Effects of leucine supplementation and serum withdrawal on branched-chain amino acid pathway gene and protein expression in mouse adipocytes

10.1371/journal.pone.0102615PLoS ONE97e10261

Reduced pH and contractility in failing rat cardiomyocytes

Aim: To determine whether reduced cardiomyocyte contractility in heart failure is associated with reduced intracellular pH (pHi). Involvement of the Na+/H+ exchanger and the H+/K+ ATPase were investigated with specific blockers. Methods: Myocardial infarction and subsequent heart failure in Sprague Dawley rats were induced by chronic occlusion of the left coronary artery. 6 weeks post-ligation, contractility (cell shortening) and pHi (BCECF fluorescence) were recorded in freshly dissociated cardiomyocytes during 2-10 Hz electrical stimulation, with or without either Na+/H+ exchanger or H+/K+ ATPase inhibition. Results: Elevatedend-diastolic and reduced peak systolic pressures confirmed heart failure. Increased heart weights (20-30%; P <= 0.01) and cardiomyocyte lengths and widths (22-25%; P <= 0.01) confirmed substantial cardiac hypertrophy. In myocytes isolated from sham operated rats, a positive staircase response occurred with stimulation rates from 2 to 7 Hz; further increases in stimulation rate up to 10 Hz reduced contractility. In contrast, pHi fell progressively over the entire stimulation range. In failing myocytes, pHi was consistently 0.07 pH units lower and contractility 40% lower (P <= 0.01) than sham control values; the shape of the contractility staircase remained similar to controls. At all stimulation frequencies, Na+/H+ exchanger inhibition reduced pHi by 0.05 pH units (P <= 0.01) and contractility by 22% ( P <= 0.05) in cardiomyocytes from the heart failure group. A significantly smaller decrease of pHi and reduction in contractility was observed after inhibition of Na+/H+ exchanger (10 mu m HOE694) in sham myocytes. H+/K+ ATPase inhibition (100 mu m SCH28080) had no effect on pHi. Conclusion: Reduced pHi is accompanied by reduced cardiomyocyte contractility in isolated myocytes from post-MI heart failure. The data suggest compensatory Na+/H+ exchanger activation in heart failure, whereas H+/K+ ATPase does not appear to contribute significantly to pHi maintenance

Holter electrocardiography in dogs showing doxorubicin-induced dilated cardiomyopathy Eletrocardiografia Holter em cães com cardiomiopatia dilatada experimental induzida pela doxorrubicina

Early identification of arrhythmias in dogs showing doxorubicin-induced cardiomyopathy was studied. Ten healthy dogs were assigned to groups A (n=5) and B (n=5). Dogs from group B were given doxorubicin 30mg/m² intravenously, every 21 days, until a cumulative dose of 180mg/m² or 240mg/m² was reached. Dogs from group A (used as control) were administered saline intravenously at the same group B intervals. As soon as myocardium dysfunction was observed in dogs from group B, determined by a shortening fraction below 20%, increased E-point to septal separation above 0.7cm, and increased end-systolic left ventricular volume index (61.4ml/m²), a 24-hour Holter was recorded in all dogs from both groups. There was an increase of minimum heart rate (44.6%) and mean heart rate (41.7%) in animals from group B in comparison with the control animals. Either supraventricular or ventricular arrhythmias were observed, despite group B dogs showed higher occurrence of supraventricular arrhytmias. Holter monitoring is efficient in early determination of heart rate and cardiac rhythm alterations in dogs showing doxorubicin-induced myocardial dysfunction.<br>O estudo consistiu na identificação precoce da ocorrência de arritmias em cães com cardiomiopatia dilatada experimental induzida pela doxorrubicina (DOX). Utilizaram-se 10 cães adultos, sadios, distribuídos nos grupos A (n=5) e B (n=5). O grupo B recebeu 30mg/m² de DOX, via intravenosa, a cada 21 dias, até a dose cumulativa de 180 ou 240mg/m². No grupo A (controle), administrou-se solução salina 0,9%, via intravenosa, nos mesmos intervalos do grupo B. Ao se evidenciar o quadro de disfunção miocárdica nos cães do grupo B, caracterizado pela fração de encurtamento menor que 20%, aumento da separação septal do ponto E acima de 0,7cm e aumento do índice volumétrico do ventrículo esquerdo ao final da sístole (61,4ml/m²), realizaram-se os eletrocardiogramas por 24 horas. Os resultados demonstraram aumentos de 44,6% e 41,7% nas freqüências cardíacas mínima e média, respectivamente, e presença, com maior freqüência, de arritmias supraventriculares do que ventriculares nos animais do grupo B. Concluiu-se que o Holter é eficaz e demonstra, com precocidade e melhor definição, as alterações da freqüência e do ritmo cardíaco de cães com disfunção miocárdica induzida pela doxorrubicina