Baseline cardiac magnetic resonance imaging versus baseline endomyocardial biopsy for the prediction of left ventricular reverse remodeling and prognosis in response to therapy in patients with idiopathic dilated cardiomyopathy.

Endomyocardial biopsy (EMB) and late gadolinium enhancement cardiovascular magnetic resonance (LGE-CMR) imaging performed at baseline are both used to evaluate the extent of myocardial fibrosis. However, no study has directly compared the effectiveness of these diagnostic tools in the prediction of left ventricular reverse remodeling (LVRR) and prognosis in response to therapy in patients with idiopathic dilated cardiomyopathy (IDCM). Seventy-five patients with newly diagnosed IDCM who were undergoing optimal therapy were assessed at baseline using LGE-CMR imaging and EMB; the former measured LGE area and the latter measured collagen volume fraction (CVF) as possible predictive indices of LVRR and cardiac event-free survival. Among all the baseline primary candidate factors with P < 0.2 as per univariate analysis, multivariate analysis indicated that only LGE area was an independent predictor of subsequent LVRR (ß = 0.44; 95 % confidence interval (CI) 0.87-2.53; P < 0.001), as indicated by decreasing left ventricular end-systolic volume index over the 1-year follow-up. Kaplan-Meier curves indicated significantly lower cardiac event-free survival rates in patients with LGE at baseline than in patients without (P < 0.01). By contrast, there was no significant difference in prognosis between patients with CVF values above (severe fibrosis) and below (mild fibrosis) the median of 4.9 %. Cox proportional hazard analysis showed that LGE area was an independent predictor of subsequent cardiac events (hazard ratio 1.06; 95 % CI 1.02-1.10; P ≤ 0.01). The degree of myocardial fibrosis estimated by baseline LGE-CMR imaging, but not that estimated by baseline EMB, can predict LVRR and cardiac event-free survival in response to therapy in patients with newly diagnosed IDCM.

Clinical significance of heart rate during acute decompensated heart failure to predict left ventricular reverse remodeling and prognosis in response to therapies in nonischemic dilated cardiomyopathy.

Although an increased heart rate (HR) is a strong predictor of poor prognosis in cases of chronic heart failure (HF), the clinical value of HR as a predictor in acute decompensated HF (ADHF) is unclear. Seventy-eight patients with nonischemic dilated cardiomyopathy (NIDCM) with sinus rhythm who were first hospitalized for ADHF from 2002 to 2010 were retrospectively investigated after exclusion of patients with tachycardia-induced cardiomyopathy. The patients were divided into two groups stratified by HR on admission with a median value of 113 beats/min (Group H with HR ≥ 113 beats/min; Group L with HR < 113 beats/min). Despite similar backgrounds, including pharmacotherapy for HF, HR changes responding to titration of ß-blocker (BB) therapy and myocardial interstitial fibrosis, left ventricular (LV) ejection fractions improved more significantly 1 year later in Group H than in Group L (57 % ± 11 % vs. 46 % ± 12 %, P < 0.001). Cardiac event-free survival rates were also significantly improved in Group H (P = 0.038). Multiple regression analysis revealed that only the peak HR on admission was an independent predictor of LV reverse remodeling (LVRR) 1 year later (ß = 0.396, P = 0.005). High HR on first admission for ADHF is a strong predictor of LVRR, with a better prognosis in the event of NIDCM in response to optimal pharmacotherapy, independent of pre-existing myocardial damage and subsequent HR reduction by BB therapy.

Molecular characterization and transcriptional regulation of nitrate reductase in a ruminal bacterium, Selenomonas ruminantium.

Nitrate reductase (NaR) of a strain of Selenomonas ruminantium was purified, and the gene encoding NaR (nar) was sequenced. The 6.4 kbp nar gene consisted of narG, H, J, and I in this order. The deduced amino acid sequences of these subunits resembled those of membrane-bound nitrate reductase-A reported for Escherichia coli. It was shown that narG, H, J, and I are transcribed as a single polycistronic message (nar operon). The level of intracellular nar-mRNA was higher when S. ruminantium was grown with nitrate than when grown without nitrate, suggesting that nar transcription is enhanced by nitrate. The level of nar-mRNA, which was in parallel to the amount of NaR per cellular nitrogen, was suggested to be enhanced in response to the deficiency of energy and electron supply. Therefore, NaR synthesis in S. ruminantium appeared to be regulated at the transcriptional level in response to the availability of energy and electrons. S. ruminantium reduced nitrate and fumarate simultaneously with no significant effect of fumarate on nar transcription. Addition of fumarate stimulated nitrate reduction, which was caused by increased cell growth because of increased acquirement of ATP via electron transport phosphorylation coupled with fumarate reduction.

Structure and transcriptional regulation of the gene encoding pyruvate formate-lyase of a ruminal bacterium, Streptococcus bovis.

The gene (pfl) encoding pyruvate formate-lyase (Pfl) from Streptococcus bovis was sequenced. The deduced amino acid sequence of Pfl was similar to Streptococcus mutans Pfl, and included the conserved regions necessary for free-radical formation and a catalytic site. The Pfl of S. bovis appeared to be a free-radical-containing enzyme because of its dioxygen sensitivity and its amino acid sequence similarity with the Escherichia coli enzyme. The pfl mRNA of S. bovis was approximately 2.3 kb and was transcribed in a monocistronic fashion. When cells were grown in batch culture at pH 6.9, the level of pfl transcript increased as the growth phase changed from exponential growth to stationary phase. This result was in constrast to the previous observation that the level of lactate dehydrogenase (Ldh) mRNA decreased during the later stages of growth. Continuous culture experiments conducted at pH 6.9 under glucose-limited and ammonia-limited conditions revealed that pfl mRNA was decreased by an excess supply of glucose, as well as by a high growth rate. On the contrary, ldh mRNA increased when excess glucose was supplied and the growth rate was high. The amount of pfl mRNA in cells was lower at pH 4.5 than pH 6.9, whereas the level of ldh mRNA was higher at pH 4.5. This result was consistent with the amounts of Pfl and Ldh in cells and the proportion of formate and lactate produced. These results support the hypothesis that S. bovis regulates Pfl and Ldh synthesis at the transcriptional level in response to growth conditions.

Regulation of lactate dehydrogenase synthesis in a ruminal bacterium, Streptococcus bovis.

Lactate dehydrogenase (LDH) was purified from three strains of Streptococcus bovis, and the gene ldh was cloned and sequenced. The ldh of S. bovis from a goat (TH1) was different from the ldhs of two other strains from cattle (TH2, JB1) in that Asp(220) was substituted for Glu. Northern blot analysis revealed that the LDH-mRNA of S. bovis was approximately 1.0 kbp, which was transcribed in a monocistronic fashion. When cells were grown at pH 6.9 in a batch culture, the level of ldh transcript decreased as the growth phase changed; from exponential growth to the cessation of growth. The level of ldh transcript was higher in cells grown at pH 4.5 than at pH 6.9. This observation was consistent with the amounts of LDH in cells and the percentages of lactate produced. These results support the hypothesis that S. bovis regulates LDH synthesis at the transcriptional level probably in response to intracellular pH.