm; P < 0.05) A FE em repouso era mais elevada no grupo VPE (VPE: 40 ± 12 %; IC: 32 ± 9 %; P < 0,0125), entretanto a FE elevou-se do repouso ao LA apenas no grupo IC (VPE: 44 ± 17 %; IC: 39 ± 11 %; P < 0,0125). A TME foi semelhante em repouso (VPE: 1,41 ± 0,55 VDF/s; IC: 1,39 ± 0,55 VDF/s; P > 0,05) e aumentou na intensidade do LA similarmente em ambos os grupos (VPE: 2,28 ± 0,55 VDF/s; IC: 2,52 ± 1,07 VDF/s; P < 0,0125). Conclusão. Pacientes submetidos a ventriculectomia parcial esquerda apresentam uma o limiar anaeróbio (LA) resposta anormal da função sistólica do ventrículo esquerdo ao exercício na intensidade do LA e uma resposta cronotrópica diminuida ao exercício máximo. Essas respostas anormais podem contribuir para a limitada capacidade ao exercício destes pacientes, a despeito da melhora na função ventricular sistólica em repouso.

Effects of isoflurane on echocardiographic parameters in healthy dogs

Obejective To study the echocardiographic effects of isoflurane at an end-tidal concentration approximating 1.0 times the minimum alveolar concentration (MAC) in healthy unpremedicated dogs.Study design Prospective experimental trial.Animals Sixteen mature mongrel dogs of either sex weighing 11.06 +/- 2.72 kg.Methods After performing a baseline echocardiogram in the awake animal, anesthesia was induced with increasing inspired concentrations of isoflurane via a face mask until tracheal intubation was possible. Following intubation, the end-tidal concentration was decreased to 1.4% for the rest of the anesthetic period. Serial echocardiograms were recorded at 25, 40, and 55 minutes after the end-tidal concentration was reached.Results No changes were observed in heart rate. However, significant decreases were seen in left ventricular end-diastolic diameter (Mean maximal change: 13.8%), interventricular septal thickness during systole (15.2%), interventricular septal thickening fraction (72.2%), left ventricular free wall thickening fraction (63.5%), ejection fraction (39.9%), and fractional shortening (46.7%). In addition, peak flow velocities across mitral, pulmonic, and aortic valves were significantly lower than baseline values. Decreases were also observed in end-diastolic left ventricular volume index (approximately 32.1% from the awake value), stroke index (58.2%), and cardiac index (55.3%) when compared with awake measurements.Conclusions Our results indicate that 1 x MAC isoflurane caused significant myocardial depression in healthy dogs. These changes in myocardial function need to be considered carefully when isoflurane is to be used in dogs with poor cardiovascular reserve.

Uso precoce e tardio de dopamina após isquemia miocárdica

OBJETIVO: Avaliar os efeitos na função ventricular esquerda do uso precoce e tardio de dopamina, em modelo experimental de coração isolado. MÉTODO: Foram utilizados 60 coelhos em modelo de coração isolado mantido por animal suporte. Um balão intraventricular foi locado no ventrículo esquerdo. Três grupos foram constituídos: grupo controle (GC); grupo que recebeu dopamina precoce (Dopa P) e grupo que recebeu dopamina tardia (após 20 minutos) (Dopa T). Foram realizadas leituras hemodinâmicas diretas e indiretas. RESULTADOS: Fluxo sangüíneo coronariano: GC(7,196 ± 1,275ml/min); Dopa P (9,477 ± 1,160ml/min); Dopa T (14,316 ± 2,308ml/min), com GC=Dopa P, GC ¹Dopa T e Dopa P¹Dopa T. Primeira derivada temporal da pressão intraventricular (dp/dt+): GC (719,61 ± 127,53ml/min); Dopa P (719,61 ± 127,53ml/min); Dopa T (1431,60 ± 230,87ml/min), p<0,05, Dopa P¹Dopa T, GC=Dopa P e GC ¹ Dopa T. Primeira derivada temporal da pressão intraventricular negativa (dp/dt-): GC (469,85 ± 107,16mmHg/s); Dopa P (716,07 ± 215,66mmHg/s); Dopa T (931,24 ± 181,46mmHg/s), p<0,05, Dopa P¹Dopa T¹GC. Delta V: GC (1,355 ± 0,2432ml); Dopa P (0,97 ± 0,3199ml); Dopa T (1,27 ± 0,2983ml), p>0,05, Dopa P=Dopa T=GC. Estresse sistólico desenvolvido: GC (27,273 ± 10,276g/cm²); Dopa P (55,219 ± 24,625g/cm²); Dopa T (79,152 ± 12,166g/cm²), Dopa P=Dopa T, Dopa P=GC e GC ¹ Dopa T.Dialdeído Malônico (MDA): GC (4,5 ± 0,527mmol/L); Dopa P (4,7 ± 1,16mmol/L); Dopa T (4,1 ± 0,7379mmol/L), p>0,05, Dopa P=Dopa T=GC. CONCLUSÕES: Concluiu-se que, no modelo experimental delineado, o uso precoce da dopamina foi deletério, segundo algumas variáveis hemodinâmicas.

