5-year mortality in cardiac surgery patients with low cardiac output syndrome treated with levosimendan: prognostic evaluation of nt-probnp and c-reactive protein.

AIM: To determine the clinical risk factors predictive of the 5--year mortality in patients with low cardiac output syndrome (LCOS) after cardiac surgery. In addition, to assess the influence of inflammation and myocardial dysfunction severity, as measured by C--reactive protein (CRP) and N--terminal pro--brain natriuretic peptide (NT--proBNP) concentrations, on outcome. METHODS: We studied 30 patients who underwent cardiac surgery and developed postoperative LCOS requiring inotropic support for longer than 48 hours after intensive care unit (ICU) admission. All patients received a 24--hour infusion of levosimendan after study enrolment. We measured the following at baseline, 24 h, 48 h and 7 days: clinical data, serum NT--proBNP and serum CRP levels. Patients were followed--up at 5 years for death by any cause. A risk--adjusted Cox proportional hazards regression model was used for statistical analysis. Hazard ratios and their 95% confidence intervals (CI) are presented. RESULTS: The 5--year mortality was 36.6% (n = 11). The predictors of 5--year mortality were the presence of dilated cardiomyopathy (HR = 36.909; 95% CI: 1.901-716.747; P = 0.017), a higher central venous pressure (CVP) at 48 hours (HR = 2.686; 95% CI: 1.383-5.214; P = 0.004), and lower CRP levels on day 7 (HR = 0.963; 95% CI: 0.933-0.994; P = 0.021). NT--proBNP levels showed a trend to higher initial levels in survivors without statistical significance, but were not associated with 5--year mortality. CONCLUSIONS: The presence of dilated cardiomyopathy, elevated CVP at 48 h and reduced CRP levels on day 7 predicted 5--year mortality in patients who developed postoperative LCOS after cardiac surgery. NT--proBNP levels in the first postoperative week were not predictors of long--term outcomes.

Context-specific social behavior is altered by orbitofrontal cortex lesions in adult rhesus macaques.

Although the orbitofrontal cortex has been implicated in important aspects of social behavior, few studies have evaluated semi-naturalistic social behavior in nonhuman primates after discrete lesions of this cortical area. In the present report, we evaluated the behavior of adult rhesus monkeys during dyadic social interactions with novel animals following discrete lesions of the orbitofrontal cortex. In a constrained condition, in which animals could engage in only restricted social behaviors, there were no significant differences in social behavior between the lesion group and the sham-operated control group. When the experimental animals could freely interact with partner animals, however, lesioned animals differed from control animals in terms of social interest and fear-related behaviors. These alterations were contingent on the partner with which they interacted. The lesioned animals, when compared to the control animals, had a significantly greater propensity to approach some but not all of their social partners. They also grimaced more towards the partner animal that they did not approach. Behavioral alterations were more apparent during the initial interactions between animals. We discuss these findings in relation to the role of the orbitofrontal cortex in context dependent modulation of social behavior.

Neonatal amygdala lesions alter responsiveness to objects in juvenile macaques.

The amygdala is widely recognized to play a central role in emotional processing. In nonhuman primates, the amygdala appears to be critical for generating appropriate behavioral responses in emotionally salient contexts. One common finding is that macaque monkeys that receive amygdala lesions as adults are behaviorally uninhibited in the presence of potentially dangerous objects. While control animals avoid these objects, amygdala-lesioned animals readily interact with them. Despite a large literature documenting the role of the amygdala in emotional processing in adult rhesus macaques, little research has assessed the role of the amygdala across the macaque neurodevelopmental trajectory. We assessed the behavioral responses of 3-year-old (juvenile) rhesus macaques that received bilateral ibotenic acid lesions of the amygdala or hippocampus at 2 weeks of age. Animals were presented with salient objects known to produce robust fear-related responses in macaques (e.g., snakes and reptile-like objects), mammal-like objects that included animal-like features (e.g., eyes and mouths) but not reptile-like features (e.g., scales), and non-animal objects. The visual complexity of objects was scaled to vary the objects' salience. In contrast to control and hippocampus-lesioned animals, amygdala-lesioned animals were uninhibited in the presence of potentially dangerous objects. They readily retrieved food rewards placed near these objects and physically explored the objects. Furthermore, while control and hippocampus-lesioned animals differentiated between levels of object complexity, amygdala-lesioned animals did not. Taken together, these findings suggest that early damage to the amygdala, like damage sustained during adulthood, permanently compromises emotional processing.

