Disconnect between the effects of serelaxin on renal function and outcome in acute heart failure.

BACKGROUND: We aimed to study whether improvement in renal function by serelaxin in patients who were hospitalized for acute heart failure (HF) might explain any potential effect on clinical outcomes. METHODS: We included 6318 patients from the RELAXin in AHF-2 (RELAX-AHF2) study. Improvement in renal function was defined as a decrease in serum creatinine of ≥ 0.3 mg/dL and ≥ 25%, or increase in estimated glomerular filtration rate of ≥ 25% between baseline and day 2. Worsening renal function (WRF) was defined as the reverse. We performed causal mediation analyses regarding 180-day all-cause mortality (ACM), cardiovascular death (CVD), and hospitalization for HF/renal failure. RESULTS: Improvement in renal function was more frequently observed with serelaxin when compared with placebo [OR 1.88 (95% CI 1.64-2.15, p < 0.0001)], but was not associated with subsequent clinical outcomes. WRF occurred less frequent with serelaxin [OR 0.70 (95% CI 0.60-0.83, p < 0.0001)] and was associated with increased risk of ACM, worsening HF and the composite of CVD and HF or renal failure hospitalization. Improvement in renal function did not mediate the treatment effect of serelaxin [CVD HR 1.01 (0.99-1.04), ACM HR 1.01 (0.99-1.03), HF/renal failure hospitalization HR 0.99 (0.97-1.00)]. CONCLUSIONS: Despite the significant improvement in renal function by serelaxin in patients with acute HF, the potential beneficial treatment effect was not mediated by improvement in renal function. These data suggest that improvement in renal function might not be a suitable surrogate marker for potential treatment efficacy in future studies with novel relaxin agents in acute HF. Central illustration. Conceptual model explaining mediation analysis; treatment efficacy of heart failure therapies mediated by renal function.

Hypothalamic biogenic amine levels in broiler chicks showing advanced sexual maturation.

Parasagittal knife cuts through the lateral hypothalamic area of 2-wk-old male broiler chicks induced precocious testes development. Two experiments were performed to determine whether hypothalamic biogenic amine levels in these chicks were changed by lateral hypothalamic deafferentation. In Experiment 1, chicks responding to surgery with advanced sexual maturation had reduced levels of norepinephrine (NE), epinephrine (E), and homovanillic acid (HVA) in the anterior hypothalamus and elevated levels of dopamine (DA) and serotonin in the median eminence, compared with controls. In Experiment 2, NE and HVA were reduced in the anterior hypothalamus of nonresponders. Dopamine was reduced in the anterior hypothalamus of nonresponders and elevated in the median eminence of responders. Serotonin was found to be higher in the median eminence of nonresponders. The increased DA in the median eminence suggests an excitatory role for this neurotransmitter in gonadotropin release at puberty.

Robust feeding following central administration of neuropeptide Y or peptide YY in chicks, Gallus domesticus.

Neuropeptide Y (NPY) and peptide YY (PYY) were injected intracerebroventricularly (ICV) in broiler chicks. Both NPY and PYY markedly increased food intake during the first hour post-injection compared to saline (SAL) controls. Food intake doubled in chicks given 5 micrograms NPY. A response surface analysis suggested that following ICV injection of NPY, maximum food intake occurred, using a dose of 9 micrograms. In contrast, an estimated dose between one and 5 micrograms PYY resulted in maximum food intake, giving the latter a slightly higher potency. Time spent drinking was not significantly different among NPY, PYY and SAL groups. Chicks given NPY or PYY also spent significantly less time standing while those given PYY spent significantly less time preening compared to controls.