Myocardial dysfunction induced by food restriction is related to morphological damage in normotensive middle-aged rats

Previous works from our laboratory have revealed that food restriction (FR) promotes discrete myocardial dysfunction in young rats. We examined the effects of FR on cardiac function, in vivo and in vitro, and ultrastructural changes in the heart of middle-aged rats. Twelve-month-old Wistar- Kyoto rats were fed a control (C) or restricted diet (daily intake reduced to 50% of the control group) for 90 days. Cardiac performance was studied by echocardiogram and in isolated left ventricular (LV) papillary muscle by isometric contraction in basal condition, after calcium chloride (5.2 mM) and beta- adrenergic stimulation with isoproterenol (10(-6) M). FR did not change left ventricular function, but increased time to peak tension, and decreased maximum rate of papillary muscle tension development. Inotropic maneuvers promoted similar effects in both groups. Ultrastructural alterations were seen in most FR rat muscle fibers and included, absence and/or disorganization of myofilaments and Z line, hyper-contracted myofibrils, polymorphic and swollen mitochondria with disorganized cristae, and a great quantity of collagen fibrils. In conclusion, cardiac muscle sensitivity to isoproterenol and elevation of extracellular calcium concentration is preserved in middle-aged FR rats. The intrinsic muscle performance depression might be related to morphological damage.

Cardiovascular assessment in horses sedated with xylazine or amitraz

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Effects of isoflurane on Tei-index of myocardial performance in healthy dogs

Recently, the Tei-index, a noninvasive index that combines systolic and diastolic time intervals, has been proposed to assess global cardiac performance. However, the effects of isoflurane on the Tei-index have not been characterized. This study aimed at studying the effects of 1.0 minimal alveolar concentration isoflurane anesthesia on the pre-ejection period (PEP), left ventricular ejection time (LVET), PEP/LVET ratio, isovolumic relaxation time (IVRT), stroke index (SI), cardiac index (CI), heart rate (HR), and the Tei-index in healthy unpremedicated dogs. We observed significant increases in PEP, PEP/LVET ratio, IVRT, and TEI, whose maximal increases obtained throughout the study were 47%, 48%, 78%, and 56%, respectively. The LVET and HR did not change significantly, whereas the SI and CI decreased during anesthesia (29% and 26%, respectively). In conclusion, isoflurane produced direct effects on the Tei-index. The changes in systolic and diastolic parameters were supportive of this finding and were consistent with an overall impairment of left ventricular function during anesthesia.

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.