Interest in infants by female rhesus monkeys with neonatal lesions of the amygdala or hippocampus.

Previous research in our laboratory has shown that damage to the amygdala in neonatal rhesus monkeys profoundly alters behaviors associated with fear processing, while leaving many aspects of social development intact. Little is known, however, about the impact of neonatal lesions of the amygdala on later developing aspects of social behavior. A well-defined phenomenon in the development of young female rhesus monkeys is an intense interest in infants that is typically characterized by initiating proximity or attempting to hold them. The extent to which young females are interested in infants may have important consequences for the development of species-typical maternal behavior. Here we report the results of a study that was designed to assess interest in infants by female rhesus monkeys that received neonatal lesions to the amygdala, hippocampus or a sham surgical procedure. Subjects were first paired with pregnant "stimulus" females to assess social interactions with them prior to the birth of the infants. There were few behavioral differences between lesion groups when interacting with the pregnant females. However, following the birth of the infants, the amygdala-lesioned females showed significantly less interest in the infants than did control or hippocampus-lesioned females. They directed fewer affiliative vocalizations and facial expressions to the mother-infant pair compared to the hippocampus-lesioned and control females. These findings suggest that neonatal damage to the amygdala, but not the hippocampus, impairs important precursors of non-human primate maternal behavior.

Emergence of stereotypies in juvenile monkeys (Macaca mulatta) with neonatal amygdala or hippocampus lesions.

The emergence of stereotypies was examined in juvenile rhesus monkeys (Macaca mulatta) who, at 2 weeks of postnatal age, received selective bilateral ibotenic acid lesions of the amygdala (N = 8) or hippocampus (N = 8). The lesion groups were compared to age-matched control subjects that received a sham surgical procedure (N = 8). All subjects were maternally reared for the first 6 months and provided access to social groups throughout development. Pronounced stereotypies were not observed in any of the experimental groups during the first year of life. However, between 1 to 2 years of age, both amygdala- and hippocampus-lesioned subjects began to exhibit stereotypies. When observed as juveniles, both amygdala- and hippocampus-lesioned subjects consistently produced more stereotypies than the control subjects in a variety of contexts. More interesting, neonatal lesions of either the amygdala or hippocampus resulted in unique repertoires of repetitive behaviors. Amygdala-lesioned subjects exhibited more self-directed stereotypies and the hippocampus-lesioned subjects displayed more head-twisting. We discuss these results in relation to the neurobiological basis of repetitive stereotypies in neurodevelopmental disorders, such as autism.

The expression of social dominance following neonatal lesions of the amygdala or hippocampus in rhesus monkeys (Macaca mulatta).

As part of ongoing studies on the neurobiology of socioemotional behavior in the nonhuman primate, the authors examined the social dominance hierarchy of juvenile macaque monkeys (Macaca mulatta) that received bilateral ibotenic acid lesions of the amygdala or the hippocampus or a sham surgical procedure at 2 weeks of age. The subjects were reared by their mothers with daily access to large social groups. Behavioral observations were conducted while monkeys were given access to a limited preferred food. This testing situation reliably elicited numerous species-typical dominance behaviors. All subjects were motivated to retrieve the food when tested individually. However, when a group of 6 monkeys was given access to only 1 container of the preferred food, the amygdala-lesioned monkeys had less frequent initial access to the food, had longer latencies to obtain the food, and demonstrated fewer species-typical aggressive behaviors. They were thus lower ranking on all indices of social dominance. The authors discuss these findings in relation to the role of the amygdala in the establishment of social rank and the regulation of aggression and fear.