Background-Nesiritide (synthetic human brain natriuretic peptide) is approved for the treatment of symptomatic heart failure. However, studies of brain natriuretic peptide in patients with heart failure have come to conflicting conclusions about effects on glomerular filtration rate (GFR), effective renal plasma flow, natriuresis, and diuresis. Methods and Results-To identify a population at high risk of renal dysfunction with conventional treatment, we selected patients with a creatinine level increased from baseline (within 6 months). We examined the effects of nesiritide on GFR (measured by iothalamate clearance), renal plasma flow (measured by para-amino hippurate clearance), urinary sodium excretion, and urine output in a double-blind, placebo-controlled, crossover study. Patients received nesiritide (2 g/kg IV bolus followed by an infusion of 0.01 g/kg per minute) or placebo for 24 hours on consecutive days. Nesiritide and placebo data were compared by repeated-measures analysis and Student t test. We studied 15 patients with a recent mean baseline creatinine of 1.5Ϯ0.4 mg/dL and serum creatinine of 1.8Ϯ0.8 mg/dL on admission to the study. There were no differences in GFR, effective renal plasma flow, urine output, or sodium excretion for any time interval or for the entire 24-hour period between the nesiritide and placebo study days. For 24 hours, urine output was 113Ϯ51 mL/h with placebo and 110Ϯ56 mL/h with nesiritide. GFR during placebo was 40.9Ϯ25.9 mL/min and with nesiritide was 40.9Ϯ25.8. Conclusions-Nesiritide did not improve renal function in patients with decompensated heart failure, mild chronic renal insufficiency, and renal function that had worsened compared with baseline. The lack of effect may be related to renal insufficiency, hemodynamic alterations, sodium balance, severity of heart failure, or drug dose. Understanding the importance of these issues will permit effective and appropriate use of nesiritide.

Bark-included junctions are frequently encountered defects within the aerial structures of trees. The presence of included bark within a branch junction can substantially reduce the junction’s factor of safety. Recent research has found naturally occurring bracing to be a primary cause of the formation of included bark within branch junctions. This study tested the load-bearing capacity of branch junctions in hawthorn (Crataegus monogyna Jacq.) using rupture tests and compared the mechanical performance of “control” branch junctions, bark-included junctions with the natural bracing retained, and bark-included junctions where we had intentionally removed their natural braces by cutting them out. Substantial variability was observed in the failure kinematics of bark-included branch junctions when their natural braces were retained. The type of natural brace present affected the mode of failure of the branch junctions when pulled apart. A single specimen with fused branches presented the strongest form of natural brace in this study, followed by entwining branches, whereas crossing branches were found to provide the least mechanical resistance. This study provides initial evidence that the type of associated natural brace is an important consideration when an arborist is trying to assess the likely mechanical performance of a bark-included junction within a tree and its likelihood of failure.

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