Influência do exercício físico na expressão da miostatina e folistatina no músculo sóleo de ratos com insuficiência cardíaca crônica

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Avaliação morfofisiológica do coração de atletas de diferentes modalidades esportivas

Pós-graduação em Pesquisa e Desenvolvimento (Biotecnologia Médica) - FMB

Mecanismos envolvidos na cardiotoxidade aguda induzida pela doxorrubicina em ratos

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Differential effects of variation in athletes training on myocardial morphophysiological adaptation in men: Focus on I-123-MIBG assessed myocardial sympathetic activity

High intensity systematic physical training leads to myocardial morphophysiological adaptations. The goal of this study was to investigate if differences in training were correlated with differences in cardiac sympathetic activity.58 males (19-47 years), were divided into three groups: strength group (SG), (20 bodybuilders), endurance group (EG), (20 endurance athletes), and a control group (CG) comprising 18 healthy non-athletes. Cardiac sympathetic innervation was assessed by planar myocardial I-123-metaiodobenzylguanidine scintigraphy using the early and late heart to mediastinal (H/M) ratio, and washout rate (WR).Left ventricular mass index was significantly higher both in SG (P < .001) and EG (P = .001) compared to CG without a statistical significant difference between SG and EG (P = .417). The relative wall thickness was significantly higher in SG compared to CG (P < .001). Both left ventricular ejection fraction and the peak filling rate showed no significant difference between the groups. Resting heart rate was significantly lower in EG compared to CG (P = .006) and SG (P = .002). The late H/M ratio in CG was significantly higher compared to the late H/M for SG (P = .003) and EG (P = .004). However, WR showed no difference between the groups. There was no significant correlation between the parameters of myocardial sympathetic innervation and parameters of left ventricular function.Strength training resulted in a significant increase in cardiac dimensions. Both strength and endurance training seem to cause a reduction in myocardial sympathetic drive. However, myocardial morphological and functional adaptations to training were not correlated with myocardial sympathetic activity.

Fatores de risco cardiovascular em mulheres com antecedente de pré-eclâmpsia e sua associação com hipertrofia miocárdica e espessamento médio-intimal de carótidas

Pós-graduação em Fisiopatologia em Clínica Médica - FMB

Higher incidence of death in multi-vessel coronary artery disease patients associated with polymorphisms in chromosome 9p21

Background: We investigated whether 9p21 polymorphisms are associated with cardiovascular events in a group of 611 patients enrolled in the Medical, Angioplasty or Surgery Study II (MASS II), a randomized trial comparing treatments for patients with coronary artery disease (CAD) and preserved left ventricular function. Methods: The participants of the MASS II were genotyped for 9p21 polymorphisms (rs10757274, rs2383206, rs10757278 and rs1333049). Survival curves were calculated with the Kaplan-Meier method and compared with the log-rank statistic. We assessed the relationship between baseline variables and the composite end-point of death, death from cardiac causes and myocardial infarction using a Cox proportional hazards survival model. Results: We observed significant differences between patients within each polymorphism genotype group for baseline characteristics. The frequency of diabetes was lower in patients carrying GG genotype for rs10757274, rs2383206 and rs10757278 (29.4%, 32.8%, 32.0%) compared to patients carrying AA or AG genotypes (49.1% and 39.2%, p = 0.01; 52.4% and 40.1%, p = 0.01; 47.8% and 37.9%, p = 0.04; respectively). Significant differences in genotype frequencies between double and triple vessel disease patients were observed for the rs10757274, rs10757278 and rs1333049. Finally, there was a higher incidence of overall mortality in patients with the GG genotype for rs2383206 compared to patients with AA and AG genotypes (19.5%, 11.9%, 11.0%, respectively; p = 0.04). Moreover, the rs2383206 was still significantly associated with a 1.75-fold increased risk of overall mortality (p = 0.02) even after adjustment of a Cox multivariate model for age, previous myocardial infarction, diabetes, smoking and type of coronary anatomy. Conclusions: Our data are in accordance to previous evidence that chromosome 9p21 genetic variation may constitute a genetic modulator in the cardiovascular system in different scenarios. In patients with established CAD, we observed an association between the rs2383206 and higher incidence of overall mortality and death from cardiac causes in patients with multi-vessel CAD.