Effect of Sacubitril/Valsartan on circulating catecholamine levels during a 6-month follow-up in heart failure patients. Timeo Danaos et dona ferentes?

We assessed the effect of Sacubitril/Valsartan on circulating catecholamine levels in patients with HF in an observational cohort study. We included 108 consecutive HF patients attending our HF Outpatients Clinic who were eligible to Sacubitril/Valsartan according to the PARADIGM-HF inclusion and exclusion criteria. We furthermore included 58 stable HF patients under optimal medical therapy as a control group. Norepinephrine and epinephrine were measured with immunoradiometric assays at baseline, at 3- and at 6-month time follow-up. Compared to baseline levels there was no change at three months in epinephrine (p = 0.177) or norepinephrine (p = 0.815) concentrations. At 6 months norepinephrine remained unchanged (p = 0.359). However, at 6 months we observed a significant increase in epinephrine levels compared to baseline [66 pg/mL (37-93) vs 38 pg/mL (18-74), p < 0.001]. In the control group no change was observed in epinephrine levels compared to baseline (p = 0.838). This study is the first to report on the effect of the new drug Sacubitril/Valsartan on circulating catecholamine levels in HF patients. Our data show a significant increase in epinephrine levels during a 6 month follow up in stable HF patients.

Dexmedetomidine effects in different experimental sepsis in vivo models.

Sepsis is a major cause of death and the most common cause of death among critically ill, non-ICU patients. Dexmedetomidine (DEX), an 2 adrenergic receptor agonist, presents sympatholytic action in certain parts of the brain with anxiolytic, sedative, and pain killing effects. Additionally, through the activation of 7 nicotinic acetylcholine receptor receptors, DEX reduces cytokine transcription and inhibits inflammation, rendering it beneficial during septic conditions. Moreover, there is a lot of interest in designing experimental sepsis models, where the administration of DEX is evaluated for its impact on multiple systems. This review focuses on experimental studies published between 1999 to March 2019 that were using DEX administration in sepsis in vivo models. From these, 36 articles were selected and summarized. Overall results show evidence that DEX may decrease mortality and inhibit inflammation, as it enhances the activity of the immune system while reducing its systemic reaction and lowering cytokine concentrations. Moreover DEX succeeds to alleviate heart injury during sepsis, acting beneficially for microcirculation and shows a neuroprotective role by inhibiting apoptotic pathways. In addition, DEX appears to have a protective role for liver and spleen as well as a beneficial role for the function of lungs and kidneys as it reduces sepsis-induced injuries and apoptosis in intra-abdominal experimental sepsis models.