Myocardial injury-related changes in plasma NT-proBNP and ANP concentrations in a canine model of ischemic myocardial injury.

Serial changes in plasma N-terminal pro-B-type natriuretic peptide (NT-proBNP) and atrial natriuretic peptide (ANP) concentrations are unknown in dogs with myocardial injury. The time-course secretory responses between NT-proBNP and ANP or cardiac troponin-T (cTnT) related to myocardial infarction (MI) were investigated in this study. Six dogs were anaesthetised and the left anterior descending artery was ligated. A transient decrease in cardiac function was detected 1h after MI but returned to baseline levels within 7 days and remained so for 6 months. Echocardiographic examination revealed focal ventricular dyskinesis throughout the study. Six months following MI, the left atrium to aorta ratio increased significantly although the relative wall thickness decreased significantly from baseline. Significantly elevated plasma NT-proBNP and cTnT concentrations were detected 1 day after MI and these gradually decreased over 28 days to baseline levels without left ventricular pressure elevation. Plasma ANP was elevated significantly 6 months after MI. The NT-proBNP assay is a helpful diagnostic indicator for identifying asymptomatic acute and subacute myocardial injury whereas plasma ANP concentration mainly reflects atrial dilation.

Differences in the duration of diuretic effects and impact on the renin-angiotensin-aldosterone system of furosemide in healthy dogs.

Our aim was to investigate the differences in the duration of diuretic effects and impact on the renin-angiotensin-aldosterone (RAA) system of furosemide as a model of short- and long-acting loop diuretics. Anesthetized dogs (n=6) were randomized into placebo, intravenous bolus administration (IB) and chronic rate infusion (CRI) groups. This study was conducted with a crossover study. Furosemide (4 mg/kg) was diluted to 18 mL in sterile saline. Furosemide was infused at 0.5 mg/kg/hr for 8 hr in the CRI group or was injected at 0 and 4 hr (both 2 mg/kg) in the IB group. Blood and urine samples were collected at baseline and at 1, 2, 4, 5, 6 and 8 hr. Compared with the baseline, the IB group had a significantly increased urine output at 1 and 5 hr. The CRI group had a significantly increased urine output persisting for 4 hr compared with the baseline. Compared with the placebo group, 8-hr urine output and 8-hr sodium excretion were significantly increased in the IB and CRI groups; the values in the CRI group were significantly higher than those in the IB group. Eight-hour potassium excretion was significantly increased in the IB and CRI groups. The plasma aldosterone concentration was significantly elevated in the IB group at 8 hr. Duration of action may be a predominant cause of loop diuretic-related differences. Persistent diuresis may cause greater diuretic effects than transient diuresis, with less elevation of the plasma aldosterone concentration.

Mouse homologues of Shisa antagonistic to Wnt and Fgf signalings.

In an effort to identify Otx2 targets in mouse anterior neuroectoderm we identified a gene, mShisa, which is homologous to xShisa1 that we previously reported as a head inducer in Xenopus. mShisa encodes an antagonist against both Wnt and Fgf signalings; it inhibits these signalings cell-autonomously as xShisa1 does. The mShisa expression is lost or greatly reduced in Otx2 mutant visceral endoderm, anterior mesendoderm and anterior neuroectoderm. However, mShisa mutants exhibited no defects in head development. Shisa is composed of five subfamilies, but normal head development in mShisa mutants is unlikely to be explained in terms of the compensation of mShisa deficiency by its paralogues or by known Wnt antagonists in anterior visceral endoderm and/or anterior mesendoderm.