Cardiogenic shock after ST elevation myocardial infarction and IABP-SHOCK II risk score validation in a cohort treated with pharmacoinvasive strategy.

Objective: To validate the Intra-aortic Balloon Pump in Cardiogenic Shock II (IABP-SHOCK II) score in patients with cardiogenic shock after ST elevation myocardial infarction (STEMI) treated with pharmacoinvasive strategy (PhIS) and to analyse the influence of ischaemia time on different risk strata. Methods: We analysed 2143 patients with STEMI who underwent reperfusion with tenecteplase in primary health services between May 2010 and April 2017 and were transferred to a tertiary hospital for cardiac catheterisation and continuity of care. Those who evolved to cardiogenic shock were scored as low (0-2), moderate (3-4) or high (5-9) risk of death in 30 days and pairwise-log-rank test was used to compare strata. Time intervals between symptoms onset and lytic (pain-to-needle) and fibrinolytic-catheterisation were also compared. Results: Cardiogenic shock occurred in 212 (9.9%) individuals. The 30-day mortality using the IABP-SHOCK II score was 26.6% for low-risk (n=94), 53.2% for moderate-risk (n=62) and 76% for high-risk (n=25) analysed patients (p<0.001). Validation of the score showed good discrimination for death, area under the curve of 0.73 (CI: 0.66 to 0.81; p<0.001). The median intervals of pain-to-needle and fibrinolytic-catheterisation showed no association with the group stratification (220 vs 251 vs 200 min; p=0.22 and 390 vs 435 vs 315 min; p=0.18, respectively). Conclusions: In patients with cardiogenic shock after STEMI treated with PhIS, risk stratification using IABP-SHOCK II score was adequate. There was no influence of pain-to-needle and fibrinolytic-catheterisation times on the ability to the score model stratification.

The influence of orexins on ethanol-induced behavioral sensitization in male mice.

Recent evidence indicates the involvement of orexin in reward circuitry and drug addiction. In the present study we evaluated the role of orexin in ethanol-induced behavioral sensitization. In the first experiment, Swiss male mice received seven administrations of saline or ethanol (2.2g/kg, i.p., chronic), every other day. On the last day of treatment, half of saline-treated mice received a saline injection (saline) whereas the other half received 2.2g/kg of ethanol (i.p., acute). Behavioral sensitization was assessed by locomotor activity tests and after the last one, immunoreactivity for orexin and Fos (ORX+Fos-ir) was assessed in the lateral hypothalamic area. Chronic ethanol treatment produced behavioral sensitization and a trend for greater ORX+Fos-ir. In the second experiment, mice were treated as in Experiment 1 and type 1 orexin receptor antagonist, SB334867 (20mg/kg), was administered before the ethanol challenge successfully blocking the expression of sensitization in mice chronically treated with EtOH. These results indicate that orexin plays a role in ethanol-induced behavioral sensitization.

Paradoxical sleep deprivation activates hypothalamic nuclei that regulate food intake and stress response.

A large body of evidence has shown that prolonged paradoxical sleep deprivation (PSD) results in hypothalamic-pituitary-adrenal (HPA) axis activation, and in loss of body weight despite an apparent increase of food intake, reflecting increased energy expenditure. The flowerpot technique for PSD is an efficient paradigm for investigating the relationships among metabolic regulation and stress response. The purpose of the present study was to examine the mechanisms involved in the effects of 96 h of PSD on metabolism regulation, feeding behaviour and stress response by studying corticotrophin-releasing hormone (CRH) and orexin (ORX) immunoreactivity in specific hypothalamic nuclei. Once-daily assessments of body weight, twice-daily measurements of (spillage-corrected) food intake, and once-daily determinations of plasma adrenocorticotropic hormone (ACTH) and corticosterone were made throughout PSD or at corresponding times in control rats (CTL). Immunoreactivity for CRH in the paraventricular nucleus of the hypothalamus and for ORX in the hypothalamic lateral area was evaluated at the end of the experimental period. PSD resulted in increased diurnal, but not nocturnal, food intake, producing no significant changes in global food intake. PSD augmented the immunoreactivity for CRH and plasma ACTH and corticosterone levels, characterizing activation of the HPA axis. PSD also markedly increased the ORX immunoreactivity. The average plasma level of corticosterone correlated negatively with body weight gain throughout PSD. These results indicate that augmented ORX and CRH immunoreactivity in specific hypothalamic nuclei may underlie some of the metabolic changes consistently described in PSD.

Long maternal separation accelerates behavioural sensitization to ethanol in female, but not in male mice.

Early life stress is associated with dysfunction of the hypothalamic-pituitary-adrenal (HPA) axis, and with aspects involved in drug abuse. In this study, we investigated the effects of brief (BMS) and long maternal separation (LMS) on the HPA axis response and behavioural sensitization to ethanol (EtOH) in male and female mice. From PND 2 to 14, pups were subjected to daily maternal separation for 15 min (BMS) or 180 min (LMS) or no separated, only handled during cage cleaning (animal facility rearing-AFR). As adults, animals were treated every other day with saline (SAL) or EtOH (2.2g/kg), i.p., for 10 days, and immediately after each administration, their locomotor response was evaluated for 15 min. Forty-eight hours after the 5th administration, all animals were challenged with saline, followed 48 h later, by an EtOH challenge. Corticosterone (CORT) plasma levels were determined 3 times: basal, after the 1st administration and after the EtOH challenge. LMS females showed higher CORT levels than BMS females at basal, but not in response to acute or chronic EtOH administration. The CORT response to EtOH was more robust in LMS and BMS male than AFR male mice. Repeated EtOH treatment induced behavioural sensitization in all groups of male mice. In females, LMS induced a faster sensitization, although BMS females also exhibited behavioural sensitization (4th day and 5th day of treatment, respectively). In conclusion, LMS and BMS produced gender-dependent effects. In females, LMS and BMS facilitated the development of behavioural sensitization, but in the LMS group this effect occurred faster, which may represent increased vulnerability to drug abuse. Moreover, LMS females showed higher basal CORT levels compared to BMS. In males, LMS and BMS increased the CORT response to EtOH but did not modify behavioural sensitization. Therefore, we postulate that LMS female mice exhibited a faster development of behavioural sensitization, but CORT levels were not involved with this effect.