Cardiac gene expression and systemic cytokine profile are complementary in a murine model of post-ischemic heart failure

After myocardial infarction (MI), activation of the immune system and inflammatory mechanisms, among others, can lead to ventricular remodeling and heart failure (HF). The interaction between these systemic alterations and corresponding changes in the heart has not been extensively examined in the setting of chronic ischemia. The main purpose of this study was to investigate alterations in cardiac gene and systemic cytokine profile in mice with post-ischemic HF. Plasma was tested for IgM and IgG anti-heart reactive repertoire and inflammatory cytokines. Heart samples were assayed for gene expression by analyzing hybridization to AECOM 32k mouse microarrays. Ischemic HF significantly increased the levels of total serum IgM (by 5.2-fold) and total IgG (by 3.6-fold) associated with a relatively high content of anti-heart specificity. A comparable increase was observed in the levels of circulating pro-inflammatory cytokines such as IL-1â (3.8X) and TNF-á (6.0X). IFN-ã was also increased by 3.1-fold in the MI group. However, IL-4 and IL-10 were not significantly different between the MI and sham-operated groups. Chemokines such as MCP-1 and IL-8 were 1.4- and 13-fold increased, respectively, in the plasma of infarcted mice. We identified 2079 well annotated unigenes that were significantly regulated by post-ischemic HF. Complement activation and immune response were among the most up-regulated processes. Interestingly, 21 of the 101 quantified unigenes involved in the inflammatory response were significantly up-regulated and none were down-regulated. These data indicate that post-ischemic heart remodeling is accompanied by immune-mediated mechanisms that act both systemically and locally.

Cardiac gene expression and systemic cytokine profile are complementary in a murine model of post-ischemic heart failure.

After myocardial infarction (MI), activation of the immune system and inflammatory mechanisms, among others, can lead to ventricular remodeling and heart failure (HF). The interaction between these systemic alterations and corresponding changes in the heart has not been extensively examined in the setting of chronic ischemia. The main purpose of this study was to investigate alterations in cardiac gene and systemic cytokine profile in mice with post-ischemic HF. Plasma was tested for IgM and IgG anti-heart reactive repertoire and inflammatory cytokines. Heart samples were assayed for gene expression by analyzing hybridization to AECOM 32k mouse microarrays. Ischemic HF significantly increased the levels of total serum IgM (by 5.2-fold) and total IgG (by 3.6-fold) associated with a relatively high content of anti-heart specificity. A comparable increase was observed in the levels of circulating pro-inflammatory cytokines such as IL-1beta (3.8X) and TNF-alpha (6.0X). IFN-gamma was also increased by 3.1-fold in the MI group. However, IL-4 and IL-10 were not significantly different between the MI and sham-operated groups. Chemokines such as MCP-1 and IL-8 were 1.4- and 13-fold increased, respectively, in the plasma of infarcted mice. We identified 2079 well annotated unigenes that were significantly regulated by post-ischemic HF. Complement activation and immune response were among the most up-regulated processes. Interestingly, 21 of the 101 quantified unigenes involved in the inflammatory response were significantly up-regulated and none were down-regulated. These data indicate that post-ischemic heart remodeling is accompanied by immune-mediated mechanisms that act both systemically and locally.

[Effects of food temperature on the esophageal motility in Chagas' megaesophagus. Manometric study]. / Efeito da temperatura dos ingesta sobre a motilidade esofagiana no megaesôfago chagásico. Estudo manométrico.

The authors studied the effects of food temperature in esophageal motility by the use of manometry in 26 cases of chagasic megaesophagus of hyperkinetic type. An assembly of three water filled polyvinyl catheters was used. Each catheter had a distal side hole and was connected proximally with a transducer. One catheter was localized at the lower esophageal sphincter and the other two respectively 5 cm and 10 cm above the sphincter. Pressure changes were recorded graphically on a direct writing multichannel recorder. 50 ml of water was introduced into the esophagus at 5 degrees C, 20 degrees C, 35 degrees C, and 50 degrees C. This produced incoordinated contractions at the three levels considered. The motility pressures were quantified by planimetry and transformed in areas of mm2. A statistic analysis showed that more activity accured with extreme temperature, specially with the water at 5 degrees C. This fact permits one to understand the reason of increasing dysphagia in patients with chagasic megaesophagus when very hot food is eaten.

Efeito da temperatura dos ingesta sobre a motilidade esofagiana no megaesofago chagasico. Estudo manometrico. / Effects of food temperature on the esophageal motility in Chagas megaesophagus. Manometric study

Os autores estudaram, pelo metodo manometrico os efeitos da temperatura dos ingesta na motilidade esofagiana em 27 casos de megaesofago chagasico do tipo hipercinetico. Utilizaram um sistema de registro de inscricao direta e um triplice cateter com orificios distais localizados, respectivamente no esfincter interior do esofago, a 5 cm e a 10 cm acima do esfincter. A introducao de 50 ml de agua no esofago a quatro diferentes temperaturas - 5 grados centigrados, 20 grados centigrados, 35 grados centigrados e 50 grados centigrados - produziu resposta motora incoordenada nos tres niveis considerados, que foi quantificada por planimetria e transformada em area, expressa em mm2. A analise estatistica demonstrou ocorrer maior atividade com as temperaturas extremas, especialmente com a agua a 5 grados centigrados. Este fato permite compreender a acentuacao da disfagia referida pelos portadores de megaesofago quando ingerem alimentos muito frios ou muito quentes